Michael Eisenberg, MD

All Publications

• Preconception Antidiabetic Drugs in Men and Birth Defects in Offspring : A Nationwide Cohort Study. Annals of internal medicine Wensink, M. J., Lu, Y., Tian, L., Shaw, G. M., Rizzi, S., Jensen, T. K., Mathiesen, E. R., Skakkebæk, N. E., Lindahl-Jacobsen, R., Eisenberg, M. L. 2022

  Abstract

  Diabetes reduces semen quality and increasingly occurs during reproductive years. Diabetes medications, such as metformin, have glucose-independent effects on the male reproductive system. Associations with birth defects in offspring are unknown.To evaluate whether the risk for birth defects in offspring varies with preconceptional pharmacologic treatment of fathers with diabetes.Nationwide prospective registry-based cohort study.Denmark from 1997 to 2016.All liveborn singletons from mothers without histories of diabetes or essential hypertension.Offspring were considered exposed if their father filled 1 or more prescriptions for a diabetes drug during the development of fertilizing sperm. Sex and frequencies of major birth defects were compared across drugs, times of exposure, and siblings.Of 1 116 779 offspring included, 3.3% had 1 or more major birth defects (reference). Insulin-exposed offspring (n = 5298) had the reference birth defect frequency (adjusted odds ratio [aOR], 0.98 [95% CI, 0.85 to 1.14]). Metformin-exposed offspring (n = 1451) had an elevated birth defect frequency (aOR, 1.40 [CI, 1.08 to 1.82]). For sulfonylurea-exposed offspring (n = 647), the aOR was 1.34 (CI, 0.94 to 1.92). Offspring whose fathers filled a metformin prescription in the year before (n = 1751) or after (n = 2484) sperm development had reference birth defect frequencies (aORs, 0.88 [CI, 0.59 to 1.31] and 0.92 [CI, 0.68 to 1.26], respectively), as did unexposed siblings of exposed offspring (3.2%; exposed vs. unexposed OR, 1.54 [CI, 0.94 to 2.53]). Among metformin-exposed offspring, genital birth defects, all in boys, were more common (aOR, 3.39 [CI, 1.82 to 6.30]), while the proportion of male offspring was lower (49.4% vs. 51.4%, P = 0.073).Information on underlying disease status was limited.Preconception paternal metformin treatment is associated with major birth defects, particularly genital birth defects in boys. Further research should replicate these findings and clarify the causation.National Institutes of Health.

  View details for DOI 10.7326/M21-4389

  View details for PubMedID 35344380

• Association of paternal age with perinatal outcomes between 2007 and 2016 in the United States: population based cohort study. BMJ (Clinical research ed.) Khandwala, Y. S., Baker, V. L., Shaw, G. M., Stevenson, D. K., Lu, Y., Eisenberg, M. L. 2018; 363: k4372

  Abstract

  OBJECTIVE: To evaluate the impact of advanced paternal age on maternal and perinatal outcomes in the United States.DESIGN: Retrospective, population based cohort study.SETTING: US.POPULATION: 40529905 documented live births between 2007 and 2016.MAIN OUTCOME MEASURES: Primary perinatal outcomes were gestational age, birth weight, Apgar score at five minutes, admission to a neonatal intensive care unit, need for postpartum antibiotics, and seizures. Primary maternal outcomes were gestational diabetes and pre-eclampsia. Secondary outcome was the number of preventable perinatal events.RESULTS: Higher paternal age was associated with an increased risk of premature birth, low birth weight, and low Apgar score. After adjustment for maternal age, infants born to fathers aged 45 years or older had 14% higher odds of premature birth (odds ratio 1.14, 95% confidence interval 1.13 to 1.15), independent of gestational age, and 18% higher odds of seizures (1.18, 0.97 to 1.44) compared with infants of fathers aged 25 to 34 years. The odds of gestational diabetes was 34% higher (1.34, 1.29 to 1.38) in mothers with the oldest partners. 13.2% (95% confidence interval 12.5% to 13.9%) of premature births and 18.2% (17.5% to 18.9%) of gestational diabetes in births associated with older fathers were estimated to be attributable to advanced paternal age.CONCLUSIONS: Advanced paternal age is associated with negative effects on both mothers and offspring. Given the relatively low prevalence of advanced paternal age in the US, population level impacts are currently modest. Nevertheless, as advanced paternal age has doubled in the US over the past generation, further investigation is warranted of the impact on birth outcomes and public health.

  View details for PubMedID 30381468

• Male infertility as a window to health. Fertility and sterility Choy, J. T., Eisenberg, M. L. 2018; 110 (5): 810–14

  Abstract

  There is an emerging body of evidence suggesting that male infertility may be a harbinger of future health. Potential associations between infertility and health may arise from genetic, developmental, and lifestyle factors. Studies have explored possible links between male infertility and oncologic, cardiovascular, metabolic, and autoimmune diseases. Male infertility may also be a predictor of hospitalization and mortality. Additional research is required to elucidate the mechanisms by which male infertility affects overall health.

  View details for PubMedID 30316415

• The age of fathers in the USA is rising: an analysis of 168 867 480 births from 1972 to 2015. Human reproduction (Oxford, England) Khandwala, Y. S., Zhang, C. A., Lu, Y. n., Eisenberg, M. L. 2017; 32 (10): 2110–16

  Abstract

  How has the mean paternal age in the USA changed over the past 4 decades?The age at which men are fathering children in the USA has been increasing over time, although it varies by race, geographic region and paternal education level.While the rise in mean maternal age and its implications for fertility, birth outcomes and public health have been well documented, little is known about paternal characteristics of births within the USA.A retrospective data analysis of paternal age and reporting patterns for 168 867 480 live births within the USA since 1972 was conducted.All live births within the USA collected through the National Vital Statistics System (NVSS) of the Centers for Disease Control and Prevention (CDC) were evaluated. Inverse probability weighting (IPW) was used to reduce bias due to missing paternal records.Mean paternal age has increased over the past 44 years from 27.4 to 30.9 years. College education and Northeastern birth states were associated with higher paternal age. Racial/ethnic differences were also identified, whereby Asian fathers were the oldest and Black fathers were the youngest. The parental age difference (paternal age minus maternal age) has decreased over the past 44 years. Births to Black and Native American mothers were most often lacking paternal data, implying low paternal reporting. Paternal reporting was higher for older and more educated women.Although we utilized IPW to reduce the impact of paternal reporting bias, our estimates may still be influenced by the missing data in the NVSS.Paternal age is rising within the USA among all regions, races and education levels. Given the implications for offspring health and demographic patterns, further research on this trend is warranted.No funding was received for this study and there are no competing interests.N/A.

  View details for PubMedID 28938735

• Frequency of the Male Infertility Evaluation: Data from the National Survey of Family Growth JOURNAL OF UROLOGY Eisenberg, M. L., Lathi, R. B., Baker, V. L., Westphal, L. M., Milki, A. A., Nangia, A. K. 2013; 189 (3): 1030-1034

  Abstract

  An estimated 7 million American couples per year seek infertility care in the United States. A male factor contributes to 50% of cases but it is unclear what proportion of infertile couples undergoes male evaluation.We analyzed data from cycles 5 to 7 of the National Survey of Family Growth performed by the Centers for Disease Control to determine the frequency of a male infertility evaluation, and associated reproductive and demographic factors.A total of 25,846 women and 11,067 men were surveyed. Male evaluation was not completed in 18% of couples when the male partner was asked vs 27% when female partners were asked. This corresponds to approximately 370,000 to 860,000 men in the population who were not evaluated at the time of infertility evaluation. Longer infertility duration and white race were associated with increased odds of male infertility evaluation. The male and female samples showed no change in the receipt of male examination with time.Many men from infertile couples do not undergo male evaluation in the United States. Given the potential implications to reproductive goals and male health, further examination of this pattern is warranted.

  View details for DOI 10.1016/j.juro.2012.08.239

  View details for PubMedID 23009868

• The paternal role in pregnancy loss. Andrology Muncey, W., Scott, M., Lathi, R. B., Eisenberg, M. L. 2024

  Abstract

  In this comprehensive review, the intricate relationship between paternal factors and pregnancy loss is examined. While pregnancy loss has historically been predominantly attributed to maternal factors, recent research underscores the significant contribution of the male partner. The review delves into various aspects of paternal influence, including paternal age, health, chromosome abnormalities, Y chromosome deletions, and sperm DNA fragmentation. Notably, advanced paternal age is found to be associated with an increased risk of recurrent pregnancy loss, shedding light on the importance of understanding the impact of aging on male fertility. Additionally, paternal health, particularly metabolic syndrome, emerges as a noteworthy factor contributing to pregnancy loss. Chromosome abnormalities in male partners, such as balanced translocations, and Y chromosome microdeletions are explored in the context of pregnancy loss risk. Moreover, the review highlights the growing body of evidence linking sperm DNA fragmentation and sperm protein abnormalities to spontaneous pregnancy loss, emphasizing the significance of sperm health in reproductive outcomes. Overall, this review provides a comprehensive overview of the multifaceted role of the male partner in pregnancy loss, calling for a more inclusive approach to pregnancy loss investigations that encompasses both maternal and paternal factors.

  View details for DOI 10.1111/andr.13603

  View details for PubMedID 38334037

• Systematic review and meta-analysis of serum total testosterone and luteinizing hormone variations across hospitalized Covid-19 patients. Scientific reports Salciccia, S., Moriconi, M., Asero, V., Canale, V., Eisenberg, M. L., Glover, F., Belladelli, F., Seranio, N., Basran, S., De Berardinis, E., Di Pierro, G., Ricciuti, G. P., Chung, B. I., Sciarra, A., Del Giudice, F. 2024; 14 (1): 2786

  Abstract

  A growing body of evidence suggests the role of male hypogonadism as a possible harbinger for poor clinical outcomes across hospitalized Covid-19 patients. Accordingly, we sought to investigate the impact of dysregulated hypothalamic-pituitary-gonadal axis on the severity of the clinical manifestations for hospitalized Covid-19 patients matched with healthy controls through a systematic review and meta-analysis. Databases were searched from inception to March 2022. A standardized mean difference (SMD) meta-analysis focused on hospitalized Covid-19 patients and healthy controls was developed for studies who reported total testosterone (TT) and luteinizing hormone (LH) levels at hospital admission. Overall, n=18 series with n=1575 patients between 2020 and 2022 were reviewed. A significant decrease in SMD of TT levels in Covid-19 patients compared to paired controls was observed (-3.25nmol/L, 95%CI -0.57 and -5.93). This reduction was even more consistent when matching severe Covid-19 patients with controls (-5.04nmol/L, 95%CI -1.26 and -8.82) but similar for Covid-19 survivors and non-survivors (-3.04nmol/L, 95%CI -2.04 and -4.05). No significant variation was observed for serum LH levels across studies. Patient related comorbidities, year of the pandemic, and total lymphocyte count were associated with the observed estimates. TT levels may be a useful serum marker of poor outcomes among Covid-19 patients. These findings may support the development of ad-hoc clinical trials in the Covid-19 risk-group classification and subsequent disease monitoring. The interplay between TT and immune response should be evaluated in future researches.

  View details for DOI 10.1038/s41598-024-53392-7

  View details for PubMedID 38307934

• A prospective cohort study of preconception COVID-19 vaccination and miscarriage. Human reproduction (Oxford, England) Yland, J. J., Wesselink, A. K., Regan, A. K., Hatch, E. E., Rothman, K. J., Savitz, D. A., Wang, T. R., Huybrechts, K. F., Hernández-Díaz, S., Eisenberg, M. L., Wise, L. A. 2023

  Abstract

  To what extent is preconception maternal or paternal coronavirus disease 2019 (COVID-19) vaccination associated with miscarriage incidence?COVID-19 vaccination in either partner at any time before conception is not associated with an increased rate of miscarriage.Several observational studies have evaluated the safety of COVID-19 vaccination during pregnancy and found no association with miscarriage, though no study prospectively evaluated the risk of early miscarriage (gestational weeks [GW] <8) in relation to COVID-19 vaccination. Moreover, no study has evaluated the role of preconception vaccination in both male and female partners.An Internet-based, prospective preconception cohort study of couples residing in the USA and Canada. We analyzed data from 1815 female participants who conceived during December 2020-November 2022, including 1570 couples with data on male partner vaccination.Eligible female participants were aged 21-45 years and were trying to conceive without use of fertility treatment at enrollment. Female participants completed questionnaires at baseline, every 8 weeks until pregnancy, and during early and late pregnancy; they could also invite their male partners to complete a baseline questionnaire. We collected data on COVID-19 vaccination (brand and date of doses), history of SARS-CoV-2 infection (yes/no and date of positive test), potential confounders (demographic, reproductive, and lifestyle characteristics), and pregnancy status on all questionnaires. Vaccination status was categorized as never (0 doses before conception), ever (≥1 dose before conception), having a full primary sequence before conception, and completing the full primary sequence ≤3 months before conception. These categories were not mutually exclusive. Participants were followed up from their first positive pregnancy test until miscarriage or a censoring event (induced abortion, ectopic pregnancy, loss to follow-up, 20 weeks' gestation), whichever occurred first. We estimated incidence rate ratios (IRRs) for miscarriage and corresponding 95% CIs using Cox proportional hazards models with GW as the time scale. We used propensity score fine stratification weights to adjust for confounding.Among 1815 eligible female participants, 75% had received at least one dose of a COVID-19 vaccine by the time of conception. Almost one-quarter of pregnancies resulted in miscarriage, and 75% of miscarriages occurred <8 weeks' gestation. The propensity score-weighted IRR comparing female participants who received at least one dose any time before conception versus those who had not been vaccinated was 0.85 (95% CI: 0.63, 1.14). COVID-19 vaccination was not associated with increased risk of either early miscarriage (GW: <8) or late miscarriage (GW: 8-19). There was no indication of an increased risk of miscarriage associated with male partner vaccination (IRR = 0.90; 95% CI: 0.56, 1.44).The present study relied on self-reported vaccination status and infection history. Thus, there may be some non-differential misclassification of exposure status. While misclassification of miscarriage is also possible, the preconception cohort design and high prevalence of home pregnancy testing in this cohort reduced the potential for under-ascertainment of miscarriage. As in all observational studies, residual or unmeasured confounding is possible.This is the first study to evaluate prospectively the relation between preconception COVID-19 vaccination in both partners and miscarriage, with more complete ascertainment of early miscarriages than earlier studies of vaccination. The findings are informative for individuals planning a pregnancy and their healthcare providers.This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Health [R01-HD086742 (PI: L.A.W.); R01-HD105863S1 (PI: L.A.W. and M.L.E.)], the National Institute of Allergy and Infectious Diseases (R03-AI154544; PI: A.K.R.), and the National Science Foundation (NSF-1914792; PI: L.A.W.). The funders had no role in the study design, data collection, analysis and interpretation of data, writing of the report, or the decision to submit the paper for publication. L.A.W. is a fibroid consultant for AbbVie, Inc. She also receives in-kind donations from Swiss Precision Diagnostics (Clearblue home pregnancy tests) and Kindara.com (fertility apps). M.L.E. received consulting fees from Ro, Hannah, Dadi, VSeat, and Underdog, holds stock in Ro, Hannah, Dadi, and Underdog, is a past president of SSMR, and is a board member of SMRU. K.F.H. reports being an investigator on grants to her institution from UCB and Takeda, unrelated to this study. S.H.-D. reports being an investigator on grants to her institution from Takeda, unrelated to this study, and a methods consultant for UCB and Roche for unrelated drugs. The authors report no other relationships or activities that could appear to have influenced the submitted work.N/A.

  View details for DOI 10.1093/humrep/dead211

  View details for PubMedID 37864485

• Use of phosphodiesterase 5 inhibitors is not associated with ocular adverse events. The journal of sexual medicine Belladelli, F., Li, S., Zhang, C. A., Muncey, W., Del Giudice, F., Glover, F., Seranio, N., Basran, S., Fallara, G., Montorsi, F., Salonia, A., Eisenberg, M. L. 2023

  Abstract

  Phosphodiesterase 5 inhibitor (PDE5i) use has been linked to a number of ocular side effects, such as serous retinal detachment (SRD), retinal vascular occlusion (RVO), and ischemic optic neuropathy (ION).We investigated the risk for SRD, RVO, and ION in patients using PDE5is.We utilized the IBM MarketScan (2007-2021) Commercial and Medicare Supplemental Databases (version 2.0) for this analysis. To estimate overall events risk, Cox proportional hazard models were applied to calculate the hazard ratios (HRs) for erectile dysfunction (ED) diagnosis and the different treatments, adjusting for region, median age, obesity, diabetes mellitus, hyperlipidemia, smoking, hypertension, coronary artery disease, and sleep apnea. Additionally, the same analyses were performed to calculate the HRs for benign prostatic hyperplasia (BPH) diagnosis and the different treatments.HRs for SRD, RVO, and ION.In total, 1 938 262 men with an ED diagnosis were observed during the study period. Among them, 615 838 (31.8%) were treated with PDE5is. In total, 2 175 439 men with a BPH diagnosis were observed during the study period. Among them, 175 725 (8.1%) were treated with PDE5is. On adjusted Cox regression analysis, PDE5i use was not associated with SRD, RVO, ION, and any ocular event when compared with ED diagnosis and other ED treatments. Importantly, as the intensity of ED treatment increased, so did the risk of ocular events. In addition, PDE5i use was not associated with SRD and ION when compared with BPH diagnosis and other BPH treatments. In contrast, in patients with BPH, PDE5i use was associated with RVO (HR, 1.14; 95% CI, 1.06-1.23). Importantly, patients with BPH receiving other medical treatment (ie, 5a reductase/alpha blocker; HR, 1.11; 95% CI, 1.06-1.16) or surgical treatment (HR, 1.10; 95% CI, 1.02-1.19) had a higher risk of RVO.We did not observe any consistent association between PDE5i use and any ocular adverse events (SRD, RVO, and ION).Because we did not have access to the patients' medical records, we recorded outcome definitions using ICD-9 and ICD-10 coding.Patients using PDE5is for ED or BPH indications did not have an increased risk of ocular events, even when compared with other treatments for ED or BPH.

  View details for DOI 10.1093/jsxmed/qdad137

  View details for PubMedID 37861186

• Frequency, morbidity and equity - the case for increased research on male fertility. Nature reviews. Urology Kimmins, S., Anderson, R. A., Barratt, C. L., Behre, H. M., Catford, S. R., De Jonge, C. J., Delbes, G., Eisenberg, M. L., Garrido, N., Houston, B. J., Jørgensen, N., Krausz, C., Lismer, A., McLachlan, R. I., Minhas, S., Moss, T., Pacey, A., Priskorn, L., Schlatt, S., Trasler, J., Trasande, L., Tüttelmann, F., Vazquez-Levin, M. H., Veltman, J. A., Zhang, F., O'Bryan, M. K. 2023

  Abstract

  Currently, most men with infertility cannot be given an aetiology, which reflects a lack of knowledge around gamete production and how it is affected by genetics and the environment. A failure to recognize the burden of male infertility and its potential as a biomarker for systemic illness exists. The absence of such knowledge results in patients generally being treated as a uniform group, for whom the strategy is to bypass the causality using medically assisted reproduction (MAR) techniques. In doing so, opportunities to prevent co-morbidity are missed and the burden of MAR is shifted to the woman. To advance understanding of men's reproductive health, longitudinal and multi-national centres for data and sample collection are essential. Such programmes must enable an integrated view of the consequences of genetics, epigenetics and environmental factors on fertility and offspring health. Definition and possible amelioration of the consequences of MAR for conceived children are needed. Inherent in this statement is the necessity to promote fertility restoration and/or use the least invasive MAR strategy available. To achieve this aim, protocols must be rigorously tested and the move towards personalized medicine encouraged. Equally, education of the public, governments and clinicians on the frequency and consequences of infertility is needed. Health options, including male contraceptives, must be expanded, and the opportunities encompassed in such investment understood. The pressing questions related to male reproductive health, spanning the spectrum of andrology are identified in the Expert Recommendation.

  View details for DOI 10.1038/s41585-023-00820-4

  View details for PubMedID 37828407

  View details for PubMedCentralID 8706130

• The association between glyphosate exposure and metabolic syndrome among US adults HUMAN AND ECOLOGICAL RISK ASSESSMENT Glover, F., Jean-Baptiste, O., Del Giudice, F., Belladelli, F., Seranio, N., Muncey, W., Eisenberg, M. L. 2023

  View details for DOI 10.1080/10807039.2023.2256886

  View details for Web of Science ID 001102853400001

• Too much or not enough: lifestyle modifcations to optimize male fertility. Fertility and sterility Eisenberg, M. L. 2023

  Abstract

  This month's Views and Reviews examines the current literature on modifiable factors that men can do to optimize reproductive health. Gaskins et al provides an overview of dietary factors including specific foods, diets and nutrients associated with male fertility. Service and colleagues then provider an update on body mass index, weight loss, and male reproduction. Garabed et al examines the data behind medications utilizing the Anatomical Therapeutic Chemical (ATC) Classification system. Mínguez-Alarcón et al review data on chemical exposures and male fertility. Overall, the goal of the section is to allow providers with up to date evidence to counsel our patients on factors they can seek or avoid.

  View details for DOI 10.1016/j.fertnstert.2023.10.010

  View details for PubMedID 37827480

• PROSPECTIVE STUDY OF SEMEN QUALITYAND FECUNDABILITY IN NORTH AMERICAN COUPLES. Lovett, S. M., Wang, T. R., Sommer, G. J., Seranio, N., Wesselink, A. K., Rothman, K. J., Hatch, E. E., Eisenberg, M., Wise, L. A. ELSEVIER SCIENCE INC. 2023: E289

  View details for Web of Science ID 001084670200682

• LEVERAGING ELECTRONIC MEDICAL RECORDS REVEALS COMORBIDITIES SIGNIFICANTLY ASSOCIATED WITH MALE INFERTILITY Woldemariam, S., Xie, F., Roldan, A., Roger, J., Tang, A., Oskotsky, T., Aghaeepour, N., Eisenberg, M., Sirota, M. ELSEVIER SCIENCE INC. 2023: E53-E54

  View details for Web of Science ID 001084670200128

• ASSOCIATION BETWEEN MALE PARTNER ALCOHOL USE AND SPONTANEOUS ABORTION: A PRECONCEPTION COHORT STUDY Seranio, N., Wang, T. R., Lovett, S. M., Wesselink, A. K., Hatch, E. E., Rothman, K. J., Wise, L. A., Eisenberg, M. ELSEVIER SCIENCE INC. 2023: E255

  View details for Web of Science ID 001084670200600

• Male infertility. Nature reviews. Disease primers Eisenberg, M. L., Esteves, S. C., Lamb, D. J., Hotaling, J. M., Giwercman, A., Hwang, K., Cheng, Y. 2023; 9 (1): 49

  Abstract

  Clinical infertility is the inability of a couple to conceive after 12 months of trying. Male factors are estimated to contribute to 30-50% of cases of infertility. Infertility or reduced fertility can result from testicular dysfunction, endocrinopathies, lifestyle factors (such as tobacco and obesity), congenital anatomical factors, gonadotoxic exposures and ageing, among others. The evaluation of male infertility includes detailed history taking, focused physical examination and selective laboratory testing, including semen analysis. Treatments include lifestyle optimization, empirical or targeted medical therapy as well as surgical therapies that lead to measurable improvement in fertility. Although male infertility is recognized as a disease with effects on quality of life for both members of the infertile couple, fewer data exist on specific quantification and impact compared with other health-related conditions.

  View details for DOI 10.1038/s41572-023-00459-w

  View details for PubMedID 37709866

• Effect of Testicular Boost in Children With Leukemia Receiving Total Body Irradiation and Stem Cell Transplant: A Single-Institution Experience. Advances in radiation oncology Blomain, E. S., Jiang, A., Donaldson, S. S., Agarwal, R., Bertaina, A., Shyr, D., Eisenberg, M. L., Hoppe, R. T., Hiniker, S. M., Oh, J. 2023; 8 (1): 101071

  Abstract

  Children with leukemia who receive fractionated total body irradiation (fTBI) with 12 to 13.2 Gy as part of conditioning for hematopoietic stem cell transplant are frequently treated with an additional 4 Gy testicular boost to reduce the risk of testicular relapse. While institutional practices vary, limited data exists regarding whether the 4-Gy testicular boost reduces the risk of relapse and whether it causes toxicity beyond that imparted by TBI. This study compared the survival and endocrine outcomes among the patients who were treated with and without a testicular boost as part of fTBI from 1990 to 2019 at our center.We retrospectively reviewed charts of male children with leukemia treated with fTBI as part of a conditioning regimen for stem cell transplant from 1990 to 2019. Reported outcomes included progression-free survival, testicular relapse rate, and overall survival. Gonadal dysfunction and fertility were assessed by comparing the rate of abnormally low testosterone or high luteinizing hormone or follicular stimulating hormone, number of offspring, fertility service use, and abnormal sperm count in the subsequent follow-up period between the testicular boost and nonboost subset.Ninety-three male patients (63 acute lymphoblastic leukemia, 30 acute myeloid leukemia) with a median age of 9 years (range, 1-22) and follow-up of 3.3 years were included. In addition to 12- to 13.2-Gy fTBI, 51 male patients (54%) received a testicular boost to 4 Gy. There was 1 testicular relapse in the boost subset and none in the nonboost subset. Five-year progression-free survival for the boost and nonboost subset was 74% and 66%, respectively (P = .31). On multivariable analysis, boost was not associated with improved relapse-free survival or overall survival. More patients in the boost subset (35 of 51, 69%) had abnormal serum gonadal blood work compared with the nonboost subset (18 of 42, 43%) (P = .03).Omission of testicular boost may be associated with comparable oncologic but improved gonadal endocrine outcomes and should be further studied.

  View details for DOI 10.1016/j.adro.2022.101071

  View details for PubMedID 36483061

  View details for PubMedCentralID PMC9723295

• The Association Between Insomnia, Insomnia Medications, and Erectile Dysfunction. European urology focus Belladelli, F., Li, S., Zhang, C. A., Del Giudice, F., Basran, S., Muncey, W., Glover, F., Seranio, N., Fallara, G., Montorsi, F., Salonia, A., Eisenberg, M. L. 2023

  Abstract

  Sleep quality and duration have been investigated for their association with health. Insomnia affects up to one-third of adults and may impact male erectile function. In addition, medical treatments for insomnia (many of which are sedatives) may also affect erectile quality.To investigate the association of erectile dysfunction (ED) in patients diagnosed with and treated for insomnia.We utilized the IBM MarketScan (2007-2016) Commercial and Medicare Supplemental Databases (v 2.0). Age- and enrollment-matched controls were selected among patients without insomnia diagnosis or treatment.Cox proportional hazard models were used to estimate the risk of incident ED (ie, diagnosis alone, or diagnosis and treatment with phosphodiesterase-5 inhibitors [PDE5i], intracavernous injection (ICI)/urethral suppositories, and penile prosthesis) after the diagnosis or treatment of insomnia while adjusting for relevant comorbidities.In total, 539 109 men with an insomnia diagnosis were identified. Of these men, 356 575 were also medically treated for insomnia. The mean (±standard deviation) follow-up times for patients diagnosed with insomnia and those diagnosed with and treated for insomnia were 2.8 ± 1.6 and 3.1 ± 1.8 yr, respectively. Men with insomnia were more commonly smokers and had a higher number of office visits and comorbidities than controls (p < 0.001). On an adjusted analysis, both untreated and treated insomnia were associated with increased risks of ED diagnosis (hazard ratio or HR [95% confidence interval {CI}]: 1.58 [1.54-1.62] and 1.66 [1.64-1.69], respectively; p < 0.001). Similarly, men with treated insomnia had a higher risk of having ED treated with PDE5i (HR [95% CI]: 1.52 [1.49-1.55]; p < 0.001) and ICI (HR [95% CI]: 1.32 [1.14-1.54]; p < 0.001) when compared with controls. A limitation of this study was that a lack of granularity regarding patient clinical characteristics (eg, severity of disease, laboratory data, etc.) is inherent to insurance claims data. In addition, the follow-up was limited and may affect associations at longer time points.In the current report, a consistent association between insomnia and ED diagnosis was identified. Men diagnosed with insomnia only were found to have a higher risk of developing ED. Moreover, men with pharmacological insomnia treatments were more often prescribed treatments for ED. Given the prevalence of insomnia, future studies are warranted to delineate the association of insomnia and its treatment with erectile function.Insomnia affects up to one-third of adults and impact male erectile function. Men only diagnosed with insomnia were found to have a higher risk of developing erectile dysfunction (ED). Moreover, men with pharmacological insomnia treatments were more often prescribed treatments for ED.

  View details for DOI 10.1016/j.euf.2023.08.005

  View details for PubMedID 37690918

• 5-alpha reductase inhibitors (5-ARi) with or without alpha-blockers (alpha-B) for Benign Prostatic Hyperplasia do NOT lower the risk of incident Bladder Cancer: United States insurance claims data. World journal of urology Del Giudice, F., Belladelli, F., Glover, F., Basran, S., Li, S., Mulloy, E., Pradere, B., Soria, F., Krajewski, W., Nair, R., Muncey, W., Seranio, N., Eisenberg, M. L. 2023

  Abstract

  BACKGROUND: Chemoprotective effect of 5-alpha reductase inhibitors (5-ARi) on bladder cancer (BCa) risk in men with Benign Prostatic Hyperplasia (BPH) has been explored with conflicting results. We sought to examine the effect of 5-ARi on new BCa diagnoses in a large US database.METHODS: Men≥50 y/o with a prescription for 5-ARi after BPH diagnosis were identified in the IBM Marketscan Research de-identified Databases between 2007 and 2016 and matched with paired controls. Incident BCa diagnoses were identified after BPH diagnosis and/or pharmacologic treatment. Multivariable regression modeling adjusting for relevant factors was implemented. Sub-group analyses by exposure risk were performed to explore the association between 5-ARi and BCa over time. Administration of alpha-blockers (alpha-B) w/o 5-ARi was also examined.RESULTS: In total, n=24,036 men on 5-ARi, n=107,086 on 5-ARi plus alpha-blockers, and n=894,275 without medical therapy for BPH were identified. The percentage of men diagnosed with BCa was 0.8% for the 5-ARi, 1.4% for the 5-ARi+alpha-B, and 0.6% for the untreated BPH group of incident BCa (adjusted hazard ratio [aHR], 0.90, 95% confidence interval [CI] 0.56 - 1.47), and 1.08, 95%CI 0.89 - 1.30, respectively). This was also true at both shorter (≤2yr) and longer-term (>2yr) follow up. In addition, alpha-B alone had no change in BCa risk (HR 1.06, 0.86-1.30).CONCLUSIONS: We did not find any diminished risk of new BCa in men treated with 5-ARi (i.e., chemoprotective effect). The current report suggests that 5-ARi do not change a man's bladder cancer risk.

  View details for DOI 10.1007/s00345-023-04551-4

  View details for PubMedID 37548746

• Diagnoses and medications associated with delayed ejaculation. Sexual medicine Mulloy, E., Zhang, A., Balladelli, F., Del Giudice, F., Glover, F., Eisenberg, M. L. 2023; 11 (4): qfad040

  Abstract

  Background: Delayed ejaculation (DE) is a disorder that can cause significant distress for sexually active men. The etiology of DE is largely idiopathic, with even less being known about clinical factors associated with the condition.Aim: We sought to use data mining techniques to examine a broad group of health conditions and pharmaceutical treatments to identify factors associated with DE.Methods: Using an insurance claims database, we evaluated all men with a diagnosis of DE and matched them to a cohort (1:1) of men with other male sexual disorders of urologic origin (ie, erectile dysfunction [ED] and Peyronie's disease [PD]). Given the low prevalence of DE, we incorporated the random forest approach for classification of DE vs controls, with a plethora of predictors and cross-validation with the least absolute shrinkage and selection operator (LASSO). We used both a high-performance generalized linear model and a multivariate logistic model. The area under the curve was reported to demonstrate classifier performance, and odds ratios were used to indicate risks of each predictor. We also evaluated for differences in the prevalence of conditions in DE by race/ethnicity.Outcomes: Clinical factors (ie, diagnoses and medications) associated with DE were identified.Results: In total, 11602 men with DE were matched to a cohort of men with PD and ED. We focused on the 20 factors with the strongest association with DE across all models. The factors demonstrating positive associations with DE compared to other disorders of male sexual dysfunction (ie, ED and PD) included male infertility, testicular dysfunction, anxiety, disorders of lipid metabolism, alpha adrenergic blocker use, anemia, antidepressant use, and psychoses such as schizophrenia or schizoaffective disorder. In addition, the prevalence of several conditions varied by race/ethnicity. For example, male infertility was present in 5% of Asian men compared to <2% of men of other races.Clinical Implications: Several medical conditions and pharmacologic treatments are associated with DE, findings that may provide insight into the etiology of DE and offer treatment options.Strengths and Limitations: This study is to our knowledge the first to use using data mining techniques to investigate the association between medical conditions/pharmacologic agents and the development of subsequent DE. The generalizability of our findings is limited given that all men were commercially insured.Conclusion: DE is associated with multiple medical conditions, a finding that may help identify the etiology for this disorder.

  View details for DOI 10.1093/sexmed/qfad040

  View details for PubMedID 37547871

• A Call for Action in Penile Augmentation: Lessons from Plastic Surgery. Urology Seranio, N., Muncey, W., Eisenberg, M. L. 2023

  View details for DOI 10.1016/j.urology.2023.07.012

  View details for PubMedID 37482103

• An Analysis of Political Contributions by Urologists in the United States: 2003-2022. Urology practice Seranio, N., Muncey, W., Eisenberg, M. L. 2023; 10 (4): 335-341

  Abstract

  We sought to better understand the amounts and distribution of political contributions made by urologists in the United States.The Federal Election Commission was analyzed for political contributions from 2003 to 2022 using the search terms "urology," "urologist," or "urologic surgeon." Contributions were classified by political party (Democratic, Republican, or Independent) and were analyzed for temporal, geographic, and demographic trends.There were a total of 26,441 unique contributions that resulted in $9,943,205 after adjusting for inflation. The total amount of political contributions increased significantly over time, with higher numbers during presidential election years. The Republican party received the highest proportion of donations (69.1%). Importantly, women urologists and urologists working in academic centers were significantly more likely to contribute to Democratic committees (P < .001 for both). Texas had the highest total amount of contributions ($395,152). Overall contributions to urology political action committees have steadily decreased since 2011, while contributions to individual campaigns and nonurology political action committees have increased.Urologists have been increasingly contributing to political campaigns over the past 19 years, with most of their individual and political action committee contributions going to Republican committees and candidates. Future research evaluating how growing political engagement by urologists affects the development of new health care policy will be important as a new generation of urologists begins to enter practice.

  View details for DOI 10.1097/UPJ.0000000000000413

  View details for PubMedID 37341369

• Should a negative microsurgical testicular sperm extraction be repeated routinely? Fertility and sterility Bole, R., Lundy, S. D., Vij, S., Lipshultz, L. I., Lindsey, J. P., Torres-Anguiano, J. R., Eisenberg, M. L. 2023

  View details for DOI 10.1016/j.fertnstert.2023.05.167

  View details for PubMedID 37395689

• Size matters: characterizing penile augmentation content from the 100 most popular YouTube videos. International journal of impotence research Seranio, N., Muncey, W., Cox, S., Belladelli, F., Del Giudice, F., Glover, F., Eisenberg, M. L. 2023

  Abstract

  Aesthetic penile augmentation is considered investigational and not shown to be safe or efficacious. This study sought to characterize the quality and reliability of YouTube videos on the topic of penile augmentation. A systematic search identifying the 100 most viewed YouTube videos on penile augmentation was conducted. The videos were then evaluated by two independent urologists for reliability and quality using a modified DISCERN scoring system and Global Quality Scale (GQS). The median total views were 530,612 (range 123,478-32,914,713). The median DISCERN and GQS scores for all 100 videos were generally poor at 1.75 (IQR 1-2.63) and 2.5 (IQR 1.5-3.5), respectively. A little under half of the videos had a physician present (44.7%). DISCERN and GQS scores were significantly higher in videos with physicians compared to those without one (p < 0.001 for both). The majority of videos discussed nonsurgical methods of penile augmentation (65.1%) with penile traction devices being the most frequently discussed (19.2%). Urologists and medical organizations should strive to have more of a presence in this space to ensure patients are appropriately educated and counseled before pursuing potentially ineffective or harmful treatments.

  View details for DOI 10.1038/s41443-023-00728-y

  View details for PubMedID 37380757

  View details for PubMedCentralID 8555574

• Hyperestrogenism is associated with sexual function impairment in men - findings from a cross-sectional, real-life study. Andrology Belladelli, F., Boeri, L., Fallara, G., Pozzi, E., Corsini, C., Cilio, S., Capogrosso, P., d'Arma, A., Eisenberg, M. L., Montorsi, F., Salonia, A. 2023

  Abstract

  Hyperestrogenism is believed to be harmful to male sexuality. We aimed to investigate the prevalence of and the impact of hyperestrogenism on sexual functioning in a cohort of men seeking medical attention for new onset erectile dysfunction (ED).Data from 547 men seeking first medical help for new-onset ED at a single andrology center were analyzed. Patients were assessed with a thorough medical and sexual history. Comorbidities were scored with the Charlson Comorbidity Index (CCI). All patients completed the International Index of Erectile Function (IIEF); the IIEF-Erectile function (IIEF-EF) domain was categorized according to Cappelleri's criteria. Circulating hormones were measured in every patient. Hyperestrogenism was defined as estradiol (E2 ) levels >42.6 pg/mL (Tan RS, et al. 2015). Descriptive statistics and logistic/linear regression models tested the association between hyperestrogenism and IIEF domains score.Overall, 96 (17.6%) participants had serum estrogen levels suggestive of hyperestrogenism. Men with hyperestrogenism were older [median (IQR) 46 (35-59) vs. 44 (31-56) years; p<0.001], had higher rate of comorbidities [CCI≥1: 26.0% vs. 7.4%; p<0.001] and higher serum total testosterone (tT) values [5.4 (5.2-8.0) vs. 4.3 (4.1-5.7) ng/mL; p = 0.01] than those with normal E2 values. A higher prevalence of severe ED [135 (29.9%) vs. 47 (48.9%) men; p = 0.01] and of hypogonadism [22 (4.8%) vs. 6 (6.3%) men; p = 0.004] were found in men with hyperestrogenism. Serum E2 levels were positively correlated with tT levels (ß 0.26, p<0.001), but negatively correlated with IIEF-OF (ß -0.24, p = 0.002) and IIEF-EF scores (ß -0.03, p<0.001). When IIEF scores were used to stratify ED patients, hyperestrogenism (OR 2.44, p = 0.02) was associated with severe ED.One out of five men seeking first medical help for ED showed elevated serum E2 values suggestive for hyperestrogenism. Hyperestrogenism was associated with health significant comorbidities, orgasmic function impairment, and ED severity. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/andr.13470

  View details for PubMedID 37261881

• Options after a failed microsurgical testicular sperm extraction. Fertility and sterility Eisenberg, M. L. 2023

  View details for DOI 10.1016/j.fertnstert.2023.05.166

  View details for PubMedID 37268045

• Association of male fatty acid intake with fecundability among couples planning pregnancy. Human reproduction (Oxford, England) Geller, R. J., Wesselink, A. K., Koenig, M. R., Eisenberg, M. L., Tucker, K. L., Hatch, E. E., Wise, L. A. 2023

  Abstract

  To what extent is male fatty acid intake associated with fecundability among couples planning pregnancy?We observed weak positive associations of male dietary intakes of total and saturated fatty acids with fecundability; no other fatty acid subtypes were appreciably associated with fecundability.Male fatty acid intake has been associated with semen quality in previous studies. However, little is known about the extent to which male fatty acid intake is associated with fecundability among couples attempting spontaneous conception.We conducted an internet-based preconception prospective cohort study of 697 couples who enrolled during 2015-2022. During 12 cycles of observation, 53 couples (7.6%) were lost to follow-up.Participants were residents of the USA or Canada, aged 21-45 years, and not using fertility treatment at enrollment. At baseline, male participants completed a food frequency questionnaire from which we estimated intakes of total fat and fatty acid subtypes. We ascertained time to pregnancy using questionnaires completed every 8 weeks by female participants until conception or up to 12 months. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% CIs for the associations of fat intakes with fecundability, adjusting for male and female partner characteristics. We used the multivariate nutrient density method to account for energy intake, allowing for interpretation of results as fat intake replacing carbohydrate intake. We conducted several sensitivity analyses to assess the potential for confounding, selection bias, and reverse causation.Among 697 couples, we observed 465 pregnancies during 2970 menstrual cycles of follow-up. The cumulative incidence of pregnancy during 12 cycles of follow-up after accounting for censoring was 76%. Intakes of total and saturated fatty acids were weakly, positively associated with fecundability. Fully adjusted FRs for quartiles of total fat intake were 1.32 (95% CI 1.01-1.71), 1.16 (95% CI 0.88-1.51), and 1.43 (95% CI 1.09-1.88) for the second, third, and fourth vs the first quartile, respectively. Fully adjusted FRs for saturated fatty acid intake were 1.21 (95% CI 0.94-1.55), 1.16 (95% CI 0.89-1.51), and 1.23 (95% CI 0.94-1.62) for the second, third, and fourth vs the first quartile, respectively. Intakes of monounsaturated, polyunsaturated, trans-, omega-3, and omega-6 fatty acids were not strongly associated with fecundability. Results were similar after adjustment for the female partner's intakes of trans- and omega-3 fats.Dietary intakes estimated from the food frequency questionnaire may be subject to non-differential misclassification, which is expected to bias results toward the null in the extreme categories when exposures are modeled as quartiles. There may be residual confounding by unmeasured dietary, lifestyle, or environmental factors. Sample size was limited, especially in subgroup analyses.Our results do not support a strong causal effect of male fatty acid intakes on fecundability among couples attempting to conceive spontaneously. The weak positive associations we observed between male dietary fat intakes and fecundability may reflect a combination of causal associations, measurement error, chance, and residual confounding.The study was funded by the National Institutes of Health, grant numbers R01HD086742 and R01HD105863. In the last 3 years, PRESTO has received in-kind donations from Swiss Precision Diagnostics (home pregnancy tests) and Kindara.com (fertility app). L.A.W. is a consultant for AbbVie, Inc. M.L.E. is an advisor to Sandstone, Ro, Underdog, Dadi, Hannah, Doveras, and VSeat. The other authors have no competing interests to report.N/A.

  View details for DOI 10.1093/humrep/dead100

  View details for PubMedID 37221671

• A North American study of anthropometric factors and semen quality. Fertility and sterility Joseph, M. D., Hatch, E. E., Koenig, M. R., Eisenberg, M. L., Wang, T. R., Sommer, G. J., Stuver, S. O., Rothman, K. J., Wise, L. A. 2023

  Abstract

  OBJECTIVE: To evaluate the association between anthropometric measures and semen parameters.DESIGN: Cross-sectional study.SETTING: General population, United States.SUBJECTS: Male participants aged ≥21 years. We analyzed data from 659 males (1,185 samples) participating in a semen testing substudy of Pregnancy Online Study (PRESTO), a North American preconception cohort study. After enrollment, we invited males aged ≥21 years to perform at-home semen testing using the Trak system.EXPOSURE: Participants reported selected anthropometric variables (current weight, height, waist circumference, and weight at age 17 years) and covariate data via online baseline questionnaire.OUTCOME: We used generalized estimating equations models to estimate the percent difference in mean log-transformed semen parameter values and 95% confidence intervals (CI) for associations between selected anthropometric variables and semen volume (mL), sperm concentration (million/mL), and total sperm count (million), adjusting for socio-demographics, lifestyle factors, and medical history. We also evaluated WHO-defined thresholds for low semen quality.RESULTS: Percentage differences in mean log-transformed semen volume, sperm concentration, and total sperm count (95% CI) comparing current BMI ≥35 vs. <25 kg/m2 were -6.3 (-15.8, 4.3), -6.4 (-24.6, 16.2) and -12.2 (-31.1, 11.8), respectively. Percentage differences (95% CIs) comparing waist circumferences of ≥42 vs. <31 inches were -4.2 (-15.0, 8.0), -6.4 (-27.6, 21.0) and -10.4 (-31.9, 17.9) for semen volume, sperm concentration, and total sperm count, respectively. Greater adult weight gain since age 17 years was associated with reduced semen volume (≥25 vs. <5 kg: percent difference -9.7, 95% CI: -18.4, 0.1), but not sperm concentration or total sperm count. The highest categories of each anthropometric variable were generally associated with WHO-defined low total sperm count (≤39 million).CONCLUSION: Selected anthropometric factors were modestly associated with poorer semen quality.

  View details for DOI 10.1016/j.fertnstert.2023.04.040

  View details for PubMedID 37164117

• Evaluation of glyphosate exposure on testosterone among US adult men HUMAN AND ECOLOGICAL RISK ASSESSMENT Glover, F., Barr, D., Eatman, J., Muncey, W., Del Giudice, F., Belladelli, F., Seranio, N., Eisenberg, M. L. 2023

  View details for DOI 10.1080/10807039.2023.2195005

  View details for Web of Science ID 000974489600001

• Efficacy of Different Bacillus of Calmette-Guérin (BCG) Strains on Recurrence Rates among Intermediate/High-Risk Non-Muscle Invasive Bladder Cancers (NMIBCs): Single-Arm Study Systematic Review, Cumulative and Network Meta-Analysis. Cancers Del Giudice, F., Asero, V., Bologna, E., Scornajenghi, C. M., Carino, D., Dolci, V., Viscuso, P., Salciccia, S., Sciarra, A., D'Andrea, D., Pradere, B., Moschini, M., Mari, A., Albisinni, S., Krajewski, W., Szydełko, T., Małkiewicz, B., Nowak, Ł., Laukhtina, E., Gallioli, A., Mertens, L. S., Marcq, G., Cimadamore, A., Afferi, L., Soria, F., Mori, K., Tully, K. H., Pichler, R., Ferro, M., Tataru, O. S., Autorino, R., Crivellaro, S., Crocetto, F., Busetto, G. M., Basran, S., Eisenberg, M. L., Chung, B. I., De Berardinis, E. 2023; 15 (7)

  Abstract

  In an era of Bacillus of Calmette-Guérin (BCG) shortages, the comparative efficacy from different adjuvant intravesical BCG strains in non-muscle invasive bladder cancer (NMIBC) has not been clearly elucidated. We aim to compare, through a systematic review and meta-analysis, the cumulative BC recurrence rates and the best efficacy profile of worldwide available BCG strains over the last forty years.PubMed, Scopus, Web of Science, Embase, and Cochrane databases were searched from 1982 up to 2022. A meta-analysis of pooled BC recurrence rates was stratified for studies with ≤3-y vs. >3-y recurrence-free survival (RFS) endpoints and the strain of BCG. Sensitivity analysis, sub-group analysis, and meta-regression were implemented to investigate the contribution of moderators to heterogeneity. A random-effect network meta-analysis was performed to compare BCG strains on a multi-treatment level.In total, n = 62 series with n = 15,412 patients in n = 100 study arms and n = 10 different BCG strains were reviewed. BCG Tokyo 172 exhibited the lowest pooled BC recurrence rate among studies with ≤3-y RFS (0.22 (95%CI 0.16-0.28). No clinically relevant difference was noted among strains at >3-y RFS outcomes. Sub-group and meta-regression analyses highlighted the influence of NMIBC risk-group classification and previous intravesical treated categories. Out of the n = 11 studies with n = 7 BCG strains included in the network, BCG RIVM, Tice, and Tokyo 172 presented with the best-predicted probability for efficacy, yet no single strain was significantly superior to another in preventing BC recurrence risk.We did not identify a BCG stain providing a clinically significant lower BC recurrence rate. While these findings might discourage investment in future head-to-head randomized comparison, we were, however, able to highlight some potential enhanced benefits from the genetically different BCG RIVM, Tice, and Tokyo 172. This evidence would support the use of such strains for future BCG trials in NMIBCs.

  View details for DOI 10.3390/cancers15071937

  View details for PubMedID 37046598

• Association between priapism and HIV disease and treatment. The journal of sexual medicine Mulloy, E., Li, S., Belladelli, F., Del Giudice, F., Glover, F., Eisenberg, M. L. 2023

  Abstract

  BACKGROUND: Priapism, a urologic emergency, has known associations with certain medical conditions. Many cases are idiopathic, suggesting an opportunity to identify novel risk factors.AIM: We sought to identify medical conditions and pharmaceutical treatments that are associated with priapism using data-mining techniques.METHODS: Using deidentified data in a large insurance claims database, we identified all men (age≥20 years) with a diagnosis of priapism from 2003 to 2020 and matched them to cohorts of men with other diseases of male genitalia: erectile dysfunction, Peyronie disease, and premature ejaculation. All medical diagnoses and prescriptions used prior to first disease diagnosis were examined. Predictors were selected by random forest, and conditional multivariate logistic regressions were applied to assess the risks of each predictor.OUTCOMES: We identified novel relationships of HIV and some HIV treatments with priapism and confirmed existing associations.RESULTS: An overall 10 459 men with priapism were identified and matched 1:1 to the 3 control groups. After multivariable adjustment, men with priapism had high associations of hereditary anemias (odds ratio [OR], 3.99; 95% CI, 2.73-5.82), use of vasodilating agents (OR, 2.45; 95% CI, 2.01-2.98), use of HIV medications (OR, 1.95; 95% CI, 1.36-2.79), and use of antipsychotic medications (OR, 1.90; 95% CI, 1.52-2.38) as compared with erectile dysfunction controls. Similar patterns were noted when compared with premature ejaculation and Peyronie disease controls.CLINICAL IMPLICATIONS: HIV and its treatment are associated with priapism, which may affect patient counseling.STRENGTHS AND LIMITATIONS: To our knowledge, this is the first study to identify risk factors for priapism utilizing machine learning. All men in our series were commercially insured, which limits the generalizability of our findings.CONCLUSION: Using data-mining techniques, we confirmed existing associations with priapism (eg, hemolytic anemias, antipsychotics) and identified novel relationships (eg, HIV disease and treatment).

  View details for DOI 10.1093/jsxmed/qdad017

  View details for PubMedID 36881738

• Worldwide Temporal Trends in Penile Length: A Systematic Review and Meta-Analysis. The world journal of men's health Belladelli, F., Giudice, F. D., Glover, F., Mulloy, E., Muncey, W., Basran, S., Fallara, G., Pozzi, E., Montorsi, F., Salonia, A., Eisenberg, M. L. 2023

  Abstract

  Normative male genital measurements are clinically useful and temporal changes would have important implications. The aim of the present study is to characterize the trend of worldwide penile length over time.A systematic review and meta-analysis using papers from PubMed, Embase, and Cochrane Library from inception to April 2022 was performed. PRISMA guidelines were used for abstracting data and assessing data quality and validity. Pooled means and standard deviations for flaccid, stretched, and erect length were obtained. Subgroup analyses were performed by looking at differences in the region of origin, population type, and the decade of publication. Metaregression analyses were to adjusted for potential confounders.Seventy-five studies published between 1942 and 2021 were evaluated including data from 55,761 men. The pooled mean length estimates were flaccid length: 8.70 cm (95% CI, 8.16-9.23), stretched length: 12.93 cm (95% CI, 12.48-13.39), and erect length: 13.93 cm (95% CI, 13.20-14.65). All measurements showed variation by geographic region. Erect length increased significantly over time (QM=4.49, df=2, p=0.04) in several regions of the world and across all age groups, while no trends were identified in other penile size measurements. After adjusting for geographic region, subject age, and subject population; erect penile length increased 24% over the past 29 years.The average erect penis length has increased over the past three decades across the world. Given the significant implications, attention to potential causes should be investigated.

  View details for DOI 10.5534/wjmh.220203

  View details for PubMedID 36792094

• Congenital male genital malformations and paternal health: an analysis of US claims data. Andrology Yu, B., Zhang, C. A., Chen, T., Mulloy, E., Shaw, G. M., Eisenberg, M. L. 2023

  Abstract

  OBJECTIVE: To investigate the potential association between paternal health and male genital malformations in the offspring.MATERIALS AND METHODS: We analyzed data from 2007 to 2016 derived from the IBM MarketScan Research database, which reports on reimbursed private healthcare claims in the United States. The association between paternal comorbidities (defined as individual and combined measures) and genital malformations in male offspring was analyzed.RESULTS: Of 376,362 male births, 22% of fathers had at least one component of the metabolic syndrome (MetS ≥1) prior to conception. Totals of 2880 cases of cryptorchidism (0.77%) and 2651 cases of hypospadias (0.70%) were identified at birth. While 0.76% of sons born to fathers with no MetS components were diagnosed with cryptorchidism, 0.82% of sons with fathers with multiple MetS components had cryptorchidism. Similarly, 0.69% vs 0.88% of sons had hypospadias when fathers had 0 or 2+ components of MetS. After adjusting for maternal and paternal factors, the odds of a son diagnosed with hypospadias increased with two or more paternal MetS components (Odds ratio [95% confidence interval]: 1.27 [1.10 - 1.47]). Specific components of paternal MetS were not generally more associated with a son's genital malformations. When we performed a subgroup analysis where genital malformations were defined based on surgical correction, the association with hypospadias persisted.CONCLUSIONS: Fathers with multiple components of the metabolic syndrome in the preconception period were observed to be at increased risks for having sons born with hypospadias. The results support the association between a man's andrological and overall health. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/andr.13404

  View details for PubMedID 36727635

• The Risks of Birth Defects and Childhood Cancer With Conception by Assisted Reproductive Technology OBSTETRICAL & GYNECOLOGICAL SURVEY Luke, B., Brown, M. B., Wantman, E., Schymura, M. J., Browne, M. L., Fisher, S. C., Forestieri, N. E., Rao, C., Nichols, H. B., Yazdy, M. M., Gershman, S. T., Sacha, C. R., Williams, M., Ethen, M. K., Canfield, M. A., Doody, K. J., Eisenberg, M. L., Baker, V. L., Williams, C., Sutcliffe, A. G., Richard, M. A., Lupo, P. J. 2023; 78 (2): 110-111

  View details for DOI 10.1097/01.ogx.0000920652.81635.c8

  View details for Web of Science ID 000940495500016

• Prosteria - National Trends and Outcomes of More Frequent than Guideline Recommended Prostate Specific Antigen Screening. Urology Peterson, D. J., Bhambhvani, H. P., Baird, D. R., Li, S., Eisenberg, M. L., Brooks, J. D. 2023

  Abstract

  To characterize national trends in and associated outcomes of more often than annual PSA screening, which we term "prosteria".Men in the Optum Clinformatics® Data Mart with ≥ 2 years from first PSA test to censoring at the end of insurance or available data (January 2003 to June 2019) or following exclusionary diagnoses or procedures, such as PCa treatment, were included. PSAs within 90 days were treated as one PSA. Prosteria was defined as having ≥3 PSA testing intervals of ≤270 days.9,734,077 PSAs on 2,958,923 men were included. The average inter-PSA testing interval was 1.5 years, and 4.5% of men had prosteria, which increased by 0.53% per year. Educated, wealthy, non-White patients were more likely to have prosteria. Men within the recommended screening age (i.e. 55-69) had lower rates of prosteria. Prosteria patients had higher average PSA values (2.5 vs 1.4 ng/ml), but lower values at PCa diagnosis. Prosteria was associated with biopsy and PCa diagnosis; however, there were comparable rates of treatment within 2 years of diagnosis.In this large cohort study, prosteria was common, increased over time, and was associated with demographic characteristics. Importantly, there were no clinically meaningful differences in PSA values at diagnosis or rates of early treatment, suggesting prosteria leads to both overdiagnosis and overtreatment. These results support current AUA and USPTF guidelines and can be used to counsel men seeking more frequent PSA screening.

  View details for DOI 10.1016/j.urology.2023.01.011

  View details for PubMedID 36708931

• Reproduction as a window for health in men. Fertility and sterility Belladelli, F., Muncey, W., Eisenberg, M. L. 2023

  Abstract

  Male factor infertility is widely considered a harbinger for a man's general health. Failure of reproduction often accompanies other underlying processes, with growing evidence suggesting that a diagnosis of infertility increases the likelihood of developing future cardiac, metabolic and oncologic disease. The goal of this review is to provide a comprehensive overview of the research on male fertility as a marker for current and future health. A multidisciplinary approach is essential, and there is growing consensus that the male fertility evaluation offers an opportunity to better men's wellness beyond their immediate reproductive ambitions.

  View details for DOI 10.1016/j.fertnstert.2023.01.014

  View details for PubMedID 36642302

• Male Fertility and Physical Exercise. The world journal of men's health Belladelli, F., Basran, S., Eisenberg, M. L. 2023

  Abstract

  According to existing studies, sedentary behavior contributes to male infertility. Both preclinical and clinical studies have investigated the association between physical exercise, semen quality, and pregnancy rates with heterogeneous results. The current review sought to examine the relationship between physical activity (PA) and male infertility, semen characteristics, and pregnancy rates. Pre-clinical studies demonstrated mixed benefits from exercise, with diet being an important consideration. Some forms of PA showed an improvement in pregnancy rates, while others did not consistently improve semen quality. Data also suggests that more intense exercise and certain types of exercise may impair male fertility. Given the limited number of randomized trials, future research is required to examine the relationship between specific forms of exercise and semen parameters along with reproductive outcomes.

  View details for DOI 10.5534/wjmh.220199

  View details for PubMedID 36649927

• Effect of Testicular Boost in Children With Leukemia Receiving Total Body Irradiation and Stem Cell Transplant: A Single-Institution Experience ADVANCES IN RADIATION ONCOLOGY Blomain, E. S., Jiang, A., Donaldson, S. S., Agarwal, R., Bertaina, A., Shyr, D., Eisenberg, M. L., Hoppe, R. T., Hiniker, S. M., Oh, J. 2023; 8 (1)

  View details for DOI 10.1016/j.adro.2022.101071

  View details for Web of Science ID 000876956000001

• Diverse monogenic subforms of human spermatogenic failure. Nature communications Nagirnaja, L., Lopes, A. M., Charng, W., Miller, B., Stakaitis, R., Golubickaite, I., Stendahl, A., Luan, T., Friedrich, C., Mahyari, E., Fadial, E., Kasak, L., Vigh-Conrad, K., Oud, M. S., Xavier, M. J., Cheers, S. R., James, E. R., Guo, J., Jenkins, T. G., Riera-Escamilla, A., Barros, A., Carvalho, F., Fernandes, S., Goncalves, J., Gurnett, C. A., Jorgensen, N., Jezek, D., Jungheim, E. S., Kliesch, S., McLachlan, R. I., Omurtag, K. R., Pilatz, A., Sandlow, J. I., Smith, J., Eisenberg, M. L., Hotaling, J. M., Jarvi, K. A., Punab, M., Rajpert-De Meyts, E., Carrell, D. T., Krausz, C., Laan, M., O'Bryan, M. K., Schlegel, P. N., Tuttelmann, F., Veltman, J. A., Almstrup, K., Aston, K. I., Conrad, D. F. 2022; 13 (1): 7953

  Abstract

  Non-obstructive azoospermia (NOA) is the most severe form of male infertility and typically incurable. Defining the genetic basis of NOA has proven challenging, and the most advanced classification of NOA subforms is not based on genetics, but simple description of testis histology. In this study, we exome-sequenced over 1000 clinically diagnosed NOA cases and identified a plausible recessive Mendelian cause in 20%. We find further support for 21 genes in a 2-stage burden test with 2072 cases and 11,587 fertile controls. The disrupted genes are primarily on the autosomes, enriched for undescribed human "knockouts", and, for the most part, have yet to be linked to a Mendelian trait. Integration with single-cell RNA sequencing data shows that azoospermia genes can be grouped into molecular subforms with synchronized expression patterns, and analogs of these subforms exist in mice. This analysis framework identifies groups of genes with known roles in spermatogenesis but also reveals unrecognized subforms, such as a set of genes expressed across mitotic divisions of differentiating spermatogonia. Our findings highlight NOA as an understudied Mendelian disorder and provide a conceptual structure for organizing the complex genetics of male infertility, which may provide a rational basis for disease classification.

  View details for DOI 10.1038/s41467-022-35661-z

  View details for PubMedID 36572685

• The association of preconception paternal metabolic syndrome on early childhood emergency department visits and hospitalizations. Andrology Chen, T., Zhang, C. A., Li, S., Schroeder, A. R., Shaw, G. M., Eisenberg, M. L. 2022

  Abstract

  Increasing preconception paternal comorbidity has been associated with adverse pregnancy outcomes. However, whether the father's health impacts the child after birth is uncertain.In the present study, we examined the association of preconception paternal metabolic syndrome status with childhood emergency department (ED) visits and hospitalizations.This is a longitudinal cohort study of children (295,355 boys and 278,735 girls) born to linked pairs of fathers and mothers in the United States between 2009 to 2016 within the IBM MarketScan® Research database. Associations between paternal and maternal metabolic syndrome (MetS) component diagnoses and subsequent hospitalizations and emergency department visits for offspring within the first two years of life were determined.35.5% (203,617/574,090) of children had at least one emergency room visit and 6.1% (35,141/574,090) of children had an inpatient admission. After adjustment, the odds of inpatient admission and emergency department visits increased in a dose-dependent fashion among fathers with higher comorbidities. Similar trends were seen for emergency department visit utilization.Increasing paternal preconception comorbidity is associated with a higher risk that a child requires emergency department and inpatient care in the first years of life. An opportunity exists to engage men in preconception counseling to optimize theirs and their offspring's health. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/andr.13370

  View details for PubMedID 36542456

• The intergenerational economics of infertility, childrearing and assisted reproduction. Fertility and sterility Connolly, M. P., Kotsopoulos, N., Eisenberg, M. 2022

  View details for DOI 10.1016/j.fertnstert.2022.12.011

  View details for PubMedID 36502934

• Comparative Prospective and Longitudinal Analysis on the Platelet-to-Lymphocyte, Neutrophil-to-Lymphocyte, and Albumin-to-Globulin Ratio in Patients with Non-Metastatic and Metastatic Prostate Cancer. Current oncology (Toronto, Ont.) Salciccia, S., Frisenda, M., Bevilacqua, G., Viscuso, P., Casale, P., De Berardinis, E., Di Pierro, G. B., Cattarino, S., Giorgino, G., Rosati, D., Del Giudice, F., Carbone, A., Pastore, A., Chung, B. I., Eisenberg, M. L., Autorino, R., Crivellaro, S., Forte, F., Sciarra, A., Mariotti, G., Gentilucci, A. 2022; 29 (12): 9474-9500

  Abstract

  PURPOSE: To prospectively evaluate the albumin/globulin ratio (AGR), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR) diagnostic and prognostic predictive value in a stratified population of prostate cancer (PC) cases.METHODS: Population was divided based on the clinical and histologic diagnosis in: Group A: benign prostatic hyperplasia (BPH) cases (494 cases); Group B: all PC cases (525 cases); Group B1: clinically significant PC (426 cases); Group B2: non-metastatic PC (416 cases); Group B3: metastatic PC (109 cases). NLR, PLR, and AGR were obtained at the time of the diagnosis, and only in cases with PC considered for radical prostatectomy, determinations were also repeated 90 days after surgery. For each ratio, cut-off values were determined by receiver operating characteristics curve (ROC) analysis and fixed at 2.5, 120.0, and 1.4, respectively, for NLR, PLR, and AGR.RESULTS: Accuracy in predictive value for an initial diagnosis of clinically significant PC (csPC) was higher using PLR (0.718) when compared to NLR (0.220) and AGR (0.247), but, despite high sensitivity (0.849), very low specificity (0.256) was present. The risk of csPC significantly increased only according to PLR with an OR = 1.646. The percentage of cases with metastatic PC significantly increased according to high NLR and high PLR. Accuracy was 0.916 and 0.813, respectively, for NLR and PLR cut-off, with higher specificity than sensitivity. The risk of a metastatic disease increased 3.2 times for an NLR > 2.5 and 5.2 times for a PLR > 120 and at the multivariate analysis.CONCLUSION: PLR and NLR have a significant predictive value towards the development of metastatic disease but not in relation to variations in aggressiveness or T staging inside the non-metastatic PC. Our results suggest an unlikely introduction of these analyses into clinical practice in support of validated PC risk predictors.

  View details for DOI 10.3390/curroncol29120745

  View details for PubMedID 36547159

• Can a father be too old? Fertility and sterility Eisenberg, M. L. 2022

  Abstract

  This month's Views and Reviews examines the current evidence regarding the association between a man's age and his reproductive health. Wood and Goriely review the link between paternal age and de novo mutations. Zweifel and Woodward expand on the implications to the offspring of older fathers by exploring the neurodevelopmental syndromes that become more prevalent in children of older fathers. Finally, Jimbo etal. examines the association between paternal age and several measures of male fertility including semen quality, birth rates, and assisted reproductive technology success rates.

  View details for DOI 10.1016/j.fertnstert.2022.09.021

  View details for PubMedID 36307289

• Counseling for the man with severe male infertility. Current opinion in urology Belladelli, F., Muncey, W., Seranio, N., Eisenberg, M. L. 2022

  Abstract

  PURPOSE OF REVIEW: This review summarize the proper counseling for men with severe male factor infertility.RECENT FINDINGS: Men who are experiencing infertility should have a semen analysis, the results of which may imply additional investigations, including genetic and hormonal. Moreover, possible modifiable factors that may harm men's reproductive health should be carefully evaluated. Finally, different treatment options are available.SUMMARY: Approximately 15% of couples struggle with infertility. Complete evaluations of both men and women are required to determine the etiology of infertility and determine appropriate treatment.

  View details for DOI 10.1097/MOU.0000000000001047

  View details for PubMedID 36210761

• THE ASSOCIATION BETWEEN A HISTORY OF PVFERNAL VAPING AND SPONTANEOUS ABORTION. Eisenberg, M., Zhang, C., Wang, T. R., Harlow, A. F., Wesselink, A. K., Hatch, E. E., Wise, L. A. ELSEVIER SCIENCE INC. 2022: E305-E306

  View details for Web of Science ID 000891804601018

• Perceived stress and semen quality. Andrology Lund, K. H., Laursen, A. S., Gronborg, T. K., Toft, G., Jacobsen, B. H., Wang, T. R., Wesselink, A. K., Hatch, E. E., Sommer, G. J., Eisenberg, M. L., Rothman, K. J., Sorensen, H. T., Wise, L. A., Mikkelsen, E. M. 2022

  Abstract

  BACKGROUND: Psychological stress is prevalent among reproductive-aged men. Assessment of semen quality for epidemiological studies is challenging as data collection is expensive and cumbersome, and studies evaluating the effect of perceived stress on semen quality are inconsistent.OBJECTIVE: To examine the association between perceived stress and semen quality.MATERIAL AND METHODS: We analyzed baseline data.RESULTS: The median PSS score and IQR was 15 (10-19) and 136 men (21.1%) had a PSS score ≥20. Comparing men with PSS scores ≥20 with<10, the adjusted percent difference was -2.7 (95% CI: -9.8; 5.0) for semen volume, 6.8 (95% CI: -10.9; 28.1) for sperm concentration, and 4.3 (95% CI: -13.8; 26.2) for total sperm count.CONCLUSION: Our findings indicate that perceived stress is not materially associated with semen volume, sperm concentration, or total sperm count. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/andr.13301

  View details for PubMedID 36151857

• The risks of birth defects and childhood cancer with conception by assisted reproductive technology. Human reproduction (Oxford, England) Luke, B., Brown, M. B., Wantman, E., Schymura, M. J., Browne, M. L., Fisher, S. C., Forestieri, N. E., Rao, C., Nichols, H. B., Yazdy, M. M., Gershman, S. T., Sacha, C. R., Williams, M., Ethen, M. K., Canfield, M. A., Doody, K. J., Eisenberg, M. L., Baker, V. L., Williams, C., Sutcliffe, A. G., Richard, M. A., Lupo, P. J. 2022

  Abstract

  STUDY QUESTION: Is there an association between fertility status, method of conception and the risks of birth defects and childhood cancer?SUMMARY ANSWER: The risk of childhood cancer had two independent components: (i) method of conception and (ii) presence, type and number of birth defects.WHAT IS KNOWN ALREADY: The rarity of the co-occurrence of birth defects, cancer and ART makes studying their association challenging. Prior studies have indicated that infertility and ART are associated with an increased risk of birth defects or cancer but have been limited by small sample size and inadequate statistical power, failure to adjust for or include plurality, differences in definitions and/or methods of ascertainment, lack of information on ART treatment parameters or study periods spanning decades resulting in a substantial historical bias as ART techniques have improved.STUDY DESIGN, SIZE, DURATION: This was a population-based cohort study linking ART cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) from 1 January 2004 to 31 December 2017 that resulted in live births in 2004-2018 in Massachusetts and North Carolina and live births in 2004-2017 in Texas and New York. A 10:1 sample of non-ART births were chosen within the same time period as the ART birth. Non-ART siblings were identified through the ART mother's information. Children from non-ART births were classified as being born to women who conceived with ovulation induction or IUI (OI/IUI) when there was an indication of infertility treatment on the birth certificate, and the woman did not link to the SART CORS; all others were classified as being naturally conceived.PARTICIPANTS/MATERIALS, SETTING, METHODS: The study population included 165 125 ART children, 31 524 non-ART siblings, 12 451 children born to OI/IUI-treated women and 1 353 440 naturally conceived children. All study children were linked to their respective State birth defect registries to identify major defects diagnosed within the first year of life. We classified children with major defects as either chromosomal (i.e. presence of a chromosomal defect with or without any other major defect) or nonchromosomal (i.e. presence of a major defect but having no chromosomal defect), or all major defects (chromosomal and nonchromosomal), and calculated rates per 1000 children. Logistic regression models were used to generate adjusted odds ratios (AORs) and 95% CIs of the risk of birth defects by conception group (OI/IUI, non-ART sibling and ART by oocyte source and embryo state) with naturally conceived children as the reference, adjusted for paternal and maternal ages; maternal race and ethnicity, education, BMI, parity, diabetes, hypertension; and for plurality, infant sex and State and year of birth. All study children were also linked to their respective State cancer registries. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs of cancer by birth defect status (including presence of a defect, type and number of defects), and conception group.MAIN RESULTS AND THE ROLE OF CHANCE: A total of 29 571 singleton children (2.0%) and 3753 twin children (3.5%) had a major birth defect (chromosomal or nonchromosomal). Children conceived with ART from autologous oocytes had increased risks for nonchromosomal defects, including blastogenesis, cardiovascular, gastrointestinal and, for males only, genitourinary defects, with AORs ranging from 1.22 to 1.85; children in the autologous-fresh group also had increased risks for musculoskeletal (AOR 1.28, 95% CI 1.13, 1.45) and orofacial defects (AOR 1.40, 95% CI 1.17, 1.68). Within the donor oocyte group, the children conceived from fresh embryos did not have increased risks in any birth defect category, whereas children conceived from thawed embryos had increased risks for nonchromosomal defects (AOR 1.20, 95% CI 1.03, 1.40) and blastogenesis defects (AOR 1.74, 95% CI 1.14, 2.65). The risk of cancer was increased among ART children in the autologous-fresh group (HR 1.31, 95% CI 1.08, 1.59) and non-ART siblings (1.34, 95% CI 1.02, 1.76). The risk of leukemia was increased among children in the OI/IUI group (HR 2.15, 95% CI 1.04, 4.47) and non-ART siblings (HR 1.63, 95% CI 1.02, 2.61). The risk of central nervous system tumors was increased among ART children in the autologous-fresh group (HR 1.68, 95% CI 1.14, 2.48), donor-fresh group (HR 2.57, 95% CI 1.04, 6.32) and non-ART siblings (HR 1.84, 95% CI 1.12, 3.03). ART children in the autologous-fresh group were also at increased risk for solid tumors (HR 1.39, 95% CI 1.09, 1.77). A total of 127 children had both major birth defects and cancer, of which 53 children (42%) had leukemia. The risk of cancer had two independent components: (i) method of conception (described above) and (ii) presence, type and number of birth defects. The presence of nonchromosomal defects increased the cancer risk, greater for two or more defects versus one defect, for all cancers and each type evaluated. The presence of chromosomal defects was strongly associated with cancer risk (HR 8.70 for all cancers and HR 21.90 for leukemia), further elevated in the presence of both chromosomal and nonchromosomal defects (HR 21.29 for all cancers, HR 64.83 for leukemia and HR 4.71 for embryonal tumors). Among the 83 946 children born from ART in the USA in 2019 compared to their naturally conceived counterparts, these risks translate into an estimated excess of 761 children with major birth defects, 31 children with cancer and 11 children with both major birth defects and cancer.LIMITATIONS, REASONS FOR CAUTION: In the SART CORS database, it was not possible to differentiate method of embryo freezing (slow freezing versus vitrification), and data on ICSI were only available in the fresh embryo ART group. In the OI/IUI group, it was not possible to differentiate type of non-ART treatment utilized, and in both the ART and OI/IUI groups, data were unavailable on duration of infertility. Since OI/IUI is underreported on the birth certificate, some OI/IUI children were likely included among the naturally conceived children, which will decrease the difference between all the groups and the naturally conceived children.WIDER IMPLICATIONS OF THE FINDINGS: The use of ART is associated with increased risks of major nonchromosomal birth defects. The presence of birth defects is associated with greater risks for cancer, which adds to the baseline risk in the ART group. Although this study does not show causality, these findings indicate that children conceived with ART, non-ART siblings, and all children with birth defects should be monitored more closely for the subsequent development of cancer.STUDY FUNDING/COMPETING INTEREST(S): This project was supported by grant R01 HD084377 from the National Institute of Child Health and Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Child Health and Human Development, or the National Institutes of Health, nor any of the State Departments of Health which contributed data. M.L.E. reports consultancy for Ro, Hannah, Dadi, Sandstone and Underdog; presidency of SSMR; and SMRU board member. The remaining authors report no conflict of interest.TRIAL REGISTRATION NUMBER: N/A.

  View details for DOI 10.1093/humrep/deac196

  View details for PubMedID 36112004

• Standards in semen examination: publishing reproducible and reliable data based on high-quality methodology. Human reproduction (Oxford, England) Bjorndahl, L., Barratt, C. L., Mortimer, D., Agarwal, A., Aitken, R. J., Alvarez, J. G., Aneck-Hahn, N., Arver, S., Baldi, E., Bassas, L., Boitrelle, F., Bornman, R., Carrell, D. T., Castilla, J. A., Cerezo Parra, G., Check, J. H., Cuasnicu, P. S., Darney, S. P., de Jager, C., De Jonge, C. J., Drevet, J. R., Drobnis, E. Z., Du Plessis, S. S., Eisenberg, M. L., Esteves, S. C., Evgeni, E. A., Ferlin, A., Garrido, N., Giwercman, A., Goovaerts, I. G., Haugen, T. B., Henkel, R., Henningsohn, L., Hofmann, M., Hotaling, J. M., Jedrzejczak, P., Jouannet, P., Jorgensen, N., Kirkman Brown, J. C., Krausz, C., Kurpisz, M., Kvist, U., Lamb, D. J., Levine, H., Loveland, K. L., McLachlan, R. I., Mahran, A., Maree, L., Martins da Silva, S., Mbizvo, M. T., Meinhardt, A., Menkveld, R., Mortimer, S. T., Moskovtsev, S., Muller, C. H., Munuce, M. J., Muratori, M., Niederberger, C., O'Flaherty, C., Oliva, R., Ombelet, W., Pacey, A. A., Palladino, M. A., Ramasamy, R., Ramos, L., Rives, N., Roldan, E. R., Rothmann, S., Sakkas, D., Salonia, A., Sanchez-Pozo, M. C., Sapiro, R., Schlatt, S., Schlegel, P. N., Schuppe, H., Shah, R., Skakkebak, N. E., Teerds, K., Toskin, I., Tournaye, H., Turek, P. J., van der Horst, G., Vazquez-Levin, M., Wang, C., Wetzels, A., Zeginiadou, T., Zini, A. 2022

  Abstract

  Biomedical science is rapidly developing in terms of more transparency, openness and reproducibility of scientific publications. This is even more important for all studies that are based on results from basic semen examination. Recently two concordant documents have been published: the 6th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen, and the International Standard ISO 23162:2021. With these tools, we propose that authors should be instructed to follow these laboratory methods in order to publish studies in peer-reviewed journals, preferable by using a checklist as suggested in an Appendix to this article.

  View details for DOI 10.1093/humrep/deac189

  View details for PubMedID 36112046

• Preconception paternal comorbidities and offspring birth defects: Analysis of a large national data set. Birth defects research Yu, B., Zhang, C. A., Li, S., Chen, T., Mulloy, E., Shaw, G. M., Eisenberg, M. L. 2022

  Abstract

  BACKGROUND: Despite the fact that the father contributes half the genome to a child, associations between paternal factors and birth defects are poorly understood.OBJECTIVES: To investigate the association between preconception paternal health and birth defects in the offspring.MATERIALS AND METHODS: We conducted analysis of a national cohort study utilizing the IBM Marketscan Research Database, which includes data on reimbursed private healthcare claims in the United States from 2007 to 2016. The potential association between paternal comorbidities, as measured by the components of metabolic syndrome (MetS), and any birth defect in the offspring was analyzed.RESULTS: Of the 712,774 live births identified, 21.2% of children were born to fathers with at least one component of the metabolic syndrome (MetS ≥1) prior to conception. Compared to infants born to fathers with no components of the metabolic syndrome, a modestly higher percentage of infants with cardiac birth defects were born to fathers with more components of MetS (MetS=1, OR [95% CI]: 1.07 [1.01-1.13]; MetS ≥2, 1.17 [1.08-1.26], in comparison to MetS=0) after adjusting for maternal and paternal factors. Similarly, a higher percentage of infants with respiratory defects were born to fathers with two or more components of metabolic syndrome (MetS ≥2, OR [95% CI]: 1.45 [1.22-1.71]).DISCUSSION AND CONCLUSION: In this private insurance claims-based study, we found that fathers with metabolic syndrome-related diseases before conception were at increased risk for having a child affected by birth defects, especially cardiac and respiratory defects, and this association was not influenced by paternal age or assessed maternal factors.

  View details for DOI 10.1002/bdr2.2082

  View details for PubMedID 36106720

• The Risk of Cardiovascular and Cerebrovascular Disease in Men with a History of Priapism. The Journal of urology Mulloy, E., Li, S., Belladelli, F., Del Giudice, F., Glover, F., Eisenberg, M. L. 2022: 101097JU0000000000002962

  Abstract

  PURPOSE: Priapism is a debilitating condition that affects sexual function. As a majority of cases are idiopathic, investigators have hypothesized underlying vascular dysfunction which may predispose men to priapism. We sought to determine if men are at risk for other sequelae of vascular dysfunction such as cardiovascular and thromboembolic disease after a priapism event.MATERIALS AND METHODS: Using a large commercial insurance claims data warehouse, we evaluated all men (age≥20) with a diagnosis of priapism from 2003-2020 and matched them to a cohort of men with other urologic disorders of sexual dysfunction (erectile dysfunction (ED), Peyronie's disease (PD), and premature ejaculation (PE)). We identified incident disease (cardiovascular disease, heart disease, embolism, thrombosis, cerebrovascular disease) for all cohorts.RESULTS: 10,459 men with priapism were identified and were matched to men with ED, PD, or PE. The mean age was 51.1 years old. Men with priapism showed increased incidence of heart disease (both ischemic HR 1.24 (95% CI 1.09-1.42) and other heart disease HR 1.24 (1.12-1.38) in the years following the priapism diagnosis. Incident cerebrovascular disease was also more likely in men with a history of priapism (HR 1.33 (1.15-1.55). Men requiring treatment for ischemic priapism had a higher hazard of cardiovascular and cerebrovascular disease. In addition, men with more priapism episodes had a higher rate of cardiovascular disease and thromboembolic events.CONCLUSIONS: Men with priapism are at increased risk for cardiovascular and cerebrovascular events in the years following a priapism.

  View details for DOI 10.1097/JU.0000000000002962

  View details for PubMedID 36083148

• Preconception Antidiabetic Drugs in Men and Birth Defects in Offspring. Annals of internal medicine Wensink, M. J., Mathiesen, E. R., Lindahl-Jacobsen, R., Eisenberg, M. L. 2022; 175 (9): W107

  View details for DOI 10.7326/L22-0233

  View details for PubMedID 36122399

• Associations between Race and Erectile Dysfunction Treatment Patterns. Urology practice Chen, T., Li, S., Eisenberg, M. L. 2022; 9 (5): 423-430

  Abstract

  While erectile dysfunction (ED) has many available and effective treatments, the decision to elect one therapy over another depends on many variables. Whether race plays a significant role in treatment decision making is uncertain. This study seeks to investigate whether there are racial differences between men receiving treatment for ED in the United States.We performed a retrospective review using the Optum® De-identified Clinformatics® Data Mart database. Administrative diagnosis and procedural and pharmacy codes were used to identify male subjects 18 years and older with a diagnosis of ED between 2003 and 2018. Demographic and clinical variables were identified. Men with a history of prostate cancer were excluded. Types and patterns of ED treatment were analyzed after adjusting for age, income, education, frequency of urologist visits, smoking status and metabolic syndrome comorbidity diagnoses.During the observation period, 810,916 men were identified who met the inclusion criteria. After matching for demographic, clinical and health care utilization factors, differences in ED treatment persisted between racial groups. Compared to Caucasians, Asian and Hispanic men had a significantly lower probability of undergoing any ED treatment, while African Americans had a higher probability of ED treatment. African American and Hispanic men had higher probabilities to undergo surgical treatment for ED than Caucasian men.Differences in ED treatment patterns exist across racial groups even after accounting for socioeconomic variables. An opportunity exists to further investigate potential barriers to men receiving care for sexual dysfunction.

  View details for DOI 10.1097/UPJ.0000000000000329

  View details for PubMedID 37145716

• Associations between Race and Erectile Dysfunction Treatment Patterns UROLOGY PRACTICE Chen, T., Li, S., Eisenberg, M. L. 2022; 9 (5): 423-430

  View details for DOI 10.1097/UPJ.0000000000000329

  View details for Web of Science ID 000963165400027

• The Association between Monthly, Yearly, and Lifetime Cannabis Use, and Semen Parameters in Asian-American Men. The world journal of men's health Belladelli, F., Chen, T., Basran, S., Greenberg, D. R., Del Giudice, F., Mulloy, E., Chen, C., Cheng, Y., Salonia, A., Eisenberg, M. L. 2022

  Abstract

  PURPOSE: Medicinal and recreational cannabis use has grown exponentially, however, its effect on testicular function and spermatogenesis remains uncertain. The aim of this study was to evaluate the association between cannabis use and semen parameters in a cohort of Asian-American men with unknown fertility.MATERIALS AND METHODS: Asian men were recruited to complete an online survey and submit a semen sample. Semen analysis, demographic data, lifestyle factors, and cannabis use habits were collected. Linear and logistic regression analyses were used to determine.RESULTS: Among the 112 men included in this study, 51 used cannabis at least once in their lifetime, 30 men used cannabis at least once in the last 12 months, and 26 men used cannabis at least once in the last 30 days. Adjusted linear regression analyses identified an association between cannabis use in the previous 30 days and worse sperm morphology (beta: -0.45, p=0.025) and sperm motility (beta: -1.64, p=0.016). However, when stratifying by subfertile semen quality (i.e., WHO criteria), no association was identified between semen quality and cannabis use. Lower sperm morphology and motility are partially associated with recent cannabis use, while all other semen parameters are not.CONCLUSIONS: We did not observe any consistent associations between cannabis use on any semen parameters in Asian-American men. Further studies within the field are needed to explore racial and ethnic differences in semen quality and lifestyle factors.

  View details for DOI 10.5534/wjmh.220106

  View details for PubMedID 36047080

• The association between organophosphate insecticides and blood pressure dysregulation: NHANES 2013-2014. Environmental health : a global access science source Glover, F., Eisenberg, M. L., Belladelli, F., Del Giudice, F., Chen, T., Mulloy, E., Caudle, W. M. 2022; 21 (1): 74

  Abstract

  BACKGROUND: Organophosphate (OP) insecticides represent one of the largest classes of sprayed insecticides in the U.S., and their use has been associated with various adverse health outcomes, including disorders of blood pressure regulation such as hypertension (HTN).METHODS: In a study of 935 adults from the NHANES 2013-2014 cycle, we examined the relationship between systolic and diastolic blood pressure changes and urinary concentrations of three OP insecticides metabolites, including 3,5,6-trichloro-2-pyridinol (TCPy), oxypyrimidine, and para-nitrophenol. These metabolites correspond to the parent compounds chlorpyrifos, diazinon, and methyl parathion, respectively. Weighted, multivariable linear regression analysis while adjusting for potential confounders were used to model the relationship between OP metabolites and blood pressure. Weighted, multivariable logistic regression analysis was used to model the odds of HTN for quartile of metabolites.RESULTS: We observed significant, inverse association between TCPy on systolic blood pressure (beta-estimate=-0.16, p<0.001) and diastolic blood pressure (beta-estimate=-0.15, p<0.001). Analysis with para-nitrophenol revealed a significant, positive association with systolic blood pressure (beta-estimate=0.03, p=0.02), and an inverse association with diastolic blood pressure (beta-estimate=-0.09, p<0.001). For oxypyrimidine, we observed significant, positive associations between systolic blood pressure (beta-estimate=0.58, p=0.03) and diastolic blood pressure (beta-estimate=0.31, p<0.001). Furthermore, we observed significant interactions between TCPy and ethnicity on systolic blood pressure (beta-estimate=1.46, p=0.0036). Significant interaction terms were observed between oxypyrimidine and ethnicity (beta-estimate=-1.73, p<0.001), as well as oxypyrimidine and BMI (beta-estimate=1.51 p<0.001) on systolic blood pressure, and between oxypyrimidine and age (beta-estimate=1.96, p=0.02), race (beta-estimate=-3.81 p=0.004), and BMI on diastolic blood pressure (beta-estimate=0.72, p=0.02). A significant interaction was observed between para-nitrophenol and BMI for systolic blood pressure (beta-estimate=0.43, p=0.01), and between para-nitrophenol and ethnicity on diastolic blood pressure (beta-estimate=2.19, p=0.006). Lastly, we observed a significant association between the odds of HTN and TCPy quartiles (OR=0.65, 95% CI [0.43,0.99]).CONCLUSION: Our findings support previous studies suggesting a role for organophosphate insecticides in the etiology of blood pressure dysregulation and HTN. Future studies are warranted to corroborate these findings, evaluate dose-response relationships between organophosphate insecticides and blood pressure, determine clinical significance, and elucidate biological mechanisms underlying this association.

  View details for DOI 10.1186/s12940-022-00887-3

  View details for PubMedID 35934697

• Male personal heat exposures and fecundability: A preconception cohort study. Andrology McKinnon, C. J., Joglekar, D. J., Hatch, E. E., Rothman, K. J., Wesselink, A. K., Willis, M. D., Wang, T. R., Mikkelsen, E. M., Eisenberg, M. L., Wise, L. A. 2022

  Abstract

  Several studies indicate adverse effects of selected heat exposures on semen quality, but few studies have directly evaluated fertility as an endpoint.We evaluated prospectively the association between male heat exposures and fecundability, the per-cycle probability of conception.We analyzed data from 3,041 couples residing in the United States or Canada who enrolled in a prospective preconception cohort study (2013-2021). At enrollment, males reported on several heat-related exposures, such as use of saunas, hot baths, seat heaters, and tight-fitting underwear. Pregnancy status was updated on female follow-up questionnaires every 8 weeks until conception or a censoring event (initiation of fertility treatment, cessation of pregnancy attempts, withdrawal, loss to follow-up, or 12 cycles), whichever came first. We used proportional probabilities models to estimate fecundability ratios (FR) and 95% confidence intervals (CI) for the association between heat exposures and fecundability, mutually adjusting for heat exposures and other potential confounders.We observed small inverse associations for hot bath/tub use (≥3 vs. 0 times/month: FR = 0.87, 95% CI: 0.70-1.07) and fever in the 3 months before baseline (FR = 0.94, 95% CI: 0.79-1.12; 1 cycle of follow-up: FR = 0.84, 95% CI: 0.64-1.11). Little association was found for sauna use, hours of laptop use on one's lap, seat heater use, time spent sitting, and use of tight-fitting underwear. Based on a cumulative heat metric, FRs for 1, 2, 3, and ≥4 vs. 0 heat exposures were 0.99 (95% CI: 0.87-1.12), 1.03 (95% CI: 0.89-1.19), 0.94 (95% CI: 0.74-1.19), and 0.77 (95% CI: 0.50-1.17), respectively. Associations were stronger among men aged ≥30 years (≥4 vs. 0 heat exposures: FR = 0.60, 95% CI: 0.34-1.04).Male use of hot tubs/baths and fever showed weak inverse associations with fecundability. Cumulative exposure to multiple heat sources was associated with a moderate reduction in fecundability, particularly among males aged ≥30 years. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/andr.13242

  View details for PubMedID 35924639

• Implementation of a comprehensive fertility biobanking initiative. F&S science Wignarajah, A., Alvero, R., Lathi, R. B., Aghajanova, L., Eisenberg, M., Winn, V. D., Behr, B., Murugappan, G. 2022; 3 (3): 228-236

  Abstract

  OBJECTIVE: To present the framework of Stanford Fertility and Reproductive Health's comprehensive reproductive biobanking initiatives and the results of the first year of recruitment.DESIGN: Technical description article.SETTING: Academic fertility center.PATIENT(S): Fertility patients >18 years of age.INTERVENTION(S): Enroll the patients interested in research in biobanking protocols.MAIN OUTCOME MEASURE(S): Patient recruitment and sample inventory from September 2020 to September2021.RESULT(S): A total of 253 patients have enrolled in the Stanford Fertility and Reproductive Health biobanking initiatives since September 2020. The current inventory consists of 1,176 samples, including serums, plasmas, buffy coats, endometria, maternal deciduae, miscarriage chorionic villi, and human embryos (zygote, cleavage, and blastocyst stages).CONCLUSION(S): This biobanking initiative addresses a critical, unmet need in reproductive health research to make it possible for patients to donate excess embryos and gametes and preserves, for future research, valuable somatic and reproductive tissues that would otherwise be discarded. We present the framework of this biobanking initiative in order to support future efforts of establishing similar biorepositories.

  View details for DOI 10.1016/j.xfss.2022.01.001

  View details for PubMedID 35977803

• Effects of recreational cannabis on testicular function in primary infertile men. Andrology Belladelli, F., Fallara, G., Pozzi, E., Corsini, C., Cilio, S., Raffo, M., d'Arma, A., Boeri, L., Capogrosso, P., Eisenberg, M., Montorsi, F., Salonia, A. 2022

  Abstract

  BACKGROUND: Male factor contributes to up to 50% of cases of couples experiencing infertility. Cannabis is one of the most commonly used recreational drugs and its effects on the reproductive system have been largely debated in the literature.OBJECTIVES: The aim of this study is to evaluate the effect of recreational cannabis use on total T (tT) levels, gonadal status, and sperm parameters in a cohort of primary infertile non-Finnish, white-European men.MATERIALS AND METHODS: Data of 2074 white-European men visited for primary couple's infertility were analyzed. Lifestyle factors and cannabis use were investigated in all participants. Semen analyses were based on the 2010 WHO reference criteria. Serum hormones were evaluated, and patients were subdivided based on their gonadal status. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). Descriptive statistics and linear regression analyses were used to test the association between cannabis use, sperm parameters, and hormonal levels. Logistic regression analyses tested potential predictors for abnormal sperm parameters and gonadal status.RESULTS: Of 2074, 225 (10.9%) patients reported cannabis use in their lifetime. Total Testosterone levels were lower in cannabis users compared to non-users (p = 0.03). In a multivariable linear regression analysis, cannabis use was inversely associated with tT levels (SS = -0.372 ng/mL; p = 0.005) but not with FSH nor with LH levels. Conversely, at multivariable logistic regression model cannabis use was not associated with the type of hypogonadism. At multivariable linear regression analysis, cannabis use was inversely associated with sperm morphology (p = 0.007), while not with both sperm concentration and sperm motility. Similarly, at adjusted logistic regression analysis cannabis use resulted associated with teratozoospermia (p = 0.039), but not with oligo-, astheno- and azoospermia.CONCLUSIONS: Infertile men using cannabis are at higher risk of having lower testosterone levels and altered sperm morphology as compared with non-users. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/andr.13235

  View details for PubMedID 35868833

• In Defense of Phosphodiesterase 5 Inhibitors. JAMA ophthalmology Belladelli, F., Del Giudice, F., Eisenberg, M. L. 2022

  View details for DOI 10.1001/jamaophthalmol.2022.2612

  View details for PubMedID 35862053

• Paternal Medications in Inflammatory Bowel Disease and Male Fertility and Reproductive Outcomes: A Systematic Review and Meta-Analysis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Gubatan, J., Barber, G. E., Nielsen, O. H., Juhl, C. B., Maxwell, C., Eisenberg, M. L., Streett, S. E. 2022

  Abstract

  Studies evaluating reproductive outcomes among male patients with inflammatory bowel disease (IBD) are limited. We evaluated use of IBD medications and association with semen parameters, a proxy of male fertility, and adverse pregnancy outcomes [early pregnancy loss (EPL), preterm birth (PB), congenital malformations (CM)].We searched Medline, Embase, Scopus, and Web of Science (PROSPERO CRD42020197098) from inception to April 2022 for studies reporting semen parameters and adverse pregnancy outcomes among male patients exposed to biologics, thiopurine, or methotrexate. Standardized mean difference, prevalence, and odds ratios of outcomes were pooled and analysed using a random effects model.Ten studies reporting semen parameters (268 IBD patients) and 16 studies reporting adverse pregnancy outcomes (over 25,000 IBD patients) were included. Biologic, thiopurine, or methotrexate use were not associated with decreased sperm count, motility, or abnormal morphology compared to non-exposed patients. The prevalence of adverse pregnancy outcomes with paternal biologic (5%), thiopurine (6%), or methotrexate (6%) exposure was comparable to non-exposed patients (5%). Biologic use was not associated with risk of EPL (OR 1.26, I2= 0%, P=0.12), PB (OR 1.10, I2= 0%, P=0.17), or CM (OR 1.03, I2=0%, P=0.69). Thiopurine use was not associated with risk of EPL (OR 1.31, I2= 19%, P=0.17), PB (OR 1.05, I2= 0%, P=0.20), or CM (OR 1.07, I2=7%, P=0.34). Methotrexate use was not associated with risk of PB (OR 1.06, I2= 0%, P=0.62) or CM (OR 1.03, I2=0%, P=0.81).Biologic, thiopurine, or methotrexate use among male patients with IBD are not associated with impairments in fertility or with increased odds of adverse pregnancy outcomes.Biologic therapy, congenital malformations, early pregnancy loss, father, inflammatory bowel disease, male, pregnancy outcomes, preterm birth, reproductive health.

  View details for DOI 10.1016/j.cgh.2022.07.008

  View details for PubMedID 35870769

• Assisted reproductive technology cycles involving male factor infertility in the United States, 2017-2018: data from the National Assisted Reproductive Technology Surveillance System. F&S reports Jewett, A., Warner, L., Kawwass, J. F., Mehta, A., Eisenberg, M. L., Nangia, A. K., Dupree, J. M., Honig, S., Hotaling, J. M., Kissin, D. M. 2022; 3 (2): 124-130

  Abstract

  Objective: To describe the prevalence and treatment characteristics of assisted reproductive technology (ART) cycles involving specific male factor infertility diagnoses in the United States.Design: Cross-sectional analysis of ART cycles in the National ART Surveillance System (NASS).Setting: Clinics that reported patient ART cycles performed in 2017 and2018.Patients: Patients who visited an ART clinic and the cycles were reported in the NASS. The ART cycles included all autologous and donor cycles that used fresh or frozen embryos.Interventions: Not applicable.Main Outcome Measures: Analyses used new, detailed reporting of male factor infertility subcategories, treatment characteristics, and male partner demographics available in the NASS.Results: Among 399,573 cycles started with intent to transfer an embryo, 30.4% (n = 121,287) included a male factor infertility diagnosis as a reason for using ART. Of these, male factor only was reported in 16.5% of cycles, and both male and female factors were reported in 13.9% of cycles; 21.8% of male factor cycles had >1 male factor. Abnormal sperm parameters were the most commonly reported diagnoses (79.7%), followed by medical condition (5.3%) and genetic or chromosomal abnormalities (1.0%).Males aged ≤40 years comprised 59.6% of cycles with male factor infertility. Intracytoplasmic sperm injection was the primary method of fertilization (81.7%). Preimplantation genetic testing was used in 26.8%, and single embryo transfer was used in 66.8% of cycles with male factor infertility diagnosis.Conclusions: Male factor infertility is a substantial contributor to infertility treatments in the United States. Continued assessment of the prevalence and characteristics of ART cycles with male factor infertility may inform treatment options and improve ART outcomes. Future studies are necessary to further evaluate male factor infertility.

  View details for DOI 10.1016/j.xfre.2022.03.004

  View details for PubMedID 35789711

• Male-Specific Late Effects in Adult Hematopoietic Cell Transplantation Recipients: A Systematic Review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation TRANSPLANTATION AND CELLULAR THERAPY Phelan, R., Im, A., Hunter, R. L., Inamoto, Y., Lupo-Stanghellini, M., Rovo, A., Badawy, S. M., Burns, L., Eissa, H., Murthy, H. S., Prasad, P., Sharma, A., Suelzer, E., Agrawal, V., Aljurf, M., Baker, K., Basak, G. W., Buchbinder, D., DeFilipp, Z., Grkovic, L., Dias, A., Einsele, H., Eisenberg, M. L., Epperla, N., Farhadfar, N., Flatau, A., Gale, R., Greinix, H., Hamilton, B. K., Hashmi, S., Hematti, P., Jamani, K., Maharaj, D., Murray, J., Naik, S., Nathan, S., Pavletic, S., Peric, Z., Pulanic, D., Ross, R., Salonia, A., Sanchez-Ortega, I., Savani, B. N., Schechter, T., Shah, A. J., Smith, S. M., Snowden, J. A., Steinberg, A., Tremblay, D., Vij, S. C., Walker, L., Wolff, D., Yared, J. A., Schoemans, H., Tichelli, A. 2022; 28 (6)

  View details for DOI 10.1016/j.jtct.2021.10.0132666-6367

  View details for Web of Science ID 000834051500022

• Does Air Pollution Impact on Semen Parameters? Findings from a Real-Life, Cross-Sectional Study in Italian Infertile Men WORLD JOURNAL OF MENS HEALTH Belladelli, F., Corsini, C., Pozzi, E., Raffo, M., Fallara, G., Costa, A., Cignoli, D., Boeri, L., Ventimiglia, E., Capogrosso, P., Eisenberg, M. L., Montorsi, F., Salonia, A. 2022

  View details for DOI 10.5534/wjmh.210240

  View details for Web of Science ID 000810035000001

• Does Air Pollution Impact on Semen Parameters? Findings from a Real-Life, Cross-Sectional Study in Italian Infertile Men. The world journal of men's health Belladelli, F., Corsini, C., Pozzi, E., Raffo, M., Fallara, G., Costa, A., Cignoli, D., Boeri, L., Ventimiglia, E., Capogrosso, P., Eisenberg, M. L., Montorsi, F., Salonia, A. 2022

  Abstract

  In industrialized countries, air pollutants levels have been monitored closely for environmental and research issues. Using Italian data, we aimed to investigate the association between air pollutants levels and semen parameters in a cohort of non-Finnish white-European men presenting for couple's infertility.Complete demographic and laboratory data from 1,152 infertile men consecutively assessed between January 2015 and January 2018 were analyzed. Semen analyses were based on the 2010 World Health Organization reference criteria. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). We analyzed the annual average level of the three main markers of air pollution (Pm10, Pm2.5, and NO2) between 2014 and 2018. Descriptive statistics, linear and logistic regression analyses tested the association between air pollutants levels and semen parameters.Of 1,152 men, 87 (7.55%) had normal sperm parameters at first semen analysis. Of 1,065 patients with abnormal semen analyses, 237 (22.25%), 324 (30.42%), and 287 (26.95%) patients presented 1, 2 or 3 abnormalities, respectively, and 217 (20.38%) were azoospermic. At linear regression analysis, Pm10, Pm2.5, and NO2 were negatively associated with sperm morphology (Pm10: β=-0.5288 µg/m3, p=0.001; Pm2.5: β=-0.5240 µg/m3, p=0.019; NO2: β=-0.4396 µg/m3, p<0.0001). Furthermore, the adjusted odds of normal sperm morphology <4% were 1.06 (95% confidence interval [CI], 1.03-1.09; p=0.007) for Pm10, 1.07 (95% CI, 1.03-1.11; p=0.007) for Pm 2.5, and 1.03 (95% CI, 1.02-1.05; p=0.001) for NO2, respectively.In a large homogenous cohort of infertile men, Pm10, Pm 2.5, and NO2 levels were negatively associated with sperm morphology. Conversely, no clear association was observed with other macroscopic sperm parameters.

  View details for DOI 10.5534/wjmh.210240

  View details for PubMedID 35791299

• The association between caffeine intake and testosterone: NHANES 2013-2014. Nutrition journal Glover, F. E., Caudle, W. M., Del Giudice, F., Belladelli, F., Mulloy, E., Lawal, E., Eisenberg, M. L. 2022; 21 (1): 33

  Abstract

  BACKGROUND: Caffeine is one of the most commonly used psychoactive drugs in the world, and provides many health benefits including alertness, improved memory, and reducing inflammation. Despite these benefits, caffeine has been implicated in a number of adverse health outcomes possibly due to effects within the endocrine system, effects that may contribute to impaired reproductive function and low testosterone in men. Previous studies have investigated associations between caffeine consumption and testosterone levels in men, although the quantity and generalizability of these studies is lacking, and the results between studies are conflicting and inconclusive.METHODS: Using data from a cross-sectional study of 372 adult men in the 2013-2014 NHANES survey cycle, the researchers set out to characterize the association between serum testosterone levels, caffeine, and 14 caffeine metabolites.RESULTS: Multivariable, weighted linear regression revealed a significant inverse association between caffeine and testosterone. Multivariable, linear regression revealed significant, inverse associations between 6 xanthine metabolic products of caffeine and testosterone. Inverse associations were observed between 5-methyluric acid products and testosterone, as well as between 5-acetlyamino-6-amino-3-methyluracil and testosterone. A significant, positive association was observed for 7-methyl xanthine, 3,7-dimethyluric acid, and 7-methyluric acid. Logistic regression models to characterize the association between 2 biologically active metabolites of caffeine (theobromine and theophylline) and odds of low testosterone (<300ng/dL) were non-significant.CONCLUSIONS: These findings suggest a potential role for caffeine's contribution to the etiology of low testosterone and biochemical androgen deficiency. Future studies are warranted to corroborate these findings and elucidate biological mechanisms underlying this association.

  View details for DOI 10.1186/s12937-022-00783-z

  View details for PubMedID 35578259

• Actionable secondary findings following exome sequencing of 836 non-obstructive azoospermia cases and their value in patient management. Human reproduction (Oxford, England) Kasak, L., Lillepea, K., Nagirnaja, L., Aston, K. I., Schlegel, P. N., Goncalves, J., Carvalho, F., Moreno-Mendoza, D., Almstrup, K., Eisenberg, M. L., Jarvi, K. A., O'Bryan, M. K., Lopes, A. M., Conrad, D. F., GEMINI Consortium, Punab, M., Laan, M., Conrad, D. F., Nagirnaja, L., Aston, K. I., Carrell, D. T., Hotaling, J. M., Jenkins, T. G., McLachlan, R., O'Bryan, M. K., Schlegel, P. N., Eisenberg, M. L., Sandlow, J. I., Jungheim, E. S., Omurtag, K. R., Lopes, A. M., Seixas, S., Carvalho, F., Fernandes, S., Barros, A., Goncalves, J., Laan, M., Punab, M., Rajpert-De Meyts, E., Jorgensen, N., Almstrup, K., Krausz, C. G., Jarvi, K. A. 2022

  Abstract

  STUDY QUESTION: What is the load, distribution and added clinical value of secondary findings (SFs) identified in exome sequencing (ES) of patients with non-obstructive azoospermia (NOA)?SUMMARY ANSWER: One in 28 NOA cases carried an identifiable, medically actionable SF.WHAT IS KNOWN ALREADY: In addition to molecular diagnostics, ES allows assessment of clinically actionable disease-related gene variants that are not connected to the patient's primary diagnosis, but the knowledge of which may allow the prevention, delay or amelioration of late-onset monogenic conditions. Data on SFs in specific clinical patient groups, including reproductive failure, are currently limited.STUDY DESIGN, SIZE, DURATION: The study group was a retrospective cohort of patients with NOA recruited in 10 clinics across six countries and formed in the framework of the international GEMINI (The GEnetics of Male INfertility Initiative) study.PARTICIPANTS/MATERIALS, SETTING, METHODS: ES data of 836 patients with NOA were exploited to analyze SFs in 85 genes recommended by the American College of Medical Genetics and Genomics (ACMG), Geisinger's MyCode, and Clinical Genome Resource. The identified 6374 exonic variants were annotated with ANNOVAR and filtered for allele frequency, retaining 1381 rare or novel missense and loss-of-function variants. After automatic assessment of pathogenicity with ClinVar and InterVar, 87 variants were manually curated. The final list of confident disease-causing SFs was communicated to the corresponding GEMINI centers. When patient consent had been given, available family health history and non-andrological medical data were retrospectively assessed.MAIN RESULTS AND THE ROLE OF CHANCE: We found a 3.6% total frequency of SFs, 3.3% from the 59 ACMG SF v2.0 genes. One in 70 patients carried SFs in genes linked to familial cancer syndromes, whereas 1 in 60 cases was predisposed to congenital heart disease or other cardiovascular conditions. Retrospective assessment confirmed clinico-molecular diagnoses in several cases. Notably, 37% (11/30) of patients with SFs carried variants in genes linked to male infertility in mice, suggesting that some SFs may have a co-contributing role in spermatogenic impairment. Further studies are needed to determine whether these observations represent chance findings or the profile of SFs in NOA patients is indeed different from the general population.LIMITATIONS, REASONS FOR CAUTION: One limitation of our cohort was the low proportion of non-Caucasian ethnicities (9%). Additionally, as comprehensive clinical data were not available retrospectively for all men with SFs, we were not able to confirm a clinico-molecular diagnosis and assess the penetrance of the specific variants.WIDER IMPLICATIONS OF THE FINDINGS: For the first time, this study analyzed medically actionable SFs in men with spermatogenic failure. With the evolving process to incorporate ES into routine andrology practice for molecular diagnostic purposes, additional assessment of SFs can inform about future significant health concerns for infertility patients. Timely detection of SFs and respective genetic counseling will broaden options for disease prevention and early treatment, as well as inform choices and opportunities regarding family planning. A notable fraction of SFs was detected in genes implicated in maintaining genome integrity, essential in both mitosis and meiosis. Thus, potential genetic pleiotropy may exist between certain adult-onset monogenic diseases and NOA.STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Estonian Research Council grants IUT34-12 and PRG1021 (M.L. and M.P.); National Institutes of Health of the United States of America grant R01HD078641 (D.F.C., K.I.A. and P.N.S.); National Institutes of Health of the United States of America grant P50HD096723 (D.F.C. and P.N.S.); National Health and Medical Research Council of Australia grant APP1120356 (M.K.O'B., D.F.C. and K.I.A.); Fundacao para a Ciencia e a Tecnologia (FCT)/Ministerio da Ciencia, Tecnologia e Inovacao grant POCI-01-0145-FEDER-007274 (A.M.L., F.C. and J.G.) and FCT: IF/01262/2014 (A.M.L.). J.G. was partially funded by FCT/Ministerio da Ciencia, Tecnologia e Ensino Superior (MCTES), through the Centre for Toxicogenomics and Human Health-ToxOmics (grants UID/BIM/00009/2016 and UIDB/00009/2020). M.L.E. is a consultant for, and holds stock in, Roman, Sandstone, Dadi, Hannah, Underdog and has received funding from NIH/NICHD. Co-authors L.K., K.L., L.N., K.I.A., P.N.S., J.G., F.C., D.M.-M., K.A., K.A.J., M.K.O'B., A.M.L., D.F.C., M.P. and M.L. declare no conflict of interest.TRIAL REGISTRATION NUMBER: N/A.

  View details for DOI 10.1093/humrep/deac100

  View details for PubMedID 35535697

• Male-specific late effects in adult hematopoietic cell transplantation recipients: a systematic review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Bone marrow transplantation Phelan, R., Im, A., Hunter, R. L., Inamoto, Y., Lupo-Stanghellini, M. T., Rovo, A., Badawy, S. M., Burns, L., Eissa, H., Murthy, H. S., Prasad, P., Sharma, A., Suelzer, E., Agrawal, V., Aljurf, M., Baker, K., Basak, G. W., Buchbinder, D., DeFilipp, Z., Grkovic, L. D., Dias, A., Einsele, H., Eisenberg, M. L., Epperla, N., Farhadfar, N., Flatau, A., Gale, R. P., Greinix, H., Hamilton, B. K., Hashmi, S., Hematti, P., Jamani, K., Maharaj, D., Murray, J., Naik, S., Nathan, S., Pavletic, S., Peric, Z., Pulanic, D., Ross, R., Salonia, A., Sanchez-Ortega, I., Savani, B. N., Schechter, T., Shah, A. J., Smith, S. M., Snowden, J. A., Steinberg, A., Tremblay, D., Vij, S. C., Walker, L., Wolff, D., Yared, J. A., Schoemans, H., Tichelli, A. 2022

  Abstract

  Male-specific late effects after hematopoietic cell transplantation (HCT) include genital chronic graft-versus-host disease (GvHD), hypogonadism, sexual dysfunction, infertility, and subsequent malignancies. They may be closely intertwined and cause prolonged morbidity and decreased quality of life after HCT. We provide a systematic review of male-specific late effects in a collaboration between transplant physicians, endocrinologists, urologists, dermatologists, and sexual health professionals through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research, and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. The systematic review summarizes incidence, risk factors, screening, prevention and treatment of these complications and provides consensus evidence-based recommendations for clinical practice and future research.

  View details for DOI 10.1038/s41409-022-01591-z

  View details for PubMedID 35523848

• IDENTIFICATION OF Y CHROMOSOME MICRODELETIONS AND ASSOCIATIONS WITH ADVERSE HEALTH OUTCOMES IN THE UK BIOBANK Peterson, D. J., Eisenberg, M. L. LIPPINCOTT WILLIAMS & WILKINS. 2022: E177-E178

  View details for Web of Science ID 000836935501153

• Medical Treatment of Disorders of Ejaculation. The Urologic clinics of North America Chen, T., Mulloy, E. A., Eisenberg, M. L. 2022; 49 (2): 219-230

  Abstract

  Ejaculation and orgasm are complex phenomena within the male sexual response cycle. Disordered ejaculation commonly presents as premature or delayed ejaculation, although issues with painful ejaculation, retrograde ejaculation, or postorgasmic illness syndrome are also seen. This article will review the pathophysiology of these conditions as well as the current pharmacologic treatments available.

  View details for DOI 10.1016/j.ucl.2021.12.001

  View details for PubMedID 35428428

• Don't forget the father. Fertility and sterility Eisenberg, M. L., Barratt, C. L., De Jonge, C. J. 2022; 117 (5): 936-937

  View details for DOI 10.1016/j.fertnstert.2022.03.012

  View details for PubMedID 35512977

• Hematospermia is rarely associated with urologic malignancy: Analysis of US claims data. Andrology Hakam, N., Lui, J., Shaw, N. M., Nabavizadeh, B., Smith, J. F., Eisenberg, M. L., Breyer, B. N. 2022

  Abstract

  Hematospermia is an alarming symptom and can cause significant patient distress, but work-up is often negative.To characterize the clinical evaluation of hematospermia and association with diagnosis of urologic malignancy.Using MarketScan® insurance claims database, we identified adult males 18 to 64 years old diagnosed with hematospermia from 2010- 2018. Benign hematospermia was defined as the absence of hematuria and elevated prostate specific antigen (PSA). Patients with a urologic cancer prior to diagnosis of hematospermia were excluded. We identified those who were diagnosed with a urologic malignancy.Annual average incidence rate of hematospermia was 56.6 per 100,000 (95% CI 55.4 - 57.8 per 100,000) in 2010 and increased to 73.6 per 100,000 (95% CI 71.7 - 75.4 per 100,000) in 2018. 56,157 patients presented with benign hematospermia. Most (57.5%) underwent at least one test, with the most common being urinalysis (51.7%), followed by PSA testing (11.9%). All other tests were performed in less than 3% of patients. 47 patients were diagnosed with a urologic cancer, including 28 with prostate cancer (0.05%), nine with testicular cancer (0.016%), six with prostate carcinoma in situ (0.01%), and four with bladder cancer (0.007%). Stratified by age, there was only one cancer diagnosis (testicular) in 15,106 patients under 40 (0.01%) and 46 cancer diagnoses in 40,611 patients 40 years old or above (0.11%). Median age of patients diagnosed with cancer was 56 (IQR 52 - 61).A small minority of patients with benign hematospermia were later diagnosed with urologic cancer in a large nationally representative sample. After excluding hematuria with urinalysis, physicians should conservatively manage and reassure patients with hematospermia especially those under 40 years of age. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/andr.13189

  View details for PubMedID 35483126

• Influence of COVID-19 pandemic on timing and outcomes of treatment for acute testicular torsion in adults: a single institution experience CANADIAN JOURNAL OF UROLOGY Frisenda, M., Signore, S., Delicato, G., Martinelli, A., Cantiani, A., Colafelice, M., Tufano, A., Del Giudice, F., Eisenberg, M. L., Sciarra, A., Canale, V. 2022; 29 (2): 11095-11100

  View details for Web of Science ID 000783714700011

• Influence of COVID-19 pandemic on timing and outcomes of treatment for acute testicular torsion in adults: a single institution experience. The Canadian journal of urology Frisenda, M., Signore, S., Delicato, G., Martinelli, A. G., Cantiani, A., Colafelice, M., Tufano, A., Del Giudice, F., Eisenberg, M. L., Sciarra, A., Canale, V. 2022; 29 (2): 11095-11100

  Abstract

  INTRODUCTION: The worldwide spread of SARS-COV2 had led to a delay in treatment of numerous urological pathologies, even in emergency conditions. We therefore sought to determine whether the timing of diagnosis and treatment and the postoperative outcome of patients with testicular torsion had been changed during the COVID pandemic.MATERIALS AND METHODS: We considered all patients evaluated in the emergency department (ED) for testicular torsion from February 2018 to August 2019 (pre-COVID period) and from February 2020 to August 2021 (during COVID pandemic). All patients underwent clinical and ultrasound evaluation and subsequently scrotal exploration. Primary outcomes were the time differences from pain onset to ED presentation and from ED presentation to surgical treatment. We also investigated whether the number or orchiectomies required changed during the pandemic.RESULTS: A total of 54 patients were divided in two groups: 40 patients in pre-COVID-19 group and 14 in the COVID-19 cohort. Mean time from symptoms onset to ED access was longer during the pandemic (4.2 ± 5.7 versus 39.6 ± 37.3 hours, p = 0.009). Mean time from ED access to surgery was similar (2.9 ± 1.1 versus 4.2 ± 2.3, p = 0.355). In addition, the number of orchiectomies was higher in COVID-19 group (2.5% versus 28.6%, p < 0.01), compared to a lower number of detorsions (97.5% versus 71.4%, p < 0.01). Elapsed time from pain onset to surgery was directly correlated with the increased white blood cell (WBC) count after surgery (r = 0.399, p = 0.002).DISCUSSION AND CONCLUSIONS: The current study identifies a significant delay in presentation of testicular torsion which resulted in a significant increase in orchiectomies with the expected decreased in detorsion/orchiopexy. In addition, there was an increase in the WBC at presentation associated with delayed presentation.

  View details for PubMedID 35429428

• Nervous system drugs taken by future fathers and birth defects in offspring: a prospective registry-based cohort study. BMJ open Wensink, M., Lu, Y., Tian, L., Jensen, T. K., Skakkebak, N. E., Lindahl-Jacobsen, R., Eisenberg, M. 2022; 12 (3): e053946

  Abstract

  OBJECTIVES: To evaluate the association of paternal intake of antipsychotics, anxiolytics, hypnotics and sedatives, antidepressants, selective serotonin reuptake inhibitors (SSRIs) and (benzo)diazepines during the development of fertilising sperm with birth defects in offspring.DESIGN: Prospective registry-based cohort study.SETTING: Total Danish birth cohort 1997-2016 using Danish national registries.PARTICIPANTS: All 1201119 Danish liveborn singletons born 1997-2016 were eligible, 39803 (3.3%) of whom had at least one major birth defect.EXPOSURE: Offspring were considered exposed if their father had filled at least one prescription in the relevant drug category during development of fertilising sperm (the 3months prior to conception).PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was the diagnosis, in the first year of life, of at least one major birth defect as categorised in the EUROCAT guidelines. Secondary outcome was the diagnosis, in the first year of life, of at least one major birth defect in any of the EUROCAT subcategories. Adjusted ORs (AORs) were calculated, along with their 95% CIs, adjusted for year, education, smoking status and age of the mother, and education, disposable income and age of the father.RESULTS: This study found weak or null associations between birth defects and selected drugs. Specifically, antidepressants (17827 exposed births) gave 3.5% birth defects (AOR 0.97 (0.89 to 1.05)). Diazepines, oxazepines, thiazepines and oxepines (as antipsychotics, 1633 offspring) gave 4.7% birth defects (AOR 1.22 (0.97 to 1.54)), attenuated to 1.13 when excluding by mothers' prescriptions. The study was well powered assuming 100% therapy adherence, while assuming 50% therapy adherence, the study remained well powered for the largest groups (SSRIs and antidepressants overall).CONCLUSIONS: Antipsychotics, anxiolytics, hypnotics and sedatives, antidepressants, SSRIs and benzodiazepine-derived anxiolytics, when taken by the father during development of fertilising sperm, are generally safe with regard to birth defects.

  View details for DOI 10.1136/bmjopen-2021-053946

  View details for PubMedID 35354621

• ALDH2 Expression, Alcohol Intake, and Semen Parameters Among East Asian Men. The Journal of urology Greenberg, D. R., Bhambvani, H. P., Basran, S. S., Salazar, B. P., Rios, L. C., Li, S. J., Chen, C. H., Mochly-Rosen, D., Eisenberg, M. L. 2022: 101097JU0000000000002682

  Abstract

  Inactivating mutations in mitochondrial aldehyde dehydrogenase-2 (ALDH2) are highly prevalent. The most common variant allele, ALDH2*2, is present in 40-50% of East Asians, and causes acetaldehyde accumulation, flushing, and tachycardia after alcohol intake. The relationship between alcohol intake and ALDH2 genotype on semen parameters remains unknown.We conducted a cross-sectional study to determine the association between ALDH2 genotype, alcohol consumption, and semen parameters among East Asian men. Volunteers completed a survey and submitted a semen sample for analysis. Participants were genotyped to determine ALDH2 status (ALDH2*1/*1, ALDH2*1/*2, ALDH2*2/*2) and immunohistochemical staining was used to determine protein expression of ALDH2 in spermatozoa.45 (40.2%) of 112 men were ALDH2*2 carriers. Among ALDH2*2 carriers, alcohol consumption was associated with significantly lower total sperm motility (median 20% [interquartile range 11-42%] vs 43% [IQR 31-57%], p=0.005) and progressive sperm motility (19% [IQR 11-37%] vs 36% [IQR 25-53%], p=0.008). Among alcohol consumers, ALDH2*2 carriers had significantly lower total sperm motility (20% [IQR 11-42%] vs 41% [IQR 19-57%], p=0.02), progressive sperm motility (19% [IQR 11-37%] vs 37% [IQR 17-50%], p=0.02) and total motile sperm count (28M [IQR 9-79M] vs 71M [IQR 23-150M], p=0.05) compared to ALDH2*1/*1 individuals. Secondly, ALDH2 expression in human spermatozoa was significantly lower in ALDH2*2 carriers (ALDH2*1/*1 vs ALDH2*1/*2, p=0.01; ALDH2*1/*1 vs ALDH2*2/*2, p<0.001).Our findings suggest genotyping ALDH2, coupled with alcohol cessation counseling, may improve semen parameters among men.

  View details for DOI 10.1097/JU.0000000000002682

  View details for PubMedID 35344413

• The association of impaired semen quality and pregnancy rates in assisted reproduction technology cycles: Systematic review and meta-analysis. Andrologia Del Giudice, F., Belladelli, F., Chen, T., Glover, F., Mulloy, E. A., Kasman, A. M., Sciarra, A., Salciccia, S., Canale, V., Maggi, M., Ferro, M., Busetto, G. M., De Berardinis, E., Salonia, A., Eisenberg, M. L. 2022: e14409

  Abstract

  Some studies suggest a relationship between semen quality and pregnancy rates of assisted reproduction technologies (ART). Others have questioned the utility of semen quality as proxy for fertility in couples attempting to conceive with or without assistance. We aimed to investigate the current body of evidence which correlates semen parameters and clinical pregnancy among couples utilizing ART (i.e. in vitro fertilization [IVF], intracytoplasmic sperm injection [ICSI]) through a systematic review and meta-analysis of cross-sectional and retrospective cohort studies. Pooled Odd Ratio (OR) for oligo-, astheno- and teratospermic compared to normospermic number of ART cycles were calculated among. Meta-regression and sub-group analysis were implemented to model the contribution of clinical/demographic and laboratory standards differences among the studies. Overall, 17studies were analysed representing 17,348 cycles were analysed. Pooled OR for impaired sperm concentration, motility and morphology was 1 (95%Confidence Interval [CI]: 0.97-1.03), 0.88 (95%CI: 0.73-1.03) and 0.88 (95%CI: 0.75-1) respectively. Further analysis on sperm morphology showed no differences with regard of IVF versus ICSI (p=0.14) nor a significant correlation with rising reference thresholds (Coeff: -0.02, p=0.38). A temporal trend towards a null association between semen parameters and clinical pregnancy was observed over the 20-year observation period (Coeff: 0.01, p=0.014). The current analysis found no association between semen quality (as measured by concentration, motility or morphology) and clinical pregnancy rates utilizing ART. Future investigations are necessary to explore the association between semen parameters and other ART outcomes (e.g. fertilization, implantation, birth and perinatal health).

  View details for DOI 10.1111/and.14409

  View details for PubMedID 35244232

• The past, present, and future of the semen analysis. Fertility and sterility Eisenberg, M. L. 1800

  Abstract

  This month's Views and Reviews provides an added perspective to the World Health Organization laboratory manual for the examination and processing of human semen, which was recently published in the 6th edition. The first artice provides a historical context of the prior editions of the World Health Organization manuals and modifications adopted over the years. The next piece then provides additional perspectives on the methodologies used for the performance of semen analysis. The third article then examines some of the new semen analytic technologies and enhancements that have become more common over the years. Finally, the last article proposed where male reproductive testing will head in the coming years with emerging research and technologies.

  View details for DOI 10.1016/j.fertnstert.2021.11.031

  View details for PubMedID 34986983

• Balsalazide Exposure During the Development of Fertilizing Sperm May Be Associated With Offspring Birth Defects. Inflammatory bowel diseases Wensink, M. J., Streett, S. E., Damkier, P., Lindahl-Jacobsen, R., Kjeldsen, J., Eisenberg, M. L. 2022

  View details for DOI 10.1093/ibd/izac038

  View details for PubMedID 35259244

• A Prospective Study of Male Depression, Psychotropic Medication Use, and Fecundability. American journal of men's health Yland, J. J., McKinnon, C. J., Hatch, E. E., Eisenberg, M. L., Nillni, Y. I., Rothman, K. J., Wise, L. A. 2022; 16 (1): 15579883221075520

  Abstract

  We examined the associations of male depression and psychotropic medication use with fecundability in a North American preconception cohort study (2013-2020). Men aged ≥21 years completed a baseline questionnaire with questions on history of diagnosed depression, the Major Depression Inventory (MDI), and psychotropic medication use. Pregnancy status was updated via bimonthly female follow-up questionnaires until pregnancy or 12 menstrual cycles, whichever occurred first. Analyses were restricted to 2,398 couples attempting conception for ≤6 menstrual cycles at entry. We fit proportional probabilities models to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs), adjusting for age (male and female), education, (male and female), race/ethnicity, physical activity, alcohol intake, body mass index, smoking, and having previously impregnated a partner. Nearly 12% of participants reported a depression diagnosis; 90.6% had low depressive symptoms (MDI <20), 3.5% had mild symptoms (MDI: 20-24), 2.7% had moderate symptoms (MDI: 25-29), and 3.3% had severe symptoms (MDI: ≥30). A total of 8.8% of participants reported current use of psychotropic medications. History of depression was associated with slightly reduced fecundability, although this result was also reasonably compatible with chance (FR = 0.89; 95% CI: [0.76, 1.04]). FRs for mild, moderate, and severe compared with low depressive symptoms were 0.89 (95% CI: [0.66, 1.21]), 0.90 (95% CI: [0.62, 1.31]), and 0.88 (95% CI: [0.65, 1.20]), respectively. This indicates little evidence of a dose-response relationship for depressive symptoms with fecundability, although estimates were imprecise. Current psychotropic medication use mediated 44% of the association between depressive symptoms and fecundability.

  View details for DOI 10.1177/15579883221075520

  View details for PubMedID 35144505

• Protocol for developing a core outcome set for male infertility research: an international consensus development study. Human reproduction open Rimmer, M. P., Howie, R. A., Anderson, R. A., Barratt, C. L., Barnhart, K. T., Beebeejaun, Y., Bertolla, R. P., Bhattacharya, S., Bjorndahl, L., Bortoletto, P., Brannigan, R. E., Cantineau, A. E., Caroppo, E., Collura, B. L., Coward, K., Eisenberg, M. L., De Geyter, C., Goulis, D. G., Henkel, R. R., Ho, V. N., Hussein, A. F., Huyser, C., Kadijk, J. H., Kamath, M. S., Khashaba, S., Kobori, Y., Kopeika, J., Kucuk, T., Lujan, S., Matsaseng, T. C., Mathur, R. S., McEleny, K., Mitchell, R. T., Mol, B. W., Murage, A. M., Ng, E. H., Pacey, A., Perheentupa, A. H., Du Plessis, S., Rives, N., Sarris, I., Schlegel, P. N., Shabbir, M., Smiechowski, M., Subramanian, V., Sunkara, S. K., Tarlarzis, B. C., Tuttelmann, F., Vail, A., van Wely, M., Vazquez-Levin, M. H., Vuong, L. N., Wang, A. Y., Wang, R., Zini, A., Farquhar, C. M., Niederberger, C., Duffy, J. M. 2022; 2022 (2): hoac014

  Abstract

  STUDY QUESTION: We aim to develop, disseminate and implement a minimum data set, known as a core outcome set, for future male infertility research.WHAT IS KNOWN ALREADY: Research into male infertility can be challenging to design, conduct and report. Evidence from randomized trials can be difficult to interpret and of limited ability to inform clinical practice for numerous reasons. These may include complex issues, such as variation in outcome measures and outcome reporting bias, as well as failure to consider the perspectives of men and their partners with lived experience of fertility problems. Previously, the Core Outcome Measure for Infertility Trials (COMMIT) initiative, an international consortium of researchers, healthcare professionals and people with fertility problems, has developed a core outcome set for general infertility research. Now, a bespoke core outcome set for male infertility is required to address the unique challenges pertinent to male infertility research.STUDY DESIGN SIZE DURATION: Stakeholders, including healthcare professionals, allied healthcare professionals, scientists, researchers and people with fertility problems, will be invited to participate. Formal consensus science methods will be used, including the modified Delphi method, modified Nominal Group Technique and the National Institutes of Health's consensus development conference.PARTICIPANTS/MATERIALS SETTING METHODS: An international steering group, including the relevant stakeholders outlined above, has been established to guide the development of this core outcome set. Possible core outcomes will be identified by undertaking a systematic review of randomized controlled trials evaluating potential treatments for male factor infertility. These outcomes will be entered into a modified Delphi method. Repeated reflection and re-scoring should promote convergence towards consensus outcomes, which will be prioritized during a consensus development meeting to identify a final core outcome set. We will establish standardized definitions and recommend high-quality measurement instruments for individual core outcomes.STUDY FUNDING/COMPETING INTERESTS: This work has been supported by the Urology Foundation small project award, 2021. C.L.R.B. is the recipient of a BMGF grant and received consultancy fees from Exscentia and Exceed sperm testing, paid to the University of Dundee and speaking fees or honoraria paid personally by Ferring, Copper Surgical and RBMO. S.B. received royalties from Cambridge University Press, Speaker honoraria for Obstetrical and Gynaecological Society of Singapore, Merk SMART Masterclass and Merk FERRING Forum, paid to the University of Aberdeen. Payment for leadership roles within NHS Grampian, previously paid to self, now paid to University of Aberdeen. An Honorarium is received as Editor in Chief of Human Reproduction Open. M.L.E. is an advisor to the companies Hannah and Ro. B.W.M. received an investigator grant from the NHMRC, No: GNT1176437 is a paid consultant for ObsEva and has received research funding from Ferring and Merck. R.R.H. received royalties from Elsevier for a book, consultancy fees from Glyciome, and presentation fees from GryNumber Health and Aytu Bioscience. Aytu Bioscience also funded MiOXYS systems and sensors. Attendance at Fertility 2020 and Roadshow South Africa by Ralf Henkel was funded by LogixX Pharma Ltd. R.R.H. is also Editor in Chief of Andrologia and has been an employee of LogixX Pharma Ltd. since 2020. M.S.K. is an associate editor with Human Reproduction Open. K.Mc.E. received an honoraria for lectures from Bayer and Pharmasure in 2019 and payment for an ESHRE grant review in 2019. His attendance at ESHRE 2019 and AUA 2019 was sponsored by Pharmasure and Bayer, respectively. The remaining authors declare no competing interests.TRIAL REGISTRATION NUMBER: Core Outcome Measures in Effectiveness Trials (COMET) initiative registration No: 1586. Available at www.comet-initiative.org/Studies/Details/1586.TRIAL REGISTRATION DATE: N/A.DATE OF FIRST PATIENTS ENROLMENT: N/A.

  View details for DOI 10.1093/hropen/hoac014

  View details for PubMedID 35402735

• Are worldwide sperm counts declining? Fertility and sterility Jorgensen, N., Lamb, D. J., Levine, H., Pastuszak, A. W., Sigalos, J. T., Swan, S. H., Eisenberg, M. L. 2021; 116 (6): 1457-1463

  View details for DOI 10.1016/j.fertnstert.2021.10.020

  View details for PubMedID 34836581

• Does my father have higher sperm counts than me? Fertility and sterility Eisenberg, M. L. 2021

  View details for DOI 10.1016/j.fertnstert.2021.10.015

  View details for PubMedID 34743913

• Male fertility as a marker for health. Reproductive biomedicine online Chen, T., Belladelli, F., Giudice, F. D., Eisenberg, M. L. 2021

  Abstract

  Male reproduction is a complex biological process, and male factor infertility is increasingly recognized as a biomarker for overall male health. Emerging data suggest associations between male reproduction and medical disease (genetic, infectious, chronic comorbid conditions), psychological disease, environmental exposures, dietary habits, medications and substances of abuse, and even socioeconomic factors. There is also evidence that a diagnosis of male fertility is associated with future disease risk including cancer, metabolic disease and mortality. As such, there is a growing view that the male fertility evaluation is an opportunity to improve a man's health beyond his immediate reproductive goals, and also highlights the necessity of a multidisciplinary approach.

  View details for DOI 10.1016/j.rbmo.2021.09.023

  View details for PubMedID 34848151

• Paternal Biologic and Thiopurine Exposure in Inflammatory Bowel Disease and Association With Adverse Pregnancy Outcomes and Semen Parameters: A Systematic Review and Meta-Analysis Gubatan, J., Barber, G., Nielsen, O., Juhl, C., Maxwell, C., Eisenberg, M., Streett, S. LIPPINCOTT WILLIAMS & WILKINS. 2021: S353

  View details for Web of Science ID 000717526101240

• ASSOCIATIONS BETWEEN RACE AND ERECTILE DYSFUNCTION TREATMENT PATTERNS Chen, T., Li, S., Eisenberg, M. LIPPINCOTT WILLIAMS & WILKINS. 2021: E1172

  View details for Web of Science ID 000693689000836

• PROSTERIA: A CLAIMS-BASED STUDY OF DEMOGRAPHIC AND TEMPORAL TRENDS IN FREQUENT PROSTATE SPECIFIC ANTIGEN TESTING Peterson, D., Li, S., Bhambhvani, H., Brooks, J., Eisenberg, M. LIPPINCOTT WILLIAMS & WILKINS. 2021: E851

  View details for Web of Science ID 000693689000201

• A PROSPECTIVE STUDY OF MALE SLEEP AND SEMEN QUALITY. Yland, J. J., Eisenberg, M. L., Willis, S. K., Wang, T. R., Hatch, E. E., Rothman, K. J., Sommer, G., Wise, L. A. ELSEVIER SCIENCE INC. 2021: E333

  View details for Web of Science ID 000699951501315

• THE ASSOCIATION OF PRECONCEPTION PATERNAL METABOLIC SYNDROME ON EARLY CHILDHOOD EMERGENCY DEPARTMENT VISITS AND HOSPITALIZATION: ANALYSIS OF US CLAIMS DATA Chen, T., Zhang, C., Li, S., Shaw, G., Schroeder, A., Eisenberg, M. LIPPINCOTT WILLIAMS & WILKINS. 2021: E526

  View details for Web of Science ID 000693688500311

• Vasectomy utilization in men aged 18-45 declined between 2002-2017: Results from the United States National Survey for Family Growth Data. Andrology Zhang, X., Eisenberg, M. L. 2021

  Abstract

  BACKGROUND: Vasectomy remains a safe, simple and effective contraceptive options. Conflicting data on the trend of vasectomy use among men have been described previously at various snapshots in time over the last two decades.OBJECTIVES: This paper seeks to describe the trend of vasectomy utilization in the last 15 years using a nationally representative United States survey.MATERIALS AND METHODS: We analyzed data from male respondents aged 18 to 45 years of the Cycle 6 (2002), 2006-2010, 2011-2013, 2013-2015, and 2015-2017 National Survey of Family Growth (NSFG) surveys. Population estimates are calculated based on the official NSFG instructions, accounting for the complex survey design. Multivariate logistic regression models are used to study demographic and socioeconomic factors associated with vasectomy use in men.RESULTS: Baseline characteristics for men undergoing vasectomy do not differ significantly across survey years. Increased age, White race, marital status, higher education level, birthplace within the United States, higher household income, non-Catholic affiliation, and higher number of biological kids have significant positive associations with vasectomy use. After accounting for factors associated with vasectomy utilization, there was a significant temporal decline in vasectomy utilization rates in all age groups across survey years which remained in subgroup analyses of all men greater than 25, 30, and 35 of age.DISCUSSION: This is the first population-based analysis of US data to observe a decline in vasectomy utilization over the past two decades. The decline was statistically significant after accounting for all demographic and socioeconomic factors.CONCLUSION: There is a steady decline in the prevalence of vasectomy use in men from 2002 to 2017. Given the limited contraceptive options for men and the importance of contraception and family planning in the US, further research is needed to understand the temporal decline. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/andr.13093

  View details for PubMedID 34390207

• Trends in Testosterone Therapy use in Prostate Cancer Survivors in the United States. The journal of sexual medicine Chen, T., Li, S., Eisenberg, M. L. 2021; 18 (8): 1346-1353

  Abstract

  Physician prescribing patterns surrounding the use of testosterone therapy (TTh) in men with a history of prostate cancer (CaP) is not well described.To characterize the demographics and usage patterns of testosterone therapy in men with a history of prostate cancer in the United States.This was a retrospective review using Optum's De-identified Clinformatics Data Mart database. Administrative diagnosis, procedural, pharmacy, and laboratory codes were used to identify male subjects 40 years and older with prostate cancer treated with surgery or radiation between 2003 and 2018 who went on to receive TTh. Demographic and clinical factors are identified. Temporal trends in TTh usage were reported.The main outcomes were rates of testosterone prescriptions in men with treated prostate cancer and associated laboratory values such as Prostate Specific Antigen (PSA) and testosterone levels before TTh.126,374 men completed treatment for CaP during the study period (42,515 surgery, 75,186 radiation, 8,673 both). Of these, 3,074 men (2.4%) received testosterone after CaP treatment. Men who received testosterone were younger, more likely to have erectile dysfunction, depressive disorder, and lower pretreatment PSA values compared to men who did not receive. Median PSA levels before TTh initiation were 0 - 0.2 depending on CaP treatment modality and median total testosterone level was <300 ng/dL. TTh began an average of 1.5 years after radical prostatectomy and 2.6 years after radiation treatment. We observed an increase in TTh after CaP from the beginning of the study period until it peaked in 2013 at 4.9%. After 2013, rates decreased annually until a plateau of approximately 1.8% of men. Approximately a third of men did not have testosterone labs checked before initiation of TTh.These findings provide insight into trends in testosterone prescriptions in men after prostate cancer treatment and may aid in clinical decision-making, as well as areas for improvement in cancer survivorship care.Strengths include the large sample size, length of data coverage, and real-world analysis of testosterone prescribing patterns across the United States. Limitations include the reliance on insurance claims data, the retrospective study design, and lack of additional relevant clinical variables that may impact decision making regarding TTh.National trends in testosterone prescriptions for men with treated prostate cancer suggest that many men are treated with TTh after prostate cancer therapy with patterns of indications and monitoring consistent with the general population.

  View details for DOI 10.1016/j.jsxm.2021.06.007

  View details for PubMedID 37057458

• The Association Between Work Hours, Shift Work, and Job Latitude With Fecundability: A Preconception Cohort Study JOURNAL OF OCCUPATIONAL HEALTH PSYCHOLOGY McKinnon, C., Hatch, E., Orta, O. R., Rothman, K. J., Eisenberg, M. L., Wefes-Potter, J., Wise, L. A. 2021

  Abstract

  The role of occupational stress on male fertility is understudied. We examined associations between male occupational stress and fecundability. We used data from Pregnancy Study Online (PRESTO), a North American preconception cohort study. At baseline (2013-2019), male participants aged ≥ 21 years completed a baseline questionnaire on employment status, hours worked per week, time of day worked (daytime, evening, nights, and changing or rotating shifts), and job title. We used the O*NET occupational database to rate independence by job title. Female partners were followed via bimonthly follow-up questionnaires for 12 months or until pregnancy. We restricted analyses to 1,818 couples attempting conception for ≤ 6 cycles at enrollment. We used proportional probabilities regression to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs). The FR comparing unemployed with employed men was0.84 (95% CI: 0.62-1.14). Among employed men, FRs and 95% CIs for evening shift work, night shift work, and rotating shift work were 0.89 (95% CI: 0.68-1.17), 0.94 (95% CI: 0.66-1.33), and 0.91 (95% CI: 0.75-1.11) relative to daytime shift work. The FR for any nondaytime shift work was 0.91 (95% CI: 0.78-1.07). Total work hours (long or short) and job independence scores were not appreciably associated with fecundability. In conclusion, working nondaytime shifts and being unemployed were associated with slightly decreased fecundability. However, the variability in these estimates was substantial and the results were reasonably consistent with chance. Little association was observed for other occupation measures. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

  View details for DOI 10.1037/ocp0000279

  View details for Web of Science ID 000733354000001

  View details for PubMedID 34323556

• Trends in Testosterone Therapy use in Prostate Cancer Survivors in the United States. The journal of sexual medicine Chen, T., Li, S., Eisenberg, M. L. 2021

  Abstract

  BACKGROUND: Physician prescribing patterns surrounding the use of testosterone therapy (TTh) in men with a history of prostate cancer (CaP) is not well described.AIM: To characterize the demographics and usage patterns of testosterone therapy in men with a history of prostate cancer in the United States.METHODS: This was a retrospective review using Optum's De-identified Clinformatics Data Mart database. Administrative diagnosis, procedural, pharmacy, and laboratory codes were used to identify male subjects 40 years and older with prostate cancer treated with surgery or radiation between 2003 and 2018 who went on to receive TTh. Demographic and clinical factors are identified. Temporal trends in TTh usage were reported.OUTCOMES: The main outcomes were rates of testosterone prescriptions in men with treated prostate cancer and associated laboratory values such as Prostate Specific Antigen (PSA) and testosterone levels before TTh.RESULTS: 126,374 men completed treatment for CaP during the study period (42,515 surgery, 75,186 radiation, 8,673 both). Of these, 3,074 men (2.4%) received testosterone after CaP treatment. Men who received testosterone were younger, more likely to have erectile dysfunction, depressive disorder, and lower pretreatment PSA values compared to men who did not receive. Median PSA levels before TTh initiation were 0 - 0.2 depending on CaP treatment modality and median total testosterone level was <300 ng/dL. TTh began an average of 1.5 years after radical prostatectomy and 2.6 years after radiation treatment. We observed an increase in TTh after CaP from the beginning of the study period until it peaked in 2013 at 4.9%. After 2013, rates decreased annually until a plateau of approximately 1.8% of men. Approximately a third of men did not have testosterone labs checked before initiation of TTh.CLINICAL IMPLICATIONS: These findings provide insight into trends in testosterone prescriptions in men after prostate cancer treatment and may aid in clinical decision-making, as well as areas for improvement in cancer survivorship care.STRENGTHS AND LIMITATIONS: Strengths include the large sample size, length of data coverage, and real-world analysis of testosterone prescribing patterns across the United States. Limitations include the reliance on insurance claims data, the retrospective study design, and lack of additional relevant clinical variables that may impact decision making regarding TTh.CONCLUSION: National trends in testosterone prescriptions for men with treated prostate cancer suggest that many men are treated with TTh after prostate cancer therapy with patterns of indications and monitoring consistent with the general population. Chen T, Li S, Eisenberg M. Trends in Testosterone Therapy use in Prostate Cancer Survivors in the United States. J Sex Med 2021;XX:XXX-XXX.

  View details for DOI 10.1016/j.jsxm.2021.06.007

  View details for PubMedID 34303630

• Peyronie's Disease as a marker of inflammation -is there hope on the horizon? The American journal of medicine Swislocki, A. L., Eisenberg, M. L. 2021

  Abstract

  While the description of Peyronie's disease, aconnective tissue disorderinvolving the growth of fibrous plaques in thesoft tissueof thepenis, is attributed to Francois de la Peyronie, Surgeon to Louis XV of France, there are earlier reports. Over the intervening 450 years, a variety of empiric treatments, varying in barbarity, have been proposed. The frequency of this condition and the etiology of the fibrosis are unknown. Quality of life for affected men, and their partners, is adversely impacted. In this review, the authors summarize the history of the discovery of this condition, review contemporary management approaches, and address the pathophysiology leading to the underlying disordered fibrosis. The potential immunomodulatory role of testosterone, as well as inflammatory conditions and environmental stimuli that may provoke fibrosis are also considered. Peyronie's disease may be part of a spectrum of fibrotic conditions, including Dupuytren's contracture. Treatment strategies to date have focused on reversing fibrosis; work is needed to prevent fibrosis and to accurately document disease prevalence.

  View details for DOI 10.1016/j.amjmed.2021.06.015

  View details for PubMedID 34273285

• The Association of Medicaid Insurance and Affordable Care Act Expansions with Survival among Patients with Testicular Cancer UROLOGY PRACTICE Bhambhvani, H. P., Hampshire, K., Eisenberg, M. L. 2021; 8 (4): 440-448

  View details for DOI 10.1097/UPJ.0000000000000229

  View details for Web of Science ID 000711780800003

• The Association of Medicaid Insurance and Affordable Care Act Expansions with Survival among Patients with Testicular Cancer. Urology practice Bhambhvani, H. P., Hampshire, K., Eisenberg, M. L. 2021; 8 (4): 440-449

  Abstract

  Following passage of the Affordable Care Act, Medicaid access was expanded in several states beginning in 2014. We sought to determine the oncologic implications by comparing outcomes between testicular germ cell tumor patients with Medicaid and those without insurance, and by assessing for changes in outcomes after 2014.A total of 18,506 men with seminomatous or nonseminomatous germ cell tumors were identified within the Surveillance, Epidemiology, and End Results database (2007-2016). Multivariable Cox proportional hazards, Fine and Gray competing-risks regression, propensity score matching, cumulative incidence plots and segmented Poisson regression models were used.Compared to no insurance, Medicaid insurance was not associated with differences in all-cause mortality or cancer-specific mortality among seminoma patients (all-cause mortality: HR=1.24, p=0.87; cancer-specific mortality: HR=0.92, p=0.75) or nonseminoma patients (all-cause mortality: HR=1.13, p=0.33; cancer-specific mortality: HR=1.10, p=0.51). Among matched Medicaid and uninsured patients, there was again no difference in cancer-specific mortality for those with seminoma (p=0.81) or nonseminoma (p=0.23). There was a 99% increase in Medicaid enrollment in expansion states in the post-Affordable Care Act era. There was no difference in post-expansion all-cause mortality between expansion states and nonexpansion states for men with seminoma (p=0.42) or nonseminoma (p=0.53).Medicaid enrollment increased in expansion states following the Affordable Care Act. However, there was no difference in survival between Medicaid patients and uninsured patients, or between patients in expansion states versus nonexpansion states, highlighting the need for population-level policy interventions to improve access and quality of care among testicular cancer patients with Medicaid.

  View details for DOI 10.1097/UPJ.0000000000000229

  View details for PubMedID 37145467

• Consumption of cruciferous vegetables and the risk of bladder cancer in a prospective US cohort: data from the NIH-AARP diet and health study. American journal of clinical and experimental urology Nguyen, T. P., Zhang, C. A., Sonn, G. A., Eisenberg, M. L., Brooks, J. D. 2021; 9 (3): 229-238

  Abstract

  Abundant pre-clinical data suggest that consumption of cruciferous vegetables might protect against bladder cancer. While small-scale clinical evidence supports this hypothesis, population-level data is lacking. We tested the hypothesis that consumption of cruciferous vegetables is associated with a lower risk of bladder cancer in a large population-based study.We investigated the association between dietary consumption of cruciferous vegetables and the risk of bladder cancer in the NIH-American Association of Retired Persons (AARP) Diet and Health Study. Diet at baseline was collected with self-administered food-frequency questionnaires. Bladder cancer diagnoses were identified through linkage with state cancer registries. Hazard ratio (HR) and 95% confidence intervals (CI) were estimated with Cox proportional hazards models.Our analysis included 515,628 individuals. Higher intake of cruciferous vegetables, both overall and when stratified by variety (broccoli vs. brussels sprouts vs. cauliflower), were not associated with bladder cancer risk for men or women. A history of smoking did not affect the results.Our study shows no association between dietary consumption of cruciferous vegetables and incident bladder cancer.

  View details for PubMedID 34327262

  View details for PubMedCentralID PMC8303025

• RUBIC - A binational clinical foundation to study risk factors, life course, and treatment of infertility and infertility-related morbidity. Andrology Priskorn, L., Tottenborg, S. S., Almstrup, K., Andersson, A., Axelsson, J., Brauner, E. V., Elenkov, A., Freiesleben, N. l., Giwercman, Y. L., Grondahl, M. L., Hansen, A. H., Hansen, L. S., Henic, E., Kitlinski, M. L., Landersoe, S. K., Lindh, C., Lokkegaard, E. L., Malm, J., Olsen, K. W., Petersen, K. U., Schmidt, L., Stormlund, S., Svendsen, P. F., Vassard, D., Wang, N. F., Zedeler, A., Bhasin, S., Chavarro, J., Eisenberg, M. L., Hauser, R., Huhtaniemi, I., Krawetz, S. A., Marko-Varga, G., Salonia, A., Toppari, J., Juul, A., Jorgensen, N., Nielsen, H. S., Pinborg, A., Rylander, L., Giwercman, A. 2021

  Abstract

  BACKGROUND: Infertility affects 15-25% of all couples during their reproductive life span. It is a significant societal and public health problem with potential psychological, social, and economic consequences. Furthermore, infertility has been linked to adverse long-term health outcomes. Despite the advanced diagnostic and therapeutic techniques available, approximately 30% of infertile couples do not obtain a live birth after fertility treatment. For these couples, there are no further options to increase their chances of a successful pregnancy and live birth.OBJECTIVES: Three overall questions will be studied: 1) What are the risk factors and natural life courses of infertility, early embryonic loss, and adverse pregnancy outcomes? 2) Can we develop new diagnostic and prognostic biomarkers for fecundity and treatment success? And 3) what are the health characteristics of women and men in infertile couples at the time of fertility treatment and during long-term follow-up?MATERIAL AND METHODS: ReproUnion Biobank and Infertility Cohort (RUBIC) is established as an add-on to the routine fertility management at Copenhagen University Hospital Departments in the Capital Region of Denmark and Reproductive Medicine Centre at Skane University Hospital in Sweden. The aim is to include a total of 5000 couples equally distributed between Denmark and Sweden. The first patients were enrolled in June 2020. All eligible infertile couples are prospectively asked to participate in the project. Participants complete an extensive questionnaire and undergo a physical examination and collection of bio-specimens (blood, urine, hair, saliva, rectal swabs, feces, semen, endometrial biopsies, and vaginal swabs). After the cohort is established, the couples will be linked to the Danish and Swedish national registers to obtain information on parental, perinatal, childhood, and adult life histories, including disease and medication history. This will enable us to understand the causes of infertility and identify novel therapeutic options for this important societal problem. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/andr.13063

  View details for PubMedID 34114375

• The Association Between Hemoglobin A1c Levels and Inflatable Penile Prosthesis Infection: Analysis of US Insurance Claims Data. The journal of sexual medicine Chen, T., Li, S., Eisenberg, M. L. 2021

  Abstract

  BACKGROUND: The association between elevated hemoglobin A1c (HbA1c) levels and the risk of postoperative infection after penile prosthesis surgery remains controversial.AIM: To examine the association between HbA1c levels and penile implant infections in men undergoing inflatable penile prosthesis (IPP) surgery for erectile dysfunction using a large insurance claims database.METHODS: This was a retrospective review using Optum's de-identified Clinformatics Data Mart Database. Male subjects 18 years and older with available laboratory data undergoing IPP insertion between 2003 and 2018 were included. Administrative diagnosis and procedural codes were used to assess subsequent penile implant revision surgery status for either infectious or noninfectious causes. Associated conditions were controlled for such as smoking status, hyperlipidemia, hypertension, obesity status, and Peyronie's disease.OUTCOMES: The main outcomes were risk of revision for infection and time to revision.RESULTS: A total of 2,363 individuals underwent initial IPP insertion and had available HbA1c data with a mean HbA1c of 6.9%. The overall IPP infection revision rate was 3.9% and the highest rate of 12.1% was seen in the highest HbA1c group (>10%). After adjusting for demographic and health factors, a higher HbA1c level was associated with a higher risk of revision for infection, with every 1 point increase in HbA1c conferring an increased risk of infection requiring revision by 29% (95% CI 17-42%). When infections did occur, they happened sooner in men with HbA1c > 10.0% with an average of 1.3 months vs 3.5 months in the HbA1c < 6.0% group.CLINICAL IMPLICATIONS: These findings provide insight into the potential relationship between HbA1c levels and postoperative risk of infection after penile prosthesis surgery and may aid in clinical decision-making.STRENGTHS AND LIMITATIONS: Strengths include the large sample size, length of data coverage, and real-world analysis of surgeries done across the United States. Limitations include the reliance on insurance claims data, the retrospective study design, and lack of additional relevant clinical variables that may impact infection rates.CONCLUSIONS: While the overall risk of penile prosthesis infection remains modest, the current report notes an increased risk of infection for diabetic men with poor glycemic control. Chen T, Li S, Eisenberg ML. The Association Between Hemoglobin A1c Levels and Inflatable Penile Prosthesis Infection: Analysis of US Insurance Claims Data. J Sex Med 2021;18:1104-1109.

  View details for DOI 10.1016/j.jsxm.2021.03.077

  View details for PubMedID 34103256

• Does semen analysis testing reveal disparities? Nature reviews. Urology Del Giudice, F., Eisenberg, M. L. 2021

  View details for DOI 10.1038/s41585-021-00485-x

  View details for PubMedID 34075226

• The Association Between Hemoglobin A1c Levels and Inflatable Penile Prosthesis Infection: Analysis of US Insurance Claims Data. The journal of sexual medicine Chen, T., Li, S., Eisenberg, M. L. 2021; 18 (6): 1104-1109

  Abstract

  The association between elevated hemoglobin A1c (HbA1c) levels and the risk of postoperative infection after penile prosthesis surgery remains controversial.To examine the association between HbA1c levels and penile implant infections in men undergoing inflatable penile prosthesis (IPP) surgery for erectile dysfunction using a large insurance claims database.This was a retrospective review using Optum's de-identified Clinformatics Data Mart Database. Male subjects 18 years and older with available laboratory data undergoing IPP insertion between 2003 and 2018 were included. Administrative diagnosis and procedural codes were used to assess subsequent penile implant revision surgery status for either infectious or noninfectious causes. Associated conditions were controlled for such as smoking status, hyperlipidemia, hypertension, obesity status, and Peyronie's disease.The main outcomes were risk of revision for infection and time to revision.A total of 2,363 individuals underwent initial IPP insertion and had available HbA1c data with a mean HbA1c of 6.9%. The overall IPP infection revision rate was 3.9% and the highest rate of 12.1% was seen in the highest HbA1c group (>10%). After adjusting for demographic and health factors, a higher HbA1c level was associated with a higher risk of revision for infection, with every 1 point increase in HbA1c conferring an increased risk of infection requiring revision by 29% (95% CI 17-42%). When infections did occur, they happened sooner in men with HbA1c > 10.0% with an average of 1.3 months vs 3.5 months in the HbA1c < 6.0% group.These findings provide insight into the potential relationship between HbA1c levels and postoperative risk of infection after penile prosthesis surgery and may aid in clinical decision-making.Strengths include the large sample size, length of data coverage, and real-world analysis of surgeries done across the United States. Limitations include the reliance on insurance claims data, the retrospective study design, and lack of additional relevant clinical variables that may impact infection rates.While the overall risk of penile prosthesis infection remains modest, the current report notes an increased risk of infection for diabetic men with poor glycemic control.

  View details for DOI 10.1016/j.jsxm.2021.03.077

  View details for PubMedID 37057465

• Trends in time-to-pregnancy in the USA: 2002 to 2017. Human reproduction (Oxford, England) Eisenberg, M. L., Thoma, M. E., Li, S., McLain, A. C. 2021

  Abstract

  STUDY QUESTION: Has there been there a temporal change in time-to-pregnancy (TTP) in the USA.SUMMARY ANSWER: Overall, TTP was stable over time, but a longer TTP for women over 30 and parous women was identified.WHAT IS KNOWN ALREADY: Fertility rates in the USA have declined over the past several years. Although these trends have been attributed to changing reproductive intentions, it is unclear whether declining fecundity (the biologic ability to reproduce measured by TTP in the current report) may also play a role. Indeed, trends based on declining sperm quality and higher utilisation of infertility treatment suggest fecundity may be falling.STUDY DESIGN, SIZE, DURATION: This cross-sectional survey data from the National Survey of Family Growth was administered from 2002 to 2017. The surveys are based on nationally representative samples of reproductive-aged women in the USA. Interviews were conducted in person or through computer-assisted self-administration of sensitive questions.PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included women who self-reported time spent trying to become pregnant allowing utilisation of the current duration approach to estimate the total duration of pregnancy attempt (i.e. TTP). In all, 1202 participants were analysed over each study period. To estimate a TTP distribution overall and by parity, we used a piecewise constant proportional hazards model that accounts for digit preference. Accelerated-failure-time regression models, which were weighted to account for the sampling design, were used to estimate time ratios (TRs). Models were adjusted for age, BMI, race, education, relationship status, parity, pelvic inflammatory disease treatment and any reproductive problems.MAIN RESULTS AND THE ROLE OF CHANCE: Of the participants analysed, the average age was 31.8 and BMI was 28.6, which was similar across the survey periods. Relationship status was the only demographic characteristic that changed over time. All other variables remained constant across the study periods. Overall, TRs comparing TTP between 2002 and 2017 increased slightly (TR: 1.02, 95% CI: 0.99, 1.04). When stratified by parity, parous women had a longer TTP over the later years of the study (TR: 1.04, 95% CI: 1.01, 1.06). TTP remained constant for nulliparous women. Similarly, TTP also increased over time for women over age thirty (TR: 1.02, 1.00, 1.05) but not for women under age thirty.LIMITATIONS, REASONS FOR CAUTION: Small changes in data collection over time may have impacted the findings. We accounted for this in sensitivity analyses using imputed data. Overall, TRs were slightly attenuated using the imputed data, but represented similar patterns to the original data. Results for parous women and women over 30 remained consistent in the sensitivity analyses.WIDER IMPLICATIONS OF THE FINDINGS: Consistent with reports of falling fertility rates and sperm counts, this study suggests parous and older couples in the USA may be taking longer to become pregnant. Although trends were suggestive of a small overall increase in TTP, particularly for parous women and women over age thirty, additional data are needed to attempt to understand these trends given the societal, economic and public health implications related to fecundity.STUDY FUNDING/COMPETING INTEREST(S): Funding was provided by National Institutes of Health grant R03HD097287 to A.C.M. There are no competing interests.TRIAL REGISTRATION NUMBER: N/A.

  View details for DOI 10.1093/humrep/deab107

  View details for PubMedID 34021350

• A North American prospective study of depression, psychotropic medication use, and semen quality. Fertility and sterility Yland, J. J., Eisenberg, M. L., Hatch, E. E., Rothman, K. J., McKinnon, C. J., Nillni, Y. I., Sommer, G. J., Wang, T. R., Wise, L. A. 2021

  Abstract

  OBJECTIVE: To evaluate the associations of a history of diagnosed depression, current depressive symptoms, and recent use of psychotropic medications with semen quality and to consider mediation of the association between depression and semen quality by medication use.DESIGN: Prospective cohort study.SETTING: United States.PATIENT(S): The patients were 329 men aged ≥21 years (566 semen samples) who participated in a semen-testing substudy of Pregnancy Study Online. Pregnancy Study Online is an ongoing, web-based preconception cohort study of couples attempting to conceive. At baseline, participants reported information about depression diagnosis, depressive symptoms using the Major Depression Inventory, medication use in the last 4 weeks, and selected covariates.INTERVENTION(S): None.MAIN OUTCOME MEASURE(S): The men used an at-home semen-testing kit (Trak; Sandstone Diagnostics, Inc., Pleasanton, California) to measure semen volume, sperm concentration, and motile sperm concentration. We calculated percent motility, total sperm count in the ejaculate, and total motile sperm count.RESULT(S): Forty-nine men (15%) reported a history of depression diagnosis, and 41 (12%) reported recent use of psychotropic medications. A history of depression diagnosis was associated with a 4.3-fold increase in the risk of low semen volume (<1.5 mL) (95% CI 1.16, 16). A 5-unit increase in Major Depression Inventory score was associated with a 1.38-fold increase in the risk of low semen volume (95% CI 0.92, 2.1). The results for other semen parameters were inconsistent. Recent use of psychotropic medications was associated with worse semen quality, and this association was confounded by a history of depression diagnosis. The observed association between depression and semen volume showed little mediation by psychotropic medication use.CONCLUSION: A history of diagnosed depression and severe depressive symptoms at enrollment were associated with low semen volume.

  View details for DOI 10.1016/j.fertnstert.2021.03.052

  View details for PubMedID 33966888

• Association of Preconception Paternal Health and Adverse Maternal Outcomes among Healthy Mothers. American journal of obstetrics & gynecology MFM Murugappan, G., Li, S., Leonard, S., Winnm, V. D., Druzin, M., Eisenberg, M. L. 2021: 100384

  Abstract

  OBJECTIVE: To examine the association of preconception paternal health and risk of adverse maternal outcomes among healthy mothers.STUDY DESIGN: Retrospective analysis of live births from 2009-2016 among healthy women 20-45 years of age in the IBM Marketscan research database. Infants were linked to paired mothers and fathers using family ID. Preconception paternal health was assessed using the number of metabolic syndrome (MetS) components and the most common individual chronic disease diagnoses (hypertension, diabetes mellitus, obesity, hyperlipidemia, COPD, cancer, and depression). Women with MetS components were excluded to avoid potential confounding of maternal and paternal factors. Adverse maternal outcomes assessed included: 1) abnormal placentation including placenta accreta spectrum, placenta previa and placental abruption 2) pre-eclampsia with and without severe features including eclampsia, and 3) severe maternal morbidity (SMM), identified as any indicator from the CDC Index of life-threatening complications at the time of delivery through 6 weeks postpartum. The trend between preconception paternal health and each maternal outcome was determined using the Cochran-Armitage Trend test. The independent association of paternal health and maternal outcomes was also determined using generalized estimating equations (GEE) models accounting for some mothers contributing multiple births and adjusting for maternal age, paternal age, region of birth, year of birth, maternal smoking, and average number of outpatient visits per year.RESULTS: Among 669,256 births to healthy mothers, there was a significant trend of all adverse maternal outcomes with worsening preconception paternal health defined either as number of MetS components or number of chronic diseases (p<0.001, Cochran-Armitage Trend test). In the GEE model, the odds of pre-eclampsia without severe features increased in a dose-dependent fashion and were 21% higher (95% CI 1.17-1.26) among women whose partners had ≥2 MetS than for women whose partners had 0 MetS. The odds of pre-eclampsia with severe features and eclampsia increased in a dose-dependent fashion and were 19% higher (95% CI 1.09-1.30) for women whose partners had ≥2 MetS than for women whose partners had 0 MetS. The odds of SMM were 9% higher (95% CI 1.002-1.19) for women whose partners had ≥2 MetS components than for women whose partners had 0 MetS. The odds of abnormal placentation was similar between groups (aOR 0.96, 95% CI 0.89-1.03).CONCLUSIONS: Among healthy mothers, we report preconception paternal health is significantly associated with increased odds of pre-eclampsia with and without severe features and weakly associated with odds of SMM. These findings suggest that paternally derived factors may play significant roles in the development of adverse maternal outcomes in healthy women with a low a priori risk of obstetric complications.

  View details for DOI 10.1016/j.ajogmf.2021.100384

  View details for PubMedID 33895399

• Female Sexual Function During the COVID-19 Pandemic in the United States. Sexual medicine Bhambhvani, H. P., Chen, T., Kasman, A. M., Wilson-King, G., Enemchukwu, E., Eisenberg, M. L. 2021; 9 (4): 100355

  Abstract

  INTRODUCTION: International studies have demonstrated increasing rates of sexual dysfunction amidst the coronavirus disease 2019 (COVID-19) pandemic; however, the impact of the pandemic on female sexual function in the United States is unknown.AIM: To assess the impact of the COVID-19 pandemic on female sexual function and frequency in the United States.METHODS: A pre-pandemic survey containing the Female Sexual Function Index (FSFI) and demographic questions was completed by adult women in the United States from October 20, 2019 and March 1, 2020. The same women were sent a follow-up survey also containing the FSFI, as well as the Patient Health Questionnaire for Depression and Anxiety with 4 items (PHQ-4), and questions pertaining to mask wearing habits, job loss, and relationship changes. Risk for female sexual dysfunction (RFSD) was defined as FSFI < 26.55.MAIN OUTCOME MEASURE: Differences in pre-pandemic and intra-pandemic female sexual function, measured by the FSFI, and sexual frequency.RESULTS: Ninety-one women were included in this study. Overall FSFI significantly decreased during the pandemic (27.2 vs 28.8, P=.002), with domain-specific decreases in arousal (4.41 vs 4.86, P=.0002), lubrication (4.90 vs 5.22, P=.004), and satisfaction (4.40 vs 4.70, P=.04). There was no change in sexual frequency. Contingency table analysis of RFSD prior to and during the pandemic revealed significantly increased RFSD during the pandemic (P=.002). Women who developed RFSD during the pandemic had higher PHQ-4 anxiety subscale scores (3.74 vs 2.53, P=.01) and depression subscale scores (2.74 vs 1.43, P=.001) than those who did not. Development of FSD was not associated with age, home region, relationship status, mask wearing habits, knowing someone who tested positive for COVID-19, relationship change, or job loss and/or reduction during the pandemic.CONCLUSION: In this population of female cannabis users, risk for sexual dysfunction increased amidst the COVID-19 pandemic and is associated with depression and anxiety symptoms. Bhambhvani HP, Chen T, Wilson-King AM, etal. Female Sexual Function During the COVID-19 Pandemic in the United States. Sex Med 2021;9:100355.

  View details for DOI 10.1016/j.esxm.2021.100355

  View details for PubMedID 34174585

• A Biofeedback guided program or pelvic floor muscle electric stimulation can improve early recovery of urinary continence after radical prostatectomy: a meta-analysis and systematic review. International journal of clinical practice Sciarra, A., Viscuso, P., Arditi, A., Mariotti, G., De Berardinis, E., Di Pierro, G. B., Canale, V., Gentilucci, A., Busetto, G. M., Maggi, M., Eisenberg, M. L., Vilson, F., Chung, B. I., Ferro, M., Salciccia, S., Del Giudice, F. 2021: e14208

  Abstract

  PURPOSE: Urinary incontinence (UI) after radical prostatectomy (RP) is an early side effect after catheter removal. This systematic review and meta-analysis was conducted to compare different forms of non-invasive treatments for post-RP UI and to analyze whether the addition of biofeedback (BF) and/or pelvic floor muscle electric stimulation (PFES) to PF muscle exercise (PFME) alone can improve results in terms of continence recovery rate.MATERIALS AND METHODS: A literature search was performed following the PRISMA guidelines. We performed a cumulative meta-analysis to explore the trend in the effect sizes across subgroups during a 12-mo follow-up.RESULTS: 26 articles were selected. At baseline after RP and catheter removal, mean pad weight varied extremely. At 1- and 3-mo intervals, mean difference in pad weight recovery from baseline was significantly higher using guided programs (BF, PFES or both) than using PFME alone (3-mo: PFME 111.09 g (95%CI 77.59-144.59), BF 213.81 g (95%CI -80.51-508-13), PFES 306.88 g (95%CI 158.11-455.66), BF+PFES 266.31 g (95%CI 22.69-302.93); p<0.01), while at 6- and 12-mo differences were similar (p>0.04). At 1- and 3-mo intervals, event rate (ER) of continence recovery was significantly higher using guided programs than using PFME alone (3-mo: PFME 0.40 (95%CI 0.30-0.49), BF 0.49 (95%CI 0.31-0.67), PFES 0.57 (95%CI 0.46-0.69), BF+PFES 0.75 (95%CI 0.60-0.91); p<0.01), while at 6- and 12-mo ERs were similar.CONCLUSIONS: Regarding non-invasive treatment of UI secondary to RP, the addition of guided programs using BF or/and PFES demonstrated to improve continence recovery rate, particularly in the first 3-mo interval, when compared to the use of PFME alone.

  View details for DOI 10.1111/ijcp.14208

  View details for PubMedID 33811418

• Modeling the Contribution of Male Testosterone Levels to the Duration of Positive COVID Testing among Hospitalized Male COVID-19 Patients. Diagnostics (Basel, Switzerland) Salciccia, S., Eisenberg, M. L., Maggi, M., Lai, S., Mastroianni, C. M., Pasculli, P., Ciardi, M. R., Canale, V., Ferro, M., Busetto, G. M., De Berardinis, E., Ricciuti, G. P., Sciarra, A., Del Giudice, F. 2021; 11 (4)

  Abstract

  Background: A growing body of evidence is emerging suggesting testosterone can affect all cells involved in the immune response to both bacterial and viral infections, and the testosterone effect on the immune response could explain the greater susceptibility of men to infections including COVID-19. We aimed to explore the predictive role of male serum total testosterone (TT) levels on the time till viral negativity testing among hospitalized COVID-19 patients. Methods: The univariate effect of risk factors for the duration of COVID-19 viral positivity was evaluated using the log-rank test and Kaplan-Meier estimates. A multivariable Cox regression model was developed to test the role of TT levels and the subsequent odds for shorter viral positivity intervals. Results: Increasing serum TT levels and the need for an oxygen administration strategy were independently predictive for respectively reduced and increased days to negativization (Hazard Ratio [HR]: 1.39, 95% CI: 0.95-2.03 and HR: 0.19, 95% CI: 0.03-1.18). Conclusion: Baseline higher TT levels for male COVID-19 patients at hospital admission are associated with shorter durations of positive COVID-19 testing and thus viral clearance. Our preliminary findings might play a relevant to help pandemic control strategies if these will be verified in future larger multicentric and possibly randomized trials.

  View details for DOI 10.3390/diagnostics11040581

  View details for PubMedID 33804969

• Efficacy of three BCG strains (Connaught, TICE and RIVM) with or without secondary resection (re-TUR) for intermediate/high-risk non-muscle-invasive bladder cancers: results from a retrospective single-institution cohort analysis. Journal of cancer research and clinical oncology Del Giudice, F., Busetto, G. M., Gross, M. S., Maggi, M., Sciarra, A., Salciccia, S., Ferro, M., Sperduti, I., Flammia, S., Canale, V., Chung, B. I., Conti, S. L., Eisenberg, M. L., Skinner, E. C., De Berardinis, E. 2021

  Abstract

  PURPOSE: (I) To evaluate the clinical efficacy of three different BCG strains in patients with intermediate-/high-risk non-muscle-invasive bladder cancer (NMIBC). (II) To determine the importance of performing routine secondary resection (re-TUR) in the setting of BCG maintenance protocol for the three strains.METHODS: NMIBCs who received an adjuvant induction followed by a maintenance schedule of intravesical immunotherapy with BCG Connaught, TICE and RIVM. Only BCG-naive and those treated with the same strain over the course of follow-up were included. Cox proportional hazards model was developed according to prognostic factors by the Spanish Urological Oncology Group (CUETO) as well as by adjusting for the implementation of re-TUR.RESULTS: n=422 Ta-T1 patients (Connaught, n=146; TICE, n=112 and RIVM, n=164) with a median (IQR) follow-up of 72 (60-85) were reviewed. Re-TUR was associated with improved recurrence and progression outcomes (HRRFS: 0.63; 95% CI 0.46-0.86; HRPFS: 0.55; 95% CI 0.31-0.86). Adjusting for CUETO risk factors and re-TUR, BGC TICE and RIVM provided longer RFS compared to Connaught (HRTICE: 0.58, 95% CI 0.39-0.86; HRRIVM: 0.61, 95% CI 0.42-0.87) while no differences were identified between strains for PFS and CSS. Sub-analysis of only re-TUR cases (n=190, 45%) showed TICE the sole to achieve longer RFS compared to both Connaught and RIVM.CONCLUSION: Re-TUR was confirmed to ensure longer RFS and PFS in intermediate-/high-risk NMIBCs but did not influence the relative single BCG strain efficacy. When routinely performing re-TUR followed by a maintenance BCG schedule, TICE was superior to the other strains for RFS outcomes.

  View details for DOI 10.1007/s00432-021-03571-0

  View details for PubMedID 33675400

• The association between testosterone, estradiol and their ratio and mortality among US men. Andrologia Belladelli, F., Del Giudice, F., Kasman, A., Salonia, A., Eisenberg, M. L. 2021: e13993

  Abstract

  While studies have suggested that testosterone is associated with a man's health, the relationship with other sex steroids remains uncertain. The current study aimed to investigate the association between sex steroids (i.e. testosterone, estradiol and the testosterone:estradiol ratio) and mortality in a representative sample of 1,109 US men. Three NHANES continuous cycles (1999-2000, 2001-2002, 2003-2004) were included in our study. Serum testosterone and estradiol levels were evaluated along with sociodemographic, lifestyle and health factors. Cox proportional hazards models were used. The adjusted risk of death for men with low testosterone levels was 1.66 (95% CI=1.00-2.74, p=.05). The adjusted risk of death for men with abnormal estradiol levels was 0.96 (95% CI=0.48-1.91, p=.91). The adjusted risk of death for men with low testosterone to estradiol ratio was 1.27 (95% CI=0.82-1.97, p=.88). Relevant lifestyle and health factors significantly attenuated the associations. The adjusted risk of CVD-related death for men with low testosterone levels was 2.43 (95% CI=1.07-5.50, p=.03). In conclusion, a significant association between testosterone and mortality and testosterone to estradiol ratio and CVD-related mortality was identified.

  View details for DOI 10.1111/and.13993

  View details for PubMedID 33666951

• Association of daily step count and serum testosterone among men in the United States. Endocrine Del Giudice, F., Glover, F., Belladelli, F., De Berardinis, E., Sciarra, A., Salciccia, S., Kasman, A. M., Chen, T., Eisenberg, M. L. 2021

  Abstract

  PURPOSE: To describe the association between daily activity (i.e., daily step counts and accelerometer intensity measures) and serum TT levels in a representative sample of US adults aged 18 years or older.METHODS: A retrospective cohort study was carried out utilizing the NHANES (National Health and Nutrition Examination Survey) 2003-2004 cycle. Physical activity was measured with a waist-worn uniaxial accelerometer (AM-7164; ActiGraph) for up to 7 days using a standardized protocol. Using linear and multivariable logistic regression controlling for relevant social, demographic, lifestyle, and comorbidity characteristics, we assessed the association between daily step counts and TT.RESULTS: A total of 279 subjects with a median age 46 (IQR: 33-56) were included in the analysis. 23.3% of the cohort had a low serum TT level (TT<350ng/dl). Compared to men who took <4000 steps per day, men who took >4000 or >8000 steps/day had a lower odd of being hypogonadal (OR 0.14, 95% CI: 0.07-0.49 and 0.08, 95%CI: 0.02-0.44, respectively). While a threshold effect was noted on average, TT increased 7ng/dL for each additional 1000 steps taken daily (beta-estimate: 0.007, 95% CI: 0.002-0.013).CONCLUSIONS: Patients with the lowest daily step counts had higher odds of being hypogonadal. The current work supports a possible association between daily steps, total testosterone, and hypogonadism for men in the US.

  View details for DOI 10.1007/s12020-021-02631-2

  View details for PubMedID 33580402

• Risks of nonchromosomal birth defects, small-for-gestational age birthweight, and prematurity with in vitro fertilization: effect of number of embryos transferred and plurality at conception versus at birth. Journal of assisted reproduction and genetics Luke, B., Brown, M. B., Wantman, E., Forestieri, N. E., Browne, M. L., Fisher, S. C., Yazdy, M. M., Ethen, M. K., Canfield, M. A., Nichols, H. B., Oehninger, S., Doody, K. J., Sutcliffe, A. G., Williams, C., Eisenberg, M. L., Baker, V. L., Sacha, C. R., Lupo, P. J. 2021

  Abstract

  PURPOSE: Excess embryos transferred (ET) (> plurality at birth) and fetal heartbeats (FHB) at 6 weeks' gestation are associated with reductions in birthweight and gestation, but prior studies have been limited by small sample sizes and limited IVF data. This analysis evaluated associations between excess ET, excess FHB, and adverse perinatal outcomes, including the risk of nonchromosomal birth defects.METHODS: Live births conceived via IVF from Massachusetts, New York, North Carolina, and Texas included 138,435 children born 2004-2013 (Texas), 2004-2016 (Massachusetts and North Carolina), and 2004-2017 (New York) were classified by ET and FHB. Major birth defects were reported by statewide registries within the first year of life. Logistic regression was used to estimate adjusted odds ratios (AORs) and 95% CIs of the risks of a major nonchromosomal birth defect, small-for-gestational age birthweight (SGA), low birthweight (LBW), and preterm birth (≤36 weeks), by excess ET, and excess ET + excess FHB, by plurality at birth (singletons and twins).RESULTS: In singletons with [2 ET, FHB =1] and [≥3 ET, FHB=1], risks [AOR (95% CI)] were increased, respectively, for major nonchromosomal birth defects [1.13 (1.00-1.27) and 1.18 (1.00-1.38)], SGA [1.10 (1.03-1.17) and 1.15 (1.05-1.26)], LBW [1.09 (1.02-1.13) and 1.17 (1.07-1.27)], and preterm birth [1.06 (1.00-1.12) and 1.14 (1.06-1.23)]. With excess ET + excess FHB, risks of all adverse outcomes except major nonchromosomal birth defects increased further for both singletons and twins.CONCLUSION: Excess embryos transferred are associated with increased risks for nonchromosomal birth defects, reduced birthweight, and prematurity in IVF-conceived births.

  View details for DOI 10.1007/s10815-021-02095-3

  View details for PubMedID 33547526

• Association between paternal health and severe maternal morbidity: analysis of US claims data Murugappan, G., Li, S., Leonard, S. A., Druzin, M. L., Eisenberg, M. L. MOSBY-ELSEVIER. 2021: S117–S118

  View details for Web of Science ID 000621547400175

• Primary malignancies of the epididymis: clinical characteristics and prognostic factors. The Canadian journal of urology Bhambhvani, H. P., Greenberg, D. R., Kasman, A. M., Eisenberg, M. L. 2021; 28 (1): 10522–29

  Abstract

  INTRODUCTION We sought to describe clinical characteristics and identify prognostic factors among patients with primary malignancies of the epididymis (PMEs).MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (1975-2015) was queried to identify patients with PME. Descriptive statistics and multivariable Cox proportional hazards models were used.RESULTS: Eighty-nine patients with PME were identified. Median age was 57 years (5-85), and median overall survival (OS) was 16.8 years. The most commonly represented histologies were rhabdomyosarcoma (19.1%), B-cell lymphoma (16.9%), leiomyosarcoma (16.9%), and liposarcoma (12.4%). In multivariable analysis, tumor size ≥ 4 cm was associated with worse OS (HR = 4.46, p = 0.01) compared to tumors < 4 cm. Patients with nonsarcomatoid histology had OS similar to patients with sarcomatoid histology (HR = 0.95, p = 0.92). Disease with regional invasion (HR = 5.19, p = 0.007) and distant metastasis (HR = 29.80, p = 0.0002) had worse OS compared to localized disease. Receipt of radiotherapy was associated with enhanced OS (HR = 0.10, p = 0.006), whereas receipt of chemotherapy was not associated with OS.CONCLUSIONS: We describe the largest cohort of PMEs to date. Larger lesions and tumor stage were independently associated with poor overall survival, while receipt of radiotherapy was associated with enhanced overall survival.

  View details for PubMedID 33625342

• The Quality of Systematic Reviews and Meta-Analyses Assessing the Treatment and Management of Male Infertility. Andrology Bhambhvani, H. P., Greenberg, D. R., Eisenberg, M. L. 2021

  Abstract

  BACKGROUND: Male factor infertility (MFI) is a common medical condition which requires high quality research to guide clinical practice; however, systematic reviews (SRs) and meta-analyses (MAs) often vary in quality, raising concerns regarding the validity of their results. We sought to perform an objective analysis of SRs and MAs in MFI treatment and management and to report on the quality of published literature.METHODS: A comprehensive search in PubMed/MEDLINE and EMBASE was used to identify relevant publications. Primary search terms were male infertility, male sterility, and male subfertility. Two authors independently performed searches, screened citations for eligibility, extracted data for analysis, and graded methodological quality using the validated AMSTAR (A Measurement Tool to Assess Systematic Reviews) instrument, a validated tool used in the critical appraisal of SRs/MAs.RESULTS: 27 publications met inclusion criteria and were included in the analysis. Mean AMSTAR score (± SD) among all publications was 7.4 (1.9) out of 11, reflecting "fair to good" quality. Non-pharmacological medical treatment for MFI was the most commonly assessed intervention (n=13, 48.1%). No publications met all AMSTAR criteria. While the number of SRs/MAs has increased over time (p=0.037), the quality of publications has not significantly changed (p=0.72). SRs/MAs of the Cochrane Library had higher AMSTAR score than non-Cochrane SRs/MAs (8.5 vs 6.3, p=0.002).CONCLUSIONS: The methodological quality of SRs/MAs should be assessed to ensure high-quality evidence for clinical practice guidelines in MFI treatment and management. This review highlights a need for increased effort to publish high-quality studies in MFI treatment and management.

  View details for DOI 10.1111/andr.12972

  View details for PubMedID 33432772

• Racial and socioeconomic disparities in retroperitoneal lymph node dissection and survival in nonseminomatous germ cell tumor: A population-based study. Urologic oncology Bhambhvani, H. P., Greenberg, D. R., Kasman, A. M., DeRouen, M. C., Cheng, I., Eisenberg, M. L., Shah, S. A. 2021

  Abstract

  BACKGROUND: Though testicular cancer is the most common cancer in young men, there is a paucity of epidemiologic studies examining sociodemographic disparities in adjuvant therapy and outcomes. We examined the associations of sociodemographic factors with retroperitoneal lymph node dissection (RPLND) and survival among patients with nonseminomatous germ cell tumors (NSGCTs).METHODS: Within the Surveillance Epidemiology and End Results database (2005-2015), we identified 8,573 patients with nonseminomatous germ cell tumors. Multivariable logistic regression and Fine-Gray competing-risks regression models were constructed to examine the association of sociodemographic factors (neighborhood SES (nSES), race, and insurance) with, respectively, adjuvant RPLND within 1 year of diagnosis and cancer-specific mortality.RESULTS: Patients in the lowest nSES quintile (OR 0.59, 95% CI = 0.40-0.88, P = 0.01) and Black patients (OR 0.41, 95% CI = 0.15-1.00, P= 0.058) with stage II disease were less likely to receive RPLND compared to those in the highest quintile and White patients, respectively. Stage III patients with Medicaid (OR 0.64, 95% CI = 0.46-0.89, P= 0.009) or without insurance (OR 0.46, 95% CI = 0.27-0.76, P= 0.003) were less likely to receive RPLND compared to patients with private insurance. Lowest quintile nSES patients of all disease stages and Black patients with stage I disease (HR = 2.64, 95% CI = 1.12-6.20, P = 0.026) or stage II disease (HR=4.93, 95% CI = 1.48-16.44, P = 0.009) had higher risks of cancer-specific mortality compared to highest quintile nSES and White patients, respectively.CONCLUSIONS: This national study found multilevel, stage-specific sociodemographic disparities in receipt of RPLND and survival.

  View details for DOI 10.1016/j.urolonc.2020.12.016

  View details for PubMedID 33423934

• Association of Infertility and All-Cause Mortality: Analysis of US Claims Data. American journal of obstetrics and gynecology Murugappan, G. n., Li, S. n., Alvero, R. J., Luke, B. n., Eisenberg, M. L. 2021

  Abstract

  The consequences of an infertility diagnosis extend beyond the pursuit of family building, as infertile women also face increased risks of severe maternal morbidity, cancer, and chronic disease.To examine the association between female infertility and all-cause mortality.Retrospective analysis of 72,786 infertile women identified in the Optum Clinformatics Datamart from 2003-2019 by infertility diagnosis, testing and treatment codes compared with 3,845,790 non-infertile women seeking routine gynecologic care. Baseline comorbidities were assessed using the presence of ≥1 metabolic syndrome (MetS) diagnoses and the Charlson Comorbidity Index (CCI). The primary outcome of all-cause mortality was identified by linkage to Social Security Administration Death Master File outcomes and medical claims. The association of infertility with mortality was examined using Cox proportional hazard regression while adjusting for age, hypertension, hyperlipidemia, type II diabetes, year of evaluation, smoking, number of visits per year, nulliparity, obesity, region of country, and race.Among 16,473,458 person-years of follow up, 13,934 women died. Infertile women had a 32% higher relative risk of death from any cause (0.42% versus 0.35%, aHR 1.32, 95% CI 1.18-1.48) compared to non-infertile women. Mean follow up time per patient was 4.0±3.7 years versus 4.2±3.8 years for infertile and non-infertile women, respectively. When stratified by age < 35 or ≥35 years or baseline medical comorbidity, the association between infertility and mortality remained. Infertile women who delivered a child during the follow up period faced similar increased risk of mortality compared to the overall infertile group. Finally, receipt of fertility treatment was not associated with a higher risk of death compared to receiving an infertility diagnosis or testing alone.While absolute risk of death was low in both groups, infertile women faced a higher relative risk of mortality compared to non-infertile women. The association remained across all age, race/ethnicity, morbidity, and delivery strata. Importantly, infertility treatment was not associated with an increased risk of death. These findings reinforce the disease burden associated with infertility and its potential for longer-term sequelae.

  View details for DOI 10.1016/j.ajog.2021.02.010

  View details for PubMedID 33577764

• Association of Bicycle-Related Genital Numbness and Female Sexual Dysfunction: Results From a Large, Multinational, Cross-Sectional Study. Sexual medicine Lui, H., Mmonu, N., Awad, M. A., Namiri, N. K., Zheng, M. Y., Amend, G. M., Eisenberg, M. L., Breyer, B. N. 2021; 9 (3): 100365

  Abstract

  Cycling can lead to microtrauma due to increased perineal pressure, possibly contributing to genital numbness and sexual dysfunction in female cyclists.We aim to explore the associations between cycling characteristics, female genital numbness, and female sexual dysfunction.We conducted a cross-sectional study on female cyclists and sexual wellness. Participants were recruited through Facebook® advertisements and online outreach at athletic clubs. Participants were asked about their cycling characteristics, genital numbness, and female sexual function using the Female Sexual Function Index (FSFI). Univariate and multivariable linear and logistic regression were used to assess risk factors for genital numbness and the association between genital numbness and the FSFI.The outcome measures were cycling characteristics, questions regarding numbness (intensity, duration, location), and the FSFI score.Eight-hundred and seventy-five women were included in the study. Total lifetime miles cycled, biking duration, frequency, distance, speed, and biking surface were not significantly associated with genital numbness. Higher handlebar height was associated with less numbness. The prevalence of sexual dysfunction in the cohort was 52%. Genital numbness was significantly associated with sexual dysfunction (OR: 1.43, 95% CI: 1.05 - 1.95). Sub-group analysis for location of numbness demonstrated significant increase in risk for sexual dysfunction in cyclists who described numbness aro`und the perineum (OR: 2.72, 95% CI: 1.05 - 7.02) and the vulva (OR: 1.55, 95% CI: 1.13 - 2.13). There was also a significant increase in the risk of sexual dysfunction in cyclists who reported a longer duration of numbness (OR: 6.58, 95% CI: 2.27 - 19.07).Genital numbness is common in women who cycle and is associated with increased risk of FSD and lower average sexual response scores on FSFI. Lui H, Mmonu N, Awad MA, et al. Association of Bicycle-Related Genital Numbness and Female Sexual Dysfunction: Results From a Large, Multinational, Cross-Sectional Study. Sex Med 2021;XX:XXX-XXX.

  View details for DOI 10.1016/j.esxm.2021.100365

  View details for PubMedID 34049264

• Male-specific late effects in adult hematopoietic cell transplantation recipients: a systematic review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Transplantation and cellular therapy Phelan, R., Im, A., Hunter, R. L., Inamoto, Y., Lupo-Stanghellini, M. T., Rovo, A., Badawy, S. M., Burns, L., Eissa, H., Murthy, H. S., Prasad, P., Sharma, A., Suelzer, E., Agrawal, V., Aljurf, M., Baker, K., Basak, G. W., Buchbinder, D., DeFilipp, Z., Grkovic, L. D., Dias, A., Einsele, H., Eisenberg, M. L., Epperla, N., Farhadfar, N., Flatau, A., Gale, R. P., Greinix, H., Hamilton, B. K., Hashmi, S., Hematti, P., Jamani, K., Maharaj, D., Murray, J., Naik, S., Nathan, S., Pavletic, S., Peric, Z., Pulanic, D., Ross, R., Salonia, A., Sanchez-Ortega, I., Savani, B. N., Schechter, T., Shah, A. J., Smith, S. M., Snowden, J. A., Steinberg, A., Tremblay, D., Vij, S. C., Walker, L., Wolff, D., Yared, J. A., Schoemans, H., Tichelli, A. 2021

  Abstract

  Male-specific late effects after hematopoietic cell transplantation (HCT) include genital chronic graft-versus-host disease (GvHD), hypogonadism, sexual dysfunction, infertility, and subsequent malignancies, such as prostate, penile, and testicular cancer. They may be closely intertwined and cause prolonged morbidity and decreased quality of life after HCT.Here, we provide a systematic review of male-specific late effects in a collaboration between transplant physicians, endocrinologists, urologists, dermatologists, and sexual health professionals through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research, and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation.We utilized systematic review methodology to summarize incidence, risk factors, screening, prevention and treatment of these complications and provide consensus evidence-based recommendations for clinical practice and future research.Most of the evidence regarding male GvHD is still based on limited data, precluding strong therapeutic recommendations. We therefore recommend to systematically screen for male genital GvHD regularly and report it to large registries to allow for a better understanding. Future research should also address treatment since little published evidence is available to date. Male-specific endocrine consequences of HCT include hypogonadism which may also affect bone health. Since the evidence is scarce, current recommendations for hormone substitution and/or bone health treatment are based on similar principles as for the general population. Following HCT, sexual health decreases and this topic should be addressed at regular intervals. Future studies should focus on interventional strategies to address sexual dysfunction. Infertility remains prevalent in patients having undergone myeloablative conditioning, which warrants offering sperm preservation in all HCT candidates. Most studies on fertility rely on descriptive registry analysis and surveys, hence the importance of reporting post-HCT conception data to large registries. Although the quality of evidence is low, the development of cancer in male genital organs does not seem more prevalent than in the general population; however, subsequent malignancies in general seem to be more prevalent in males than females, and special attention should be given to skin and oral mucosa.Male-specific late effects, probably more under-reported than female-specific complications, should be systematically considered during the regular follow-up visits of male survivors who have undergone HCT. Care of patients with male-specific late effects warrants close collaboration between transplant physicians and specialists from other involved disciplines. Future research should be directed towards better data collection on male-specific late effects and on studies about the interrelationship between these late effects, to allow the development of evidence based effective management practices.

  View details for DOI 10.1016/j.jtct.2021.10.013

  View details for PubMedID 34757220

• Testosterone target therapy: focus on immune response, controversies and clinical implications in patients with COVID-19 infection. Therapeutic advances in endocrinology and metabolism Salciccia, S., Del Giudice, F., Eisenberg, M. L., Mastroianni, C. M., De Berardinis, E., Ricciuti, G. P., Viscuso, P., Zingaropoli, A., Pasculli, P., Ciardi, M. R., Sciarra, A., Maggi, M. 2021; 12: 20420188211010105

  Abstract

  The pandemic acute respiratory syndrome coronavirus 2 (SARS-CoV-2) named COVID-19 is causing a severe health emergency, and an individual's hormonal milieu may play an important role in both susceptibility to infection and severity of clinical course. We analyzed the role of testosterone in the immune response, and we hypothesized possible mechanisms to explain the high incidence of COVID-19 infection and a worse clinical course in elderly male patients. Testosterone may impair the immune response, and this effect could explain the greater susceptibility of men to infection. Transmembrane serine protease 2 (TMPRSS2) plays a crucial role in the entry of the virus into the respiratory epithelial cells, leading to COVID-19 disease. It is crucial to emphasize that testosterone levels and chemical castration (e.g. by androgen deprivation therapy for prostate cancer) may have contrasting roles in the phases of COVID-19 infection. Whereas low testosterone levels may be protective against the initial susceptibility (due to a restoration of immunological functions and a block of TMPRSS2), low testosterone may stimulate a worse clinical course in the advanced COVID-19 infection as it could exacerbate or activate the cytokine storm. If testosterone levels play these different roles, it is necessary to carefully identify patients for any indicated testosterone manipulation.

  View details for DOI 10.1177/20420188211010105

  View details for PubMedID 34104394

• The Association between Mortality and Male Infertility: Systematic Review and Meta-analysis. Urology Francesco, D. G., Alex M, K. n., Tony, C. n., Ettore, D. B., Maria, B. G., Alessandro, S. n., Matteo, F. n., Giuseppe, L. n., Federico, B. n., Andrea, S. n., Michael L, E. n. 2021

  Abstract

  To summarize the current body of evidence on the relationship between impaired male fertility and the risk of early death through a systematic review and meta-analysis of population-based retrospective cohort studies.PubMed, Web of Science, Embase, Cochrane Library, and Scopus databases were searched from inception to August 2020 according to the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Pooled Risk Ratio (RR), Risk Difference (Δr), Hazard Ratio (HR) and Standardized Mortality Ratio (SMR) differences among male factor infertility cohorts were compared to fertile/normospermic control populations or to national mortality data.Six studies from 2006 to 2020 met inclusion criteria. Three studies examined male infertility and mortality (ntot=202,456; ndeaths=1396), while four studies examined survival in relation to semen parameters (ntot= 59,291; ndeaths= 643). Comparing infertile to fertile men, pooled HR for the risk of death was 1.26 (95%CI:1.01-1.59). Pooled RR and Δr of death for combined oligo- and azoospermic men vs. normospermic men was 1.67 (95%CI:1.26-2.21) and 0.37% (95%CI:0.18-0.55%) respectively. When comparing oligo- and normospermic men to azoospermic men, the cumulative HR was 1.31 (95%CI:1.11-1.54) and 2.17 (95%CI:1.55-3.04) respectively. Infertile men had a lower overall risk of death compared to the overall population (SMR, 0.38, 95%CI:0.31-0.45).Compared to fertile men, infertile men had a higher risk of death. Moreover, the risk of death increased with increasing severity of semen quality impairment. However, compared to men from the general population, infertile men have a lower risk of death suggesting that social determinants of health are also important.

  View details for DOI 10.1016/j.urology.2021.02.041

  View details for PubMedID 33819517

• The Association of the COVID-19 Pandemic on Male Sexual Function in the United States: A Survey Study of Male Cannabis Users. Sexual medicine Chen, T. n., Bhambhvani, H. P., Kasman, A. M., Eisenberg, M. L. 2021; 9 (3): 100340

  Abstract

  International studies have suggested that social disruptions caused by the COVID-19 pandemic have led to sexual dysfunction, but the impact on males in the United States is less defined.To examine changes in male sexual function during the COVID-19 pandemic and to evaluate associated demographic variables.Prepandemic survey data was collected between October 20, 2019 and March 1, 2020 on adult males in the United States. Follow-up survey data collected for comparison during the COVID-19 pandemic between August 1, 2020 and October 10, 2020 included International Index of Erectile Function (IIEF) scores, Patient Health Questionnaire for Depression and Anxiety with 4 items (PHQ-4) scores, and questions regarding sexual frequency. Questions were also asked about mask-wearing habits, job loss, relationship changes, and proximity to individuals who tested positive for COVID-19.Differences in prepandemic and pandemic male sexual function assessed by self-reported IIEF domain scores and sexual frequency RESULTS: Seventy six men completed both prepandemic and pandemic surveys with a mean age of 48.3 years. Overall, there were no differences in either overall IIEF score or any subdomain score when comparing men's pre-pandemic and pandemic survey data. There was an increase in sexual frequency during the pandemic with 45% of men reporting sex ten or more times per month during the pandemic compared to only 25% of men prior to the pandemic (P = .03). Among the subgroup of 36 men who reported a decrease in IIEF, the decrease was an average of 3.97, and significantly associated with higher PHQ-4 depression subscale scores (1.78 vs 1.03, P = .02).The COVID-19 pandemic is associated with increased sexual frequency and no change in overall sexual function in males in the United States. Interventions intended to promote male sexual health during the COVID-19 pandemic should include a focus on mental health. T Chen, HP Bhambhvani, AM Kasman, et al. The Association of the COVID-19 Pandemic on Male Sexual Function in the United States: A Survey Study of Male Cannabis Users. J Sex Med 2021;XX:XXX-XXX.

  View details for DOI 10.1016/j.esxm.2021.100340

  View details for PubMedID 33789175

• A global approach to addressing the policy, research and social challenges of male reproductive health. Human reproduction open Barratt, C. L., De Jonge, C. J., Anderson, R. A., Eisenberg, M. L., Garrido, N., Rautakallio Hokkanen, S., Krausz, C., Kimmins, S., O'Bryan, M. K., Pacey, A. A., Tuttelmann, F., Veltman, J. A. 2021; 2021 (1): hoab009

  Abstract

  Male infertility is a global health issue; yet to a large extent, our knowledge of its causes, impact and consequence is largely unknown. Recent data indicate that infertile men have an increased risk of somatic disorders such as cancer and die younger compared to fertile men. Moreover, several studies point to a significant adverse effect on the health of the offspring. From the startling lack of progress in male contraception combined with the paucity of improvements in the diagnosis of male infertility, we conclude there is a crisis in male reproductive health. The Male Reproductive Health Initiative has been organized to directly address these issues (www.eshre.eu/Specialty-groups/Special-Interest-Groups/Andrology/MRHI). The Working Group will formulate an evidence-based strategic road map outlining the ways forward. This is an open consortium desiring to engage with all stakeholders and governments.

  View details for DOI 10.1093/hropen/hoab009

  View details for PubMedID 33768166

• AUTHOR REPLY. Urology Del Giudice, F. n., Kasman, A. M., Eisenberg, M. L. 2021; 147: 148–49

  View details for DOI 10.1016/j.urology.2020.07.089

  View details for PubMedID 33390199

• Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline PART II. The Journal of urology Schlegel, P. N., Sigman, M., Collura, B., De Jonge, C. J., Eisenberg, M. L., Lamb, D. J., Mulhall, J. P., Niederberger, C., Sandlow, J. I., Sokol, R. Z., Spandorfer, S. D., Tanrikut, C., Treadwell, J. R., Oristaglio, J. T., Zini, A. 2021; 205 (1): 44–51

  Abstract

  PURPOSE: The summary presented herein represents Part II of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part II outlines the appropriate management of the male in an infertile couple. Medical therapies, surgical techniques, as well as use of intrauterine insemination (IUI)/in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) are covered to allow for optimal patient management. Please refer to Part I for discussion on evaluation of the infertile male and discussion of relevant health conditions that are associated with male infertility.MATERIALS/METHODS: The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed, Embase, and Medline from January 2000 through May 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table[Table: see text]). This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology.RESULTS: This Guideline provides updated, evidence-based recommendations regarding management of male infertility. Such recommendations are summarized in the associated algorithm (figure[Figure: see text]).CONCLUSION: Male contributions to infertility are prevalent, and specific treatment as well as assisted reproductive techniques are effective at managing male infertility. This document will undergo additional literature reviews and updating as the knowledge regarding current treatments and future treatment options continues to expand.

  View details for DOI 10.1097/JU.0000000000001520

  View details for PubMedID 33295258

• Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline Part I. The Journal of urology Schlegel, P. N., Sigman, M., Collura, B., De Jonge, C. J., Eisenberg, M. L., Lamb, D. J., Mulhall, J. P., Niederberger, C., Sandlow, J. I., Sokol, R. Z., Spandorfer, S. D., Tanrikut, C., Treadwell, J. R., Oristaglio, J. T., Zini, A. 2021; 205 (1): 36–43

  Abstract

  PURPOSE: The summary presented herein represents Part I of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part I outlines the appropriate evaluation of the male in an infertile couple. Recommendations proceed from obtaining an appropriate history and physical exam (Appendix I), as well as diagnostic testing, where indicated.MATERIALS/METHODS: The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed, Embase, and Medline from January, 2000 through May, 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]). This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology.RESULTS: This Guideline provides updated, evidence-based recommendations regarding evaluation of male infertility as well as the association of male infertility with other important health conditions. The detection of male infertility increases the risk of subsequent development of health problems for men. In addition, specific medical conditions are associated with some causes for male infertility. Evaluation and treatment recommendations are summarized in the associated algorithm (figure[Figure: see text]).CONCLUSION: The presence of male infertility is crucial to the health of patients and its effects must be considered for the welfare of society. This document will undergo updating as the knowledge regarding current treatments and future treatment options continues to expand.

  View details for DOI 10.1097/JU.0000000000001521

  View details for PubMedID 33295257

• The impact of physician productivity models on access to subspecialty care: A white paper from the Society for the Study of Male Reproduction and the Society for Male Reproduction and Urology. Urology Dupree, J. M., Coward, R. M., Hsieh, M. n., Tanrikut, C. n., Shin, P. n., Mehta, A. n., Hotaling, J. M., Pastuszak, A. W., Williams, D. n., Alukal, J. n., Lipshultz, L. I., Schlegel, P. n., Walsh, T. J., Eisenberg, M. L., Shin, D. n., Honig, S. n., Nagler, H. M., Samplaski, M. n., Nangia, A. n., Sandlow, J. n., Smith, J. F. 2021

  Abstract

  Male infertility is a common disease. Male infertility is also a core competency of urology training and clinical practice. In this white paper from the Society for the Study of Male Reproduction and Society for Male Reproduction and Urology, we identify and define different physician productivity plans. We then describe the advantages and disadvantages of various physician productivity measurement systems for male infertility practices. We close with recommendations for measuring productivity in male infertility practices that we hope urologists and administrators can use when creating productivity plans for male infertility practices.

  View details for DOI 10.1016/j.urology.2021.01.016

  View details for PubMedID 33484822

• Consumption of cruciferous vegetables and the risk of bladder cancer in a prospective US cohort: data from the NIH-AARP diet and health study AMERICAN JOURNAL OF CLINICAL AND EXPERIMENTAL UROLOGY Nguyen, T. P., Zhang, C. A., Sonn, G. A., Eisenberg, M. L., Brooks, J. D. 2021; 9 (3): 229-238

  View details for Web of Science ID 000672671600004

• Modeling the contribution of the obesity epidemic to the temporal decline in sperm counts. Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica Kasman, A., Del Giudice, F., Shkolyar, E., Porreca, A., Busetto, G. M., Lu, Y., Eisenberg, M. L. 2020; 92 (4)

  Abstract

  OBJECTIVE: Total sperm count (TSC) has been declining worldwide over the last several decades due to unknown etiologies. Our aim was to model the contribution that the obesity epidemic may have on declining TSC.MATERIALS AND METHODS: Obesity rates were determined since 1973 using the WHO's Global Health Observatory data. A literature review was performed to determine the association between TSC and obesity. Using the measured obesity rates and published TSC since 1973, a model was created to evaluate the association between temporal trends in obesity/temperature and sperm count.RESULTS: Since 1973, obesity prevalence in the United States was increased from 41% to 67.9%. A review of the literature showed that body mass index (BMI) categories 2, 3, and 4 were associated with TSC (millions) of 164.27, 155.71, and 142.29, respectively. The contribution to change over time for obesity from 1974 to 2011 was modeled at 1.8%. When the model was changed to represent the most extreme possible contribution to obesity reported, the modeled change over time rose to 7.2%. When stratified according to fertility status, the contribution that BMI had to falling sperm counts for all comers was 1.7%, while those presenting for fertility evaluation was 2.1%.CONCLUSIONS: While the decline in TSC may be partially due to rising obesity rates, these contributions are minimal which highlights the complexity of this problem.

  View details for DOI 10.4081/aiua.2020.4.357

  View details for PubMedID 33348967

• Parental age and preterm birth: a population-based cohort of nearly 3 million California livebirths from 2007 to 2012. Journal of perinatology : official journal of the California Perinatal Association Mayo, J. A., Lu, Y., Stevenson, D. K., Shaw, G. M., Eisenberg, M. L. 2020

  Abstract

  PURPOSE: To assess the relationships between parental ages and preterm birth subtypes.METHODS: A population-based cohort analysis of California livebirths 2007-2012. Associations between maternal and paternal age with spontaneous and medically indicated preterm birth were estimated from Cox proportional hazard models. Parental age was modeled with restricted cubic splines to account for nonlinear relationships.RESULTS: Young paternal age was associated with increased hazard ratios for spontaneous and medically indicated preterm birth. Older fathers showed elevated hazards for preterm birth in crude analysis but after adjustment the relationship was generally not observed. Aging mothers showed increased hazard ratios for both preterm birth phenotypes.CONCLUSIONS: After adjusting for parental demographics, births to younger fathers and older mothers had the highest risks for spontaneous preterm birth. The paternal influence on preterm birth was observed to be independent of maternal factors.

  View details for DOI 10.1038/s41372-020-00894-7

  View details for PubMedID 33293667

• Diagnosis and treatment of infertility in men: AUA/ASRM guideline part II. Fertility and sterility Schlegel, P. N., Sigman, M., Collura, B., De Jonge, C. J., Eisenberg, M. L., Lamb, D. J., Mulhall, J. P., Niederberger, C., Sandlow, J. I., Sokol, R. Z., Spandorfer, S. D., Tanrikut, C., Treadwell, J. R., Oristaglio, J. T., Zini, A. 2020

  Abstract

  PURPOSE: The summary presented herein represents Part II of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part II outlines the appropriate management of the male in an infertile couple. Medical therapies, surgical techniques, as well as use of intrauterine insemination (IUI)/invitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) are covered to allow for optimal patient management. Please refer to Part I for discussion on evaluation of the infertile male and discussion of relevant health conditions that are associated with male infertility.MATERIALS/METHODS: The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed, Embase, and Medline from January 2000 through May 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. (Table1) This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology.RESULTS: This Guideline provides updated, evidence-based recommendations regarding management of male infertility. Such recommendations are summarized in the associated algorithm. (Figure1) CONCLUSION: Male contributions to infertility are prevalent, and specific treatment as well as assisted reproductive techniques are effective at managing male infertility. This document will undergo additional literature reviews and updating as the knowledge regarding current treatments and future treatment options continues to expand.

  View details for DOI 10.1016/j.fertnstert.2020.11.016

  View details for PubMedID 33309061

• Diagnosis and treatment of infertility in men: AUA/ASRM guideline part I. Fertility and sterility Schlegel, P. N., Sigman, M., Collura, B., De Jonge, C. J., Eisenberg, M. L., Lamb, D. J., Mulhall, J. P., Niederberger, C., Sandlow, J. I., Sokol, R. Z., Spandorfer, S. D., Tanrikut, C., Treadwell, J. R., Oristaglio, J. T., Zini, A. 2020

  Abstract

  PURPOSE: The summary presented herein represents Part I of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part I outlines the appropriate evaluation of the male in an infertile couple. Recommendations proceed from obtaining an appropriate history and physical exam (Appendix I), as well as diagnostic testing, where indicated.MATERIALS/METHODS: The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed, Embase, and Medline from January, 2000 through May, 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. (Table1) This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology.RESULTS: This Guideline provides updated, evidence-based recommendations regarding evaluation of male infertility as well as the association of male infertility with other important health conditions. The detection of male infertility increases the risk of subsequent development of health problems for men. In addition, specific medical conditions are associated with some causes for male infertility. Evaluation and treatment recommendations are summarized in the associated algorithm. (Figure1) CONCLUSION: The presence of male infertility is crucial to the health of patients and its effects must be considered for the welfare of society. This document will undergo updating as the knowledge regarding current treatments and future treatment options continues to expand.

  View details for DOI 10.1016/j.fertnstert.2020.11.015

  View details for PubMedID 33309062

• Reproductive sequelae of parental severe illness before the pandemic: implications for the COVID-19 pandemic. Fertility and sterility Kasman, A. M., Bhambhvani, H. P., Li, S., Zhang, C. A., Stevenson, D. K., Shaw, G. M., Simard, J. F., Eisenberg, M. L. 2020; 114 (6): 1242–49

  Abstract

  OBJECTIVE: To investigate, with pre-COVID-19 data, whether parental exposure to severe systemic infections near the time of conception is associated with pregnancy outcomes.DESIGN: Retrospective cohort study.SETTING: Population-based study covering births within the United States from 2009 to2016.PARTICIPANTS: The IBM MarketScan Research database covers reimbursed health care claims data on inpatient and outpatient encounters that are privately insured through employment-sponsored health insurance. Our analytic sample included pregnancies to paired fathers and mothers.INTERVENTIONS(S): Parental preconception exposure (0-6 months before conception) to severe systemic infection (e.g., sepsis, hypotension, respiratory failure, critical care evaluation).MAIN OUTCOME MEASURE(S): Preterm birth (i.e., live birth before 37 weeks) and pregnancy loss.RESULT(S): A total of 999,866 pregnancies were recorded with 214,057 pregnancy losses (21.4%) and 51,759 preterm births (5.2%). Mothers receiving intensive care in the preconception period had increased risk of pregnancy loss, as did fathers. Mothers with preconception sepsis had higher risk of preterm birth and pregnancy loss, and paternal sepsis exposure was associated with an increased risk of pregnancy loss. Similar results were noted for hypotension. In addition, a dose response was observed for both mothers and fathers between preconception time in intensive care and the risk of preterm birth and pregnancy loss.CONCLUSION(S): In a pre-COVID-19 cohort, parental preconception severe systemic infection was associated with increased odds of preterm birth and pregnancy loss when conception was soon after the illness.

  View details for DOI 10.1016/j.fertnstert.2020.09.153

  View details for PubMedID 33280730

• A Spotlight on Patient- and Physician-Driven Digital Health and Mobile Innovation in Male Reproductive Medicine CURRENT SEXUAL HEALTH REPORTS Balasubramanian, A., Yu, J., Rivera-Mirabal, J., Eisenberg, M. L., Spitz, A., Thirumavalavan, N., Lipshultz, L., Pastuszak, A. W. 2020; 12 (4): 261-265

  View details for DOI 10.1007/s11930-020-00280-6

  View details for Web of Science ID 000703028000007

• The risk of birth defects with conception by ART. Human reproduction (Oxford, England) Luke, B., Brown, M. B., Wantman, E., Forestieri, N. E., Browne, M. L., Fisher, S. C., Yazdy, M. M., Ethen, M. K., Canfield, M. A., Watkins, S., Nichols, H. B., Farland, L. V., Oehninger, S., Doody, K. J., Eisenberg, M. L., Baker, V. L. 2020

  Abstract

  STUDY QUESTION: What is the association between ART conception and treatment parameters and the risk of birth defects?SUMMARY ANSWER: Compared to naturally conceived singleton infants, the risk of a major nonchromosomal defect among ART singletons conceived with autologous oocytes and fresh embryos without use of ICSI was increased by 18%, with increases of 42% and 30% for use of ICSI with and without male factor diagnosis, respectively.WHAT IS KNOWN ALREADY: Prior studies have indicated that infertility and ART are associated with an increased risk of birth defects but have been limited by small sample size and inadequate statistical power, failure to differentiate results by plurality, differences in birth defect definitions and methods of ascertainment, lack of information on ART treatment parameters or study periods spanning decades resulting in a substantial historical bias as ART techniques have improved.STUDY DESIGN, SIZE, DURATION: This was a population-based cohort study linking ART cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) from 1 January 2004 to 31 December 2015 that resulted in live births from 1 September 2004 to 31 December 2016 in Massachusetts and North Carolina and from 1 September 2004 to 31 December 2015 for Texas and New York: these were large and ethnically diverse States, with birth defect registries utilizing the same case definitions and data collected, and with high numbers of ART births annually. A 10:1 sample of non-ART births were chosen within the same time period as the ART birth. Naturally conceived ART siblings were identified through the mother's information. Non-ART children were classified as being born to women who conceived with ovulation induction (OI)/IUI when there was an indication of infertility treatment on the birth certificate, but the woman did not link to the SART CORS; all others were classified as being naturally conceived.PARTICIPANTS/MATERIALS, SETTING, METHODS: The study population included 135051 ART children (78362 singletons and 56689 twins), 23647 naturally conceived ART siblings (22301 singletons and 1346 twins) and 9396 children born to women treated with OI/IUI (6597 singletons and 2799 twins) and 1067922 naturally conceived children (1037757 singletons and 30165 twins). All study children were linked to their respective State birth defect registries to identify major defects diagnosed within the first year of life. We classified children with major defects as either chromosomal (i.e. presence of a chromosomal defect with or without any other major defect) or nonchromosomal (i.e. presence of a major defect but having no chromosomal defect), or all major defects (chromosomal and nonchromosomal). Logistic regression models were used to generate adjusted odds ratios (AORs) and 95% CI to evaluate the risk of birth defects due to conception with ART (using autologous oocytes and fresh embryos), and with and without the use of ICSI in the absence or presence of male factor infertility, with naturally conceived children as the reference. Analyses within the ART group were stratified by combinations of oocyte source (autologous, donor) and embryo state (fresh, thawed), with births from autologous oocytes and fresh embryos as the reference. Analyses limited to fresh embryos were stratified by oocyte source (autologous, donor) and the use of ICSI. Triplets and higher-order multiples were excluded.MAIN RESULTS AND THE ROLE OF CHANCE: A total of 21998 singleton children (1.9%) and 3037 twin children (3.3%) had a major birth defect. Compared to naturally conceived children, ART singletons (conceived from autologous oocytes, fresh embryos without the use of ICSI) had increased risks of a major nonchromosomal birth defect (AOR 1.18, 95% 1.05, 1.32), cardiovascular defects (AOR 1.20, 95% CI 1.03, 1.40), and any birth defect (AOR 1.18, 95% CI 1.09, 1.27). Compared to naturally conceived children, ART singletons conceived (from autologous oocytes, fresh embryos) with the use of ICSI, the risks were increased for a major nonchromosomal birth defect (AOR 1.30, 95% CI 1.16, 1.45 without male factor diagnosis; AOR 1.42, 95% CI 1.28, 1.57 with male factor diagnosis); blastogenesis defects (AOR 1.49, 95% CI 1.08, 2.05 without male factor; AOR 1.56, 95% CI 1.17, 2.08 with male factor); cardiovascular defects (AOR 1.28, 95% CI 1.10,1.48 without male factor; AOR 1.45, 95% CI 1.27, 1.66 with male factor); in addition, the risk for musculoskeletal defects was increased (AOR 1.34, 95% CI 1.01, 1.78 without male factor) and the risk for genitourinary defects in male infants was increased (AOR 1.33, 95% CI 1.08, 1.65 with male factor). Comparisons within ART singleton births conceived from autologous oocytes and fresh embryos indicated that the use of ICSI was associated with increased risks of a major nonchromosomal birth defect (AOR 1.18, 95% CI 1.03, 1.35), blastogenesis defects (AOR 1.65, 95% CI 1.08, 2.51), gastrointestinal defects (AOR 2.21, 95% CI 1.28, 3.82) and any defect (AOR 1.11, 95% CI 1.01, 1.22). Compared to naturally conceived children, ART singleton siblings had increased risks of musculoskeletal defects (AOR 1.32, 95% CI 1.04, 1.67) and any defect (AOR 1.15, 95% CI 1.08, 1.23). ART twins (conceived with autologous oocytes, fresh embryos, without ICSI) were at increased risk of chromosomal defects (AOR 1.89, 95% CI 1.10, 3.24) and ART twin siblings were at increased risk of any defect (AOR 1.26, 95% CI 1.01, 1.57). The 18% increased risk of a major nonchromosomal birth defect in singleton infants conceived with ART without ICSI (36% of ART births), the 30% increased risk with ICSI without male factor (33% of ART births), and the 42% increased risk with ICSI and male factor (31% of ART births) translates into an estimated excess of 386 major birth defects among the 68908 singleton children born by ART in 2017.LIMITATIONS, REASONS FOR CAUTION: In the SART CORS database, it was not possible to differentiate method of embryo freezing (slow freezing vs vitrification), and data on ICSI was only available in the fresh embryo ART group. In the OI/IUI group, it was not possible to differentiate type of non-ART treatment utilized, and in both the ART and OI/IUI groups, data were unavailable on duration of infertility.WIDER IMPLICATIONS OF THE FINDINGS: The use of ART is associated with increased risks of a major nonchromosomal birth defect, cardiovascular defect and any defect in singleton children, and chromosomal defects in twins; the use of ICSI further increases this risk, the most with male factor infertility. These findings support the judicious use of ICSI only when medically indicated. The relative contribution of ART treatment parameters versus the biology of the subfertile couple to this increased risk remains unclear and warrants further study.STUDY FUNDING/COMPETING INTEREST(S): This project was supported by grant R01 HD084377 from the National Institute of Child Health and Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Child Health and Human Development, or the National Institutes of Health, nor any of the State Departments of Health which contributed data. E.W. is a contract vendor for SART; all other authors report no conflicts.TRIAL REGISTRATION NUMBER: N/A.

  View details for DOI 10.1093/humrep/deaa272

  View details for PubMedID 33251542

• The association between cannabis use and testicular function in men: a systematic review and meta-analysis. Andrology Belladelli, F., Del Giudice, F., Kasman, A., Jensen, T. K., Jorgensen, N., Salonia, A., Eisenberg, M. L. 2020

  Abstract

  OBJECTIVE: To evaluate the association between cannabis use and testicular function (as assessed through semen quality and serum hormone levels) in different populations.EVIDENCE REVIEW: Systematic review and meta-analysis of population-based retrospective cohort studies. PRISMA guidelines were used for abstracting data and assessing data quality and validity. Data were pooled using a fixed-effect or random-effects model depending on the heterogeneity of studies included. Pooled risk ratio (RR) of having any sperm abnormality and Testosterone, FSH, and LH standardized mean differences among male cannabis users and non-users, and meta-regression analysis according to age, and year of publication.RESULTS: Nine studies were evaluted which included 4014 men with semen data and 4787 with hormonal data. Overall among 1158 cannabis users, 44.9% had impaired semen parameters. Compared to 24.5% of the 2856 nonusers. The relative risk among cannabis users for any abnormal semen parameter was 1.159 (95%CI: 0.840; 1.599, p=0.369). The standardized mean difference between users and non-users testosterone levels was -0.139 (95%CI: -0.413; 0.134, p= 0.318). For FSH, the standardized mean difference estimate was -0.142 (95%CI: -0.243; -0.0425, p=0.005), while for LH the standardized mean difference estimate was -0.318 (95%CI: -0.810-0.175; p= 0.206).CONCLUSIONS: The current evidence does not suggest clinically significant associations between cannabis use and testicular function. However, we cannot exclude an effect of cannabis due to the limited and heterogeneous studies. Additional, well-designed studies will be needed to define the association between cannabis use and the male reproductive system.

  View details for DOI 10.1111/andr.12953

  View details for PubMedID 33251770

• Risk of pre-term births and major birth defects resulting from paternal intake of COVID-19 medications prior to conception. BMC research notes Rizzi, S., Wensink, M. J., Lindahl-Jacobsen, R., Tian, L., Lu, Y., Eisenberg, M. L. 2020; 13 (1): 509

  Abstract

  OBJECTIVE: With the ongoing COVID-19 pandemic, large numbers of people will receive one of the several medications proposed to treat COVID-19, including patients of reproductive age. Given that some medications have shown adverse effects on sperm quality, there might be a transgenerational concern. We aim at examining the association between drugs proposed to treat COVID-19 when taken by the father around conception and any pre-term birth or major birth defects in offspring in a nation-wide cohort study using Danish registry data. Offspring whose father filled at least one prescription of the following medications in the 3months preceding conception were considered exposed: chloroquine, hydroxychloroquine, losartan, azithromycin, naproxen, dexamethasone and prednisone.RESULTS: For azithromycin and naproxen, large numbers of offspring were exposed (>1800 offspring), and we found no association with adverse birth outcomes. For chloroquine, losartan and dexamethasone, exposure was intermediate (~900 offspring), and there was no statistically significant association with birth defects. For hydroxychloroquine and prednisone, exposure was limited (<300 offspring). Our evidence suggests that azithromycin and naproxen are safe with respect to pre-term birth and birth defects. For the other drugs investigated larger exposures are needed for conclusive statements.

  View details for DOI 10.1186/s13104-020-05358-x

  View details for PubMedID 33160408

• Public Interest in Elective Urological Procedures in the COVID-19 Pandemic: A Google Trends Analysis UROLOGY PRACTICE Bhambhvani, H. P., Tijerina, J. D., Parham, M. J., Greenberg, D. R., Eisenberg, M. L. 2020; 7 (6): 496–501

  View details for DOI 10.1097/UPJ.0000000000000179

  View details for Web of Science ID 000587796800021

• Public Interest in Elective Urological Procedures in the COVID-19 Pandemic: A Google Trends Analysis. Urology practice Bhambhvani, H. P., Tijerina, J. D., Parham, M. J., Greenberg, D. R., Eisenberg, M. L. 2020; 7 (6): 496-501

  Abstract

  We sought to characterize public interest in elective urological procedures amid the COVID-19 pandemic, and specifically after the Centers for Medicare and Medicaid Services and the American Urological Association recommended cessation of all nonessential procedures.We extracted relative search volumes from Google Trends™ (January 2015 to May 2020) for keywords related to the 4 procedure categories of male infertility, erectile dysfunction, Peyronie's disease and vasectomy. The most popular keywords in each category were used to assess immediate (30 days preceding and following official recommendation from Centers for Medicare and Medicaid Services on March 18, 2020) and long-term (January 1, 2015 to March 18, 2020 vs March 19, 2020 to May 21, 2020) shifts in public interest. Lastly, we assessed geographical variations in public interest during the phase I reopening period from April 24 to May 31, 2020.There was an immediate reduction in interest across all 4 categories following the Centers for Medicare and Medicaid Services recommendation. Long-term post-announcement relative search volume was lower than pre-announcement relative search volume in all categories as well, namely male infertility (54.33% vs 68.74%, p=0.02), erectile dysfunction (45.00% vs 76.74%, p <0.0001), Peyronie's disease (48.33% vs 77.95%, p <0.0001) and vasectomy (51.33% vs 66.73%, p=0.0005). During the phase I reopening period the relative search volume for vasectomy was higher in states that reopened early than in states that reopened late (60.29% vs 50.52%, p=0.029).Public interest in elective urological procedures decreased following the onset of the COVID-19 pandemic and recommendations from the Centers for Medicare and Medicaid Services. Interest rebounded in May, seemingly driven by states that lifted their stay-at-home order earlier than others.

  View details for DOI 10.1097/UPJ.0000000000000179

  View details for PubMedID 37287180

• A preliminary study of sperm identification in microdissection testicular sperm extraction samples with deep convolutional neural networks. Asian journal of andrology Wu, D. J., Badamjav, O., Reddy, V. V., Eisenberg, M., Behr, B. 2020

  Abstract

  Sperm identification and selection is an essential task when processing human testicular samples for in vitro fertilization. Locating and identifying sperm cell(s) in human testicular biopsy samples is labor intensive and time consuming. We developed a new computer-aided sperm analysis (CASA) system, which utilizes deep learning for near human-level performance on testicular sperm extraction (TESE), trained on a custom dataset. The system automates the identification of sperm in testicular biopsy samples. A dataset of 702 de-identified images from testicular biopsy samples of 30 patients was collected. Each image was normalized and passed through glare filters and diffraction correction. The data were split 80%, 10%, and 10% into training, validation, and test sets, respectively. Then, a deep object detection network, composed of a feature extraction network and object detection network, was trained on this dataset. The model was benchmarked against embryologists' performance on the detection task. Our deep learning CASA system achieved a mean average precision (mAP) of 0.741, with an average recall (AR) of 0.376 on our dataset. Our proposed method can work in real time; its speed is effectively limited only by the imaging speed of the microscope. Our results indicate that deep learning-based technologies can improve the efficiency of finding sperm in testicular biopsy samples.

  View details for DOI 10.4103/aja.aja_66_20

  View details for PubMedID 33106465

• Safety and Feasibility of Outpatient Surgery in Benign Prostatic Hyperplasia: a Systematic Review and Meta-analysis. Journal of endourology Salciccia, S., Del Giudice, F., Maggi, M., Eisenberg, M., Chung, B. I., Conti, S. L., Kasman, A., Vilson, F. L., Ferro, M., Lucarelli, G., Viscuso, P., Di Pierro, G., Busetto, G. M., Luzi, M., Sperduti, I., Ricciuti, G. P., De Berardinis, E., Sciarra, A. 2020

  Abstract

  PURPOSE: Most of endourological procedures along the urinary tract have been widely practiced as outpatient operations, including surgery for BPH. This systematic review and meta-analysis was conducted to assess safety and feasibility of outpatient surgery for patients suffering from symptomatic BPH candidate for endoscopic disobstruction.MATERIALS AND METHODS: PubMed, Web of Science, Cochrane, and Embase were searched up until March 30, 2020. MINORS tool was utilized to assess the quality of included studies and a pooled measure of failure or event rate (FR, ER) estimate was calculated. Further sensitivity analysis, subgroup analysis, and meta-regression were conducted to investigate contribution of moderators to heterogeneity.RESULTS: Twenty studies with a total of 1626 patients treated according to outpatient criteria for endoscopic BPH surgery were included. In total, 18 studies reporting data on immediate hospital readmission and/or inability to discharge after endoscopic procedure presented FR estimates ranging from 1.7% to 51.1%. Pooled FR estimate was 7.8% (95% confidence interval [CI]: 5.2%-10.3%); Heterogeneity: Q=76.85; d.f.=17, p<.001; I2= 75.12%. Subgroup analysis according to surgical technique revealed difference among the three approaches with pooled FR of 3% (95%CI: 1%-4.9%), 7.1% (95%CI: 3.9-10.4) and 11.8% (95%CI: 7-16.7%) for TURP, Green-light and HoLEP respectively (p<.001). At meta-regression analysis, none of the retrieved covariates were able to significantly influence the cumulative outcomes reported. ER for postoperative complications and early outpatient visit showed a pooled estimate of 18.6% (95%CI: 13.2%-23.9%) and 7.7% (95%CI: 4.3%-11%) respectively.CONCLUSIONS: Our analysis revealed how transurethral procedures for BPH on an outpatient setting are overall reliable and safe. Of note, there were significant outcome differences between groups with regard of type of surgical procedure, perioperative prostate volume and discharge protocol suggesting the need for further prospective analysis to better elucidate the best strategy in such outpatient conduct.

  View details for DOI 10.1089/end.2020.0538

  View details for PubMedID 33081521

• Delayed Ejaculation After Lumbar Spine Surgery: A Claims Database Analysis. Global spine journal Bhambhvani, H. P., Kasman, A. M., Zhang, C. A., Hu, S. S., Eisenberg, M. L. 2020: 2192568220962435

  Abstract

  STUDY DESIGN: Retrospective cohort.OBJECTIVES: Delayed ejaculation (DE) is a distressing condition characterized by a notable delay in ejaculation or complete inability to achieve ejaculation, and there are no existing reports of DE following lumbar spine surgery. Inspired by our institutional experience, we sought to assess national rates of DE following surgery of the lumbar spine.METHODS: We queried the Optum De-identified Clinformatics Database for adult men undergoing surgery of the lumbar spine between 2003 and 2017. The primary outcome was the development of DE within 2 years of surgery. Multivariable logistic regression was performed to identify factors associated with the development of DE.RESULTS: We identified 117918 men who underwent 162646 lumbar spine surgeries, including anterior lumbar interbody fusion (ALIF), posterior lumbar fusion (PLF), and more. The overall incidence of DE was 0.09%, with the highest rate among ALIF surgeries at 0.13%. In multivariable analysis, the odds of developing DE did not vary between anterior/lateral lumbar interbody fusion, PLF, and other spine surgeries. A history of tobacco smoking (OR = 1.47, 95% CI 1.00-2.16, P = .05) and obesity (OR = 1.56, 95% CI 1.00-2.44, P = .05) were associated with development of DE.CONCLUSIONS: DE is a rare but distressing complication of thoracolumbar spine surgery, and patients should be queried for relevant symptoms at postoperative visits when indicated.

  View details for DOI 10.1177/2192568220962435

  View details for PubMedID 33047620

• In Vitro Fertilization and Risk for Hypertensive Disorders of Pregnancy: Associations With Treatment Parameters OBSTETRICAL & GYNECOLOGICAL SURVEY Luke, B., Brown, M. B., Eisenberg, M. L., Callan, C., Botting, B. J., Pacey, A., Sutcliffe, A. G., Baker, V. L. 2020; 75 (10): 608–9

  View details for DOI 10.1097/OGX.0000000000000852

  View details for Web of Science ID 000583052500016

• Assessment of Birth Defects and Cancer Risk in Children Conceived via In Vitro Fertilization in the US. JAMA network open Luke, B., Brown, M. B., Nichols, H. B., Schymura, M. J., Browne, M. L., Fisher, S. C., Forestieri, N. E., Rao, C., Yazdy, M. M., Gershman, S. T., Ethen, M. K., Canfield, M. A., Williams, M., Wantman, E., Oehninger, S., Doody, K. J., Eisenberg, M. L., Baker, V. L., Lupo, P. J. 2020; 3 (10): e2022927

  Abstract

  Importance: Children with birth defects have a greater risk of developing cancer, but this association has not yet been evaluated in children conceived with in vitro fertilization (IVF).Objective: To assess whether the association between birth defects and cancer is greater in children conceived via IVF compared with children conceived naturally.Design, Setting, and Participants: This cohort study of live births, birth defects, and cancer from Massachusetts, New York, North Carolina, and Texas included 1 000 639 children born to fertile women and 52 776 children conceived via IVF (using autologous oocytes and fresh embryos) during 2004-2016 in Massachusetts and North Carolina, 2004-2015 in New York, and 2004-2013 in Texas. Children were followed up for an average of 5.7 years (6 008 985 total person-years of exposure). Data analysis was conducted from April 1 to August 31, 2020.Exposures: Conception by IVF for state residents who gave birth to liveborn singletons during the study period. Birth defect diagnoses recorded by statewide registries.Main Outcomes and Measures: Cancer diagnosis as recorded by state cancer registries. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs for birth defect-cancer associations separately in fertile and IVF groups.Results: A total of 1 000 639 children (51.3% boys; 69.7% White; and 38.3% born between 2009-2012) were in the fertile group and 52 776 were in the IVF group (51.3% boys; 81.3% White; and 39.6% born between 2009-2012). Compared with children without birth defects, cancer risks were higher among children with a major birth defect in the fertile group (hazard ratio [HR], 3.15; 95% CI, 2.40-4.14) and IVF group (HR, 6.90; 95% CI, 3.73-12.74). The HR of cancer among children with a major nonchromosomal defect was 2.07 (95% CI, 1.47-2.91) among children in the fertile group and 4.04 (95% CI, 1.86-8.77) among children in the IVF group. The HR of cancer among children with a chromosomal defect was 15.45 (95% CI, 10.00-23.86) in the fertile group and 38.91 (95% CI, 15.56-97.33) in the IVF group.Conclusions and Relevance: This study found that among children with birth defects, those conceived via IVF were at greater risk of developing cancer compared with children conceived naturally.

  View details for DOI 10.1001/jamanetworkopen.2020.22927

  View details for PubMedID 33119107

• Relationship Between Male Age, Semen Parameters and Assisted Reproductive Technology Outcomes. Andrology Kasman, A. M., Li, S., Zhao, Q., Behr, B., Eisenberg, M. L. 2020

  Abstract

  BACKGROUND: Low semen quality often obligates the use of assisted reproductive technology (ART); however, the association between semen quality and ART outcomes is uncertain.OBJECTIVES: To further assess the impact of semen quality on ART outcomes.MATERIALS AND METHODS: A retrospective cohort study was carried out at a single academic reproductive medicine center (January 2012-December 2018). Patients undergoing at least one ART cycle utilizing freshly ejaculated sperm from the male partner were included. We assessed the association between semen quality (as stratified based on WHO 5th edition criteria), paternal age (< or ≥40), and reproductive/perinatal outcomes. To evaluate the differences in ART outcomes by semen parameters and age, generalized estimating equations were applied for rates of fertilization, pregnancy, implantation, miscarriage, live birth, blast formation, gestational age, and normal embryo biopsy.RESULTS: 2063 couples were identified who underwent 4517 ART cycles. Average ages of the male and female partners were 39.8 and 37.7, respectively. Lower pregnancy rates were observed in cycles with lower sperm motility (i.e. <40%; 39.9% vs 44.1%) and total motile count (i.e. <9 million; 38.3% vs 43.5%). When examining only cycles utilizing ICSI, only a lower motility count was associated with a decline in pregnancy rate (39.1% vs 44.9%). No association was identified between semen quality and gestational age or birth weight. Paternal age was not associated with ART outcomes. However, among ART cycles in women <40, aneuploidy rate was higher for older men (p< 0.001). In cycles with women>40, no association between aneuploidy and male age was identified.DISCUSSION: Sperm motility is associated with pregnancy rates, while other semen parameters are not. In cycles in women <40, paternal age is associated with embryo aneuploidy rate.CONCLUSION: Paternal factors are associated with ART outcomes and future studies should explore mechanisms by which semen quality is associated with ART outcomes.

  View details for DOI 10.1111/andr.12908

  View details for PubMedID 32964702

• Clinicopathologic features, outcomes, and prognostic factors of testicular sarcoma: a population-based study. International urology and nephrology Bhambhvani, H. P., Greenberg, D. R., Kasman, A. M., Eisenberg, M. L. 2020

  Abstract

  PURPOSE: To describe clinical characteristics and identify prognostic factors among men with testicular sarcoma, and to compare survival with other testicular cancers.METHODS: The surveillance, epidemiology, and end results (SEER) database (1975-2016) was queried to identify adults with testicular sarcoma. Multivariable Cox proportional hazards, Fine and Gray competing-risks regression, propensity score matching, and Kaplan-Meier analyses were used.RESULTS: 230 men were included in this study. Median age at diagnosis was 58years (range 18-94), and median OS was 10.3years. Patients with tumors larger than 8cm in size had worse OS (HR 1.88, p=0.016) compared to patients with tumors<8cm. Disease with distant metastasis was associated with worse OS (HR 4.70, p<0.0001) and worse CSS (HR 11.41, p<0.0001) as compared to disease localized to the testis. Men with rhabdomyosarcoma had worse CSS (HR 3.25, p=0.03) as compared to men with liposarcoma. Testicular sarcoma patients had worse OS than matched patients with either seminomatous germ cell tumors (GCTs, p<0.0001) or nonseminomatous GCTs (p=0.0019), and similar survival to matched patients with sex cord stromal tumors, testicular lymphoma, or sarcomas of the lower limb-the most common anatomic site of origin of soft tissue sarcomas.CONCLUSIONS: In the largest cohort of men with testicular sarcoma to date, we identified tumor size, disease extent, and rhabdomyosarcoma histology as independent predictors of worse survival. Stage-adjusted survival was worse as compared to men with GCTs, and similar to men with sex cord stromal tumors, testicular lymphoma, and sarcomas of other primary sites.

  View details for DOI 10.1007/s11255-020-02634-4

  View details for PubMedID 32895865

• MALE INFERTILITY DIAGNOSES AMONG PATIENTS WHO USED ASSISTED REPRODUCTIVE TECHNOLOGY IN THE UNITED STATES, 2016-2018. Jewett, A., Warner, L., Dupree, J. M., Honig, S., Nangia, A. J., Eisenberg, M. L., Kawwass, J. F., Hotaling, J., Mehta, A., Kissin, D. M. ELSEVIER SCIENCE INC. 2020: E367–E368

  View details for Web of Science ID 000579355301167

• A NORTH AMERICAN PROSPECTIVE COHORT STUDY OF ANTHROPOMETRIC FACTORS AND SEMEN QUALITY. Joseph, M. D., Hatch, E. E., Eisenberg, M. L., Rothman, K. J., Wang, T. R., Wise, L. A. ELSEVIER SCIENCE INC. 2020: E391–E392

  View details for Web of Science ID 000579355301223

• ASSOCIATION BETWEEN INFERTILITY AND MORTALITY: ANALYSIS OF US CLAIMS DATA. Murugappan, G., Li, S., Alvero, R. J., Eisenberg, M. L. ELSEVIER SCIENCE INC. 2020: E50–E51

  View details for Web of Science ID 000579355300122

• Assessment of the Association of Cannabis on Female Sexual Function With the Female Sexual Function Index. Sexual medicine Kasman, A. M., Bhambhvani, H. P., Wilson-King, G., Eisenberg, M. L. 2020

  Abstract

  INTRODUCTION: Cannabis use has increased in the last decade, and the impact of cannabis on female sexual function remains unclear.AIM: To assess the impact of frequency of use, chemovar (tetrahydrocannabinol, cannabinol, or both) type, and method of consumption on female sexual function among cannabis users.METHODS: Adults who visited a single-partner cannabis dispensary's locations were invited to participate in an uncompensated, anonymous online survey October 20, 2019 and March 12, 2020. The survey assessed baseline demographics, health status, cannabis use habits as well as used the validated Female Sexual Function Index (FSFI) to assess sexual function.MAIN OUTCOME MEASURE: The main outcomes of this study are the total FSFI score (sexual dysfunction cutoff <26.55) and subdomain scores including desire, arousal, lubrication, orgasm, satisfaction, and pain.RESULTS: A total of 452 women responded with the majority between the ages of 30-49years (54.7%) and in a relationship or married (81.6%). Of them,72.8% reported using cannabis more than 6 times per week, usually through smoking flower (46.7%). Women who reported more cannabis use, reported higher FSFI scores (29.0 vs 26.7 for lowest vs highest frequencies of reported use, P=.003). Moreover, an increase in cannabis use frequency by one additional use per week was associated with an increase in total FSFI (beta=0.61, P=.0004) and subdomains including desire domain (P=.02), arousal domain (P=.0002), orgasm domain (P=.002), and satisfaction domain (P=.003). For each additional step of cannabis use intensity (ie, times per week), the odds of reporting female sexual dysfunction declined by 21% (odds ratio: 0.79, 95% confidence interval: 0.68-0.92, P=.002). Method of consumption of cannabis and chemovar type did not consistently impact FSFI scores or odds of sexual dysfunction.CONCLUSION: Increased frequency of marijuana use is associated with improved sexual function among female users, whereas chemovar type, method of consumption, and reason for use does not impact outcomes. Kasman AM, Bhambhvani HP, Wilson-King G, etal. Assessment of the Association of Cannabis on Female Sexual Function With the Female Sexual Function Index. Sex Med 2020;XX:XXX-XXX.

  View details for DOI 10.1016/j.esxm.2020.06.009

  View details for PubMedID 32713800

• Association between male infertility and male-specific malignancies: systematic review and meta-analysis of population-based retrospective cohort studies. Fertility and sterility Del Giudice, F., Kasman, A. M., De Berardinis, E., Busetto, G. M., Belladelli, F., Eisenberg, M. L. 2020

  Abstract

  OBJECTIVE: To investigate the current evidence that correlates impaired male fertility with the risk of developing male-related malignancies.DESIGN: Systematic review and meta-analysis of population-based retrospective cohort studies.SETTING: Not applicable.PATIENT(S): Men diagnosed with impaired fertility status and subsequently observed to determine incidence risk in developing testicular cancer (TCa) or prostate cancer (PCa).INTERVENTION(S): Not applicable.MAIN OUTCOME MEASURE(S): Pooled risk ratio (RR) differences among male factor infertility subjects compared with a fertile control population, and meta-regression analysis according to age at baseline, mean follow-up, range of study time, and year of publication.RESULT(S): Six studies met the inclusion criteria and were critically examined. Four studies examined male infertility and TCa (n = 161,634; 174 TCa cases), and four examined infertility in relation to PCa (n = 183,950 men; 377 PCa cases) from 1963 to 2014. The pooled RR was 2.033 (95% confidence interval [CI], 1.66-2.48); heterogeneity: Q = 3.04 (degree of freedom [df] = 3); I2 = 1.55% for TCa and 1.68 (95% CI, 1.17-2.4); Q = 23.3(df = 3); I2 = 87.1% for PCa.CONCLUSION(S): Male infertility was associated with a subsequent risk of both TCa and PCa. Although the clinical significance of these findings remains uncertain, future studies should evaluate the underlying mechanisms to determine whether testis and prostate screening practices should be altered in men with male infertility.CLINICAL TRIAL REGISTRATION NUMBER: PROSPERO 167277.

  View details for DOI 10.1016/j.fertnstert.2020.04.042

  View details for PubMedID 32709378

• Clinical correlation among male infertility and overall male health: A systematic review of the literature. Investigative and clinical urology Del Giudice, F., Kasman, A. M., Ferro, M., Sciarra, A., De Berardinis, E., Belladelli, F., Salonia, A., Eisenberg, M. L. 2020; 61 (4): 355–71

  Abstract

  Purpose: Ongoing evidence has suggested the role of male factor infertility as a potential predictor of mortality and general health status. The aim of the present review is to update the current knowledge base regarding the association between male factor infertility and general health through a critical review of the literature.Materials and Methods: A systematic review of the literature was carried out from inception to November 2019 in order to evaluate significant associations between male infertility and adverse health outcomes such as cardiovascular, oncologic, metabolic and autoimmune diseases as well as overall mortality.Results: In all, 27 studies met inclusion criteria and were critically examined. Five studies examined male infertility and cardiovascular disease risk, 11 examined oncologic risk (e.g., overall cancer risk, testis and prostate cancer), 8 examined aggregate chronic medical diseases and 5 infertility related to incidence of mortality, for a total of 599,807 men diagnosed with any male factor infertility covering a period from 1916 to 2016.Conclusions: A man's fertility and overall health appear to be interconnected. Therefore, a diagnosis of male infertility may allow a window into future comorbidity and/or mortality which may help guide clinical decisions and counseling. Several possible etiologies such as genetic, epigenetic, developmental, and lifestyle-based factors need to be further evaluated in order to establish the underlying mechanisms between male infertility and health.

  View details for DOI 10.4111/icu.2020.61.4.355

  View details for PubMedID 32665992

• Male and Female Sexual Dysfunction in Pediatric Cancer Survivors. The journal of sexual medicine Greenberg, D. R., Khandwala, Y. S., Bhambhvani, H. P., Simon, P. J., Eisenberg, M. L. 2020

  Abstract

  BACKGROUND: Pediatric cancer survivors suffer indirect long-term effects of their disease; however, there is a paucity of data regarding the effect of pediatric cancer survivorship on sexual function.AIM: To assess the prevalence and risk factors associated with sexual dysfunction among pediatric cancer survivors.METHODS: Pediatric cancer survivors were recruited to complete an online survey using the Female Sexual Function Index (FSFI) or the International Index of Erectile Function (IIEF-5), both validated questionnaires to assess female sexual dysfunction (FSD) and erectile dysfunction (ED). Patient demographics, oncologic history, prior treatment, and sexual habits were also queried. Logistic regression was used to evaluate risk factors for sexual dysfunction, and Mann-Whitney U test was used to identify factors associated with individual domains of the FSFI.OUTCOMES: The main outcome measures were FSFI and IIEF-5 score, which are used to diagnose FSD (FSFI<26.55) and ED (IIEF-5<22).RESULTS: A total of 21 (72.4%) female respondents and 20 (71.4%) male respondents were sexually active and completed the survey and FSFI or IIEF-5 questionnaire, respectively. Mean (±SD) age was 23.7 (4.1) years, andaverage age at diagnosis was 9.1 (5.0), with no difference between genders. Overall, 25.0% (5/20) of male and 52.4% (11/21) of female pediatric cancer survivors reported sexual dysfunction (P=.11). Oncologic history and prior treatment were not associated with sexual function. Females who reported difficulty relaxing during intercourse in the last 6months had higher odds of reporting sexual dysfunction (odds ratio: 13.6, 95% confidence interval: 1.2-151.2, P=.03). Subgroup analysis of FSFI domains found that previous radiation therapy was correlated with decreased lubrication and satisfaction during intercourse, whereas previous treatment to the pelvic region significantly reduced satisfaction and increased pain during intercourse.CLINICAL IMPLICATIONS: Female pediatric cancer survivors have higher odds of reporting sexual dysfunction after treatment and should be screened appropriately to provide early intervention and to mitigate risk.STRENGTH & LIMITATIONS: Our study includes validated questionnaires to assess FSD and ED and queries specific characteristics to assess their association with sexual dysfunction. However, the study is limited by sample size and its cross-sectional survey design.CONCLUSIONS: The prevalence of female sexual dysfunction in this cohort is higher than that in the general population of equivalent-aged individuals, and clinicians should be aware of these potential long-term sequelae. Greenberg DR, Khandwala YS, Bhambhvani HP, et-al. Male and Female Sexual Dysfunction in Pediatric Cancer Survivors. J Sex Med;XX:XXX-XXX.

  View details for DOI 10.1016/j.jsxm.2020.05.014

  View details for PubMedID 32622765

• Towards personalized medicine in maternal and child health: integrating biologic and social determinants. Pediatric research Stevenson, D. K., Wong, R. J., Aghaeepour, N., Maric, I., Angst, M. S., Contrepois, K., Darmstadt, G. L., Druzin, M. L., Eisenberg, M. L., Gaudilliere, B., Gibbs, R. S., Gotlib, I. H., Gould, J. B., Lee, H. C., Ling, X. B., Mayo, J. A., Moufarrej, M. N., Quaintance, C. C., Quake, S. R., Relman, D. A., Sirota, M., Snyder, M. P., Sylvester, K. G., Hao, S., Wise, P. H., Shaw, G. M., Katz, M. 2020

  View details for DOI 10.1038/s41390-020-0981-8

  View details for PubMedID 32454518

• The Most Common Reasons for Health Care Provider Visits in Reproductive Aged Men Differ by Race and Age Stratification UROLOGY PRACTICE Balasubramanian, A., Zhang, C. A., Spradling, K., Eisenberg, M. L. 2020; 7 (3): 194–98

  View details for DOI 10.1097/UPJ.0000000000000091

  View details for Web of Science ID 000531471800010

• The Most Common Reasons for Health Care Provider Visits in Reproductive Aged Men Differ by Race and Age Stratification. Urology practice Balasubramanian, A., Zhang, C. A., Spradling, K., Eisenberg, M. L. 2020; 7 (3): 194-198

  Abstract

  We assessed common reasons for health care provider visits among reproductive aged men.We used the Optum® Clinformatics® Data Mart, a de-identified insurance claims database encompassing commercial and Medicare Advantage health plan data from all 50 states, to analyze men 20 to 49 years old who were enrolled between January 1 and December 31, 2017. Men with at least 1 health care provider visit were included and were stratified into age groups of 20 to 29, 30 to 39 and 40 to 49 years old. For each age group the top 100 urological and nonurological ICD-10 diagnosis codes were aggregated and assessed per unit of observation. Groups were further stratified by race. Descriptive statistics are presented in counts and percentages.A total of 3,027,585 men 20 to 49 years old were enrolled in Optum Data Mart in 2017. Of these men 1,915,027 (63%) had at least 1 visit with a health care provider. Musculoskeletal pain was the top reason for visits across all age groups. Sexually transmitted diseases were the top urological complaint in men 20 to 29 and 30 to 39 years old. Sterilization was among the top reasons for visits in white men and was less common in black, Hispanic and Asian men. Testicular hypofunction was the most common urological complaint in men 40 to 49 years old and erectile dysfunction was also noted.We identified urological concerns as common drivers for reproductive aged men to visit providers. Urological issues including sexually transmitted diseases, testicular hypofunction and erectile dysfunction motivate these men to seek medical attention, with rates differing based on age and race.

  View details for DOI 10.1097/UPJ.0000000000000091

  View details for PubMedID 37317416

• Coronavirus disease 2019 and men's reproductive health. Fertility and sterility Eisenberg, M. L. 2020

  View details for DOI 10.1016/j.fertnstert.2020.04.039

  View details for PubMedID 32387274

• Co-Manifestations of Genital Neurofibromatosis in a Patient with Neurofibromatosis Type 1. Urology Ku, S., Balasubramanian, A., Kao, C., Eisenberg, M. L., Skinner, E. C. 2020

  Abstract

  Genitourinary (GU) presentation of neurofibromatosis type 1 (NF-1) is rare, amongst which bladder involvement is the most common. Sporadic case reports do highlight infrequent external genitalia involvement in NF-1. We present a 21-year-old male with prior childhood history of partial cystectomy for an NF-1 related bladder tumor, who more recently presented with gross hematuria. Workup revealed multiple ganglioneuromas involving the bladder, prostate, and penis, and the patient underwent radical cystoprostatectomy and penile mass excision. Recurrences of previously excised urologic tumors or new tumors may appear many years later, and long-term monitoring of NF-1 patients with urologic involvement is necessary.

  View details for DOI 10.1016/j.urology.2020.03.030

  View details for PubMedID 32289361

• RELATIONSHIP BETWEEN SEMEN PARAMETERS AND ASSISTED REPRODUCTIVE TECHNOLOGY OUTCOMES Kasman, A., Li, S., Behr, B., Eisenberg, M. LIPPINCOTT WILLIAMS & WILKINS. 2020: E538

  View details for Web of Science ID 000527010302406

• Parental comorbidity and medication use in the USA: a panel study of 785000 live births. Human reproduction (Oxford, England) Sun, A. J., Li, S., Zhang, C. A., Jensen, T. K., Lindahl-Jacobsen, R., Eisenberg, M. L. 2020

  Abstract

  STUDY QUESTION: How prevalent is paternal medication use and comorbidity, and are rates of these rising?SUMMARY ANSWER: Paternal medication use and comorbidity is common and rising, similar to trends previously described in mothers.WHAT IS KNOWN ALREADY: Maternal medication use and comorbidity has been rising for the past few decades. These trends have been linked to potential teratogenicity, maternal morbidity and mortality and poorer fetal outcomes.STUDY DESIGN, SIZE, DURATION: This is a Panel (trend) study of 785809 live births from 2008 to 2016.PARTICIPANTS/MATERIALS, SETTING, METHODS: We used the IBM© Marketscan database to gather data on demographic information and International Classification of Diseases codes and Charlson comorbidity index (CCI) during the 12months prior to the estimated date of conception for mothers and fathers. We similarly examined claims of prescriptions in the 3months prior to conception. We performed companion analyses of medications used for >90days in the 12months prior to conception and of any medication use in the 12months prior to conception.MAIN RESULTS AND THE ROLE OF CHANCE: We confirmed that both maternal medication use and comorbidity (e.g. hypertension, diabetes, hyperlipidemia) rose over the study period, consistent with prior studies. We found a concurrent rise in both paternal medication use 3months prior to conception (overall use, 31.5-34.9% during the study period; P<0.0001) and comorbidity (CCI of≥1 and 10.6-18.0% over study period; P<0.0001). The most common conditions seen in the CCI were chronic obstructive pulmonary disease for mothers (6.6-11.6%) and hyperlipidemia for fathers (8.6-13.7%). Similar trends for individual medication classes and specific comorbidities such as hypertension, diabetes and hyperlipidemia were also seen. All primary result trends were statistically significant, making the role of chance minimal.LIMITATIONS, REASONS FOR CAUTION: As this is a descriptive study, the clinical impact is uncertain and no causal associations may be made. Though the study uses a large and curated database that includes patients from across the USA, our study population is an insured population and our findings may not be generalizable. Mean parental age was seen to slightly increase over the course of the study (<1year) and may be associated with increased comorbidity and medication use.WIDER IMPLICATIONS OF THE FINDINGS: As parental comorbidity and certain medication use may impact fecundability, temporal declines in parental health may impact conception, pregnancy and fetal outcomes.STUDY FUNDING/COMPETING INTEREST(S): None.TRIAL REGISTRATION NUMBER: N/A.

  View details for DOI 10.1093/humrep/deaa022

  View details for PubMedID 32187368

• The Association Between Pelvic Discomfort and Erectile Dysfunction in Adult Male Bicyclists. The journal of sexual medicine Balasubramanian, A., Yu, J., Breyer, B. N., Minkow, R., Eisenberg, M. L. 2020

  Abstract

  BACKGROUND: Bicycle riding's impact on erectile function remains a topic of great interest given cycling's popularity as a mode of transportation and exercise.AIM: We evaluated risk factors for sexual dysfunction in male cyclists with the primary intention of determining if genital/pelvic pain and numbness are associated with erectile dysfunction (ED).METHODS: We surveyed male cyclists using an online anonymous questionnaire. Cyclists were queried on their demographics, cycling experience, and sexual function using the Sexual Health Inventory for Men (SHIM). ED was diagnosed when a completed SHIM score was <22. Regression analysis was used to evaluate the risk of ED in men with genital/pelvic pain or numbness after riding. The survey was designed in the United States.OUTCOMES: Quantitative characterization of cycling habits, onset and timing of genital pain and numbness, and SHIM score.RESULTS: A total of 1635 participants completed the survey. A majority of men were over the age of 50 (58%, 934/1,607), Caucasian (88%, 1,437/1,635), had been active cyclists for over 10years (63%, 1,025/1,635) and used road bikes (97%, 1,578/1,635). Overall, 22%, 30%, and 57% of men reported ED, genital pain, and genital numbness, respectively. While controlling for cohort demographics, body mass index, cycling intensity and equipment, and medical comorbidities, no saddle characteristics were associated with the risk of developing genital numbness. However, men reporting penile numbness were at higher risk of reporting ED (odds ratio [OR]=1.453, P=.048). In addition, quicker onset of numbness and resolution of numbness within a day was associated with impaired erectile function. For example, numbness occurring less than 1hour after cycling had greater odds of leading to ED than numbness after 5hours (OR=2.002, P=.032). Similarly, genital pain occurring less than 1hour (OR=2.466, P=.031) after cycling was associated with higher ED risk.STRENGTHS & LIMITATIONS: Strengths include a large sample size of high-intensity cyclists and validated questionnaire use. Limitations include reliance on anonymous self-reported survey data and minimal inquiry into the riding preferences and terrain traversed by cyclists.CONCLUSIONS: Pelvic pain and numbness are common complaints among male riders in the United States. Men with such complaints are more likely to also report ED especially if it occurs earlier in the ride. Although direction of causality and temporality are uncertain, alleviation of factors resulting in pelvic discomfort may reduce cycling's impact on sexual function. Such interventions are critical given that cycling for both active travel and aerobic exercise confers numerous health benefits. Balasubramanian A, Yu J, Breyer BN, etal. The Association Between Pelvic Discomfort and Erectile Dysfunction in Adult Male Bicyclists. J Sex Med 2020;XX:XXX-XXX.

  View details for DOI 10.1016/j.jsxm.2020.01.022

  View details for PubMedID 32156585

• Association of preconception paternal health on perinatal outcomes: analysis of U.S. claims data. Fertility and sterility Kasman, A. M., Zhang, C. A., Li, S., Stevenson, D. K., Shaw, G. M., Eisenberg, M. L. 2020

  Abstract

  OBJECTIVE: To assess whether paternal health is associated with maternal peripartum and neonatal outcomes.DESIGN: Retrospective cohort study.SETTING: University research departments.PATIENT(S): Analytic sample of children born to paired fathers and mothers covering live births within the United States between 2009-2016.INTERVENTION(S): Paternal health status (e.g., metabolic syndrome diagnoses, individual chronic disease diagnoses).MAIN OUTCOME MEASURE(S): Primary outcome of preterm birth (i.e., live birth before 37 weeks), and secondary outcomes of low birth weight, neonatal intensive care unit (NICU) stay, gestational diabetes, preeclampsia, eclampsia, and length of maternal stay.RESULT(S): The IBM Marketscan Research database covers reimbursed health care claims data on inpatient and outpatient encounters who are privately insured through employment-sponsored health insurance. We assessed 785,809 singleton live births, with 6.6% born preterm. The presence of paternal comorbidities was associated with higher odds of preterm birth, low birth weight (LBW), and NICU stay. After adjusting for maternal factors, fathers with most or all components of the metabolic syndrome had 19% higher odds of having a child born preterm (95% CI 1.11-1.28), 23% higher odds of LBW (95% CI 1.01-1.51), and 28% higher odds of NICU stay (95% CI 1.08-1.52). Maternal morbidity (e.g., gestational diabetes or preeclampsia) was also positively associated with preconception paternal health.CONCLUSION(S): Increased preconception paternal comorbidity may be associated with negative infant and maternal outcomes. Although the paternal effect remains modest, these findings highlight the importance of the health of both parents, particularly the mother, on healthy pregnancy.

  View details for DOI 10.1016/j.fertnstert.2019.12.026

  View details for PubMedID 32147174

• Comprehensive men's health and male infertility. Translational andrology and urology Choy, J. T., Eisenberg, M. L. 2020; 9 (Suppl 2): S239-S243

  Abstract

  There is increasing evidence that male infertility may be a harbinger of comorbid medical illness. Existing studies have shed light on associations between infertility and the prevalence of cardiovascular, metabolic, and oncologic disease, along with rates of hospitalization and overall mortality. Although theorized mechanisms include genetic, developmental, and behavioral precipitants, the exact nature of these associations remains unclear and warrants further investigation.

  View details for DOI 10.21037/tau.2019.08.35

  View details for PubMedID 32257864

  View details for PubMedCentralID PMC7108997

• A review of the evolving landscape between the consumer Internet and men's health. Translational andrology and urology Balasubramanian, A., Yu, J., Srivatsav, A., Spitz, A., Eisenberg, M. L., Thirumavalavan, N., McBride, J. A., Lipshultz, L. I., Pastuszak, A. W. 2020; 9 (Suppl 2): S123-S134

  Abstract

  Internet adoption continues to increase as broadband access and mobile connectivity penetrate developing global markets. Alongside increasing adoption, the Internet continues to evolve and usher in new modes of user interaction. Social media and search engines have facilitated the emergence of the participatory web, in which users are able to contribute content, form online communities, and disseminate information. This participatory web is reshaping the patient-physician relationship as patients are able to search for medical information, directly engage with healthcare practitioners through social media, and make therapeutic decisions via online marketplaces. The ability for patients to self-diagnose and self-treat is highly relevant to andrology, given that men have a baseline reluctance to visit healthcare providers. Furthermore, men's health issues such as erectile dysfunction and male infertility are stigmatized, with men turning to the Internet for guidance. The focus of this review is to survey the academic literature that evaluates the quality of online content for four common men's health conditions: hypogonadism, male infertility, erectile dysfunction, and Peyronie's disease.

  View details for DOI 10.21037/tau.2019.09.29

  View details for PubMedID 32257853

  View details for PubMedCentralID PMC7108985

• A review of the evolving landscape between the consumer Internet and men's health TRANSLATIONAL ANDROLOGY AND UROLOGY Balasubramanian, A., Yu, J., Srivatsav, A., Spitz, A., Eisenberg, M. L., Thirumavalavan, N., McBride, J., Lipshultz, L. I., Pastuszak, A. W. 2020; 9: S123–S134

  View details for DOI 10.21037/tau.2019.09.29

  View details for Web of Science ID 000519277600003

• Comprehensive men's health and male infertility TRANSLATIONAL ANDROLOGY AND UROLOGY Choy, J. T., Eisenberg, M. L. 2020; 9: S239–S243

  View details for DOI 10.21037/tau.2019.08.35

  View details for Web of Science ID 000519277600014

• Perspective Regarding "Is Peyronie's Disease an IgG4-Related Disease". The journal of sexual medicine Eisenberg, M. L. 2020; 17 (8): 1583

  View details for DOI 10.1016/j.jsxm.2020.04.003

  View details for PubMedID 32718696

• Challenges in Survey-Based Research. The journal of sexual medicine Chen, T. n., Eisenberg, M. L. 2020

  View details for DOI 10.1016/j.jsxm.2020.08.013

  View details for PubMedID 32943376

• Androgen-deprivation therapy and SARS-Cov-2 infection: the potential double-face role of testosterone. Therapeutic advances in endocrinology and metabolism Salciccia, S., Del Giudice, F., Eisenberg, M. L., Mastroianni, C. M., De Berardinis, E., Ricciuti, G. P., Maggi, M., Sciarra, A. 2020; 11: 2042018820969019

  View details for DOI 10.1177/2042018820969019

  View details for PubMedID 33194171

• Association between infertility and mental health of offspring in the United States: a population based cohort study. Human fertility (Cambridge, England) Kasman, A. M., Zhang, C. A., Luke, B. n., Eisenberg, M. L. 2020: 1–6

  Abstract

  There exist conflicting data in regard to the health outcomes of offspring born to infertile couples and follow up of offspring can be challenging. The objective of the study was to determine the association between infertility in men and women and the mental health of their offspring. The present study analyzes data obtained from the IBM Marketscan™ Commercial Claims and Encounters database from 2007 through 2015. Overall, 271,603 children of males with male factor infertility, 328,571 children of females with female factor infertility, 663,568 children of males who later underwent vasectomy were identified. The odds of psychosis were increased in offspring of those with male factor infertility (OR 1.25, 95% CI 1.22-1.29) and female factor infertility (OR 1.20, 95% CI 1.17-1.23). Offspring of infertile males (OR 1.19, 95% CI 1.13-1.26) and infertile females (OR 1.20, 95% CI 1.14-1.26) had an increased odds of autism compared to the reference group. In addition, offspring of infertile males (OR 1.48, 95% CI 1.28-1.7) and infertile females (OR 1.52, 95% CI 1.33-1.73) had higher odds of being diagnosed with an intellectual disability. Therefore, offspring of infertile men or women may have an increased risk of developing psychosis, autism, or intellectual disability.

  View details for DOI 10.1080/14647273.2020.1805799

  View details for PubMedID 32781859

• Risk of pre-term births and major birth defects resulting from paternal intake of COVID-19 medications prior to conception. Research square Rizzi, S. n., Wensink, M. J., Lindahl-Jacobsen, R. n., Tian, L. n., Lu, Y. n., Eisenberg, M. n. 2020

  Abstract

  With the ongoing COVID-19 pandemic, large numbers of people will receive one of the several medications proposed to treat COVID-19, including patients of reproductive age. Given that some medications have shown adverse effects on sperm quality, there might be a transgenerational concern. We aim at examining the association between drugs proposed to treat COVID-19 when taken by the father around conception and any pre-term birth or major birth defects in offspring in a nation-wide cohort study using Danish registry data. Offspring whose father filled at least one prescription of the following medications in the three months preceding conception were considered exposed: chloroquine, hydroxychloroquine, losartan, azithromycin, naproxen, dexamethasone and prednisone.For azithromycin and naproxen, large numbers of offspring were exposed (> 1800 offspring), and we found no association with adverse birth outcomes. For chloroquine, losartan and dexamethasone, exposure was intermediate (~ 900 offspring), and there was no statistically significant association with birth defects. For hydroxychloroquine and prednisone, exposure was limited (< 300 offspring). There is strong evidence that azithromycin and naproxen are safe with respect to pre-term birth and birth defects. With some caution, the other drugs investigated can be considered safe.

  View details for DOI 10.21203/rs.3.rs-59420/v1

  View details for PubMedID 32869015

  View details for PubMedCentralID PMC7457584

• Increased mortality among men diagnosed with impaired fertility: analysis of US claims data. Urology Giudice, F. D., Kasman, A. M., Li, S. n., Belladelli, F. n., Ferro, M. n., de Cobelli, O. n., De Berardinis, E. n., Gian, M. B., Eisenberg, M. L. 2020

  Abstract

  to determine whether male infertility or impaired spermatogenesis is associated with mortality.The Optum de-identified Clinformatics® Data Mart database was queried from 2003 through 2017. Infertile men were compared to subjects undergoing semen analysis (i.e. infertility testing). Infertile men with oligozoospermia or azoospermia were included. Mortality was determined by data linkage to the Social Security Administration Death Master File. Results were adjusted for age, smoking, obesity, year of evaluation and health care visits as well as for most prevalent comorbidities. We separately examined men with prevalent or incident cardiovascular disease (CVD) and cancer (Ca) diagnoses to determine associations with mortality.A total of 134,796 infertile men and 242,282 controls were followed for a mean of 3.6 and 3.1 years respectively. Overall, infertile men had a higher risk of death (Hazard Ratio [HR]= 1.42, 95%CI: 1.27-1.60) The diagnosis of azoospermia was associated with a significantly increased risk of death (HR= 2.01, 95%CI: 1.60 - 2.53) with a higher trend among men with oligospermia (HR: 1.17, 95%CI: 0.92-1.49) compared to controls. Sub-analysis was done excluding prevalent cardiovascular and malignant disease (alone and combined) showing similar hazard ratios.Male infertility is associated with a higher risk of mortality especially among azoospermic men. Prevalent disease (which is known to be higher among infertile men) did not explain the higher risk of death among infertile men. The implications for treatment and surveillance of infertile men require further study.

  View details for DOI 10.1016/j.urology.2020.07.087

  View details for PubMedID 33017614

• Ejaculatory Dysfunction in Patients Presenting to a Men's Health Clinic: A Retrospective Cohort Study. Sexual medicine Kasman, A. M., Bhambhvani, H. P., Eisenberg, M. L. 2020

  Abstract

  Prevalence and bother of ejaculatory dysfunction (EjD) has yet to be evaluated in a men's health referral population.To evaluate the prevalence and associated risk factors of EjD in men presenting to a men's health clinic.A retrospective review examined patients presenting to an outpatient men's health clinic who completed the Sexual Health Inventory for Men and the Male Sexual Health Questionnaire Ejaculatory Dysfunction (MSHQ-EjD) Short Form. Patient factors including demographics, comorbidities, and medication were examined. Descriptive statistics and multivariable logistic regression were used.The main outcomes of this study are Sexual Health Inventory for Men and MSHQ-EjD scores.A total of 63 (24%) of patients presenting to the urology clinic were characterized as having EjD based on questionnaire responses. The mean age for men with EjD was 53.8 years, while those without was 42.6 years (P < .001). Of men with EjD, 74.6% were at least moderately bothered (MSHQ-EjD ≥3). Men with EjD were more likely to have erectile dysfunction (77.8%) compared with those without (21%, P < .001) as well as a history of a pelvic cancer (20.6% vs 6%, P = .001). On multivariable regression, erectile dysfunction (odds ratio: 15.04, 95% confidence interval: 6.76-35.92, P < .0001) and alpha inhibitor prescription (odds ratio: 6.82, 95% confidence interval: 1.57-30.16, P = .01) were associated with a higher odds of EjD. ED was found to be a mediator of the relationship between EjD and age, as the age association was lost in the ED population on multivariable regression compared with the non-ED population where it remained significant.EjD is common among patients presenting to a men's health clinic and may present at varying ages, though it is more common in those aged 50 years or older; it is independent of age and race. EjD is associated with erectile dysfunction, pelvic cancer history, and use of alpha inhibitors, presenting a population that could be considered for screening. Kasman AM, Bhambhvani HP, Eisenberg ML. Ejaculatory Dysfunction in Patients Presenting to a Men's Health Clinic: A Retrospective Cohort Study. J Sex Med 2020;XX:XXX-XXX.

  View details for DOI 10.1016/j.esxm.2020.05.002

  View details for PubMedID 32553504

• A Survey Exploring the Relationship Between Cannabis Use Characteristics and Sexual Function in Men. Sexual medicine Bhambhvani, H. P., Kasman, A. M., Wilson-King, G. n., Eisenberg, M. L. 2020

  Abstract

  Cannabis is the most commonly used drug in the United States; however, the effects of cannabis use on male sexual function are poorly understood.To characterize the contemporary landscape of cannabis use and to assess the associations between male sexual function and the frequency of use, the primary method of consumption, or cannabis chemovar (tetrahydrocannabinol or cannabidiol) among current users.We surveyed adults who visited a single cannabis dispensary for baseline demographic information, medical history, cannabis use habits, and sexual function as assessed by the International Index of Erectile Function (IIEF). An IIEF-5 < 21 was considered erectile dysfunction.The main outcome measure of the study was male sexual function via the IIEF domain scores.A total of 325 men completed the survey with a mean age of 46.7 years. 71.1% of the men were Caucasian and 52.6% were married. 13 men (4%) were never users; 29 men (8.9%) used 1-2 times/week; 51 men (15.7%) used 3-5 times/week, and 232 men (71.4%) used 6+ times/week. The average IIEF-5 score was 22.3 with 19.4% of the men having erectile dysfunction. In univariate analysis, men using cannabis more frequently had a higher overall IIEF (65.36 vs 60.52, P = .001), erectile domain (27.32 vs 25.74, P = .03), orgasm domain (9.08 vs 8.12, P < .001), intercourse satisfaction domain (12.42 vs 11.31, P = .006), and overall satisfaction domain (8.11 vs 7.05, P = .002). In multivariable analysis, compared to men who used cannabis 0 times/week, those who used 6 times/week had an increased overall IIEF (69.08 vs 64.64, P-value adjusted = 0.02), intercourse satisfaction domain (P-value adjusted = 0.04), and overall satisfaction domain (P-value adjusted = 0.02). The primary method of consumption (eg, smoking, edibles, etc.) and cannabinoid composition (eg, cannabidiol vs tetrahydrocannabinol dominant) were not associated with sexual function.We report an association between the increased frequency of cannabis use and increased male sexual function. However, while the increased frequency of use was statistically significant with regard to the IIEF scores, the clinical significance of this is likely low, and selection bias may limit the generalizability of these findings. The method of consumption and cannabis chemovar were not associated with sexual function. Bhambhvani HP, Kasman AM, Wilson-King G, et al. A Survey Exploring the Relationship Between Cannabis Use Characteristics and Sexual Function in Men. J Sex Med 2020;XX:XXX-XXX.

  View details for DOI 10.1016/j.esxm.2020.06.002

  View details for PubMedID 32561331

• INCREASED RISK OF SEVERE MATERNAL MORBIDITY AMONG INFERTILE WOMEN: ANALYSIS OF US CLAIMS DATA. American journal of obstetrics and gynecology Murugappan, G. n., Li, S. n., Lathi, R. B., Baker, V. L., Luke, B. n., Eisenberg, M. L. 2020

  Abstract

  Severe maternal morbidity continues to be an issue of national and global concern and is increasing in incidence. The incidence of infertility is also on the rise, and infertile women experience a higher risk of incident chronic medical disease and cancer, suggesting that fertility may serve as a window to a woman's overall health.To investigate the risk of severe maternal morbidity by maternal fertility status.Retrospective cohort analysis using Optum's de-identifed Clinformatics® Data Mart Database between 2003-2015. Infertile women stratified by infertility diagnosis, testing or treatment were compared to fertile women seeking routine gynecologic care. In both groups, only women who underwent pregnancy and delivery of a singleton during the follow up period were included. Main outcomes were severe maternal morbidity indicators, defined by the CDC, and identified by ICD-10 and CPT codes within 6 weeks of each delivery. Results were adjusted for maternal age, race, education, nulliparity, race, smoking, obesity, delivery mode, preterm birth, number of prenatal visits, and year of delivery.19,658 women comprised the infertile group and 525,695 women comprised the fertile group. The overall incidence of any severe maternal morbidity indicator was 7.0% among women receiving fertility treatment, 6.4% among women receiving a fertility diagnosis, 5.5% among women receiving fertility testing and 4.3% among fertile women.. Overall, infertile women had a significantly higher risk of developing any severe maternal morbidity indicator (AOR 1.22, CI 1.14-1.31, p<0.01) as well as a significantly higher risk of disseminated intravascular coagulation (DIC) (AOR 1.48, CI 1.26 - 1.73, p<0.01), eclampsia (AOR 1.37, CI 1.05 - 1.79, p<0.01), heart failure during procedure or surgery (AOR 1.54, CI 1.21 - 1.97, p<0.01), internal injuries of the thorax, abdomen or pelvis (AOR 1.59, CI 1.12 - 2.26, p<0.01), intracranial injuries (AOR 1.77, CI 1.20- 2.61, p<0.01), pulmonary edema (AOR 2.18, CI 1.54 - 3.10, p<0.01), thrombotic embolism (AOR 1.58, CI 1.14 - 2.17, p<0.01), and blood transfusion (AOR 1.50, CI 1.30 - 1.72, p<0.01) compared to fertile women. Fertile women did not face a significantly higher risk of any maternal morbidity indicator compared to infertile women. In subgroup analysis by maternal race/ethnicity, the likelihood of severe morbidity was significantly higher among fertile Black women compared to fertile Caucasian women. There was no difference between infertile Black and Caucasian women after multivariable adjustment.Using an insurance claims database, we report that women diagnosed with infertility and women receiving fertility treatment experience a significantly higher risk of multiple indicators of severe maternal morbidity compared to fertile women. The increased risk of severe maternal morbidity noted among fertile Black women compared to fertile Caucasian women is attenuated among infertile Black women, who face similar risks as infertile Caucasian women.

  View details for DOI 10.1016/j.ajog.2020.02.027

  View details for PubMedID 32112734

• Defining critical factors in multi-country studies of assisted reproductive technologies (ART): data from the US and UK health systems. Journal of assisted reproduction and genetics Eisenberg, M. L., Luke, B. n., Cameron, K. n., Shaw, G. M., Pacey, A. A., Sutcliffe, A. G., Williams, C. n., Gardiner, J. n., Anderson, R. A., Baker, V. L. 2020

  Abstract

  As the worldwide use of assisted reproductive technologies (ART) continues to grow, there is a critical need to assess the safety of these treatment parameters and the potential adverse health effects of their use in adults and their offspring. While key elements remain similar across nations, geographic variations both in treatments and populations make generalizability challenging. We describe and compare the demographic factors between the USA and the UK related to ART use and discuss implications for research. The USA and the UK share some common elements of ART practice and in how data are collected regarding long-term outcomes. However, the monitoring of ART in these two countries each brings strengths that complement each other's limitations.

  View details for DOI 10.1007/s10815-020-01951-y

  View details for PubMedID 32995971

• A population-level analysis of nonsquamous penile cancer: The importance of histology. Urologic oncology Bhambhvani, H. P., Greenberg, D. R., Parham, M. J., Eisenberg, M. L. 2020

  Abstract

  Nonsquamous penile cancers comprise 5% of penile malignancies, though their clinicopathologic features and prognostic significance remain unknown. We used a national cancer registry to detail clinical characteristics and compare cancer-specific mortality (CSM) of nonsquamous cancers with squamous cell carcinoma (SCC).The Surveillance, Epidemiology, and End Results (SEER) database (1975-2016) was queried to identify adults with nonsquamous penile cancer and penile SCC. Multivariable Fine and Gray competing-risks regression, propensity score matching, and cumulative incidence plots were used.666 men with nonsquamous penile cancer and 5,894 men with penile SCC were identified. The most commonly represented nonsquamous histological subtypes were Kaposi sarcoma (n = 183, 27.5%), melanoma (n = 74, 11.1%), basal cell carcinoma (n = 65, 9.8%), and extramammary Paget disease (n = 42, 6.3%). Cumulative incidence plots revealed a 10-year CSM rate of 32.6% in the nonsquamous penile cancer group and 25.6% in the matched penile SCC group (P < 0.0001). Among Kaposi sarcoma patients and matched SCC patients, we found a 10-year CSM rate of 29.6% in the Kaposi sarcoma group and 15.3% in the penile SCC group (P = 0.002). Similarly, a comparison of penile melanoma patients with matched SCC patients revealed a 10-year CSM rate of 38.4% in the melanoma group and 16.6% in the SCC group (P = 0.002). There was no difference in CSM between patients with basal cell carcinoma and SCC. In a sensitivity analysis limiting year of diagnosis to 2000 and onward, we found no difference in CSM between the general nonsquamous cohort or the Kaposi sarcoma cohort and matched SCC patients, but contemporary melanoma patients maintained worse CSM with a 10-year rate of 38.4% vs. 15.8% in matched SCC patients (P = 0.045).The most common nonsquamous penile cancers are Kaposi sarcoma, melanoma, and basal cell carcinoma. Overall, CSM is higher in nonsquamous penile cancers as compared to stage-matched SCC. Outcomes are similar in modern patients, likely due to improved control of systemic HIV in patients with Kaposi sarcoma. However, men with penile melanoma continue to experience a higher rate of CSM.

  View details for DOI 10.1016/j.urolonc.2020.11.025

  View details for PubMedID 33257222

• Sudden PSA rise to ≥20 ng/ml and prostate cancer diagnosis in the United States: A population-based study. The Prostate Vilson, F. L., Li, S. n., Brooks, J. D., Eisenberg, M. L. 2020

  Abstract

  While prostate-specific antigen (PSA) screening protocols vary, many clinicians have anecdotes of screened men with low PSA levels that rise significantly and are associated with high-risk prostate cancer (PC). We sought to better understand the frequency of high-risk cases that appear suddenly in a screened population.We utilized data from a Commercial and Medicare advantage claims database to identify all US men ages 50 and above undergoing PSA screening who then had a sudden interval rise in PSA (e.g., PSA ≥ 20) and diagnosis of PC. We determined associations with age, race, screening intensity, and baseline PSA levels.In all, 526,120 men met entry criteria with an average age of 60.7 and follow-up of 5.6 years. As the baseline PSA increased, the rate of high-risk PC increased from 2/10,000 persons among men with the lowest baseline PSA (<1 ng/ml) to 14/10,000 person-years among men with a baseline PSA < 5 ng/ml. Moreover, as a man's age at baseline PSA increased, the rate of high-risk PC also increased. In contrast, the incidence of high-risk PC did not vary significantly by race/ethnicity. More screening PSAs and shorter intervals between PSA screenings were associated with a lower incidence of high-risk PC.The incidence of high-risk PC in a screened population is low (<0.1%). Our findings suggest that systematic screening cannot eliminate all PC deaths and provide an estimate for the risk of the rapid development of high-risk cancers that is comparable to that observed in active surveillance populations.

  View details for DOI 10.1002/pros.24075

  View details for PubMedID 32956488

• New insights to guide patient care: the bidirectional relationship between male infertility and male health. Fertility and sterility Kasman, A. M., Del Giudice, F. n., Eisenberg, M. L. 2020

  Abstract

  Male reproduction is a complex process, and numerous medical conditions have the potential to alter spermatogenesis. In addition, male factor infertility may be a biomarker for future health. In the present review, we discuss the current literature regarding the association between systemic diseases and fertility, which may impact clinical outcomes or semen parameters. A number of conditions that have systemic consequences were identified, including genetic (e.g., cystic fibrosis, DNA mismatch repair alterations), obesity, psychological stress, exogenous testosterone, and a variety of common medications. As such, the infertility evaluation may offer an opportunity for health counseling beyond the discussion of reproductive goals. Moreover, male infertility has been suggested as a marker of future health, given that poor semen parameters and a diagnosis of male infertility are associated with an increased risk of hypogonadism, cardiometabolic disease, cancer, and even mortality. Therefore, male fertility requires multidisciplinary expertise for evaluation, treatment, and counseling.

  View details for DOI 10.1016/j.fertnstert.2020.01.002

  View details for PubMedID 32089256

• Male Infertility and Somatic Health. The Urologic clinics of North America Murshidi, M. M., Choy, J. T., Eisenberg, M. L. 2020; 47 (2): 211–17

  Abstract

  Somatic health is associated with male infertility; potential links between infertility and health may arise from genetic, developmental, and lifestyle factors. Studies have explored possible connections between male infertility and oncologic, cardiovascular, metabolic, chronic, and autoimmune diseases. Male infertility also may be a predictor of hospitalization and mortality. Additional research is required to elucidate the mechanisms by which male infertility affects overall health.

  View details for DOI 10.1016/j.ucl.2019.12.008

  View details for PubMedID 32272993

• Association between preconception paternal health and pregnancy loss in the USA: an analysis of US claims data. Human reproduction (Oxford, England) Kasman, A. M., Zhang, C. A., Li, S. n., Lu, Y. n., Lathi, R. B., Stevenson, D. K., Shaw, G. M., Eisenberg, M. L. 2020

  Abstract

  Is preconception paternal health associated with pregnancy loss?Poor preconception paternal health is associated with a higher risk of pregnancy loss as confirmed in sensitivity analyses accounting for maternal age and health.Preconception paternal health can negatively impact perinatal outcomes.Retrospective cohort study of US insurance claims database from 2009 to 2016 covering 958 804 pregnancies.US insurance claims database including women, men and pregnancies within the USA between 2007 and 2016. Paternal preconception health status (e.g. metabolic syndrome diagnoses (MetS), Charlson comorbidity index (CCI) and individual chronic disease diagnoses) was examined in relation to pregnancy loss (e.g. ectopic pregnancy, miscarriage and stillbirth).In all, 958 804 pregnancies were analyzed. The average paternal age was 35.3 years (SD 5.3) and maternal age was 33.1 years (SD 4.4). Twenty-two percent of all pregnancies ended in a loss. After adjusting for maternal factors, the risk of pregnancy loss increased with increasing paternal comorbidity. For example, compared to men with no components of MetS, the risk of pregnancy loss increased for men with one (relative risk (RR) 1.10, 95% CI 1.09-1.12), two (RR 1.15, 95% CI 1.13-1.17) or three or more (RR 1.19, 95% CI 1.14-1.24) components. Specifically, less healthy men had a higher risk of siring a pregnancy ending in spontaneous abortion, stillbirth and ectopic pregnancies. Similar patterns remained with other measures of paternal health (e.g. CCI, chronic diseases, etc.). When stratifying by maternal age as well as maternal health, a similar pattern of increasing pregnancy loss risk for men with 1, 2 or 3+ MetS was observed. A statistically significant but weak association between timing of pregnancy loss and paternal health was found.Retrospective study design covering only employer insured individuals may limit generalizability.Optimization of a father's health may improve pregnancy outcomes.National Institutes of Health National Center for Advancing Translational Science Clinical and Translational Science Award (UL1 TR001085). M.L.E. is an advisor for Sandstone Diagnostics, Dadi, Hannah and Underdog. No other competing interests were declared.N/A.

  View details for DOI 10.1093/humrep/deaa332

  View details for PubMedID 33336240

• Evaluation, treatment, and insurance coverage for couples with male factor infertility in the US: A cross-sectional analysis of survey data. Urology Glazer, C. H., Anderson-Bialis, J. n., Anderson-Bialis, D. n., Eisenberg, M. L. 2020

  Abstract

  To characterize the evaluation, treatment, and insurance coverage among couples with male factor infertility in the US.A cohort of 969 couples undergoing fertility treatment with a diagnosis of male factor infertility were identified from an online survey. The proportion of men that were seen/not seen by a male were compared. Insurance coverage related to male factor was also assessed.Overall, 98.0% of the men reported at least one abnormal semen parameter. Of these, 72.0% were referred to a male fertility specialist with the majority being referred by the gynecologist of their female partner. As part of the male evaluation, 72.2% had blood hormone testing. Of the 248 men who were not recommended to see a male fertility specialist, 96.0% had an abnormal semen analysis including 7.6% who had azoospermia. Referral to a male fertility specialist was largely driven by severity of male factor infertility rather than socioeconomic status. Insurance coverage related to male factor infertility was poor with low coverage for sperm extractions (72.9% reported 0-25% coverage) and sperm freezing (83.7 reported 0-25% coverage).Although this cohort includes couples with abnormal semen parameters, 28% of the men were not evaluated by a male fertility specialist. In addition, insurance coverage for services related to male factor were low. These findings may be of concern as insufficient evaluation and coverage of the infertile man could lead to missed opportunities for identifying reversible causes of infertility/medical comorbidities and places an unfair burden on the female partner.

  View details for DOI 10.1016/j.urology.2019.12.035

  View details for PubMedID 32057791

• Interplay between male testosterone levels and the risk for subsequent invasive respiratory assistance among COVID-19 patients at hospital admission. Endocrine Salciccia, S. n., Del Giudice, F. n., Gentile, V. n., Mastroianni, C. M., Pasculli, P. n., Di Lascio, G. n., Ciardi, M. R., Sperduti, I. n., Maggi, M. n., De Berardinis, E. n., Eisenberg, M. L., Sciarra, A. n. 2020

  View details for DOI 10.1007/s12020-020-02515-x

  View details for PubMedID 33030665

• Male-to-Female Ratios, Race/Ethnicity, and Spontaneous Preterm Birth among 11 Million California Infants. American journal of perinatology Shaw, G. M., Mayo, J. A., Eisenberg, M. L., Catalano, R., Stevenson, D. K. 2019

  Abstract

  OBJECTIVE: An observed disparity in population-scale data are a larger number of males among preterm births (PTBs). We investigated spontaneous PTB risk among women of various race/ethnic groups in combination with infants' sex.STUDY DESIGN: This observational study was conducted in>10 million California births (1991-2012) using birth certificates linked with maternal and infant hospital discharge data.RESULTS: Male-to-female ratios among term (37-42 weeks) infants exhibited the narrow ratio range 1.02 to 1.06 across race/ethnic groups. Such ratios among spontaneous PTBs were generally larger for all race/ethnic groups except non-Hispanic blacks. For blacks, ratios tended to be lower and similar to their term birth counterpart, 1.03. Hazard ratios adjusted for maternal age and education for non-Hispanic blacks were 0.99 (95% confidence interval [CI] 0.90-1.09), 1.01 (95% CI 0.95-1.08), 0.98 (95% CI 0.94-1.03), and 1.03 (95% CI 1.01-1.05), respectively, for gestational week groupings of 20 to 23, 24 to 27, 28 to 321, and 32 to 36. Hazard ratios for non-Hispanic whites for the same groupings were 1.08 (95% CI 0.98-1.18), 1.13 (95% CI 1.07-1.19), 1.21 (95% CI 1.17-1.25), and 1.18 (95% CI 1.17-1.19).CONCLUSION: Why male-to-female ratios are similar across gestational ages in blacks but substantially higher in other race/ethnic groups is theoretically considered relative to inflammation, stress, and other influences.

  View details for DOI 10.1055/s-0039-3400449

  View details for PubMedID 31756757

• A systematic review and meta-analysis of clinical trials implementing aromatase inhibitors to treat male infertility. Asian journal of andrology Giudice, F. D., Busetto, G. M., De Berardinis, E., Sperduti, I., Ferro, M., Maggi, M., Gross, M. S., Sciarra, A., Eisenberg, M. L. 2019

  Abstract

  Aromatase activity has commonly been associated with male infertility characterized by testicular dysfunction with low serum testosterone and/or testosterone to estradiol ratio. In this subset of patients, and particularly in those with hypogonadism, elevated levels of circulating estradiol may establish a negative feedback on the hypothalamic-pituitary-testicular axis by suppressing follicle-stimulating hormone (FSH) and luteinizing hormone (LH) production and impaired spermatogenesis. Hormonal manipulation via different agents such as selective estrogen modulators or aromatase inhibitors to increase endogenous testosterone production and improve spermatogenesis in the setting of infertility is an off-label option for treatment. We carried out a systematic review and meta-analysis of the literature of the past 30 years in order to evaluate the benefits of the use of aromatase inhibitors in the medical management of infertile/hypoandrogenic males. Overall, eight original articles were included and critically evaluated. Either steroidal (Testolactone) or nonsteroidal (Anastrozole and Letrozole) aromatase inhibitors were found to statistically improve all the evaluated hormonal and seminal outcomes with a safe tolerability profile. While the evidence is promising, future prospective randomized placebo-controlled multicenter trials are necessary to better define the efficacy of these medications.

  View details for DOI 10.4103/aja.aja_101_19

  View details for PubMedID 31621654

• Increased Risk of Cancer in Men With Peyronie's Disease: A Cohort Study Using a Large United States Insurance Claims Database. Sexual medicine Pastuszak, A. W., Thirumavalavan, N., Kohn, T. P., Lipshultz, L. I., Eisenberg, M. L. 2019

  Abstract

  BACKGROUND: Men with Peyronie's disease (PD) may have an increased prevalence of certain comorbidities, including malignancy. We sought to examine the clinical relationship between PD and subsequent diagnosis of malignancy.METHODS: Using data from the IBM Health MarketScan claims database from 2007 to 2013, we compared men with PD to a control group of men without PD or erectile dysfunction matched for age and duration of follow-up. We compared incidence of 18 categories of malignancy between both groups using a Cox regression model.RESULTS: In total, 48,423 men with PD and 484,230 controls were identified. The mean age within both cohorts was 50 ± 9.4 years old, and mean follow-up time was approximately 4.4 ± 2.1 years. After being controlled for age, year of evaluation, obesity, smoking, number of outpatient visits, number of urologist visits, and duration of follow-up, men with PD had an increased risk of all cancers (hazard ratio= 1.10, 95% CI= 1.06-1.14), stomach cancer (1.43, 1.06-1.14), testis cancer (1.39, 1.05-1.84), and melanoma (1.19, 1.02-1.38) when compared with controls. The strengths in using the MarketScan database are the anonymous nature of the data, accessibility, and the power provided by the large number of patient visits recorded. Limitations include a lack of detail in certain facets of patient clinical data, and the lack of long-term follow-up to assess the impact of time on other potentially associated conditions.CONCLUSIONS: This manuscript is the first to our knowledge to describe a relationship between PD and cancer. Men with PD may be at increased risk for certain malignancies compared with age-matched controls. Further investigation is needed to explore the clinical implications of these findings. Pastuszak AW, Thirumavalavan N, Kohn TP, etal. Increased Cancer Risk in Men With Peyronie's Disease: A Cohort Study Using a Large US Insurance Claims Database. Sex Med 2019;XX:XXX-XXX.

  View details for DOI 10.1016/j.esxm.2019.08.007

  View details for PubMedID 31530474

• IN VITRO FERTILIZATION AND GESTATIONAL HYPERTENSION/PREECLAMPSIA RISK: EFFECT OF DIAGNOSIS VERSUS TREATMENT PARAMETERS. Luke, B., Brown, M. B., Eisenberg, M. L., Callan, C. M., Botting, B., Pacey, A., Sutcliffe, A. G., Baker, V. L. ELSEVIER SCIENCE INC. 2019: E299

  View details for DOI 10.1016/j.fertnstert.2019.07.874

  View details for Web of Science ID 000487821302245

• MALE MULTIVITAMIN USE AND SEMEN QUALITY. Willis, S. K., Hatch, E. E., Sommer, G., Eisenberg, M. L., Wang, T., Wise, L. A. ELSEVIER SCIENCE INC. 2019: E370

  View details for DOI 10.1016/j.fertnstert.2019.07.1059

  View details for Web of Science ID 000487821303183

• THIRD GRADE ACADEMIC ACHIEVEMENT AMONG CHILDREN CONCEIVED WITH IVF: A POPULATION-BASED STUDY IN TEXAS. Watkins, S., Brown, M. B., Luke, B., Ethen, M. K., Canfield, M. A., Wantman, E., Forestieri, N. E., Yazdy, M. M., Fisher, S. C., Browne, M. L., Nichols, H. B., Baker, V. L., Eisenberg, M. L., Oehninger, S. C., Doody, K. J. ELSEVIER SCIENCE INC. 2019: E6

  View details for DOI 10.1016/j.fertnstert.2019.07.152

  View details for Web of Science ID 000487821300014

• Genital Pain and Numbness and Female Sexual Dysfunction in Adult Bicyclists. The journal of sexual medicine Greenberg, D. R., Khandwala, Y. S., Breyer, B. N., Minkow, R., Eisenberg, M. L. 2019

  Abstract

  INTRODUCTION: Bicycle seat pressure on the perineum may impair arousal and clitoral erection, likely contributing to genital pain and numbness experienced by female cyclists.AIM: We aimed to identify the association between genital pain and numbness experienced by female cyclists and female sexual dysfunction (FSD).METHODS: Female cyclists were recruited to complete an online survey using the Female Sexual Function Index (FSFI), a validated questionnaire to assess FSD. Cyclist demographics, experience, preferred riding style, use of ergonomic cycle modifications, and genital discomfort while riding were also queried. Multivariate logistic regression analysis was used to evaluate risk factors of FSD.MAIN OUTCOME MEASURES: The main outcome was FSFI score, which is used to diagnose FSD when the FSFI score is <26.55.RESULTS: Of the survey respondents, 178 (53.1%) completed the survey and FSFI questionnaire. Mean age was 48.1 years (±0.8 standard error [SE]), and the average riding experience was 17.1 years (±0.9 SE). Overall, 53.9% of female cyclists had FSD, 58.1% reported genital numbness, and 69.1% reported genital pain. After adjusting for age, body mass index, relationship status, smoking history, comorbidities, and average time spent cycling per week, females who reported experiencing genital numbness half the time or more were more likely to have FSD (adjusted odds ratio [aOR], 6.0; 95% CI, 1.5-23.6; P= .01), especially if localized to the clitoris (aOR, 2.5; 95% CI, 1.2-5.5; P= .02). Females that reported genital pain half the time or more while cycling also were more likely to have FSD (aOR, 3.6; 95% CI, 1.2-11.1; P= .02). Cyclists experiencing genital pain within the first hour of their ride were more likely to have FSD (aOR, 12.6; 95% CI, 2.5-63.1; P= .002). Frequency and duration of cycling were not associated with FSD. Analysis of FSFI domains found that the frequency of numbness was correlated with decreased arousal, orgasm, and satisfaction during intercourse, whereas the frequency of pain significantly reduced arousal, orgasm, and genital lubrication.CLINICAL IMPLICATIONS: Female cyclists that experience numbness and/or pain have higher odds of reporting FSD.STRENGTHS & LIMITATIONS: Our study includes a validated questionnaire to assess FSD and queries specific characteristics and symptoms of genital pain and genital numbness; however, the study is limited by its cross-sectional survey design.CONCLUSION: This study highlights the need for cyclists to address genital pain and numbness experienced while cycling, and future studies are required to determine if alleviating these symptoms can reduce the impact of cycling on female sexual function. Greenberg GR, Khandwala YS, Breyer BN, etal. Genital Pain and Numbness and Female Sexual Dysfunction in Adult Bicyclists. J Sex Med 2019; XX:XXX-XXX.

  View details for DOI 10.1016/j.jsxm.2019.06.017

  View details for PubMedID 31402178

• The association of bicycle-related genital numbness and Sexual Health Inventory for Men (SHIM) score: results from a large, multinational, cross-sectional study BJU INTERNATIONAL Baradaran, N., Awad, M., Gaither, T. W., Fergus, K. B., Ndoye, M., Cedars, B. E., Balakrishnan, A. S., Eisenberg, M. L., Sanford, T., Breyer, B. N. 2019; 124 (2): 336–41

  View details for DOI 10.1111/bju.14396

  View details for Web of Science ID 000481428300025

• Demographics, Usage Patterns, and Safety of Male Users of Clomiphene in the United States. The world journal of men's health Guo, D. P., Zlatev, D. V., Li, S., Baker, L. C., Eisenberg, M. L. 2019

  Abstract

  PURPOSE: The aim of this study was to characterize the demographics, usage patterns and complication rates of clomiphene use in male patients.MATERIALS AND METHODS: We retrospectively analyzed male patients from ages 20 to 55 years old who were prescribed clomiphene citrate from 2001 to 2014 using the Truven Health MarketScan, a US claims database. We collected data regarding associated medical diagnoses, diagnostic testing, duration of use, and reported side effects including thrombotic events, vision problems, gynecomastia, mental disorders, liver disease, nausea, or skin problems.RESULTS: In total, 12,318 men took clomiphene and represented the primary study cohort, with a mean age of 37.8 years. The percentage of men prescribed clomiphene increased over the study period, as did the average age of clomiphene users. Associated diagnoses included male infertility (52.0%), testicular hypofunction (13.5%), erectile dysfunction (2.4%), and low libido (0.4%). Associated testing included semen analysis (43.7%), testosterone (23.5%), luteinizing hormone (19.3%), and follicle-stimulating hormone (21.1%) levels. The median time of clomiphene use was 3.6 months, with 63% of men stopping within 6 months. No increased risk of reported clomiphene side effects were apparent in men taking the medication.CONCLUSIONS: There is a rising prevalence of clomiphene usage without associated adverse side effects in the US. The variability in associated diagnoses, diagnostic testing, and duration of use suggest a need for greater awareness of the proper evaluation and treatment of the men who are prescribed clomiphene.

  View details for DOI 10.5534/wjmh.190028

  View details for PubMedID 31385473

• Increased risk of incident chronic medical conditions in infertile women: analysis of US claims data Murugappan, G., Li, S., Lathi, R. B., Baker, V. L., Eisenberg, M. L. MOSBY-ELSEVIER. 2019

  View details for DOI 10.1016/j.ajog.2019.01.214

  View details for Web of Science ID 000467043800012

• Risk of cancer in infertile women: analysis of US claims data HUMAN REPRODUCTION Murugappan, G., Li, S., Lathi, R. B., Baker, V. L., Eisenberg, M. L. 2019; 34 (5): 894–902

  View details for DOI 10.1093/humrep/dez018

  View details for Web of Science ID 000484054400014

• The Impact of Clostridium Histolyticum Collagenase on the Prevalence and Management of Peyronie's Disease in the United States WORLD JOURNAL OF MENS HEALTH Sun, A. J., Li, S., Eisenberg, M. L. 2019; 37 (2): 234–39

  View details for DOI 10.5534/wjmh.180073

  View details for Web of Science ID 000465475300013

• The risk of birth defects is not associated with semen parameters or mode of conception in offspring of men visiting a reproductive health clinic HUMAN REPRODUCTION Pastuszak, A. W., Herati, A. S., Eisenberg, M. L., Cengiz, C., Langlois, P. H., Kohn, T. P., Lamb, D. J., Lipshultz, L. I. 2019; 34 (4): 733–39

  View details for DOI 10.1093/humrep/dez005

  View details for Web of Science ID 000465098600015

• PATERNAL MEDICATION USE AND COMORBIDITY IN THE UNITED STATES: A REVIEW OF OVER 1 MILLION LIVE BIRTHS Sun, A., Li, S., Zhang, C., Eisenberg, M. LIPPINCOTT WILLIAMS & WILKINS. 2019: E556–E557

  View details for Web of Science ID 000473345201557

• PRELIMINARY APPLICATION OF CONVOLUTIONAL NEURAL NETWORK TO IMPROVE THE EFFICIENCY OF FINDING RARE SPERMATOZOA IN MICRO-TESE SAMPLES. Badamjav, O., Reddy, V., Meyer, D., Eisenberg, M., Behr, B. ELSEVIER SCIENCE INC. 2019: E28

  View details for DOI 10.1016/j.fertnstert.2019.02.076

  View details for Web of Science ID 000463487700040

• Risk of cancer in infertile women: analysis of us claims data. Human reproduction (Oxford, England) Murugappan, G., Li, S., Lathi, R. B., Baker, V. L., Eisenberg, M. L. 2019

  Abstract

  STUDY QUESTION: Is female infertility associated with higher risk of cancer?SUMMARY ANSWER: Although absolute risks are low, infertility is associated with higher risk of cancer compared to a group of non-infertile women.WHAT IS KNOWN ALREADY: Infertile women are at higher risk of hormone-sensitive cancers. Information on risk of non-gynecologic cancers is rare and conflicting, and the effect of pregnancy on these risk associations is known for only a minority of cancer types.STUDY DESIGN, SIZE, DURATION: Retrospective cohort analysis between 2003 and 2016 using an insurance claims database.PARTICIPANTS/MATERIALS, SETTING, METHODS: In all, 64 345 infertile women identified by infertility diagnosis, testing or treatment were compared to 3 128 345 non-infertile patients seeking routine gynecologic care. Women with prior diagnosis of cancer or within 6 months of index event were excluded. Main outcomes were development of any malignancy and individual cancers as identified by ICD-9/ICD-10 codes. Results were adjusted for age at index date, index year, nulliparity, race, smoking, obesity, number of visits per year and highest level of education.MAIN RESULTS AND THE ROLE OF CHANCE: Infertile women had an overall higher risk of developing cancer compared to non-infertile women (2.0 versus 1.7%, adjusted hazard ratio (aHR) = 1.18; CI: 1.12-1.24). In addition, the risk of uterine cancer (0.10 versus 0.06%, aHR = 1.78; CI: 1.39-2.28), ovarian cancer (0.14 versus 0.09%, aHR 1.64; CI: 1.33-2.01), lung cancer (0.21 versus 0.21%, aHR = 1.38; CI: 1.01-1.88), thyroid cancer (0.21 versus 0.16%, aHR = 1.29; CI: 1.09-1.53), leukemia (0.10 versus 0.06%, aHR = 1.55; CI: 1.21-1.98) and liver and gallbladder cancer (0.05 versus 0.03%, aHR = 1.59; CI: 1.11-2.30) were higher in infertile women compared to non-infertile women. In a subgroup analysis of women in each cohort who became pregnant and had a delivery during enrollment, the risk of uterine and ovarian cancer were similar between infertile and non-infertile women. In a subgroup analysis excluding women with PCOS and endometriosis from both cohorts, the risk of uterine cancer was similar between infertile and non-infertile women.LIMITATIONS, REASONS FOR CAUTION: Absolute risk of cancer was low, average follow up for each individual was limited, and average age at index date was limited. Insurance databases have known limitations.WIDER IMPLICATIONS OF THE FINDINGS: Using claims-based data, we report that infertile women may have a higher risk of certain cancers in the years after infertility evaluation; continued follow up should be considered after reproductive goals are achieved.STUDY FUNDING/COMPETING INTEREST(S): None.

  View details for PubMedID 30863841

• The Quality of Systematic Reviews and Meta-Analyses in Erectile Dysfunction Treatment and Management Published in the Sexual Medicine Literature JOURNAL OF SEXUAL MEDICINE Greenberg, D. R., Richardson, M. T., Tijerina, J. D., Bass, M. B., Eisenberg, M. L. 2019; 16 (3): 394–401

  View details for DOI 10.1016/j.jsxm.2019.01.009

  View details for Web of Science ID 000464913100006

• Parental age and stillbirth: a population-based cohort of nearly 10 million California deliveries from 1991 to 2011 ANNALS OF EPIDEMIOLOGY Mayo, J. A., Lu, Y., Stevenson, D. K., Shaw, G. M., Eisenberg, M. L. 2019; 31: 32–37

  View details for DOI 10.1016/j.annepidem.2018.12.001

  View details for Web of Science ID 000462806400007

• The Quality of Systematic Reviews and Meta-Analyses in Erectile Dysfunction Treatment and Management Published in the Sexual Medicine Literature. The journal of sexual medicine Greenberg, D. R., Richardson, M. T., Tijerina, J. D., Bass, M. B., Eisenberg, M. L. 2019

  Abstract

  INTRODUCTION: Erectile dysfunction (ED) is a common medical condition that requires high-quality evidence to guide clinical practice; however, systematic reviews (SRs) and meta-analyses (MAs) often vary in quality, raising concerns regarding the validity of their results.AIM: To perform an objective analysis of SRs and MAs in ED treatment and management and to report on the quality of published literature.METHODS: A comprehensive search in PubMed/MEDLINE and EMBASE of 12 high-impact urology journals was used to identify relevant publications. 2 authors independently performed searches, screened citations for eligibility, extracted data for analysis, and graded methodologic quality using A Measurement Tool to Assess Systematic Reviews (AMSTAR) criteria.MAIN OUTCOME MEASURES: The main outcome was AMSTAR score, which is a validated tool to evaluate the quality of SRs and MAs.RESULTS: 31 publications met inclusion criteria and were included in the analysis. The mean AMSTAR score (± SD) among all publications was 6.5 (±2.2) of 11, reflecting "fair to good" quality. 74.2% of systematic reviews and meta-analyses focused on pharmaceutical therapy for ED, with 51.6% studying the effect of phosphodiesterase-5 inhibitors. Only 1 SR/MA studied intracavernosal injection therapy and vacuum erection devices. No publications studied intraurethral injection therapy or implantable penile prostheses. Although not statistically significant, there has been a trend of increasing quality of SRs/MAs over time (P= .072).CLINICAL IMPLICATION: The methodologic quality of SRs/MAs should be assessed to ensure high-quality evidence for clinical practice guidelines in ED treatment and management.STRENGTH & LIMITATION: The data showed that methodologic quality of SRs/MAs in the treatment and management of ED is increasing over time. 12 high-impact urology journals were included in our search, which may introduce selection bias in our results.CONCLUSIONS: This review highlights a need for increased effort to study second- and third-line treatments for patients who fail oral therapy. Greenberg DR, Richardson MT, Tijerina JD, etal. The Quality of Systematic Reviews and Meta-Analyses in Erectile Dysfunction Treatment and Management Published in the Sexual Medicine Literature. J Sex Med 2019;XX:XXX-XXX.

  View details for PubMedID 30773501

• The risk of birth defects is not associated with semen parameters or mode of conception in offspring of men visiting a reproductive health clinic. Human reproduction (Oxford, England) Pastuszak, A. W., Herati, A. S., Eisenberg, M. L., Cengiz, C., Langlois, P. H., Kohn, T. P., Lamb, D. J., Lipshultz, L. I. 2019

  Abstract

  STUDY QUESTION: What is the relationship between semen parameters and birth defect (BD) rates in offspring of men evaluated for infertility?SUMMARY ANSWER: Among men undergoing infertility evaluation, there is no significant relationship between semen parameters and defect rates in live or still births, even when considering mode of conception.WHAT IS KNOWN ALREADY: Approximately 15% of couples have fertility difficulties, with up to a 50% male factor contribution. An increased risk of BDs exists in couples using ART, particularly IVF and ICSI, but it is unknown if this related to the ART procedures or an underlying male factor.STUDY DESIGN, SIZE, DURATION: To determine if the severity of male factor infertilty, as assessed via sperm quality and mode of conception, is associated with BD rates, we performed a retrospective cohort study. Fathers with semen analysis data in the Baylor College of Medicine Semen Database (BCMSD) were linked with their offspring using Texas Birth Defects Registry (TBDFR) data between 1999 and 2009. In this 10-year period, a total of 1382 men were identified in linkage between the BCMSD and TBDFR. A total of 109 infants with and 2115 infants without BDs were identified.PARTICIPANTS/MATERIALS, SETTING, METHODS: To determine the association between BDs and semen parameters, we used hierarchical linear modeling to determine odds ratios between BD rates, semen parameters, and mode of conception before and after adjustment for paternal, maternal and birth covariates. Semen parameters were stratified based on thresholds defined by the WHO fifth edition laboratory manual for the examination and processing of human semen.MAIN RESULTS AND THE ROLE OF CHANCE: In total 4.9% of 2224 infants were identified with a BD. No statistically significant association was observed between BD rates and semen parameters, before or after adjustment for covariates. The association between sperm concentration and BDs demonstrated an odds ratio (OR) of 1.07 (95% confidence interval: 0.63-1.83); motility: OR 0.91 (0.52-2.22); and total motile count: OR 1.21 (0.70-2.08). Likewise, mode of conception, including infertility treatment and ART, did not affect BD rates (P > 0.05).LIMITATIONS, REASONS FOR CAUTION: BDs recorded in the TBDFR only include live born infants or still births after 20 weeks, our study did not evaluate the effect of impaired semen parameters on developmental defects prior to 20 weeks of gestation. With 109 BDs, our statistical analysis was powered to detect moderate differences associated with particular semen parameters. Additionally, data about mode of conception was not available for 1053 of 2224 births.WIDER IMPLICATIONS OF THE FINDINGS: BD rates are not associated with semen quality or mode of conception. The current study suggests that the severity of male factor infertility does not impact the rate of congenital anomalies. This information is important when counseling couples concerned about the relationship between impaired semen quality and BDs.STUDY FUNDING/COMPETING INTEREST(S): Supported in part by the NIH Men's Reproductive Health Research (MRHR) K12 HD073917 (D.J.L.), the Multidisciplinary K12 Urologic Research (KURe) Career Development Program (D.J.L.), P01HD36289 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development, NIH (D.J.L.), and by U01DD000494 from the Centers for Disease Control and Prevention and the Title V Block Grant to the Texas Department of State Health Services. A.W.P. is a National Institutes of Health K08 Scholar supported by a Mentored Career Development Award (K08DK115835-01) from the from the National Institute of Diabetes and Digestive and Kidney Diseases. This work is also supported in part through a Urology Care Foundation Rising Stars in Urology Award (to A.W.P.) None of the authors has a conflict of interest.TRIAL REGISTRATION NUMBER: Not applicable.

  View details for PubMedID 30753581

• Increased Risk of Incident Chronic Medical Conditions in Infertile Women: Analysis of Us Claims Data. American journal of obstetrics and gynecology Murugapppan, G., Li, S., Lathi, R. B., Baker, V. L., Eisenberg, M. L. 2019

  Abstract

  BACKGROUND: The risk of common chronic medical conditions among infertile women is not known.OBJECTIVE: To study the association between female infertility and risk of incident chronic disease.STUDY DESIGN: Retrospective cohort analysis using the Optum de-identified Clinformatics© Datamart from 2003-2016. 64,345 infertile women were identified by infertility diagnosis, testing or treatment and compared to 3,128,345 non-infertile patients seeking routine gynecologic care. Women with prior diagnosis of the relevant chronic disease or cancer or with either diagnosis within six months of index event were excluded. Main outcome was diagnosis of incident chronic disease as identified by ICD-9/ICD-10 codes. Results were adjusted for age, index year, nulliparity, race, smoking, obesity, number of visits per year and highest level of education.RESULTS: Infertile patients were more likely to develop diabetes (aHR 1.44, CI 1.38-1.49), renal disease (aHR 1.22, CI 1.12-1.32), liver disease (aHR 1.25, CI 1.20-1.30), cerebrovascular disease (aHR 1.26, CI 1.15-1.38), ischemic heart disease (aHR 1.16, CI 1.09-1.24), other heart disease (aHR 1.16, CI 1.12-1.20), and drug abuse (aHR 1.24, CI 1.15-1.33) compared to non-infertile patients. Infertile patients were significantly less likely to develop alcohol abuse (aHR 0.86, CI 0.79-0.95) compared to non-infertile patients. Risk associations were similar after excluding women with PCOS and POI. In subgroup analyses of women who underwent pregnancy and childbirth during enrollment, several previously noted risk associations were attenuated compared to the overall cohort.CONCLUSION: While the absolute risk of chronic disease is low, infertility is associated with increased risk of incident chronic disease compared to a group of non-infertile women.

  View details for PubMedID 30710512

• In Vitro Fertilization and Risk for Hypertensive Disorders of Pregnancy: Associations with Treatment Parameters. American journal of obstetrics and gynecology Luke, B. n., Brown, M. B., Eisenberg, M. L., Callan, C. n., Botting, B. J., Pacey, A. n., Sutcliffe, A. G., Baker, V. L. 2019

  Abstract

  Although in vitro fertilization (IVF) has been associated with an increased risk for hypertensive disorders of pregnancy, the association of risk with IVF treatment parameters is unclear.To evaluate risk for hypertensive disorders of pregnancy by maternal fertility status, and IVF treatment parameters.Women in 8 States who underwent IVF resulting in a live birth during 2004 through 2013 were linked to their infant's birth certificates. A 10:1 sample of births from non-IVF deliveries were selected for comparison. Those with an indication of infertility treatment on the birth certificate were categorized as subfertile and omitted for the study population; all others were categorized as fertile. The IVF pregnancies were additionally categorized by oocyte source (autologous vs donor) and embryo state (fresh vs thawed). Both the fertile and IVF births were limited to singletons only, and the IVF pregnancies were limited to those using partner sperm. Hypertensive disorders of pregnancy (including gestational hypertension and preeclampsia) were identified from the birth certificate, modeled using logistic regression, and reported as adjusted odds ratios (AOR) and 95% confidence intervals. For analyses of IVF pregnancies from autologous oocytes-fresh embryos, the reference group was fertile women (subgroup analysis 1). For analyses within the IVF group, the reference group was autologous oocytes- fresh embryos (subgroup analysis 2).The study population included 1,465,893 pregnancies (1,382,311 births to fertile women and 83,582 births to IVF-treated women). Compared to fertile women, IVF women with autologous-fresh cycles did not have an increased risk for hypertensive disorders of pregnancy [AOR 1.04, 95% CI 0.99, 1.08]. Among IVF births (subgroup analysis 2), the risk for hypertensive disorders of pregnancy was increased for autologous-thawed, 1.30 [1.20, 1.40]; donor-fresh, 1.92 [1.71, 2.15]; donor-thawed, 1.70 [1.47, 1.96]. Excluding women with pregestational diabetes or chronic hypertension, and adjusting for body mass index and infertility diagnoses did not substantially change the results. When stratified by <34 weeks (early onset hypertensive disorders of pregnancy) versus ≥34 weeks (late onset hypertensive disorders of pregnancy), only the donor-fresh group had an increased risk for early-onset, but the risks for all other oocyte source-embryo state groups compared to autologous-fresh were increased for late-onset.The risk for hypertensive disorders of pregnancy is increased for IVF-treated women and in pregnancies conceived via frozen embryo transfer (with both autologous or donor oocyte) and fresh donor oocyte embryo transfer. No increase in risk was seen with fresh autologous IVF cycles. Excluding women with pregestational diabetes or chronic hypertension, and adjusting for body mass index and infertility diagnoses did not substantially change the results.

  View details for DOI 10.1016/j.ajog.2019.10.003

  View details for PubMedID 31629726

• Racial and Sociodemographic Differences of Semen Parameters Among US Men Undergoing a Semen Analysis UROLOGY Glazer, C., Li, S., Zhang, C., Giwercman, A., Bonde, J., Eisenberg, M. L. 2019; 123: 126–32

  View details for DOI 10.1016/j.urology.2018.09.029

  View details for Web of Science ID 000454535600041

• At-home sperm testing for epidemiologic studies: Evaluation of the Trak male fertility testing system in an internet-based preconception cohort. Paediatric and perinatal epidemiology Sommer, G. J., Wang, T. R., Epperson, J. G., Hatch, E. E., Wesselink, A. K., Rothman, K. J., Fredriksen, L. L., Schaff, U. Y., Behr, B. n., Eisenberg, M. L., Wise, L. A. 2019

  Abstract

  Semen quality assessment in population-based epidemiologic studies presents logistical and financial challenges due to reliance on centralised laboratory semen analysis. The Trak Male Fertility Testing System is an FDA-cleared and validated at-home test for sperm concentration and semen volume, with a research use only sperm motility test. Here we evaluate the Trak System's overall utility among men participating in Pregnancy Study Online (PRESTO), a web-based study of North American couples planning pregnancy.US male participants aged ≥21 years with ≤6 months of pregnancy attempt time at study enrolment were invited to participate in the semen testing substudy after completing their baseline questionnaire. Consenting participants received a Trak Engine (battery-powered centrifuge) and two test kits. Participants shared their test results via smartphone images uploaded to online questionnaires. Data were then linked with covariate data from the baseline questionnaire.Of the 688 men invited to participate, 373 (54%) provided consent and 271 (73%) completed at least one semen test result. The distributions of semen volume, sperm concentration, motile sperm concentration, total sperm count, and total motile sperm count were similar to 2010 World Health Organization (WHO) semen parameter data of men in the general population. The overall usability score for the Trak System was 1.4 on a 5-point Likert scale (1 = Very Easy, 5 = Difficult), and 92% of participants believed they performed the test correctly and received an accurate result. Lastly, men with higher motile sperm count were more likely to report feeling "at ease" or "excited" following testing, while men with low motile sperm count were more likely to report feeling "concerned" or "frustrated." Overall, 91% of men reported they would like to test again.The Trak System provides a simple and potentially cost-effective means of measuring important semen parameters and may be useful in population-based epidemiologic fertility studies.

  View details for DOI 10.1111/ppe.12612

  View details for PubMedID 31838751

• Male factor infertility and risk of death: a nationwide record-linkage study. Human reproduction (Oxford, England) Glazer, C. H., Eisenberg, M. L., Tøttenborg, S. S., Giwercman, A. n., Flachs, E. M., Bräuner, E. V., Vassard, D. n., Pinborg, A. n., Schmidt, L. n., Bonde, J. P. 2019

  Abstract

  What is the risk of death among men with oligospermia, unspecified male factor and azoospermia in the years following fertility treatment?No significantly elevated risk was observed among men with oligospermia and unspecified male factor, while an increased risk was found among men with azoospermia.Previous studies have shown associations between male factor infertility and risk of death, but these studies have relied on internal reference groups and the risk of death according to type of male infertility is not well characterized.In this prospective record-linkage cohort study, we identified men who had undergone medically assisted reproduction (MAR) between 1994 and 2015. Data was linked to the Danish causes of death register and sociodemographic registers through personal identification numbers assigned to all Danish citizens at birth.Men that had undergone MAR in Denmark (MAR Cohort; n = 64 563) were identified from the Danish IVF register, which includes data on whether infertility was due to male factor. For each man in the MAR cohort, five age-matched men who became fathers without fertility treatment were selected from the general population (non-MAR fathers; n = 322 108). Men that could not adequately be tracked in the Danish CPR register (n = 1259) and those that were censored prior to study entry (n = 993) were excluded, leaving a final population of 384 419 men. Risk of death was calculated by Cox regression analysis with age as an underlying timeline and adjustments for educational attainment, civil status and year of study entry. The risk of death was compared among men with and without male factor infertility identified from the IVF register (internal comparisons) as well as to the non-MAR fathers (external comparison).The risk of death between the MAR cohort (all men, regardless of infertility) and the non-MAR fathers was comparable [hazard ratio (HR), 1.07; 95% CI, 0.98-1.15]. When the MAR cohort was limited to infertile men, these men were at increased risk of death [HR, 1.27; 95% CI, 1.12-1.44]. However, when stratified by type of male factor infertility, men with azoospermia had the highest risk of death, which persisted when in both the internal [HR, 2.30; 95% CI, 1.54-3.41] and external comparison [HR, 3.32; 95% CI, 2.02-5.40]. No significantly elevated risk of death was observed among men with oligospermia [HR, 1.14; 95% CI, 0.87-1.50] and unspecified male factor [HR, 1.10; 95% CI, 0.75-1.61] compared with the non-MAR fathers. The same trends were observed for the internal comparison.Duration of the follow-up was limited and there is limited generalizability to infertile men who do not seek fertility treatment.Using national health registers, we found an increased risk of death among azoospermic men while no increased risk was found among men with other types of infertility. For the azoospermic men, further insight into causal pathways is needed to identify options for monitoring and prevention.This study is part of the ReproUnion collaborative study, co-financed by the European Union, Interreg V ÖKS. C.G.'s research stay at Stanford was funded by grants from the University of Copenhagen, Kong Christian den Tiendes Fond, Torben og Alice Frimodt Fond and Julie Von Müllen Fond. M.E. is an advisor for Sandstone and Dadi. All other authors declare no conflict of interests.Not relevant.

  View details for DOI 10.1093/humrep/dez189

  View details for PubMedID 31725880

• Microsurgical varicocelectomy: novel applications to optimize patient outcomes. Fertility and sterility Lipshultz, L. I., Ramasamy, R. n., Sandlow, J. I., Hotaling, J. n., Eisenberg, M. n., Niederberger, C. n., Brannigan, R. E. 2019; 112 (4): 632–39

  View details for DOI 10.1016/j.fertnstert.2019.08.057

  View details for PubMedID 31561866

• Male infertility and future cardiometabolic health: Does the association vary by sociodemographic factors? Urology Kasman, A. M., Li, S. n., Luke, B. n., Sutcliffe, A. G., Pacey, A. A., Eisenberg, M. L. 2019

  Abstract

  To determine whether the association between male infertility and incident cardiometabolic disease is modified by socioeconomics, race, or geographic region.Retrospective review of data from insurance claims from Optum's de-identified Clinformatics® Data Mart Database. Subjects were men, 18-50 years old, with an associated diagnosis of infertility in the United States between 2003 and 2016. Analytic sample were men captured by the Optum's de-identified Clinformatics® Data Mart Database with an associated diagnosis of infertility. Men were classified as either infertile, or not, based on diagnosis or procedural codes. Cardiometabolic health outcomes were then assessed using CPT codes for diabetes, hypertension, hyperlipidemia, and heart disease. Confounding factors were controlled for such as race, education, socioecomonic status, and region. The main outcomes were development of diabetes, hypertension, hyperlipidemia, and heart disease.A total of 76,343 males were diagnosed with male factor infertility, 60,072 males who underwent fertility testing, and 183,742 males that underwent vasectomy (control population). For all men, infertile men had a higher risk of incident hypertension, diabetes, hyperlipidemia, and heart disease when compared to those undergoing vasectomy. Identical associations were found across all education, income, racial, and geographic strata.Our study suggests that men with infertility have a higher risk of cardiometabolic disease in the years following a fertility evaluation regardless of race, region, or socioeconomic status.

  View details for DOI 10.1016/j.urology.2019.06.041

  View details for PubMedID 31377255

• Parental age and stillbirth: a population-based cohort of nearly 10 million California deliveries from 1991 to 2011. Annals of epidemiology Mayo, J. A., Lu, Y., Stevenson, D. K., Shaw, G. M., Eisenberg, M. L. 2018

  Abstract

  PURPOSE: Parental age at delivery in the United States has been rising. Advanced maternal and paternal ages have been associated with adverse pregnancy outcomes including stillbirth. However, these relationships come from studies that often do not present results for both mother and father concurrently. The purpose of this study was to estimate the risk of stillbirth for maternal and paternal age in the same cohort of deliveries.METHODS: This is a population-based cohort study of all live birth and stillbirth deliveries in California from 1991 to 2011. The individual associations between maternal and paternal ages and stillbirth were estimated with hazard ratios from Cox proportional hazard models. Age was modeled continuously with restricted cubic splines to account for nonlinear relationships. Mean parental age was used as the referent group.RESULTS: J-shaped associations between maternal and paternal ages were observed in crude models where older mothers and fathers had the highest hazard ratios for stillbirth. In maternal models, after adjusting for maternal and paternal covariates, young maternal age no longer showed increased hazard ratio for stillbirth, whereas the association with older mothers remained. In adjusted paternal models, the relationship between young paternal age and stillbirth was unchanged while the hazard ratio for older fathers was slightly smaller.CONCLUSIONS: After adjusting for both parents' age, education, race/ethnicity, along with parity, older mothers and fathers were independently associated with elevated hazard ratios for stillbirth.

  View details for PubMedID 30642694

• Male factor infertility and risk of multiple sclerosis: A register-based cohort study MULTIPLE SCLEROSIS JOURNAL Glazer, C., Tottenborg, S., Giwercman, A., Brauner, E., Eisenberg, M. L., Vassard, D., Magyari, M., Pinborg, A., Schmidt, L., Bonde, J. 2018; 24 (14): 1835–42

  View details for DOI 10.1177/1352458517734069

  View details for Web of Science ID 000468193600008

• The Impact of Clostridium Histolyticum Collagenase on the Prevalence and Management of Peyronie's Disease in the United States. The world journal of men's health Sun, A. J., Li, S., Eisenberg, M. L. 2018

  Abstract

  PURPOSE: We evaluated the impact of collagenase clostridium histolyticum (CCH) on rates of diagnosis, treatment, and corporal rupture in Peyronie's disease (PD). We examined the impact of CCH on cost of PD treatment.MATERIALS AND METHODS: We extracted data on PD diagnosis (ICD-9 607.95 and ICD-10 N48.6), corporal rupture (ICD-9 959.13 and ICD-10 S39.840A), CCH use (J0775), penile injections (CPT 54200), and corporal rupture repair from 2008 to 2016 in men over 40 years old using the Clinformatics Data Mart Database (3.7 to 4.9 million males). We analyzed for prevalence of PD, rates of PD treatments, cost associated with treatment, and rates of corporal rupture and repair by year.RESULTS: The prevalence of PD was 0.29% in 2013 and did not increase after CCH entered the market in 2014. An average of 2.52% of men with PD received treatment before CCH, compared with 3.75% after (p<0.0001). Penile injection rates increased (1.34% vs. 2.61%, p<0.0001), while rates of surgical treatments decreased between these periods. There was no change in rate of corporal rupture in men with PD before (0.024%) and after (0.024%) CCH. Overall, only 20.0% of corporal ruptures were repaired. After CCH entered practice, a significant increase in cost occurred (p=0.013).CONCLUSIONS: The prevalence of men with PD did not change after CCH. However, more men with PD received treatment due to an increase in penile injections. The cost of treating PD increased after CCH became available. The overall prevalence of corporal rupture did not change after CCH entered the market.

  View details for PubMedID 30588781

• Association of paternal age with perinatal outcomes between 2007 and 2016 in the United States: population based cohort study BMJ-BRITISH MEDICAL JOURNAL Khandwala, Y. S., Baker, V. L., Shaw, G. M., Stevenson, D. K., Lu, Y., Eisenberg, M. L. 2018; 363

  View details for DOI 10.1136/bmj.k4372

  View details for Web of Science ID 000449564200004

• Racial and Sociodemographic Differences of Semen Parameters among US Men Undergoing a Semen Analysis. Urology Glazer, C. H., Li, S., Zhang, C. A., Giwercman, A., Bonde, J. P., Eisenberg, M. L. 2018

  Abstract

  OBJECTIVE: To characterize sociodemographic differences in semen parameters among US undergoing a semen analysis.MATERIALS AND METHODS: Men that provided a semen sample were identified from insurance claims between 2007-2016. Differences in semen parameters were characterized according to age, race, education and region. Mean semen parameters and proportions of men with suboptimal parameters was compared and risks of oligospermia and azoospermia was assessed by logistic regression.RESULTS: Of the 7,263 men included, most men were White (55.1%), Hispanic (20.2%) or Asian (10.2%). Asians had the highest mean semen concentrations (69.2 * 106/mL) whereas Blacks had the lowest (51.3 * 106/mL). Men from the Midwest were more likely to have oligospermia (OR 1.62; 95% CI 1.34-1.94) whereas men from the West were less likely (OR 0.82, 95% CI 0.82-0.94) when compared with men from South. An association between education and sperm concentration was observed. For example, men with a high school diploma or less were more likely to have oligospermia (OR 1.09; 95% CI: 0.95-1.26) whereas men with at least a bachelor degree were less likely (OR 0.87; 95%CI 0. 0.76-1.0) when compared with men with less than a bachelor degree.CONCLUSION: As we observed differences in semen quality based on sociodemographic factors, these findings may have clinical implications as relying on a single reference value when guiding infertile couples may be problematic given these variations. Further work is warranted to understand the etiology of such differences and determine if different normative reference values may apply for different populations.

  View details for PubMedID 30300659

• Male infertility as a window to health FERTILITY AND STERILITY Choy, J. T., Eisenberg, M. L. 2018; 110 (5): 810-814

  View details for DOI 10.1016/j.fertnstert.2018.08.015

  View details for Web of Science ID 000446885700006

• The Relationship between Neonatal Circumcision, Urinary Tract Infection, and Health WORLD JOURNAL OF MENS HEALTH Eisenberg, M. L., Galusha, D., Kennedy, W. A., Cullen, M. R. 2018; 36 (3): 176–82

  View details for DOI 10.5534/wjmh.180006

  View details for Web of Science ID 000443344400002

• Trends in Prevalence, Management and Cost of Scrotal Pain in the United States between 2007 and 2014 UROLOGY PRACTICE Khandwala, Y. S., Zhang, C. A., Eisenberg, M. L. 2018; 5 (4): 272–77

  View details for DOI 10.1016/j.urpr.2017.06.002

  View details for Web of Science ID 000437135000007

• Risk of Melanoma With Phosphodiesterase Type 5 Inhibitor Use Among Patients With Erectile Dysfunction, Pulmonary Hypertension, and Lower Urinary Tract Symptoms JOURNAL OF SEXUAL MEDICINE Shkolyar, E., Li, S., Tang, J., Eisenberg, M. L. 2018; 15 (7): 982–89

  View details for DOI 10.1016/j.jsxm.2018.05.002

  View details for Web of Science ID 000438163300011

• Trends in Prevalence, Management and Cost of Scrotal Pain in the United States between 2007 and 2014. Urology practice Khandwala, Y. S., Zhang, C. A., Eisenberg, M. L. 2018; 5 (4): 272-278

  Abstract

  We characterize trends in the prevalence, diagnosis and management of scrotal pain in men in the United States and the financial impact on the health care system.We analyzed subjects from the Truven Health MarketScan® claims database from 2007 to 2014. Clinical encounters and diagnoses of scrotal pain were identified using ICD-9 and CPT® codes. Trends in office visits, emergency department encounters, radiological evaluation, scrotal surgeries and pharmaceutical prescription were identified, as well as net financial cost.A total of 1,083,350 men with scrotal pain were analyzed during 8 years, amounting to 4,356,581 patient-years of followup. Overall prevalence increased from 0.8% to 1% between 2007 and 2014. Increasing numbers of varicoceles, hydroceles, spermatoceles and testicular torsion were also noted in these men. The percentage of men with scrotal pain evaluated by ultrasonography increased from 39% to 45%, while the percentage of those with scrotal pain presenting to the emergency department increased from 8% to 10%. Scrotal surgery rates did not change substantially (decreasing from 1.7% to 1.6%). However, prescription of opiates and nonsteroidal anti-inflammatory drugs increased from 14% to 42% and from 13% to 46% for all clinic visits, respectively. Yearly cost attributable to scrotal pain was $55,923,986 and median annual cost per patient increased between 2007 and 2014.Incidence of scrotal pain and associated use of prescription medication have increased in the last decade, contributing to a high economic burden. A greater understanding of the evaluation and management of scrotal pain is necessary.

  View details for DOI 10.1016/j.urpr.2017.06.002

  View details for PubMedID 37312309

• Use of secondary contraception following vasectomy: insights from the Pregnancy Risk Assessment Monitoring System, 2007-2011. Translational andrology and urology Patel, D. P., Williams, L., Warner, L., O'Neil, M. E., Aston, K., Carrell, D. T., Grigorescu, V., Jamieson, D. J., Gannon, J. R., Eisenberg, M. L., Walsh, T. J., Hotaling, J. M. 2018; 7 (Suppl 3): S264-S270

  Abstract

  To assess postpartum use of secondary contraception with vasectomy within Pregnancy Risk Assessment Monitoring System (PRAMS).Secondary contraception and type of method used were assessed among married women reporting partner vasectomy 4 months after a recent live birth in female residents of 15 US states and New York City who participated in the 2007-2011 PRAMS.Between 2007 and 2011, 1,004 married women who had a recent live birth participating in PRAMS reported they and their partners relied on vasectomy for postpartum contraception. Among these couples, 57.8% reported not using additional forms of contraception postpartum. Of those reporting additional contraception, condoms were most commonly used (50.0%), followed by oral contraceptive pills (26.5%), and withdrawal (9.5%). Multivariable modeling showed that use of secondary contraception was twice as high among women reporting a second birth versus women reporting a fourth or higher birth [adjusted prevalence odds ratio (POR) =2.0 (1.1-3.2)]. No other sociodemographic characteristics (maternal age, maternal race, parental education, household income) were significantly associated with use of secondary contraception with vasectomy.Most couples within PRAMS reporting partner vasectomy as postpartum contraception did not use secondary contraception in the months immediately after vasectomy, and, of those who did, most relied on less effective methods. Clinicians need to better understand reasons for limited use of secondary contraception with vasectomy to improve counseling strategies for reducing unintended pregnancy.

  View details for DOI 10.21037/tau.2018.04.15

  View details for PubMedID 30159231

  View details for PubMedCentralID PMC6087841

• Use of secondary contraception following vasectomy: insights from the Pregnancy Risk Assessment Monitoring System, 2007-2011 TRANSLATIONAL ANDROLOGY AND UROLOGY Patel, D. P., Williams, L., Warner, L., O'Neil, M. E., Aston, K., Carrell, D. T., Grigorescu, V., Jamieson, D. J., Gannon, J. R., Eisenberg, M. L., Walsh, T. J., Hotaling, J. M. 2018; 7: S264–S270

  View details for DOI 10.21037/tau.2018.04.15

  View details for Web of Science ID 000441614400002

• Risk of Melanoma With Phosphodiesterase Type 5 Inhibitor Use Among Patients With Erectile Dysfunction, Pulmonary Hypertension, and Lower Urinary Tract Symptoms. The journal of sexual medicine Shkolyar, E., Li, S., Tang, J., Eisenberg, M. L. 2018

  Abstract

  BACKGROUND: Phosphodiesterase type 5 inhibitors (PDE5is), a treatment for erectile dysfunction, pulmonary hypertension (pHTN), and lower urinary tract symptoms (LUTS), have been implicated in melanoma development.AIM: We sought to determine the association between PDE5i use and melanoma development among patients with erectile dysfunction, pHTN, and LUTS.METHODS: This was a retrospective cohort study of subjects contained within the Truven Health MarketScan claims database, which provides information on insurance claims in the United States for privately insured individuals, from 2007-2015. Individuals taking PDE5i were identified through pharmacy claims. A comparison group of men diagnosed with conditions for which PDE5i are prescribed was assembled.OUTCOMES: Cox proportional hazard models were used to estimate the hazard ratio (HR) (95% CI) of incident melanoma, basal cell carcinoma, and squamous cell carcinoma.RESULTS: Of 610,881 subjects prescribed PDE5i, 636 developed melanoma (0.10%). The control group had 8,711 diagnoses of melanoma. There was an association between increased PDE5i tablet use and melanoma (HR1.05, 95% CI 1.05-1.09). This association was also present between PDE5i use and basal cell carcinoma (HR 1.04, 95% CI 1.02-1.07) and squamous cell carcinoma (HR 1.04, 95% CI 1.01-1.07). In patients with pHTN and LUTS prescribed PDE5is, there was no relationship between exposure and melanoma incidence (HR 0.74, 95% CI 0.48-1.13; and HR 1.03, 95% CI 0.97-1.10, respectively).CLINICAL IMPLICATIONS: There is little evidence for a clinically relevant association between PDE5i use and melanoma incidence.STRENGTHS & LIMITATIONS: Our current work represents the largest study to date evaluating the relationship between PDE5i use and melanoma risk, and the first to examine all current indications of PDE5i use among men and women. Limitations include a patient population limited to commercially insured individuals, unknown patient medication compliance, and lack of information on patient skin type, lifestyle, and sun-exposure habits.CONCLUSION: There is a slight association between higher-volume PDE5i use and development of melanoma, basal cell carcinoma, and squamous cell carcinoma. This association among all skin cancers implies that confounding may account for the observed association. Shkolyar E, Li S, Tang J, etal. Risk of Melanoma With Phosphodiesterase Type 5 Inhibitor Use Among Patients With Erectile Dysfunction, Pulmonary Hypertension, and Lower Urinary Tract Symptoms. J Sex Med 2018;XX:XXX-XXX.

  View details for PubMedID 29884444

• Increased Risk of Incident Disease in Men with Peyronie's Disease: Analysis of US Claims Data JOURNAL OF SEXUAL MEDICINE Pastuszak, A. W., Rodriguez, K. M., Solomon, Z. J., Kohn, T. P., Lipshultz, L., Eisenberg, M. L. 2018; 15 (6): 894–901

  Abstract

  The subsequent health risks associated with Peyronie's disease (PD) are unknown.This cohort study assesses the risk of developing auto-immune conditions and common chronic health conditions after a diagnosis of PD. We hypothesize that an increase in auto-immune disease will be evident in men with PD, as has been suggested in smaller studies.We determined the longitudinal incidence of 13 auto-immune diseases and 25 common chronic conditions in a cohort from the Truven Health Analytics (Ann Arbor, Michigan, USA) database from 2007-2013. The cohort included men with 1 of 3 exposures in 2007: (1) men with PD, (2) men with erectile dysfunction (ED) but not PD, and (3) men without PD or ED, matched on age and follow-up duration.To assess incidence, we utilized a Cox regression model adjusting for age, smoking, obesity, health care visits per year, urology visits per year, and years of follow-up.We included 8,728 men with PD; 204,147 men with ED; and 87,280 controls. Men with PD had an increased risk of developing benign prostatic hyperplasia (hazard ratio [HR] 1.21, 95% CI 1.16-1.27), prostatitis (HR 1.21, 95% CI 1.12-1.31), and lower urinary tract symptoms (HR 1.10, 95% CI 1.05-1.16) when compared to both men with ED and age-matched controls without ED or PD even when controlling for the number of urology visits per year. Compared to controls, men with PD also had an increased risk of developing keloids. No significant risk for any auto-immune disease was observed.Clinicians should have heightened awareness for these relevant co-morbidities when treating men with PD.Utilizing a claims database provides one of the largest cohorts of men with PD ever published but claims databases lack some individual patient data such as risk factors and demographic information relevant to PD, including: penile injury, history of urologic procedures, and other lifestyle factors.Men with PD had a higher risk of benign prostatic hyperplasia, lower urinary tract symptoms, prostatitis, and keloids after a diagnosis of PD, but no increased risk of auto-immune conditions. These findings suggest a common etiology for these conditions that may manifest itself in diseases at different times in men's life cycle. Pastuszak AW, Rodriguez KM, Solomon ZJ, et al. Increased Risk of Incident Disease in Men with Peyronie's Disease: Analysis of U.S. Claims Data. J Sex Med 2018;15:894-901.

  View details for PubMedID 29803352

• The association of bicycle-related genital numbness and Sexual Health Inventory for Men (SHIM) score: results from a large, multinational, cross-sectional study. BJU international Baradaran, N., Awad, M., Gaither, T. W., Fergus, K. B., Ndoye, M., Cedars, B. E., Balakrishnan, A. S., Eisenberg, M. L., Sanford, T., Breyer, B. N. 2018

  Abstract

  OBJECTIVE: To assess the association of genital numbness and erectile dysfunction in male cyclists.SUBJECTS AND METHODS: Cyclists were recruited through Facebook advertisements and outreach to sporting clubs. This is a secondary analysis of a larger epidemiological population-based study that examined sexual and urinary wellness in athletes. We queried cycling habits and erectile function using Sexual Health Inventory for Men (SHIM).RESULTS: A total of 2774 male cyclists were included in the analysis. Amongst cyclists, there was a statistically significant increase in the trend of genital numbness presence with more years of cycling (P = 0.002), more frequent weekly cycling (P < 0.001), and longer cycling distance at each ride (P < 0.001). Less frequent use of padded shorts (odds ratio [OR] 0.14, P < 0.001) and lower handlebar (OR 0.49, P < 0.001) were associated with numbness, but body mass index (BMI) (OR 1.1, P = 0.33) and age (OR 1.2, P = 0.15) were not. In a multivariate logistic regression model, after adjusting for age, BMI, and lifetime miles (calculated by average daily cycling mileage * cycling days/week * cycling years.), there were no statistically significant differences in mean SHIM score between cyclists with and cyclists without numbness (20.3 vs 20.2, P = 0.83). However, interestingly, the subset of cyclists who reported numbness in the buttock reported statistically significantly worse SHIM scores (20.3 vs 18.4, P < 0.001). This association was not present in cyclists who reported numbness in the scrotum, penis, or perineum and remained significant after adjusting for overall biking intensity.CONCLUSION: Cyclists report genital numbness in proportion with biking intensity but numbness is not associated with worse sexual function in this cohort.

  View details for PubMedID 29790643

• Association between use of marijuana and time to pregnancy in men and women: findings from the National Survey of Family Growth FERTILITY AND STERILITY Kasman, A. M., Thoma, M. E., McLain, A. C., Eisenberg, M. L. 2018; 109 (5): 866–71

  Abstract

  To determine if regular use of marijuana has an impact on time to pregnancy.Retrospective review of cross-sectional survey data from male and female respondents aged 15-44 years who participated in the 2002, 2006-2010, and 2011-2015 National Survey of Family Growth.Not applicable.The National Survey of Family Growth is a nationally representative population-based sample derived from stratified multistage area probability sampling of 121 geographic areas in the U.S. Our analytic sample was participants who were actively trying to conceive.Exposure status was based on the respondents' answers regarding their marijuana use in the preceding 12 months.The main outcome was estimated time to pregnancy, which was hypothesized before analysis to be delayed by regular marijuana use.A total of 758 male and 1,076 female participants responded that they were actively trying to conceive. Overall, 16.5% of men reported using any marijuana while attempting to conceive, versus 11.5% of women. The time ratio to pregnancy for never smokers versus daily users of marijuana in men was 1.08 (95% confidence interval 0.79-1.47) and in women 0.92 (0.43-1.95), demonstrating no statistically significant impact of marijuana use on time to pregnancy.Our study suggests that neither marijuana use nor frequency of marijuana use was associated with time to pregnancy for men and women.

  View details for PubMedID 29555335

• Registries and Databases in Sexual Medicine: Utility? JOURNAL OF SEXUAL MEDICINE Sun, A. J., Eisenberg, M. L. 2018; 15 (4): 426–27

  View details for PubMedID 29609911

• PEYRONIE'S DISEASE: THE IMPACT OF COLLAGENASE CLOSTRIDIUM HISTOLYTICUM ON DIAGNOSIS, TREATMENT, AND COST Sun, A., Li, S., Eisenberg, M. ELSEVIER SCIENCE INC. 2018: E883

  View details for Web of Science ID 000429166602512

• Cycling and Female Sexual and Urinary Function: Results From a Large, Multinational, Cross-Sectional Study JOURNAL OF SEXUAL MEDICINE Gaither, T. W., Awad, M. A., Murphy, G. P., Metzler, I., Sanford, T., Eisenberg, M. L., Sutcliffe, S., Osterberg, E., Breyer, B. N. 2018; 15 (4): 510–18

  Abstract

  Bicycle riding has become an increasingly popular mode of transportation and exercise, especially among women, and previous studies have demonstrated a relationship between cycling and sexual dysfunction, albeit using non-validated questionnaires.We aimed to explore the relationship between cycling and sexual and urinary dysfunction.Cyclists were recruited to complete a survey through Facebook advertisements and outreach to sporting clubs across 5 English-speaking countries. Swimmers and runners were recruited as a comparison group.Participants were queried using validated questionnaires, including the Female Sexual Function Index, the American Urological Association Symptom Index, and non-validated questions about history of urinary tract infections (UTIs), genital numbness, and genital saddle sores (all self-reported).3,118 (53.3%) Women completed the survey, comprising 1,053 (34%) non-cyclists, 1,656 (53%) low-intensity cyclists, and 409 (13%) high-intensity cyclists. After adjusting for age, body mass index, hypertension, diabetes, ischemic heart disease, tobacco use, race, marital status, urinary symptoms, and sexual activity, high-intensity cyclists had lower odds of self-reported sexual dysfunction compared to non-cyclists (adjusted odds ratio [aOR] 0.7, P = .02). There were no statistically significant differences in urinary symptoms across groups. Compared to non-cyclists, both low- and high-intensity cyclists had higher odds of reporting a previous UTI (aOR 1.4, P < .001, and aOR 1.4, P = .009, respectively), genital numbness (odds ratio [OR] 6.5, P < .001, and OR 9.1, P < .001, respectively), and saddle sores (OR 6.3, P < .001, and OR 22.7, P < .001, respectively).Women cyclists were more likely to report other genitourinary conditions, including UTIs, genital numbness, and saddle sores.This is the largest study comparing cyclists to other athletes with respect to sexual and urinary function. The study is limited by its cross-sectional design and sampling methods. We found that women cyclists were no more likely to report sexual dysfunction or urinary symptoms than swimmers or runners. Gaither TW, Awad MA, Murphy GP, et al. Cycling and Female Sexual and Urinary Function: Results From a Large, Multinational, Cross-Sectional Study. J Sex Med 2018;15:510-518.

  View details for PubMedID 29548713

• The Relationship between Neonatal Circumcision, Urinary Tract Infection, and Health. The world journal of men's health Eisenberg, M. L., Galusha, D., Kennedy, W. A., Cullen, M. R. 2018

  Abstract

  The risk-benefit profile of neonatal circumcision is not clear. Most studies have focused on urinary tract infections but other health sequelae have not been evaluated. While evidence supports benefits of circumcision, a lack of randomized trials has been cited as a weakness. National guidelines provide mixed recommendations regarding neonatal circumcision. We review the weight of evidence and utilize current statistical methodology on observational data to examine the risks and benefits of neonatal circumcision.

  View details for PubMedID 29623700

• A MAGNETIC LEVITATION PLATFORM FOR THE ISOLATION OF MATURE SPERM FROM TESE/TESA SAMPLES Durmus, G., Gupta, R., Badamjav, O., Reddy, V., Eisenberg, M. L., Behr, B., Demirci, U. ELSEVIER SCIENCE INC. 2018: E26–E27

  View details for Web of Science ID 000427891800035

• Cycling, and Male Sexual and Urinary Function: Results from a Large, Multinational, Cross-Sectional Study. The Journal of urology Awad, M. A., Gaither, T. W., Murphy, G. P., Chumnarnsongkhroh, T., Metzler, I., Sanford, T., Sutcliffe, S., Eisenberg, M. L., Carroll, P. R., Osterberg, E. C., Breyer, B. N. 2018; 199 (3): 798-804

  Abstract

  We explored the relation of cycling to urinary and sexual function in a large multinational sample of men.Cyclists were recruited to complete a survey through Facebook® advertisements and outreach to sporting clubs. Swimmers and runners were recruited as a comparison group. Cyclists were categorized into low and high intensity cyclists. Participants were queried using validated questionnaires, including SHIM (Sexual Health Inventory for Men), I-PSS (International Prostate Symptom Score) and NIH-CPSI (National Institutes of Health Chronic Prostatitis Symptom Index), in addition to questions about urinary tract infections, urethral stricture, genital numbness and saddle sores.Of 5,488 complete survey responses 3,932 (72%) were included in our analysis. On multivariate analysis swimmers/runners had a lower mean SHIM score than low and high intensity cyclists (19.5 vs 19.9 and 20.7, p = 0.02 and <0.001, respectively). No significant differences were found in I-PSS or NIH-CPSI scores, or urinary tract infection history. Cyclists had statistically higher odds of urethral stricture compared to swimmers/runners (OR 2.5, p = 0.042). Standing more than 20% of the time while cycling significantly reduced the odds of genital numbness (OR 0.4, p = 0.006). Adjusting the handlebar higher or even with the saddle had lower odds of genital numbness and saddle sores (OR 0.8, p = 0.005 and 0.6, p <0.001, respectively).Cyclists had no worse sexual or urinary functions than swimmers or runners but cyclists were more prone to urethral stricture. Increased time standing while cycling and a higher handlebar height were associated with lower odds of genital sores and numbness.

  View details for DOI 10.1016/j.juro.2017.10.017

  View details for PubMedID 29031767

• Cycling, and Male Sexual and Urinary Function: Results from a Large, Multinational, Cross-Sectional Study JOURNAL OF UROLOGY Awad, M. A., Gaither, T. W., Murphy, G. P., Chumnarnsongkhroh, T., Metzler, I., Sanford, T., Sutcliffe, S., Eisenberg, M. L., Carroll, P. R., Osterberg, E., Breyer, B. N. 2018; 199 (3): 798–803

  View details for DOI 10.1016/j.juro.2017.10.017

  View details for Web of Science ID 000424884600103

• Male infertility: a biomarker of individual and familial cancer risk FERTILITY AND STERILITY Hanson, B. M., Eisenberg, M. L., Hotaling, J. M. 2018; 109 (1): 6–19

  Abstract

  Associations between male infertility and cancer are gaining clinical attention. Relationships between infertility and cancer have traditionally been studied in women, but recent work has focused on the male component of reproduction. Infertile men are at an elevated risk to develop various malignancies later in life, primarily genitourinary malignancies such as testicular and prostate cancer. Rates of testicular and high-grade prostate cancer in infertile men appear to be at least double the risk in the general population. The link between infertility and malignancy highlights the importance of thorough evaluation and long-term follow up-beyond a simple semen analysis. A detailed urologic evaluation, possibly including scrotal ultrasound, may be beneficial to screen infertile men for testicular cancer. Publications have also demonstrated that male infertility can be a biomarker for cancer risk in first- and second-degree relatives. Testicular cancer risk in first-degree relatives of infertile men is 52% higher than the risk in relatives of fertile control men, and male infertility has been associated with a two- to threefold elevation in risk of childhood cancer in the siblings of infertile men. Links between infertility and malignancy are multifactorial, and exact mechanistic explanations are still not fully understood. Although more studies are needed to assess levels of risk and create screening recommendations in this population, understanding the relationship between male infertility and malignancy is crucial to provide comprehensive counseling for infertile men and their families.

  View details for PubMedID 29307404

• Association Between Marijuana Use and Sexual Frequency in the United States: A Population-Based Study JOURNAL OF SEXUAL MEDICINE Sun, A. J., Eisenberg, M. L. 2017; 14 (11): 1342–47

  Abstract

  Marijuana use is increasingly prevalent in the United States. Effects of marijuana use on sexual function are unclear, with contradictory reports of enhancement and detriment existing.To elucidate whether a relation between marijuana use and sexual frequency exists using a nationally representative sample of reproductive-age men and women.We analyzed data from cycle 6 (2002), cycle 7 (2006-2010), and continuous survey (2011-2015) administrations of the National Survey of Family Growth, a nationally representative cross-sectional survey. We used a multivariable model, controlling for demographic, socioeconomic, and anthropographic characteristics, to evaluate whether a relationship between marijuana use and sexual frequency exists.Sexual frequency within the 4 weeks preceding survey administration related to marijuana use and frequency in the year preceding survey administration.The results of 28,176 women (average age = 29.9 years) and 22,943 men (average age = 29.5) were analyzed. More than 60% of men and women were Caucasian, and 76.1% of men and 80.4% of women reported at least a high school education. After adjustment, female monthly (incidence rate ratio [IRR] = 1.34, 95% CI = 1.07-1.68, P = .012), weekly (IRR = 1.36, 95% CI = 1.15-1.60, P < .001), and daily (IRR = 1.16, 95% CI = 1.01-1.32, P = .035) marijuana users had significantly higher sexual frequency compared with never users. Male weekly (IRR = 1.22, 95% CI = 1.06-1.41, P = .006) and daily (IRR = 1.36, 95% CI = 1.21-1.53, P < .001) users had significantly higher sexual frequency compared with never users. An overall trend for men (IRR = 1.08, 95% CI = 1.05-1.11, P < .001) and women (IRR = 1.07, 95% CI = 1.04-1.10, P < .001) was identified showing that higher marijuana use was associated with increased coital frequency.Marijuana use is independently associated with increased sexual frequency and does not appear to impair sexual function.Our study used a large well-controlled cohort and clearly defined end points to describe a novel association between marijuana use and sexual frequency. However, survey responses were self-reported and represent participants only at a specific point in time. Participants who did not answer questions related to marijuana use and sexual frequency were excluded.A positive association between marijuana use and sexual frequency is seen in men and women across all demographic groups. Although reassuring, the effects of marijuana use on sexual function warrant further study. Sun AJ, Eisenberg ML. Association Between Marijuana Use and Sexual Frequency in the United States: A Population-Based Study. J Sex Med 2017;14:1342-1347.

  View details for PubMedID 29110804

• Evaluation of external vibratory stimulation as a treatment for chronic scrotal pain in adult men: A single center open label pilot study SCANDINAVIAN JOURNAL OF PAIN Khandwala, Y. S., Serrano, F., Eisenberg, M. L. 2017; 17: 403–7

  Abstract

  Chronic scrotal pain is a common yet poorly understood urologic disease. Current treatment paradigms are sub-optimal and include anti-inflammatory drugs and opioids as well as invasive surgical management such as microdenervation of the spermatic cord. In this study, the efficacy of external vibratory stimulation (EVS) was evaluated as an alternative treatment option for idiopathic scrotal pain.Ten consecutive patients presenting to an academic urology clinic between December 2016 and April 2017 with scrotal pain were prospectively enrolled. After a comprehensive history and physical exam, patients were presented with and oriented to a spherical vibratory device that they were instructed to use topically each day for four weeks. Average and maximum pain severity, frequency, and bother scores were tracked at 2-week intervals using a visual analog scale (0-10) via survey. Descriptive statistics facilitated interpretation of individual changes in pain.Nine men, with a median age of 46 years, completed at least 2 weeks of the study intervention. 78% (7/9) of men achieved some improvement in daily scrotal pain levels. Overall, average pain decreased from 4.9 to 2.7 (p=0.009) while maximum pain severity decreased from 6.3 to 4.0 (p=0.013). The frequency of pain also decreased for 55.6% (5/9) of men. No severe side effects were noted by any of the participants though several patients reported mild paresthesia only during application of the device. The majority of men expressed interest in continuing treatment after conclusion of the study.External vibratory stimulation has been suggested as a promising non-invasive tool to alleviate chronic pain. As a proof-of-concept, we implemented EVS to treat men with idiopathic orchialgia. The majority of patients noted benefit in both severity and frequency of pain. Given its low risk profile, EVS deserves further evaluation and inclusion in treatment guidelines as a promising experimental therapy for a disease with few conservative treatment options available to providers.In this longitudinal study, external vibratory stimulation was found to decrease chronic scrotal pain without any adverse effects. The use of this non-invasive, non-pharmaceutical therapy to treat chronic scrotal pain has the potential to decrease physician and patient dependence on surgical procedures and opioid prescriptions. Future randomized, double blind clinical trials with a placebo arm are required to corroborate these findings and establish the true efficacy of EVS.

  View details for PubMedID 29126848

• Male factor infertility and risk of multiple sclerosis: A register-based cohort study. Multiple sclerosis (Houndmills, Basingstoke, England) Glazer, C. H., Tottenborg, S. S., Giwercman, A., Brauner, E. V., Eisenberg, M. L., Vassard, D., Magyari, M., Pinborg, A., Schmidt, L., Bonde, J. P. 2017: 1352458517734069

  Abstract

  BACKGROUND: Gender, possibly due to the influence of gonadal hormones, is presumed to play a role in the pathogenesis of multiple sclerosis (MS), but no studies have evaluated whether male infertility is associated with MS.OBJECTIVE: To study the association between male factor infertility and prevalent as well as incident MS.METHOD: Our cohort was established by linkage of the Danish National in vitro fertilization (IVF) registry to The Danish Multiple Sclerosis Registry and consisted of 51,063 men whose partners had undergone fertility treatment in all public and private fertility clinics in Denmark between 1994 and 2015.RESULTS: With a median age of 34 years at baseline, 24,011 men were diagnosed with male factor infertility and 27,052 did not have male factor infertility and made up the reference group. Men diagnosed with male factor infertility had a higher risk of prevalent (odds ratio (OR) = 1.61, 95% confidence interval (95% CI) 1.04-2.51) and incident MS (hazard ratio (HR) = 1.28, 95% CI 0.76-2.17) when compared to the reference group.CONCLUSION: This nationwide cohort study has shown, for the first time, an association between male infertility and MS which may be due to underlying common etiologies such as hypogonadism, shared genetics, or a joint autoimmune component.

  View details for PubMedID 29027840

• Semen quality and pregnancy loss in a contemporary cohort of couples recruited before conception: data from the Longitudinal Investigation of Fertility and the Environment (LIFE) Study FERTILITY AND STERILITY Eisenberg, M. L., Sapra, K. J., Kim, S., Chen, Z., Louis, G. 2017; 108 (4): 613–19

  Abstract

  To study the relationship between semen quality and pregnancy loss in a cohort of couples attempting to conceive.Observational prospective cohort.Not applicable.Three hundred and forty-four couples with a singleton pregnancy observed daily through 7 postconception weeks of gestation.None.Association between semen quality and pregnancy loss.Ninety-eight (28%) of the couples experienced a pregnancy loss after singleton pregnancy. No differences were observed in semen volume, sperm concentration, total sperm count, sperm viability, or sperm morphology (World Health Organization [WHO] and strict criteria) by couple's pregnancy loss status irrespective of whether they were analyzed continuously or as dichotomous variables per the WHO 5th edition semen criteria. A dichotomous DNA fragmentation measure of ≥30% was statistically significantly associated with pregnancy loss. No association was identified with other sperm morphometric or movement measures. Of the 70 couples who re-enrolled after a pregnancy loss, 14 experienced a second loss. Similar findings were identified when examining semen quality from couples with recurrent pregnancy loss.Although a few trends were identified (e.g., DNA fragmentation), general semen parameters seemed to have little relation with risk of pregnancy loss or recurrent pregnancy loss at the population level. However, given that 30% of pregnancies end in miscarriage and half the fetal genome is paternal in origin, the findings await corroboration.

  View details for PubMedID 28863939

  View details for PubMedCentralID PMC5657506

• Practical applications of sperm DNA fragmentation testing and its role in infertility TRANSLATIONAL ANDROLOGY AND UROLOGY Khandwala, Y. S., Eisenberg, M. L. 2017; 6: S397–S398

  View details for PubMedID 29082151

  View details for PubMedCentralID PMC5643692

• Validity of Claims Data for the Identification of Male Infertility CURRENT UROLOGY REPORTS Khandwala, Y. S., Zhang, C. A., Li, S., Cullen, M. R., Eisenberg, M. L. 2017; 18 (9): 68

  Abstract

  We sought to determine whether infertile men can accurately be identified within a large insurance claims database to validate its use for reproductive health research.Prior literature suggests that men coded for infertility are at higher risk for chronic disease though it was previously unclear if these diagnostic codes correlated with true infertility. We found that the specificity of one International Classification of Disease (9th edition) code in predicting abnormal semen parameters was 92.4%, rising to 99.8% if a patient had three different codes for infertility. The positive predictive value was as high as 85%. The use of claims data for male infertility research has been rapidly progressing due to its high power and feasibility. The high specificity of ICD codes for men with abnormal semen parameters is reassuring and validates prior studies as well as future investigation into men's health.

  View details for PubMedID 28718160

• Racial Variation in Semen Quality at Fertility Evaluation. Urology Khandwala, Y. S., Zhang, C. A., Li, S., Behr, B., Guo, D., Eisenberg, M. L. 2017

  Abstract

  To identify racial differences in semen quality among men living in the same geographic area and seeking fertility evaluation.Men obtaining a semen analysis for infertility evaluation or treatment between 2012 and 2016 at a single center were identified, and demographic data including height, weight, body mass index (BMI), and age were described. Mean semen parameters and the proportions of men with suboptimal parameters based on the World Health Organization's fifth edition criteria were also compared based on race. Multivariable regression analysis was conducted incorporating age, BMI, and year of evaluation. Further subanalyses based on BMI were subsequently performed.White men produced greater volumes of semen on average; however, Asian men had higher sperm concentrations and total sperm count. A lower proportion of Asian men compared to white men had semen quality in the suboptimal range for most semen parameters, whereas a higher proportion of white men were found to have azoospermia. Stratification by BMI groups attenuated the observed differences between whites and Asians, yet Asian male semen quality remained higher.Among men evaluated for infertility at a single center, Asians had lower volume but higher sperm concentrations compared with whites, which was influenced by differences in azoospermia prevalence. Although anthropometric and demographic factors attenuated the differences, even after adjustment, the contrasts remained. Our study suggests that racial differences exist in semen quality at the time of infertility evaluation.

  View details for DOI 10.1016/j.urology.2017.03.064

  View details for PubMedID 28522219

• The Relationship Between Offspring Sex Ratio and Vasectomy Utilization UROLOGY Lamberts, R. W., Guo, D. P., Li, S., Eisenberg, M. L. 2017; 103: 112-116

  Abstract

  To determine if there was an association between vasectomy utilization and offspring sex ratio (male offspring : total offspring), as offspring sex preference may have an impact on family planning in the United States.Using data from the National Institutes of Health-AARP Diet and Health Study, we calculated the number of sons and daughters of all men stratified by vasectomy status. We utilized a logistic regression model to determine if vasectomy utilization varies based on offspring sex ratio while accounting for known factors that impact vasectomy utilization.Of these men, 30,927 (30.8%) underwent vasectomy. Marital status, race, age, education level, region or state, and number of offspring were all significantly correlated with vasectomy utilization (P < .01). The sex ratio for vasectomized fathers (51.3%) was significantly higher than for fathers who had not undergone vasectomy (50.7%, P < .01). This difference remained even after we stratified by the total number of offspring: vasectomized men with 4 or more children had a sex ratio of 947 girls per 1000 boys, whereas the no vasectomy group had a sex ratio of 983 girls per 1000 boys (P < .01). For men with at least 2 children, each additional son increased the likelihood of vasectomy by 4% (P < .01), whereas each additional daughter led to a 2% decrease in vasectomy utilization (P = .03).Vasectomized fathers have a higher proportion of sons compared with non-vasectomized fathers, suggesting that offspring sex ratio is associated with a man's decision to undergo vasectomy. Further research is indicated to understand how offspring sex ratio impacts a man's contraceptive decisions.

  View details for DOI 10.1016/j.urology.2016.11.039

  View details for Web of Science ID 000400429800031

• Male Infertility and Risk of Nonmalignant Chronic Diseases: A Systematic Review of the Epidemiological Evidence SEMINARS IN REPRODUCTIVE MEDICINE Glazer, C., Bonde, J., Eisenberg, M. L., Giwercman, A., Haervig, K., Rimborg, S., Vassard, D., Pinborg, A., Schmidt, L., Brauner, E. 2017; 35 (3): 282–90

  View details for PubMedID 28658712

• Human semen quality and the secondary sex ratio ASIAN JOURNAL OF ANDROLOGY Bae, J., Kim, S., Chen, Z., Eisenberg, M. L., Louis, G. M. 2017; 19 (3): 374-381

  Abstract

  The aim of this study was to evaluate the association between semen quality and the secondary sex ratio (SSR), defined as the ratio of male to female live births. Our study cohort comprised 227 male partners who were enrolled prior to conception in Michigan and Texas between 2005 and 2009, and prospectively followed through delivery of a singleton birth. The male partners provided a baseline and a follow-up semen sample a month apart. Semen analysis was conducted to assess 27 parameters including five general characteristics, six sperm head measures, 14 morphology measures, and two sperm chromatin stability assay measures. Modified Poisson regression models with a robust error variance were used to estimate the relative risk (RR) and 95% confidence interval (95% CI) of a male birth for each semen parameter, after adjusting for potential confounders. Of the 27 semen parameters, only the percentage of bicephalic sperm was significantly associated with the SSR (2 nd vs 1 st quartile, RR, 0.65, 95% CI, 0.45-0.95, P = 0.03; 4 th vs 1 st quartile, RR, 0.61, 95% CI, 0.38-1.00, P < 0.05 before rounding to two decimal places), suggestive of a higher percentage of bicephalic sperm being associated with an excess of female births. Given the exploratory design of the present study, this preconception cohort study suggests no clear signal that human semen quality is associated with offspring sex determination.

  View details for DOI 10.4103/1008-682X.173445

  View details for Web of Science ID 000400828700019

• Trends in Testosterone Replacement Therapy Use from 2003 to 2013 among Reproductive-Age Men in the United States JOURNAL OF UROLOGY Rao, P. K., Boulet, S. L., Mehta, A., Hotaling, J., Eisenberg, M. L., Honig, S. C., Warner, L., Kissin, D. M., Nangia, A. K., Ross, L. S. 2017; 197 (4): 1121-1126

  Abstract

  Although testosterone replacement therapy use in the United States has increased dramatically in the last decade, to our knowledge trends in testosterone replacement therapy use among reproductive-age men have not been investigated. We assessed changes in testosterone replacement therapy use and practice patterns among 18 to 45-year-old American men from 2003 to 2013 and compared them to older men.This is a retrospective, cross-sectional analysis of men 18 to 45 and 56 to 64 years old who were enrolled in the Truven Health MarketScan® Commercial Claims Databases throughout each given calendar year from 2003 to 2013, including 5,094,868 men in 2013. Trends in the yearly rates of testosterone replacement therapy use were calculated using Poisson regression. Among testosterone replacement therapy users, the Cochran-Armitage test was used to assess temporal trends in age, formulation type, semen analysis and serum testosterone level testing during the 12 months preceding the documented use of testosterone replacement therapy.Between 2003 and 2013, there was a fourfold increase in the rate of testosterone use among 18 to 45-year-old men from 29.2/10,000 person-years to 118.1/10,000 person-years (p <0.0001). Among testosterone replacement therapy users, topical gel formulations were initially most used. Injection use then doubled between 2009 and 2012 (23.5% and 46.2%, respectively) and surpassed topical gel use in 2013. In men 56 to 64 years old there was a statistically significant threefold increase in testosterone replacement therapy use (p <0.0001), which was significantly smaller than the fourfold increase in younger men (p <0.0001).In 2003 to 2013, testosterone replacement therapy use increased fourfold in men 18 to 45 years old compared to threefold in older men. This younger age group should be a focus for future studies due to effects on fertility and unknown long-term sequelae.

  View details for DOI 10.1016/j.juro.2016.10.063

  View details for Web of Science ID 000398050600062

• DEMOGRAPHICS, USAGE PATTERNS, AND SAFETY OF MALE USERS OF CLOMIPHENE IN THE UNITED STATES Zlatev, D. V., Li, S., Baker, L. C., Eisenberg, M. L. ELSEVIER SCIENCE INC. 2017: E1342

  View details for DOI 10.1016/j.juro.2017.02.3137

  View details for Web of Science ID 000398276605412

• Trends in Testosterone Replacement Therapy Use from 2003 to 2013 among Reproductive-Age Men in the United States. journal of urology Rao, P. K., Boulet, S. L., Mehta, A., Hotaling, J., Eisenberg, M. L., Honig, S. C., Warner, L., Kissin, D. M., Nangia, A. K., Ross, L. S. 2017; 197 (4): 1121-1126

  Abstract

  Although testosterone replacement therapy use in the United States has increased dramatically in the last decade, to our knowledge trends in testosterone replacement therapy use among reproductive-age men have not been investigated. We assessed changes in testosterone replacement therapy use and practice patterns among 18 to 45-year-old American men from 2003 to 2013 and compared them to older men.This is a retrospective, cross-sectional analysis of men 18 to 45 and 56 to 64 years old who were enrolled in the Truven Health MarketScan® Commercial Claims Databases throughout each given calendar year from 2003 to 2013, including 5,094,868 men in 2013. Trends in the yearly rates of testosterone replacement therapy use were calculated using Poisson regression. Among testosterone replacement therapy users, the Cochran-Armitage test was used to assess temporal trends in age, formulation type, semen analysis and serum testosterone level testing during the 12 months preceding the documented use of testosterone replacement therapy.Between 2003 and 2013, there was a fourfold increase in the rate of testosterone use among 18 to 45-year-old men from 29.2/10,000 person-years to 118.1/10,000 person-years (p <0.0001). Among testosterone replacement therapy users, topical gel formulations were initially most used. Injection use then doubled between 2009 and 2012 (23.5% and 46.2%, respectively) and surpassed topical gel use in 2013. In men 56 to 64 years old there was a statistically significant threefold increase in testosterone replacement therapy use (p <0.0001), which was significantly smaller than the fourfold increase in younger men (p <0.0001).In 2003 to 2013, testosterone replacement therapy use increased fourfold in men 18 to 45 years old compared to threefold in older men. This younger age group should be a focus for future studies due to effects on fertility and unknown long-term sequelae.

  View details for DOI 10.1016/j.juro.2016.10.063

  View details for PubMedID 27789218

• Is human fecundity changing? A discussion of research and data gaps precluding us from having an answer HUMAN REPRODUCTION Smarr, M. M., Sapra, K. J., Gemmill, A., Kahn, L. G., Wise, L. A., Lynch, C. D., Factor-Litvak, P., Mumford, S. L., Skakkebaek, N. E., Slama, R., Lobdell, D. T., Stanford, J. B., Jensen, T. K., Boyle, E. H., Eisenberg, M. L., Turek, P. J., Sundaram, R., Thoma, M. E., Louis, G. M. 2017; 32 (3): 499-504

  Abstract

  Fecundity, the biologic capacity to reproduce, is essential for the health of individuals and is, therefore, fundamental for understanding human health at the population level. Given the absence of a population (bio)marker, fecundity is assessed indirectly by various individual-based (e.g. semen quality, ovulation) or couple-based (e.g. time-to-pregnancy) endpoints. Population monitoring of fecundity is challenging, and often defaults to relying on rates of births (fertility) or adverse outcomes such as genitourinary malformations and reproductive site cancers. In light of reported declines in semen quality and fertility rates in some global regions among other changes, the question as to whether human fecundity is changing needs investigation. We review existing data and novel methodological approaches aimed at answering this question from a transdisciplinary perspective. The existing literature is insufficient for answering this question; we provide an overview of currently available resources and novel methods suitable for delineating temporal patterns in human fecundity in future research.

  View details for DOI 10.1093/humrep/dew361

  View details for Web of Science ID 000398060700004

• Effects of age on fertility and sexual function FERTILITY AND STERILITY Eisenberg, M. L., Meldrum, D. 2017; 107 (2): 301-304

  Abstract

  As paternal age increases in the developed world, more attention has been given to the effects of age on male reproductive and sexual function. Although the biologic potential for reproductive continues for most of a man's life, changes in sperm production do occur. In addition, erectile function changes with age, caused by the same factors that lead to other vascular disease.

  View details for DOI 10.1016/j.fertnstert.2016.12.018

  View details for Web of Science ID 000396910200004

  View details for PubMedID 28160919

• Novel centrifugal technology for measuring sperm concentration in the home FERTILITY AND STERILITY Schaff, U. Y., Fredriksen, L. L., Epperson, J. G., Quebral, T. R., Naab, S., Sarno, M. J., Eisenberg, M. L., Sommer, G. J. 2017; 107 (2): 358-?

  Abstract

  To evaluate the analytical performance and usability of the Trak Male Fertility Testing System, a semiquantitative (categorical) device recently US Food and Drug Administration (FDA)-cleared for measuring sperm concentration in the home by untrained users.A three-site clinical trial comparing self-reported lay user results versus reference results obtained by computer-aided semen analysis (CASA).Simulated home use environments at fertility centers and urologist offices.A total of 239 untrained users.None.Sperm concentration results reported from self-testing lay users and laboratory reference method by CASA were evaluated semiquantitatively against the device's clinical cutoffs of 15 M/mL (current World Health Organization cutoff) and 55 M/mL (associated with faster time to pregnancy). Additional reported metrics include assay linearity, precision, limit of detection, and ease-of-use ratings from lay users.Lay users achieved an accuracy (versus the reference) of 93.3% (95% confidence interval [CI] 84.1%-97.4%) for results categorized as ≤15 M/mL, 82.4% (95% CI 73.3%-88.9%) for results categorized as 15-55 M/mL, and 95.5% (95% CI 88.9%-98.2%) for results categorized as >55 M/mL. When measured quantitatively, Trak results had a strong linear correlation with CASA measurements (r = 0.99). The precision and limit of detection studies show that the device has adequate reproducibility and detection range for home use. Subjects generally rated the device as easy to use.The Trak System is an accurate tool for semiquantitatively measuring sperm concentration in the home. The system may enable screening and longitudinal assessment of sperm concentration at home.ClinicalTrials.gov identifier: NCT02475395.

  View details for DOI 10.1016/j.fertnstert.2016.10.025

  View details for Web of Science ID 000396910200016

  View details for PubMedID 27887718

• Is human fecundity changing? A discussion of research and data gaps precluding us from having an answer. Human reproduction Smarr, M. M., Sapra, K. J., Gemmill, A., Kahn, L. G., Wise, L. A., Lynch, C. D., Factor-Litvak, P., Mumford, S. L., Skakkebaek, N. E., Slama, R., Lobdell, D. T., Stanford, J. B., Jensen, T. K., Boyle, E. H., Eisenberg, M. L., Turek, P. J., Sundaram, R., Thoma, M. E., Buck Louis, G. M. 2017

  Abstract

  Fecundity, the biologic capacity to reproduce, is essential for the health of individuals and is, therefore, fundamental for understanding human health at the population level. Given the absence of a population (bio)marker, fecundity is assessed indirectly by various individual-based (e.g. semen quality, ovulation) or couple-based (e.g. time-to-pregnancy) endpoints. Population monitoring of fecundity is challenging, and often defaults to relying on rates of births (fertility) or adverse outcomes such as genitourinary malformations and reproductive site cancers. In light of reported declines in semen quality and fertility rates in some global regions among other changes, the question as to whether human fecundity is changing needs investigation. We review existing data and novel methodological approaches aimed at answering this question from a transdisciplinary perspective. The existing literature is insufficient for answering this question; we provide an overview of currently available resources and novel methods suitable for delineating temporal patterns in human fecundity in future research.

  View details for DOI 10.1093/humrep/dew361

  View details for PubMedID 28137753

• The sixth vital sign: what reproduction tells us about overall health. Proceedings from a NICHD/CDC workshop. Human reproduction open Cedars, M. I., Taymans, S. E., DePaolo, L. V., Warner, L., Moss, S. B., Eisenberg, M. L. 2017; 2017 (2): hox008

  Abstract

  STUDY QUESTION: Does the fertility status of an individual act as a biomarker for their future health?SUMMARY ANSWER: Data support an association between reproductive health and overall health for men and women.WHAT IS ALREADY KNOWN: Various chronic conditions, such as diabetes, obesity and cancer, can compromise fertility, but there are limited data for the converse situation, in which fertility status can influence or act as a marker for future health. Data reveal an association between infertility and incident cardiovascular disease and cancer in both men and women.STUDY DESIGN SIZE AND DURATION: A National Institute of Child Health and Human Development-Centers for Disease Control and Prevention workshop in April 2016 was convened that brought together experts in both somatic diseases and conditions, and reproductive health. Goals of the workshop included obtaining information about the current state of the science linking fertility status and overall health, identifying potential gaps and barriers limiting progress in the field, and outlining the highest priorities to move the field forward.PARTICIPANTS/MATERIALS SETTING AND METHODS: Approximately 40 experts participated in the workshop.MAIN RESULTS AND THE ROLE OF CHANCE: While the etiology remains uncertain for infertility, there is evidence for an association between male and female infertility and later health. The current body of evidence suggests four main categories for considering biological explanations: genetic factors, hormonal factors, in utero factors, and lifestyle/health factors. These categories would be key to include in future studies to develop a comprehensive and possibly standardized look at fertility status and overall health. Several themes emerged from the group discussion including strategies for maximizing use of existing resources and databases, the need for additional epidemiologic studies and public health surveillance, development of strategies to frame research so results could ultimately influence clinical practice, and the identification of short and long-term goals and the best means to achieve them.LIMITATIONS REASONS FOR CAUTION: Further research may not indicate an association between fertility status and overall health.WIDER IMPLICATIONS OF THE FINDINGS: Currently medical care is compartmentalized. Reproductive medicine physicians treat patients for a short period of time before they transition to others for future care. Going forward, it is critical to take an interdisciplinary patient care approach that would involve experts in a broad range of medical specialties in order to more fully understand the complex interrelationships between fertility and overall health. If infertility is confirmed as an early marker of chronic disease then screening practices could be adjusted, as they are for patients with a family history of malignancy.STUDY FUNDING/COMPETING INTERESTS: Funding for the workshop was provided by the Fertility and Infertility Branch, National Institute of Child Health and Human Development, National Institutes of Health and the Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control. There are no conflicts of interest to declare. The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention or the National Institutes of Health.TRIAL REGISTRATION NUMBER: Not applicable.

  View details for PubMedID 30895226

• Hypertension and Male Fertility. The world journal of men's health Guo, D. n., Li, S. n., Behr, B. n., Eisenberg, M. L. 2017; 35 (2): 59–64

  Abstract

  As the age of paternity rises in the developed world, issues of chronic disease may affect prospective fathers. Given the high prevalence of hypertension, researchers have begun to explore the relationship between hypertensive disease and male fertility. The current literature suggests an association between hypertension and semen quality. The use of various antihypertensive medications has also been linked to impaired semen parameters, making it difficult to discern whether the association exists with hypertension or its treatment. Further investigation is warranted to determine whether the observed associations are causal.

  View details for PubMedID 28868816

  View details for PubMedCentralID PMC5583372

• The Relationship Between Offspring Sex Ratio and Vasectomy Utilization. Urology Lamberts, R. W., Guo, D. P., Li, S., Eisenberg, M. L. 2016

  Abstract

  To determine if there was an association between vasectomy utilization and offspring sex ratio (male offspring : total offspring), as offspring sex preference may have an impact on family planning in the United States.Using data from the National Institutes of Health-AARP Diet and Health Study, we calculated the number of sons and daughters of all men stratified by vasectomy status. We utilized a logistic regression model to determine if vasectomy utilization varies based on offspring sex ratio while accounting for known factors that impact vasectomy utilization.Of these men, 30,927 (30.8%) underwent vasectomy. Marital status, race, age, education level, region or state, and number of offspring were all significantly correlated with vasectomy utilization (P < .01). The sex ratio for vasectomized fathers (51.3%) was significantly higher than for fathers who had not undergone vasectomy (50.7%, P < .01). This difference remained even after we stratified by the total number of offspring: vasectomized men with 4 or more children had a sex ratio of 947 girls per 1000 boys, whereas the no vasectomy group had a sex ratio of 983 girls per 1000 boys (P < .01). For men with at least 2 children, each additional son increased the likelihood of vasectomy by 4% (P < .01), whereas each additional daughter led to a 2% decrease in vasectomy utilization (P = .03).Vasectomized fathers have a higher proportion of sons compared with non-vasectomized fathers, suggesting that offspring sex ratio is associated with a man's decision to undergo vasectomy. Further research is indicated to understand how offspring sex ratio impacts a man's contraceptive decisions.

  View details for DOI 10.1016/j.urology.2016.11.039

  View details for PubMedID 27919667

• Improving the Precision of the Male Fertility Evaluation EUROPEAN UROLOGY Eisenberg, M. L. 2016; 70 (6): 924–25

  View details for PubMedID 27417032

• Leydig cell tumor found incidentally during microscopic testicular sperm extraction in patient with mosaic Klinefelter syndrome: case report FERTILITY AND STERILITY Shaw, N. M., Stauffer, C., Eisenberg, M. L. 2016; 106 (6): 1344-1347

  Abstract

  To report the finding and management of a case of Leydig cell tumor discovered during the infertility evaluation of a patient with mosaic Klinefelter syndrome.Single case report.Academic hospital.Patient seeking assistance with fertility after a diagnosis of mosaic Klinefelter syndrome.The patient underwent microscopic testicular sperm extraction (mTESE) for sperm identification after the diagnosis of mosaic Klinefelter syndrome. Abnormal testicular tissue was identified during mTESE and histologically confirmed to be a Leydig cell tumor. The patient was informed of this incidental discovery and later underwent orchiectomy for conservative oncologic control.Histologic testicular assessment.Patient was found to have no viable sperm on mTESE, but achieved oncologic control with bilateral orchiectomy.The presented case emphasizes the importance of awareness and expedient appropriate management to achieve oncologic control of a rare tumor with low malignant potential discovered during otherwise routine mTESE. In particular, it highlights the role of the infertility specialist in aiding in diagnosis and treatment of incidental and rare findings.

  View details for DOI 10.1016/j.fertnstert.2016.07.1116

  View details for Web of Science ID 000386829800018

  View details for PubMedID 27523297

• Diabetes, medical comorbidities and couple fecundity. Human reproduction Eisenberg, M. L., Sundaram, R., Maisog, J., Buck Louis, G. M. 2016; 31 (10): 2369-2376

  Abstract

  What is the relationship between couple's health and fecundity in a preconception cohort?Somatic health may impact fecundity in men and women as couples whose male partner had diabetes or whose female partner had two or more medical conditions had a longer time-to-pregnancy (TTP).The impact of somatic health on human fecundity is hypothesized given the reported declines in spermatogenesis and ovulation among individuals with certain medical comorbidities.A population-based prospective cohort study recruiting couples from 16 counties in Michigan and Texas (2005-2009) using sampling frameworks allowing for identification of couples planning pregnancy in the near future. Five hundred and one couples desiring pregnancy and discontinuing contraception were followed-up for 12 months or until a human chorionic gonadotropin pregnancy was detected.In all, 33 (21.4%) female and 41 (26.6%) male partners had medical conditions at baseline.Couples' medical comorbidity was associated with pregnancy status. Diabetes in either partner was associated with diminished fecundity, as measured by a longer TTP. Specifically, fecundability odds ratios (FORs) were below 1, indicating a longer TTP, for male partners with diabetes (0.35, 95% confidence interval (CI): 0.14-0.86) even in adjusted models (0.35, 95% CI: 0.13-0.88). Female partners with diabetes had comparable reductions in FORs; however, the analyses did not reach statistical significance (0.26, 95% CI: 0.03-1.98). Female partners with two or more medical conditions had a significantly longer TTP compared with women with no health problems (0.36, 95% CI: 0.14-0.92). Importantly, the presence of medical conditions was not associated with sexual frequency. We cannot rule out residual confounding, Type 2 errors for less prevalent medical conditions, or chance findings in light of the multiple comparisons made in the analysis.The findings require cautious interpretation given that medical diagnoses are subject to possible reporting errors, although we are unaware of any potential biases that may have been introduced, as participants were unaware of how long it would take to become pregnant upon enrollment.The current report suggests a relationship between male and female diabetes and fecundity, and possibly somatic health more globally. Moreover, while the mechanism is uncertain, if corroborated, our data suggest that early evaluation and treatment may be warranted for diabetics prior to attempting to conceive.Intramural research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Contract nos. #N01-HD-3-3355, N01-HD-3-3356 and N01-HD-3-3358). The authors have no conflicts of interest to declare.

  View details for DOI 10.1093/humrep/dew200

  View details for PubMedID 27591240

  View details for PubMedCentralID PMC5027928

• Diabetes, medical comorbidities and couple fecundity HUMAN REPRODUCTION Eisenberg, M. L., Sundaram, R., Maisog, J., Louis, G. M. 2016; 31 (10): 2369-2376

  Abstract

  What is the relationship between couple's health and fecundity in a preconception cohort?Somatic health may impact fecundity in men and women as couples whose male partner had diabetes or whose female partner had two or more medical conditions had a longer time-to-pregnancy (TTP).The impact of somatic health on human fecundity is hypothesized given the reported declines in spermatogenesis and ovulation among individuals with certain medical comorbidities.A population-based prospective cohort study recruiting couples from 16 counties in Michigan and Texas (2005-2009) using sampling frameworks allowing for identification of couples planning pregnancy in the near future. Five hundred and one couples desiring pregnancy and discontinuing contraception were followed-up for 12 months or until a human chorionic gonadotropin pregnancy was detected.In all, 33 (21.4%) female and 41 (26.6%) male partners had medical conditions at baseline.Couples' medical comorbidity was associated with pregnancy status. Diabetes in either partner was associated with diminished fecundity, as measured by a longer TTP. Specifically, fecundability odds ratios (FORs) were below 1, indicating a longer TTP, for male partners with diabetes (0.35, 95% confidence interval (CI): 0.14-0.86) even in adjusted models (0.35, 95% CI: 0.13-0.88). Female partners with diabetes had comparable reductions in FORs; however, the analyses did not reach statistical significance (0.26, 95% CI: 0.03-1.98). Female partners with two or more medical conditions had a significantly longer TTP compared with women with no health problems (0.36, 95% CI: 0.14-0.92). Importantly, the presence of medical conditions was not associated with sexual frequency. We cannot rule out residual confounding, Type 2 errors for less prevalent medical conditions, or chance findings in light of the multiple comparisons made in the analysis.The findings require cautious interpretation given that medical diagnoses are subject to possible reporting errors, although we are unaware of any potential biases that may have been introduced, as participants were unaware of how long it would take to become pregnant upon enrollment.The current report suggests a relationship between male and female diabetes and fecundity, and possibly somatic health more globally. Moreover, while the mechanism is uncertain, if corroborated, our data suggest that early evaluation and treatment may be warranted for diabetics prior to attempting to conceive.Intramural research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Contract nos. #N01-HD-3-3355, N01-HD-3-3356 and N01-HD-3-3358). The authors have no conflicts of interest to declare.

  View details for DOI 10.1093/humrep/dew200

  View details for Web of Science ID 000386087000025

  View details for PubMedCentralID PMC5027928

• Relationship between paternal somatic health and assisted reproductive technology outcomes. Fertility and sterility Eisenberg, M. L., Li, S., Wise, L. A., Lynch, C. D., Nakajima, S., Meyers, S. A., Behr, B., Baker, V. L. 2016; 106 (3): 559-565

  Abstract

  To study the association between paternal medical comorbidities and the outcomes of assisted reproductive technology (ART).Retrospective cohort study.Academic reproductive medicine center.We analyzed fresh ART cycles uszing freshly ejaculated sperm from the male partner of couples undergoing ART cycles from 2004 until 2014. We recorded patient and partner demographic characteristics. The cohort was linked to hospital billing data to obtain information on selected male partners' comorbidities identified using ICD-9-CM codes.None.Fertilization, clinical pregnancy, miscarriage, implantation, and live-birth rates as well as birth weights and gestational ages.In all, we identified 2,690 men who underwent 5,037 fresh ART cycles. Twenty-seven percent of men had at least one medical diagnosis. Men with nervous system diseases had on average lower pregnancy rates (23% vs. 30%) and live-birth rates (15% vs. 23%) than men without nervous system diseases. Lower fertilization rates were also observed among men with respiratory diseases (61% vs. 64%) and musculoskeletal diseases (61% vs. 64%) relative to those without these diseases. In addition, men with diseases of the endocrine system had smaller children (2,970 vs. 3,210 g) than men without such diseases. Finally, men with mental disorders had children born at an earlier gestational age (36.5 vs. 38.0 weeks).The current report identified a possible relationship between a man's health history and IVF outcomes. As these are potentially modifiable factors, further research should determine whether treatment for men's health conditions may improve or impair IVF outcomes.

  View details for DOI 10.1016/j.fertnstert.2016.04.037

  View details for PubMedID 27179785

• Comparability and reproducibility of adult male anogenital distance measurements for two different methods. Andrology Mendiola, J., Oñate-Celdrán, J., Samper-Mateo, P., Arense-Gonzalo, J. J., Torres-Roca, M., Sánchez-Rodríguez, C., García-Escudero, D., Fontana-Compiano, L. O., Eisenberg, M. L., Swan, S. H., Torres-Cantero, A. M. 2016; 4 (4): 626-631

  Abstract

  The distance from the genitals to the anus, anogenital distance, reflects androgen concentration during prenatal development in mammals. The use of anogenital distance in human studies is still very limited and the quality and consistency of measurements is an important methodological issue. The aim of this study was to assess the feasibility and reproducibility of adult male anogenital distance measurements by two different methods. All men were attending an outpatient clinic at a university hospital and underwent an andrological examination and completed a brief questionnaire. Two variants of anogenital distance [from the anus to the posterior base of the scrotum (AGDAS ) and to the cephalad insertion of the penis (AGDAP )] by two methods (lithotomy or frog-legged position) were assessed in 70 men. Within and between coefficient of variations, intra-class correlation coefficients, two-way repeated-measures analysis of variance, and scatter and Bland-Altman plots were calculated. The two methods produced similar values for AGDAP but different estimates for AGDAS . Nonetheless, the overall agreement (ICC ≥ 0.80) was acceptable for both measures. Therefore, both methods are internally consistent and adequate for epidemiological studies, and may be used depending on the available medical resources, clinical setting, and populations.

  View details for DOI 10.1111/andr.12202

  View details for PubMedID 27153294

• Choice of underwear and male fecundity in a preconception cohort of couples. Andrology Sapra, K. J., Eisenberg, M. L., Kim, S., Chen, Z., Buck Louis, G. M. 2016; 4 (3): 500-508

  Abstract

  Our objective was to investigate the relationship between male underwear-type worn during daytime/bedtime and male fecundity as measured by semen quality and time-to-pregnancy. We used data from a prospective preconception cohort conducted in 16 counties in Michigan and Texas, USA. 501 couples were enrolled and followed for 12 months of trying, which facilitated capture of time-to-pregnancy (in cycles), 6-cycle conception delay, and 12-month infertility. Male partners provided semen samples via in-home collection for next-day semen analysis comprised of 35 semen quality endpoints. At enrollment, men provided information on type of underwear worn during daytime and bedtime and were classified into 6 categories by underwear choice (n = 491): (i) briefs day/night, (ii) boxer-briefs day/night, (iii) boxers day/night, (iv) briefs day and boxers/none at night, (v) boxer-briefs day and boxers/none at night, (vi) boxers day and none at night. 473 (96%) men had semen analysis performed. Men switching from their usual daytime underwear to boxers/none for bed (groups 4, 5, 6) had the most evidence of change in semen quality endpoints (10 of 11 differences) relative to men wearing briefs day/night (group 1). Group 4 men had lower percent of sperm with coiled tail (β = -0.18, 95% CI: -0.35, -0.01), higher percent round (β = 0.22, 95% CI: 0.01, 0.42), number of immature sperm (β = 0.44, 95% CI: 0.11, 0.77), and amplitude head displacement (β = 0.57, 95% CI: 0.10, 1.03). Group 5 men had higher sperm head perimeter (β=0.17, 95% CI: 0.002, 0.34), amplitude head displacement (β = 0.47, 95% CI: 0.03, 0.91), percent cytoplasmic droplet (β = 0.44, 95% CI: 0.11, 0.77) and high DNA stainability (β=0.39, 95% CI: 0.01, 0.78). After false discovery rate control, no differences remained significant. No significant differences in time-to-pregnancy, conception delay, or infertility were observed. In summary, male underwear choice is associated with few differences in semen parameters; no association with time-to-pregnancy is observed providing reassurance to couples attempting pregnancy.

  View details for DOI 10.1111/andr.12163

  View details for PubMedID 26939021

• Paternal aging and increased risk of congenital disease, psychiatric disorders, and cancer ASIAN JOURNAL OF ANDROLOGY Conti, S. L., Eisenberg, M. L. 2016; 18 (3): 420-424

  Abstract

  As couples are increasingly delaying parenthood, the effect of the aging men and women on reproductive outcomes has been an area of increased interest. Advanced paternal age has been shown to independently affect the entire spectrum of male fertility as assessed by reductions in sperm quality and fertilization (both assisted and unassisted). Moreover, epidemiological data suggest that paternal age can lead to higher rates of adverse birth outcomes and congenital anomalies. Mounting evidence also suggests increased risk of specific pediatric and adult disease states ranging from cancer to behavioral traits. While disease states associated with advancing paternal age have been well described, consensus recommendations for neonatal screening have not been as widely implemented as have been with advanced maternal age.

  View details for DOI 10.4103/1008-682X.175097

  View details for Web of Science ID 000374857800024

  View details for PubMedID 26975491

  View details for PubMedCentralID PMC4854094

• Trends in Testosterone Prescription and Public Health Concerns UROLOGIC CLINICS OF NORTH AMERICA Gabrielsen, J. S., Najari, B. B., Alukal, J. P., Eisenberg, M. L. 2016; 43 (2): 261-?

  Abstract

  Testosterone supplementation therapy (TST) has become increasingly popular since the turn of the century. Most prescriptions in the U.S. are written by primary care providers, endocrinologists, or urologists. The FDA has requests pharmaceutical companies provide more long term data on efficacy and safety of testosterone products. Results from these studies will help define the appropriate population for TST going forward. It is hoped that these data combined with physician and public education will minimize inappropriate prescribing and allow those likely to benefit from TST to receive it.

  View details for DOI 10.1016/j.ucl.2016.01.010

  View details for Web of Science ID 000376792400015

  View details for PubMedID 27132584

• Choice of underwear and male fecundity in a preconception cohort of couples ANDROLOGY Sapra, K. J., Eisenberg, M. L., Kim, S., Chen, Z., Louis, G. M. 2016; 4 (3): 500-508

  View details for DOI 10.1111/andr.12163

  View details for Web of Science ID 000375881200019

• INCREASED RISK OF AUTOIMMUNE DISORDERS IN INFERTILE MEN: ANALYSIS OF US CLAIMS DATA Brubaker, W. D., Li, S., Baker, L. C., Eisenberg, M. L. ELSEVIER SCIENCE INC. 2016: E1153–E1154

  View details for DOI 10.1016/j.juro.2016.02.2590

  View details for Web of Science ID 000375540000595

• VASECTOMY AND THE RISK OF PROSTATE CANCER IN A PROSPECTIVE US COHORT: ANALYSIS IN THE PRESENCE OF SELECTION BIAS Davenport, M., Li, S., Brooks, J., Cullen, M., Eisenberg, M. ELSEVIER SCIENCE INC. 2016: E34

  View details for DOI 10.1016/j.juro.2016.02.1950

  View details for Web of Science ID 000375278600076

• VARICOCELES ARE ASSOCIATED WITH INCREASED RISK OF CARDIAC DISEASE AND OTHER COMORBIDITIES: AN ANALYSIS OF US CLAIMS DATA. Dallas, K. B., Wang, N. N., Li, S., Baker, L. C., Eisenberg, M. ELSEVIER SCIENCE INC. 2016: E1155

  View details for DOI 10.1016/j.juro.2016.02.2593

  View details for Web of Science ID 000375540000598

• Human semen quality and the secondary sex ratio. Asian journal of andrology Bae, J., Kim, S., Chen, Z., Eisenberg, M. L., Buck Louis, G. M. 2016

  Abstract

  The aim of this study was to evaluate the association between semen quality and the secondary sex ratio (SSR), defined as the ratio of male to female live births. Our study cohort comprised 227 male partners who were enrolled prior to conception in Michigan and Texas between 2005 and 2009, and prospectively followed through delivery of a singleton birth. The male partners provided a baseline and a follow-up semen sample a month apart. Semen analysis was conducted to assess 27 parameters including five general characteristics, six sperm head measures, 14 morphology measures, and two sperm chromatin stability assay measures. Modified Poisson regression models with a robust error variance were used to estimate the relative risk (RR) and 95% confidence interval (95% CI) of a male birth for each semen parameter, after adjusting for potential confounders. Of the 27 semen parameters, only the percentage of bicephalic sperm was significantly associated with the SSR (2 nd vs 1 st quartile, RR, 0.65, 95% CI, 0.45-0.95, P = 0.03; 4 th vs 1 st quartile, RR, 0.61, 95% CI, 0.38-1.00, P < 0.05 before rounding to two decimal places), suggestive of a higher percentage of bicephalic sperm being associated with an excess of female births. Given the exploratory design of the present study, this preconception cohort study suggests no clear signal that human semen quality is associated with offspring sex determination.

  View details for DOI 10.4103/1008-682X.173445

  View details for PubMedID 26975484

• Increased risk of incident chronic medical conditions in infertile men: analysis of United States claims data FERTILITY AND STERILITY Eisenberg, M. L., Li, S., Cullen, M. R., Baker, L. C. 2016; 105 (3): 629-636

  Abstract

  To determine the incidence of chronic medical conditions of men with infertility.Retrospective cohort study.Not applicable.Subjects contained within the Truven Health MarketScan claims database from 2001 to 2009.Not applicable.The development of chronic medical conditions including hypertension, diabetes, hyperlipidemia, renal disease, pulmonary disease, liver disease, depression, peripheral vascular disease, cerebrovascular disease, heart disease, injury, alcohol abuse, drug abuse, anxiety disorders, and bipolar disorder.In all, 13,027 men diagnosed with male factor infertility were identified with an additional 23,860 receiving only fertility testing. The average age was 33.1 years for men diagnosed with infertility and 32.8 years for men receiving testing alone. After adjusting for confounding factors, men diagnosed with male factor infertility had a higher risk of developing diabetes (hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.10-1.53), ischemic heart disease (HR 1.48, 95% CI 1.19-1.84), alcohol abuse (HR 1.48, 95% CI 1.07-2.05), and drug abuse (1.67, 95% CI 1.06-2.63) compared with men who only received infertility testing. Similar patterns were identified when comparing those with male factor infertility to vasectomized men. The association between male factor infertility and later health outcomes were strongest for men with longer follow-up.In this cohort of patients in a national insurance database, men diagnosed with male factor infertility had a significantly higher risk of adverse health outcomes in the years after an infertility evaluation. These findings suggest the overall importance of men's reproductive health and warrant additional investigation to understand the association and identify interventions to improve outcomes for these patients.

  View details for DOI 10.1016/j.fertnstert.2015.11.011

  View details for Web of Science ID 000373406300015

  View details for PubMedID 26674559

• Decline in sperm count and motility in young adult men from 2003 to 2013: observations from a US sperm bank ANDROLOGY Centola, G. M., Blanchard, A., Demick, J., Li, S., Eisenberg, M. L. 2016; 4 (2): 270-276

  View details for DOI 10.1111/andr.12149

  View details for Web of Science ID 000372417000010

• Decline in sperm count and motility in young adult men from 2003 to 2013: observations from a U.S. sperm bank. Andrology Centola, G. M., Blanchard, A., Demick, J., Li, S., Eisenberg, M. L. 2016; 4 (2): 270-276

  Abstract

  Controversy exists regarding stability of semen quality over time with papers reporting decrease, increase or stable parameters in heterogeneous populations. The current study examined semen parameters of young adult men from 2003 to 2013 at an urban U.S. sperm bank. Semen parameters were analyzed before and after cryopreservation for a total of 9425 specimens from 489 individuals. Demographic information was obtained from a social and medical history questionnaire. Following 2-3 days abstinence, the specimens were collected at the laboratory and assessed by uniform technicians and techniques. The data were analyzed using generalized linear regression after adjustment for age, days of abstinence, for repeated samples, as well as by the Cochran-Armitage trend test. The within variability was accounted for by the repeated measures model. All p values were two-sided with p < 0.05 considered significant. There was a significant decline in sperm concentration (-3.55, 95% CI -4.87, -2.23; p < 0.001), total motility (-1.23, 95% CI -1.65, -0.82; p < 0.001), total count (-10.75, 95% CI -15.95, -5.54; p < 0.001) and total motile count (-9.43, 95% CI -13.14, -5.73; p < 0.001). There was no significant change in semen volume (0.03, 95% CI -0.02, 0.09; p = 0.2). The post-thaw total motility significantly (-2.30, 95% CI -2.72, -1.87; p < 0.001) decreased with time. Importantly, demographic and lifestyle factors were stable or improved over the study period. There was a decline in age (ptrend  = 0.003) and alcohol use (ptrend  = 0.005) and an increase in college GPA (Grade Point Average) (ptrend  = 0.02). BMI (ptrend  = 0.73), educational attainment (ptrend  = 0.2), race/ethnicity (ptrend  = 0.53), and lifestyle habits (weekly exercise, ptrend  = 0.21; smoking, ptrend  = 0.99; marital status, ptrend  = 0.85) remained constant. Uniform technicians and techniques over the study period make measurement bias unlikely. This report demonstrates a decline in semen quality among young adult men in the Boston area who were attending or completed a college education during the past 10 years, and requires further study.

  View details for DOI 10.1111/andr.12149

  View details for PubMedID 26789272

• PARENTAL SOURCE OF ANEUPLOIDY MAY BE DIFFERENT BETWEEN SPORADIC AND RECURRENT MISCARRIAGES Apple, M., Shah, M., Eisenberg, M., Lathi, R. B. ELSEVIER SCIENCE INC. 2016: E4

  View details for DOI 10.1016/j.fertnstert.2015.12.027

  View details for Web of Science ID 000373405200002

• Risks beyond reproduction for infertile men FERTILITY AND STERILITY Eisenberg, M. L. 2016; 105 (2): 300–301

  View details for PubMedID 26677791

• Male Reproductive Disorders and Fertility Trends: Influences of Environment and Genetic Susceptibility. Physiological reviews Skakkebaek, N. E., Rajpert-De Meyts, E., Buck Louis, G. M., Toppari, J., Andersson, A., Eisenberg, M. L., Jensen, T. K., Jørgensen, N., Swan, S. H., Sapra, K. J., Ziebe, S., Priskorn, L., Juul, A. 2016; 96 (1): 55-97

  Abstract

  It is predicted that Japan and European Union will soon experience appreciable decreases in their populations due to persistently low total fertility rates (TFR) below replacement level (2.1 child per woman). In the United States, where TFR has also declined, there are ethnic differences. Caucasians have rates below replacement, while TFRs among African-Americans and Hispanics are higher. We review possible links between TFR and trends in a range of male reproductive problems, including testicular cancer, disorders of sex development, cryptorchidism, hypospadias, low testosterone levels, poor semen quality, childlessness, changed sex ratio, and increasing demand for assisted reproductive techniques. We present evidence that several adult male reproductive problems arise in utero and are signs of testicular dysgenesis syndrome (TDS). Although TDS might result from genetic mutations, recent evidence suggests that it most often is related to environmental exposures of the fetal testis. However, environmental factors can also affect the adult endocrine system. Based on our review of genetic and environmental factors, we conclude that environmental exposures arising from modern lifestyle, rather than genetics, are the most important factors in the observed trends. These environmental factors might act either directly or via epigenetic mechanisms. In the latter case, the effects of exposures might have an impact for several generations post-exposure. In conclusion, there is an urgent need to prioritize research in reproductive physiology and pathophysiology, particularly in highly industrialized countries facing decreasing populations. We highlight a number of topics that need attention by researchers in human physiology, pathophysiology, environmental health sciences, and demography.

  View details for DOI 10.1152/physrev.00017.2015

  View details for PubMedID 26582516

  View details for PubMedCentralID PMC4698396

• Testosterone Replacement Therapy and Prostate Cancer Incidence. The world journal of men's health Eisenberg, M. L. 2015; 33 (3): 125-129

  Abstract

  While early studies demonstrated a positive association between testosterone and prostate cancer, evidence on the nature of the relationship has evolved with time and newer data. Studies examining links between baseline testosterone levels as well as testosterone therapy and incident prostate cancer, reveal a more complex relationship. Moreover, investigators have reported their initial experiences with supplementing testosterone in men with a history of both treated and untreated prostate cancer.

  View details for DOI 10.5534/wjmh.2015.33.3.125

  View details for PubMedID 26770932

• Selling blood and gametes during tough economic times: insights from Google search. Canadian journal of urology Wu, J. A., Ngo, T. C., Rothman, C., Breyer, B. N., Eisenberg, M. L. 2015; 22 (5): 7973-7977

  Abstract

  To use Google Insights search volume and publicly available economic indicators to test the hypothesis that sperm, egg, and blood donations increase during economic downturns and to demonstrate the feasibility of using Google search volume data to predict national trends in actual sperm, egg, and blood donations rates.Cross-correlation statistical analysis comparing Google search data for terms relating to blood, egg, and sperm donations with various economic indicators including the S&P 500 closing values, gross domestic product (GDP), the U.S. Index of Leading Indicators (U.S. Leading Index), gross savings rate, mortgage interest rates, unemployment rate, and consumer price index (CPI) from 2004-2011. A secondary analysis determined the Pearson correlation coefficient between Google search data with actual sperm, egg, and blood donation volume in the U.S. as measured by California Cryobank, the National Assisted Reproductive Technology Surveillance System, and the National Blood Collection and Utilization Survey, respectively. Significance of cross-correlation and Pearson correlation analysis as indicated by p value.There were several highly significant cross-correlation relationships between search volume and various economic indicators. Correlation between Google search volume for the term 'sperm donation,' 'egg donation,' and 'blood donation' with actual number of sperm, egg and blood donations in the United States demonstrated Pearson correlation coefficients of 0.2 (p > 0.10), -0.1 (p > 0.10), and 0.07 (p > 0.10), respectively. Temporal analysis showed an improved correlation coefficient of 0.9 (p < 0.05) for blood donation when shifted 12 months later relative to Google search volume.Google search volume data for search terms relating to sperm, egg, and blood donation increase during economic downturns. This finding suggests gamete and bodily fluid donations are influenced by market forces like other commodities. Google search may be useful for predicting blood donation trends but is more limited in predicting actual semen and oocyte donation patterns.

  View details for PubMedID 26432967

• Invited Commentary: The Association Between Marijuana Use and Male Reproductive Health AMERICAN JOURNAL OF EPIDEMIOLOGY Eisenberg, M. L. 2015; 182 (6): 482–84

  Abstract

  Approximately 15% of all couples are unable to conceive after a year and are labeled infertile. In recent years, increasing attention has been given to lifestyle factors that may impact fertility. In the United States, it is estimated that there are more than 17 million current users of marijuana with 4.6 million using marijuana almost daily. Although common, to date, little data exist on the impact of marijuana use on male fertility. In the current issue of the Journal, Gundersen et al. (Am J Epidemiol. 2015;182(6):473-481) provide data examining the relationship between marijuana use and semen quality from young men recruited out of the general Danish population. Men who reported daily marijuana use displayed significant lower sperm concentration and sperm counts compared with nonusers, while testosterone levels were higher. The current report provides important information for patients and providers regarding the negative association of marijuana use on semen quality. Although the benefit of marijuana cessation on recovery is uncertain, further study on the impact of marijuana use on male reproductive health is warranted as more states explore marijuana legalization.

  View details for DOI 10.1093/aje/kwv137

  View details for Web of Science ID 000361756000002

  View details for PubMedID 26283091

• Relationship between Vasectomy and Sexual Frequency JOURNAL OF SEXUAL MEDICINE Guo, D. P., Lamberts, R. W., Eisenberg, M. L. 2015; 12 (9): 1905-1910

  Abstract

  Men who are considering vasectomy as a means of contraception may have significant anxiety about their future sexual potency. As a result, couples may choose other forms of contraception with lower efficacy.We sought to determine the relationship between vasectomy and the frequency of sexual intercourse.We analyzed data from cycles 6 (2002) to 7 (2006-2008) of the National Survey of Family Growth to compare the frequency of sexual intercourse of men who had undergone vasectomy with men who had not. Analysis was performed using data from male and female responders, and excluded men who had never had sex and those below age 25. We constructed a multivariate logistic regression model to adjust for demographic, socioeconomic, reproductive, and health factors.The main outcome measure was the sexual frequency in the last 4 weeks.Among male responders, a total of 5838 men met criteria for our study; 353 had undergone vasectomy. For vasectomized men, the average frequency of sexual intercourse was 5.9 times per month compared with 4.9 times for nonvasectomized men. After adjusting for age, marital status, race, education, health, body mass index, children, and income, vasectomized men had an 81% higher odds (95% confidence interval [CI] 6-201%) of having intercourse at least once a week compared with nonvasectomized men. A total number of 5211 female respondents reported 670 of their partners had undergone vasectomy. For partners of vasectomized men, the average frequency of intercourse was 6.3 times per month, compared with 6.0 times for partners of nonvasectomized men. After adjustment, women with vasectomized partners had a 46% higher odds (95% CI 5-103%) of having sexual intercourse at least once a week compared with women with nonvasectomized partners (P = 0.024).Vasectomy is not associated with decreased sexual frequency. This finding may be helpful to couples as they consider contraceptive options.

  View details for DOI 10.1111/jsm.12962

  View details for Web of Science ID 000363456400008

  View details for PubMedID 26272461

• Demographic and socio-economic differences between men seeking infertility evaluation and those seeking surgical sterilization: from the National Survey of Family Growth BJU INTERNATIONAL Hotaling, J. M., Patel, D. P., Brant, W. O., Myers, J. B., Cullen, M. R., Eisenberg, M. L. 2015; 116 (2): 288-292

  Abstract

  To identify differences in demographic and socio-economic factors between men seeking infertility evaluation and those undergoing vasectomy, to address disparities in access to these services.Data from Cycle 6 and Cycle 7 (2002 and 2006-2008) of the National Survey of Family Growth (NSFG) were reviewed. The NSFG is a multistage probability survey designed to capture a nationally representative sample of households with men and women aged 15-45 years in the USA. The variables analysed included age, body mass index, self-reported health, alcohol use, race, religious affiliation, marital status, number of offspring, educational attainment, income level, insurance status and metropolitan home designation. Our primary outcome was the correlation of these demographic and socio-economic factors with evaluation for male infertility or vasectomy.Of the 11 067 men identified through the NSFG, 466 men (4.2%) sought infertility evaluation, representing 2 187 455 men nationally, and 326 (2.9%) underwent a vasectomy, representing 1 510 386 men nationally. Those seeking infertility evaluation were more likely to be younger and have fewer children (P = 0.001, 0.001) and less likely to be currently married (78 vs 74%; P = 0.010) or ever married (89 vs 97%; P = 0.002). Men undergoing a vasectomy were more likely to be white (86 vs 70%; P = 0.001). Men seeking infertility evaluation were more likely to have a college or graduate degree compared with men undergoing a vasectomy (68 vs 64%; P = 0.015). There was no difference between the two groups for all other variables.While differences in demographic characteristics such as age, offspring number and marital status were identified, measures of health, socio-economic status, religion and insurance were similar between men undergoing vasectomy and those seeking infertility services. These factors help characterize the utilization of male reproductive health services in the USA and may help address disparities in access to these services and improve public health strategies.

  View details for DOI 10.1111/bju.13012

  View details for Web of Science ID 000358529500024

• Demographic and socio-economic differences between men seeking infertility evaluation and those seeking surgical sterilization: from the National Survey of Family Growth. BJU international Hotaling, J. M., Patel, D. P., Brant, W. O., Myers, J. B., Cullen, M. R., Eisenberg, M. L. 2015; 116 (2): 288-92

  Abstract

  To identify differences in demographic and socio-economic factors between men seeking infertility evaluation and those undergoing vasectomy, to address disparities in access to these services.Data from Cycle 6 and Cycle 7 (2002 and 2006-2008) of the National Survey of Family Growth (NSFG) were reviewed. The NSFG is a multistage probability survey designed to capture a nationally representative sample of households with men and women aged 15-45 years in the USA. The variables analysed included age, body mass index, self-reported health, alcohol use, race, religious affiliation, marital status, number of offspring, educational attainment, income level, insurance status and metropolitan home designation. Our primary outcome was the correlation of these demographic and socio-economic factors with evaluation for male infertility or vasectomy.Of the 11 067 men identified through the NSFG, 466 men (4.2%) sought infertility evaluation, representing 2 187 455 men nationally, and 326 (2.9%) underwent a vasectomy, representing 1 510 386 men nationally. Those seeking infertility evaluation were more likely to be younger and have fewer children (P = 0.001, 0.001) and less likely to be currently married (78 vs 74%; P = 0.010) or ever married (89 vs 97%; P = 0.002). Men undergoing a vasectomy were more likely to be white (86 vs 70%; P = 0.001). Men seeking infertility evaluation were more likely to have a college or graduate degree compared with men undergoing a vasectomy (68 vs 64%; P = 0.015). There was no difference between the two groups for all other variables.While differences in demographic characteristics such as age, offspring number and marital status were identified, measures of health, socio-economic status, religion and insurance were similar between men undergoing vasectomy and those seeking infertility services. These factors help characterize the utilization of male reproductive health services in the USA and may help address disparities in access to these services and improve public health strategies.

  View details for DOI 10.1111/bju.13012

  View details for PubMedID 25777585

• Adult Ureterocele Presenting with Ureteral Obstruction and Urosepsis during Pregnancy UROLOGY JOURNAL Harris, C. R., Alwaal, A., Yang, G., Eisenberg, M. L., Breyer, B. N. 2015; 12 (4): 2285-2286

  View details for Web of Science ID 000363226100015

  View details for PubMedID 26341774

• Sperm Parameters and Semen Levels of Inflammatory Cytokines in Helicobacter pylori-infected Men UROLOGY Eisenberg, M. L. 2015; 86 (1): 46–47

  View details for PubMedID 26142580

• Prognostic features for testicular cancers (TCs): Can this be gleaned from pathology reports? Srinivas, S., Eisenberg, M., Skinner, E. C. AMER SOC CLINICAL ONCOLOGY. 2015

  View details for Web of Science ID 000358036903097

• Increased Risk of Cancer in Infertile Men: Analysis of US Claims Data JOURNAL OF UROLOGY Eisenberg, M. L., Li, S., Brooks, J. D., Cullen, M. R., Baker, L. C. 2015; 193 (5): 1596-1601

  Abstract

  Aberrations in reproductive fitness may be a harbinger of medical diseases in men. Data suggest a higher risk of testicular cancer in infertile men. However, the relationship between infertility and other cancers remains uncertain.We analyzed subjects from the Truven Health MarketScan® claims database from 2001 to 2009. Infertile men were identified through diagnosis and treatment codes. Comparison groups were created of men who underwent vasectomy and a control cohort of men who were not infertile and had not undergone vasectomy. The incidence of cancer was compared to national U.S. estimates. Infertile men were also compared to men who underwent vasectomy and the control cohort using a Cox regression model.A total of 76,083 infertile men were identified with an average age of 35.1 years. Overall 112,655 men who underwent vasectomy and 760,830 control men were assembled. Compared to age adjusted national averages, infertile, vasectomy and control subjects in the study cohorts had higher rates of all cancers and many individual cancers. In time to event analysis, infertile men had a higher risk of cancer than those who underwent vasectomy or controls. Infertile men had a higher risk of testis cancer, nonHodgkin lymphoma and all cancers than the vasectomy and control groups.Consistent with prior reports, we identified an increased risk of testicular cancer in infertile men. The current data also suggest that infertile men are at a mildly increased risk of all cancers in the years after infertility evaluation. Future research should focus on confirming these associations and elucidating pathways between infertility and cancer.

  View details for DOI 10.1016/j.juro.2014.11.080

  View details for Web of Science ID 000353113200052

  View details for PubMedID 25463997

• Relationship between physical occupational exposures and health on semen quality: data from the Longitudinal Investigation of Fertility and the Environment (LIFE) Study FERTILITY AND STERILITY Eisenberg, M. L., Chen, Z., Ye, A., Louis, G. M. 2015; 103 (5): 1271-1277

  Abstract

  To study the relationship among occupation, health, and semen quality in a cohort of men attempting to conceive.Observational prospective cohort.Not applicable.A total of 501 couples discontinuing contraception were followed for 1 year while trying to conceive; 473 men (94%) provided one semen sample, and 80% provided a second sample.None.Semen data obtained through at-home semen collection with next-day analysis/quantification.In all, complete data were available for 456 men, with a mean age of 31.8 years. Work-related heavy exertion was consistently associated with lower semen concentration and total sperm count. Thirteen percent of men who reported heavy exertion displayed oligospermia, compared with 6% who did not report workplace exertion. Shift work, night work, vibration, noise, heat, and prolonged sitting were not associated with semen quality. Men with high blood pressure had significantly lower strict morphology scores compared with normotensive men (17% vs. 21%). In contrast, hyperlipidemia, diabetes, and composite of total comorbidities were not associated with semen quality. The number of medications a man was taking as a proxy of health status was associated with semen quality. There was a negative association between number of medications and sperm count.A negative relationship among occupational exertion, hypertension, and the number of medications with semen quality was identified. As these are potentially modifiable factors, further research should determine whether treatment or cessation may improve male fecundity.

  View details for DOI 10.1016/j.fertnstert.2015.02.010

  View details for Web of Science ID 000353843700031

  View details for PubMedCentralID PMC4417418

• Relationship between physical occupational exposures and health on semen quality: data from the Longitudinal Investigation of Fertility and the Environment (LIFE) Study. Fertility and sterility Eisenberg, M. L., Chen, Z., Ye, A., Buck Louis, G. M. 2015; 103 (5): 1271-1277

  Abstract

  To study the relationship among occupation, health, and semen quality in a cohort of men attempting to conceive.Observational prospective cohort.Not applicable.A total of 501 couples discontinuing contraception were followed for 1 year while trying to conceive; 473 men (94%) provided one semen sample, and 80% provided a second sample.None.Semen data obtained through at-home semen collection with next-day analysis/quantification.In all, complete data were available for 456 men, with a mean age of 31.8 years. Work-related heavy exertion was consistently associated with lower semen concentration and total sperm count. Thirteen percent of men who reported heavy exertion displayed oligospermia, compared with 6% who did not report workplace exertion. Shift work, night work, vibration, noise, heat, and prolonged sitting were not associated with semen quality. Men with high blood pressure had significantly lower strict morphology scores compared with normotensive men (17% vs. 21%). In contrast, hyperlipidemia, diabetes, and composite of total comorbidities were not associated with semen quality. The number of medications a man was taking as a proxy of health status was associated with semen quality. There was a negative association between number of medications and sperm count.A negative relationship among occupational exertion, hypertension, and the number of medications with semen quality was identified. As these are potentially modifiable factors, further research should determine whether treatment or cessation may improve male fecundity.

  View details for DOI 10.1016/j.fertnstert.2015.02.010

  View details for PubMedID 25765658

• Anogenital distance as a measure of human male fertility JOURNAL OF ASSISTED REPRODUCTION AND GENETICS Eisenberg, M. L., Lipshultz, L. I. 2015; 32 (3): 479-484

  Abstract

  In humans, recent studies have correlated anogenital distance (AGD) in adult men to testicular function. While studies of a group of men suggest an association, the utility of AGD in an infertility evaluation remains uncertain. We sought to determine the utility of AGD to predict male fertility.Between 2010 and 2011, men were recruited at a urology clinic to participate. AGD was measured using digital calipers in men being evaluated at a urology clinic. ANOVA and ROC analyses were used to determine correlations between AGD, fatherhood status, and semen parameters.In all, 473 men were included in the analysis with a mean age of 43 ± 13 years. Anogenital distance was significantly longer in men with higher sperm concentration, total sperm count, and total motile sperm count. In order to evaluate the discriminating ability of AGD, ROC curves were created comparing AGD and total testis volume. The area under the curve (AUC) was significantly larger for total testis volume compared to AGD when evaluating fertility (0.71 vs 0.63, p = 0.02). Similarly, there was a trend towards a higher AUC for testis volume compared to AGD for sperm concentration and total sperm count. Stratification of men with long/short AGD and large/small testes also did not improve the predictive value of AGD.While AGD is associated with sperm production on a population level, at the individual level the distinction based AGD alone cannot accurately estimate the efficiency of spermatogenesis.

  View details for DOI 10.1007/s10815-014-0410-1

  View details for Web of Science ID 000351509400021

  View details for PubMedID 25533333

  View details for PubMedCentralID PMC4363236

• Testosterone therapy and mortality risk INTERNATIONAL JOURNAL OF IMPOTENCE RESEARCH Eisenberg, M. L., Li, S., Herder, D., LAMB, D. J., Lipshultz, L. I. 2015; 27 (2): 46-48

  Abstract

  Recent data suggest an increased risk of cardiovascular events and mortality in men on testosterone therapy (TT). To date, there are no long-term, prospective studies to determine safety. In such cases, retrospective observational studies can be helpful. We examined our patient database to determine whether TT altered the risk of all-cause mortality in men. We queried our hormone database for all men with a serum testosterone level and then examined charts to determine testosterone status. In all, 509 men had charts available for review. We linked our patient records to the National Death Index to determine mortality. Of the 509 men who met inclusion criteria, 284 were on TT and 225 did not use testosterone. Age (mean 54 years) and follow-up time (mean 10 years) were similar for both groups. In all, 19 men died--10 (4.4%) men not on TT and 9 (3.2%) men on TT. After adjusting for age and year of evaluation, there was no significant difference in the risk of death based on TT (hazard ratio 0.92, 95% confidence interval 0.36-2.35, P=1.0). There appears to be no change in mortality risk overall for men utilizing long-term testosterone therapy.

  View details for DOI 10.1038/ijir.2014.29

  View details for Web of Science ID 000351022400002

  View details for PubMedID 25078049

  View details for PubMedCentralID PMC4312542

• Testosterone therapy and cancer risk. BJU international Eisenberg, M. L., Li, S., Betts, P., Herder, D., Lamb, D. J., Lipshultz, L. I. 2015; 115 (2): 317-321

  Abstract

  To determine if testosterone therapy (TT) status modifies a man's risk of cancer.The Urology clinic hormone database was queried for all men with a serum testosterone level and charts examined to determine TT status. Patient records were linked to the Texas Cancer Registry to determine the incidence of cancer. Men accrued time at risk from the date of initiating TT or the first office visit for men not on TT. Standardised incidence rates and time to event analysis were performed.In all, 247 men were on TT and 211 did not use testosterone. In all, 47 men developed cancer, 27 (12.8%) were not on TT and 20 (8.1%) on TT. There was no significant difference in the risk of cancer incidence based on TT (hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.57-1.9; P = 1.8). There was no difference in prostate cancer risk based on TT status (HR 1.2, 95% CI 0.54-2.50).There was no change in cancer risk overall, or prostate cancer risk specifically, for men aged >40 years using long-term TT.

  View details for DOI 10.1111/bju.12756

  View details for PubMedID 24684569

• The relationship between male BMI and waist circumference on semen quality: data from the LIFE study. Human reproduction (Oxford, England) Eisenberg, M. L., Kim, S., Chen, Z., Sundaram, R., Schisterman, E. F., Louis, G. M. 2015; 30 (2): 493-494

  View details for DOI 10.1093/humrep/deu322

  View details for PubMedID 25516559

• Relationship between semen production and medical comorbidity FERTILITY AND STERILITY Eisenberg, M. L., Li, S., Behr, B., Pera, R. R., Cullen, M. R. 2015; 103 (1): 66-71

  Abstract

  To study the relationship between semen quality and current health status in a cohort of men evaluated for infertility.Cross-sectional study.Fertility clinic.Nine thousand three hundred eighty-seven men evaluated for infertility between 1994 and 2011.None.Charlson comorbidity index, medical diagnoses by organ system.At the time of evaluation, 9,387 men with a mean age of 38 years had semen data available. Of these men, 44% had at least one medical diagnosis unrelated to infertility. When stratifying the cohort by the Charlson comorbidity index (CCI), differences in all measured semen parameters were identified. Men with a higher CCI had lower semen volume, concentration, motility, total sperm count, and morphology scores. In addition, men with diseases of the endocrine, circulatory, genitourinary, and skin diseases all showed significantly higher rates of semen abnormalities. Upon closer examination of diseases of the circulatory system, men with hypertensive disease, peripheral vascular and cerebrovascular disease, and nonischemic heart disease all displayed higher rates of semen abnormalities.The current report identified a relationship between medical comorbidites and male semen production. Although genetics help guide a man's sperm production, his current condition and health play an important role.

  View details for DOI 10.1016/j.fertnstert.2014.10.017

  View details for Web of Science ID 000346911400015

  View details for PubMedID 25497466

• Semen quality, infertility and mortality in the USA. Human reproduction Eisenberg, M. L., Li, S., Behr, B., Cullen, M. R., Galusha, D., Lamb, D. J., Lipshultz, L. I. 2014; 29 (7): 1567-1574

  Abstract

  What is the relationship between semen parameters and mortality in men evaluated for infertility?Among men undergoing an infertility evaluation, those with abnormal semen parameters have a higher risk of death, suggesting a possible common etiology between infertility and mortality.Conflicting data exist that suggest either an inverse relationship or no relationship between semen quality and mortality.A study cohort was identified from two centers, each specializing in infertility care. In California, we identified men with data from 1994 to 2011 in the Stanford Reproductive Endocrinology and Infertility semen database. In Texas, we identified men with data from 1989 to 2009 contained in the andrology database at the Baylor College of Medicine Special Procedures Laboratory who were evaluated for infertility. Mortality was determined by data linkage to the National Death Index or Social Security Death Index. Comorbidity was estimated based on calculation of the Charlson Comorbidity Index or Centers for Medicare & Medicaid Services-Hierarchical Condition Categories Model.In all, 11,935 men were evaluated for infertility from 1989 to 2011. During 92 104 person years of follow-up, 69 of 11,935 men died (0.58%). The mean age at infertility evaluation was 36.6 years with a mean follow-up of 7.7 years.Compared with the general population, men evaluated for infertility had a lower risk of death with 69 deaths observed compared with 176.7 expected (Standardized mortality rate 0.39, 95% CI 0.30-0.49). When stratified by semen parameters, however, men with impaired semen parameters (i.e. male factor infertility) had significantly higher mortality rates compared with men with normal parameters (i.e. no male factor infertility). Low semen volume, sperm concentration, sperm motility, total sperm count and total motile sperm count were all associated with higher risk of death. In contrast, abnormal sperm morphology was not associated with mortality. While adjusting for current health status attenuated the association between semen parameters and mortality, men with two or more abnormal semen parameters still had a 2.3-fold higher risk of death compared with men with normal semen (95% CI 1.12-4.65).Our cohort represents infertile men, which may limit generalizability. As comorbidity relied on administrative data, granular information on each man regarding infertility diagnosis and lifestyle factors was unavailable.Men with impaired semen parameters have an increased mortality rate in the years following an infertility evaluation suggesting semen quality may provide a marker of health.This study is supported in part by P01HD36289 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development, National Institutes of Health (to D.J.L. and L.I.L.). The project was also partially supported by an NIH CTSA award number UL1 RR025744. None of the authors has any conflict of interest to declare.

  View details for PubMedID 24838701

• Semen quality, infertility and mortality in the USA HUMAN REPRODUCTION Eisenberg, M. L., Li, S., Behr, B., Cullen, M. R., Galusha, D., Lamb, D. J., Lipshultz, L. I. 2014; 29 (7): 1567-1574

  Abstract

  What is the relationship between semen parameters and mortality in men evaluated for infertility?Among men undergoing an infertility evaluation, those with abnormal semen parameters have a higher risk of death, suggesting a possible common etiology between infertility and mortality.Conflicting data exist that suggest either an inverse relationship or no relationship between semen quality and mortality.A study cohort was identified from two centers, each specializing in infertility care. In California, we identified men with data from 1994 to 2011 in the Stanford Reproductive Endocrinology and Infertility semen database. In Texas, we identified men with data from 1989 to 2009 contained in the andrology database at the Baylor College of Medicine Special Procedures Laboratory who were evaluated for infertility. Mortality was determined by data linkage to the National Death Index or Social Security Death Index. Comorbidity was estimated based on calculation of the Charlson Comorbidity Index or Centers for Medicare & Medicaid Services-Hierarchical Condition Categories Model.In all, 11,935 men were evaluated for infertility from 1989 to 2011. During 92 104 person years of follow-up, 69 of 11,935 men died (0.58%). The mean age at infertility evaluation was 36.6 years with a mean follow-up of 7.7 years.Compared with the general population, men evaluated for infertility had a lower risk of death with 69 deaths observed compared with 176.7 expected (Standardized mortality rate 0.39, 95% CI 0.30-0.49). When stratified by semen parameters, however, men with impaired semen parameters (i.e. male factor infertility) had significantly higher mortality rates compared with men with normal parameters (i.e. no male factor infertility). Low semen volume, sperm concentration, sperm motility, total sperm count and total motile sperm count were all associated with higher risk of death. In contrast, abnormal sperm morphology was not associated with mortality. While adjusting for current health status attenuated the association between semen parameters and mortality, men with two or more abnormal semen parameters still had a 2.3-fold higher risk of death compared with men with normal semen (95% CI 1.12-4.65).Our cohort represents infertile men, which may limit generalizability. As comorbidity relied on administrative data, granular information on each man regarding infertility diagnosis and lifestyle factors was unavailable.Men with impaired semen parameters have an increased mortality rate in the years following an infertility evaluation suggesting semen quality may provide a marker of health.This study is supported in part by P01HD36289 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development, National Institutes of Health (to D.J.L. and L.I.L.). The project was also partially supported by an NIH CTSA award number UL1 RR025744. None of the authors has any conflict of interest to declare.

  View details for DOI 10.1093/humrep/deu106

  View details for Web of Science ID 000338126500027

  View details for PubMedCentralID PMC4059337

• Parental age at delivery and a mans semen quality HUMAN REPRODUCTION Priskorn, L., Jensen, T. K., Lindahl-Jacobsen, R., Skakkebaek, N. E., Bostofte, E., Eisenberg, M. L. 2014; 29 (5): 1097-1102

  Abstract

  Is parental age at delivery associated with a man's semen quality?In this large register-based study both mother's and father's age are found to have minimal effects on semen quality in men.Both maternal and paternal age have been associated with a range of adverse health effects in the offspring. Given the varied health effects of parental age upon offspring, and the sensitivity of genital development to external factors, it is plausible that the age of a man's mother and father at conception may impact his reproductive health. To our knowledge this is the first examination of the effects of parental age on semen quality.A retrospective cohort study of 10 965 men with semen data and parental data.The study was based on Danish men referred to the Copenhagen Sperm Analysis Laboratory due to infertility in their partnership. Men born from 1960 and delivering a semen sample until year 2000 were included. The men were linked to the Danish Civil Registration System to obtain information on parent's age at delivery. Logistic regression analyses were used to calculate odds ratios and 95% confidence intervals for impaired semen quality. Linear regression analyses were used to examine a relationship between semen parameters and paternal age.There were no convincing effect of either mother's or father's age on a man's semen quality. As no trends were noted, the few statistically significant results are likely attributable to chance.Information regarding individual subject characteristics which may impact sperm production (i.e. smoking, BMI) were not available. While our sample size was large, we cannot exclude the possibility that a trend may have been identified with a still larger sample. In addition, the Danish Civil Registration System is merely administrative and hence does not discriminate between biological and adopted children. However, the low rate of adoption (≈2%) suggests that misclassification would have a minimal impact. The men were all referred to the laboratory for infertility problems in their partnership and, therefore, do not represent the general population. We, however, compared semen quality among men within the cohort, and it is therefore less important whether they, in fact, represent the general population.The current study found no link between parental age and a son's semen quality, suggesting other factors may explain recent impairments in men's reproductive health.This work was supported by the Hans and Nora Buchard's Fund and the Kirsten and Freddy Johansen's Fund. No competing interests.Not relevant.

  View details for DOI 10.1093/humrep/deu039

  View details for Web of Science ID 000334921400021

  View details for PubMedID 24578474

• Fertility issues in cancer survivorship. CA: a cancer journal for clinicians Kort, J. D., Eisenberg, M. L., Millheiser, L. S., Westphal, L. M. 2014; 64 (2): 118-134

  Abstract

  Answer questions and earn CME/CNE Breakthroughs in cancer diagnosis and treatment have led to dramatic improvements in survival and the need to focus on survivorship issues. Chemotherapy and radiotherapy can be gonadotoxic, resulting in impaired fertility. Techniques to help cancer survivors reproduce have been improving over the past decade. Discussion of the changes to a patient's reproductive health after cancer treatment is essential to providing comprehensive quality care. The purpose of this review is to aid in pre- and posttreatment counseling, focusing on fertility preservation and other strategies that may mitigate risks to the patient's reproductive, sexual, and overall health. CA Cancer J Clin 2014;64:118-134. (©) 2013 American Cancer Society.

  View details for DOI 10.3322/caac.21205

  View details for PubMedID 24604743

• Impact of fresh versus cryopreserved testicular sperm upon intracytoplasmic sperm injection pregnancy outcomes in men with azoospermia due to spermatogenic dysfunction: a meta-analysis FERTILITY AND STERILITY Ohlander, S., Hotaling, J., Kirshenbaum, E., Niederberger, C., Eisenberg, M. L. 2014; 101 (2): 344-349

  Abstract

  To determine if clinical pregnancy rates and fertilization rates with the use of cryopreserved sperm for intracytoplasmic sperm injection (ICSI) in patients with azoospermia due to spermatogenic dysfunction (i.e., nonobstructive azoospermia) are similar to those with fresh sperm.Systematic review and meta-analysis.Academic medical center.Azoospermic men secondary to spermatogenic dysfunction.Not applicable.Clinical pregnancy rate, fertilization rate.Eleven studies met criteria for the outcome of clinical pregnancy rate. Seventy-nine (28.7%) of 275 intracytoplasmic sperm injection cycles using fresh testicular sperm resulted in a clinical pregnancy, compared with 84 (28.1%) of 299 intracytoplasmic sperm injection cycles using cryopreserved sperm (relative risk [RR] 1.00, 95% confidence interval [CI] 0.75-1.33). Ten studies met criteria for the outcome of fertilization rate. A total of 1,422 (52.9%) of 2,687 oocytes injected with fresh testicular sperm were fertilized, compared with 1,490 (54.0%) of 2,757 oocytes injected with cryopreserved sperm (RR 0.97, 95% CI 0.92-1.02).In men with azoospermia due to spermatogenic dysfunction, there is no statistical difference between the use of fresh versus cryopreserved-thawed testicular sperm when assessing clinical pregnancy or fertilization rates in couples undergoing ICSI.

  View details for DOI 10.1016/j.fertnstert.2013.10.012

  View details for Web of Science ID 000330578000014

  View details for PubMedID 24345355

• Use of fresh versus cryopreserved sperm. Fertility and sterility Ohlander, S., Hotaling, J., Kirshenbaum, E., Niederberger, C., Eisenberg, M. L. 2014; 101 (2)

  View details for DOI 10.1016/j.fertnstert.2013.12.017

  View details for PubMedID 24485506

• The relationship between male BMI and waist circumference on semen quality: data from the LIFE study. Human reproduction Eisenberg, M. L., Kim, S., Chen, Z., Sundaram, R., Schisterman, E. F., Buck Louis, G. M. 2014; 29 (2): 193-200

  Abstract

  What is the relationship between body size, physical activity and semen parameters among male partners of couples attempting to become pregnant?Overweight and obesity are associated with a higher prevalence of low ejaculate volume, sperm concentration and total sperm count.Higher BMI is associated with impaired semen parameters, while increasing waist circumference (WC) is also associated with impaired semen parameters in infertile men.Data from the Longitudinal Investigation of Fertility and the Environment (LIFE) Study were utilized. The LIFE study is a population-based prospective cohort of 501 couples attempting to conceive in two geographic areas (Texas and Michigan, USA) recruited in 2005-2009. Couples were recruited from four counties in Michigan and 12 counties in Texas to ensure a range of environmental exposures and lifestyle characteristics. In person interviews were conducted to ascertain demographic, health and reproductive histories followed by anthropometric assessment.We categorized BMI (kg/m(2)) as <25.0 (underweight and normal), 25.0-29.9 (overweight) 30.0-34.9 (obese, class I) and ≥35 (obese, class II) for analysis. Data were available for analysis in 468 men (93% participation), with a mean ± SD age of 31.8 ± 4.8 years, BMI of 29.8 ± 5.6 kg/m(2) and WC of 100.8 ± 14.2 cm. The majority of the cohort (82%) was overweight or obese with 58% reporting physical activity <1 time/week. The median sperm concentration for the men in the cohort was 60.2 M/ml with 8.6% having oligospermia (<15 M/ml).When examining semen parameters, ejaculate volume showed a linear decline with increasing BMI and WC (P < 0.01). Similarly, the total sperm count showed a negative linear association with WC (P < 0.01). No significant relationship was seen between body size (i.e. BMI or WC) and semen concentration, motility, vitality, morphology or DNA fragmentation index. The percentage of men with abnormal volume, concentration and total sperm increased with increasing body size (P < 0.05). No relationship between physical activity and semen parameters was identified.Our cohort was largely overweight and sedentary, which may result in limited external validity, i.e. generalizability. The lack of physical activity did preclude examination of exercise more frequently than once per week, thus our ability to examine more active individuals is limited.Body size (as measured by BMI or WC) is negatively associated with semen parameters with little influence of physical activity. Our findings are the first showing a relationship between WC and semen parameters in a sample of men without known infertility. Given the worldwide obesity epidemic, further study of the role of weight loss to improve semen parameters is warranted.Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Contracts #N01-HD-3-3355, N01-HD-3-3356 and N01-HD-3-3358). There are no competing interests.

  View details for DOI 10.1093/humrep/det428

  View details for PubMedID 24306102

  View details for PubMedCentralID PMC3896223

• Semen quality and time to pregnancy: the Longitudinal Investigation of Fertility and the Environment Study FERTILITY AND STERILITY Louis, G. M., Sundaram, R., Schisterman, E. F., Sweeney, A., Lynch, C. D., Kim, S., Maisog, J. M., Gore-Langton, R., Eisenberg, M. L., Chen, Z. 2014; 101 (2): 453-462

  Abstract

  To assess semen parameters and couple fecundity as measured by time to pregnancy (TTP).Observational prospective cohort with longitudinal measurement of TTP.Sixteen Michigan/Texas counties.A total of 501 couples discontinuing contraception were followed for 1 year while trying to conceive; 473 men (94%) provided one semen sample, and 80% provided two samples.None.Using prospectively measured TTP, fecundability odds ratios (FORs) and 95% confidence intervals (CIs) were estimated for 36 individual semen quality parameters accounting for repeated semen samples, time off contraception, abstinence, enrollment site, and couples' ages, body mass indices, and serum cotinine concentrations.In adjusted models, semen quality parameters were associated with significantly shorter TTP as measured by FORs >1: percent motility, strict and traditional morphology, sperm head width, elongation factor, and acrosome area. Significantly longer TTPs or FORs <1 were observed for morphologic categories amorphous and round sperm heads and neck/midpiece abnormalities. No semen quality parameters achieved significance when simultaneously modeling all other significant semen parameters and covariates, except for percent coiled tail when adjusting for sperm concentration (FOR 0.99; 95% CI 0.99-1.00). Male age was consistently associated with reduced couple fecundity (FOR 0.96; 95% CI 0.93-0.99), reflecting a longer TTP across all combined models. Female but not male body mass index also conferred a longer TTP (FOR 0.98; 95% CI 0.96-0.99).Several semen measures were significantly associated with TTP when modeled individually but not jointly and in the context of relevant couple-based covariates.

  View details for DOI 10.1016/j.fertnstert.2013.10.022

  View details for Web of Science ID 000330578000030

  View details for PubMedID 24239161

  View details for PubMedCentralID PMC3946620

• The relationship between male BMI and waist circumference on semen quality: data from the LIFE study HUMAN REPRODUCTION Eisenberg, M. L., Kim, S., Chen, Z., Sundaram, R., Schisterman, E. F., Louis, G. M. 2014; 29 (2): 193-200

  Abstract

  What is the relationship between body size, physical activity and semen parameters among male partners of couples attempting to become pregnant?Overweight and obesity are associated with a higher prevalence of low ejaculate volume, sperm concentration and total sperm count.Higher BMI is associated with impaired semen parameters, while increasing waist circumference (WC) is also associated with impaired semen parameters in infertile men.Data from the Longitudinal Investigation of Fertility and the Environment (LIFE) Study were utilized. The LIFE study is a population-based prospective cohort of 501 couples attempting to conceive in two geographic areas (Texas and Michigan, USA) recruited in 2005-2009. Couples were recruited from four counties in Michigan and 12 counties in Texas to ensure a range of environmental exposures and lifestyle characteristics. In person interviews were conducted to ascertain demographic, health and reproductive histories followed by anthropometric assessment.We categorized BMI (kg/m(2)) as <25.0 (underweight and normal), 25.0-29.9 (overweight) 30.0-34.9 (obese, class I) and ≥35 (obese, class II) for analysis. Data were available for analysis in 468 men (93% participation), with a mean ± SD age of 31.8 ± 4.8 years, BMI of 29.8 ± 5.6 kg/m(2) and WC of 100.8 ± 14.2 cm. The majority of the cohort (82%) was overweight or obese with 58% reporting physical activity <1 time/week. The median sperm concentration for the men in the cohort was 60.2 M/ml with 8.6% having oligospermia (<15 M/ml).When examining semen parameters, ejaculate volume showed a linear decline with increasing BMI and WC (P < 0.01). Similarly, the total sperm count showed a negative linear association with WC (P < 0.01). No significant relationship was seen between body size (i.e. BMI or WC) and semen concentration, motility, vitality, morphology or DNA fragmentation index. The percentage of men with abnormal volume, concentration and total sperm increased with increasing body size (P < 0.05). No relationship between physical activity and semen parameters was identified.Our cohort was largely overweight and sedentary, which may result in limited external validity, i.e. generalizability. The lack of physical activity did preclude examination of exercise more frequently than once per week, thus our ability to examine more active individuals is limited.Body size (as measured by BMI or WC) is negatively associated with semen parameters with little influence of physical activity. Our findings are the first showing a relationship between WC and semen parameters in a sample of men without known infertility. Given the worldwide obesity epidemic, further study of the role of weight loss to improve semen parameters is warranted.Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Contracts #N01-HD-3-3355, N01-HD-3-3356 and N01-HD-3-3358). There are no competing interests.

  View details for DOI 10.1093/humrep/det428

  View details for Web of Science ID 000330842800003

  View details for PubMedCentralID PMC3896223

• Diabetes Severity, Metabolic Syndrome, and the Risk of Erectile Dysfunction JOURNAL OF SEXUAL MEDICINE Weinberg, A. E., Eisenberg, M., Patel, C. J., Chertow, G. M., Leppert, J. T. 2013; 10 (12): 3102-3109

  Abstract

  Erectile dysfunction (ED) is more common in men with type 2 diabetes mellitus (T2DM), obesity, and/or the metabolic syndrome (MetS).The aim of this study is to investigate the associations among proxy measures of diabetic severity and the presence of MetS with ED in a nationally representative U.S. data sample.We performed a cross-sectional analysis of adult participants in the 2001-2004 National Health and Nutrition Examination Survey.ED was ascertained by self-report. T2DM severity was defined by calculated measures of glycemic control and insulin resistance (IR). IR was estimated using fasting plasma insulin (FPI) levels and the homeostasis model assessment of IR (HOMA-IR) definition. We classified glycemic control using hemoglobin-A1c (HbA1c) and fasting plasma glucose (FPG) levels. MetS was defined by the American Heart Association and National Heart, Lung, and Blood Institute criteria. Logistic regression models, adjusted for sociodemographics, risk factors, and comorbidities, were fitted for each measure of T2DM severity, MetS, and the presence of ED.Proxy measures of glycemic control and IR were associated with ED. Participants with FPG between 100-126 mg/dL (5.6-7 mmol/L) and ≥ 126 mg/dL (>7 mmol/L) had higher odds of ED, odds ratio (OR) 1.22 (confidence interval or CI, 0.83-1.80), and OR 2.68 (CI, 1.48-4.86), respectively. Participants with HbA1c 5.7-6.4% (38.8-46.4 mmol/mol) and ≥ 6.5% (47.5 mmol/mol) had higher odds of ED (OR 1.73 [CI, 1.08-2.76] and 3.70 [CI, 2.19-6.27], respectively). When FPI and HOMA-IR were evaluated by tertiles, there was a graded relation among participants in the top tertile. In multivariable models, a strong association remained between HbA1c and ED (OR 3.19 [CI,1.13-9.01]). MetS was associated with >2.5-fold increased odds of self reported ED (OR 2.55 [CI, 1.85-3.52]).Poor glycemic control, impaired insulin sensitivity, and the MetS are associated with a heightened risk of ED.

  View details for DOI 10.1111/jsm.12318

  View details for PubMedID 24010555

• Increased risk of cancer among azoospermic men. Fertility and sterility Eisenberg, M. L., Betts, P., Herder, D., Lamb, D. J., Lipshultz, L. I. 2013; 100 (3): 681-685 e1

  Abstract

  To determine whether men with azoospermia are at an elevated risk of developing cancer in the years following an infertility evaluation.Cohort study.United States andrology clinic.A total of 2,238 men with complete records were evaluated for infertility at a single andrology clinic in Texas from 1989 to 2009.None.Cancer incidence was determined by linkage to the Texas Cancer Registry.In all, 451 men had azoospermia, and 1,787 were not azoospermic, with a mean age at infertility evaluation of 35.7 years. Compared with the general population, infertile men had a higher risk of cancer, with 29 cases observed compared with 16.7 expected (standardized incidence rate [SIR] 1.7, 95% confidence interval [CI] 1.2-2.5). When stratifying by azoospermia status, azoospermic men had an elevated risk of cancer (SIR 2.9, 95% CI 1.4-5.4). Infertile men without azoospermia had a trend toward a higher rate of cancer (SIR 1.4, 95% CI 0.9-2.2). The Cox regression model revealed that azoospermic men had 2.2-fold higher cancer risk compared with nonazoospermic men (hazard ratio 2.2, 95% CI 1.0-4.8).Men with azoospermia have an increased risk of subsequently developing cancer, suggesting a possible common etiology between azoospermia and cancer development. Additional follow-up of azoospermic men after reproductive efforts end may be warranted.

  View details for DOI 10.1016/j.fertnstert.2013.05.022

  View details for PubMedID 23790640

• The relationship between anogenital distance and the androgen receptor CAG repeat length. Asian journal of andrology Eisenberg, M. L., Hsieh, T., Pastuszak, A. W., McIntyre, M. G., Walters, R. C., Lamb, D. J., Lipshultz, L. I. 2013; 15 (2): 286-289

  Abstract

  Anogenital distance (AGD) is used to define degree of virilization of genital development, with shorter length being associated with feminization and male infertility. The first exon of the androgen receptor (AR) consists of a polymorphic sequence of cytosine-adenine-guanine (CAG) repeats, with longer CAG repeat lengths being associated with decreased receptor function. We sought to determine if there is an association between AGD and AR CAG repeat length. A cross-sectional, prospective cohort of men evaluated at a urology clinic at a single institution was recruited. AGD (the distance from the posterior scrotum to the anal verge) and penile length (PL) were measured. Sanger DNA sequence analysis was used to define CAG repeat length. AGD and CAG repeat lengths in 195 men were determined. On unadjusted analysis, there was no linear relationship between CAG repeat length and PL (P=0.17) or AGD (P=0.31). However, on sub-population analyses, those men with longer CAG repeat lengths (>26) had significantly shorter AGDs compared to men with shorter CAG repeat lengths. For example, the mean AGD was 41.9 vs. 32.4 mm with a CAG repeat length ≤26 vs. >26 (P=0.01). In addition, when stratifying the cohort based on AGD, those with AGD less than the median (i.e. 40 mm) had a longer CAG repeat length compared to men with an AGD >40 mm (P=0.02). In summary, no linear relationship was found between AGD and AR CAG repeat length overall.

  View details for DOI 10.1038/aja.2012.126

  View details for PubMedID 23334200

• The relationship between anogenital distance and age ANDROLOGY Eisenberg, M. L., Hsieh, T., Lipshultz, L. I. 2013; 1 (1): 90-93

  Abstract

  In humans, recent studies have correlated anogenital distance (AGD) in adult men to intrinsic testicular function. Although rodent studies suggest that AGD is determined in utero and remains constant in adult life, it is not certain if AGD remains constant across a man's adult life. We sought to determine if adult male AGD varies based on age. A cross-sectional study of men being evaluated at a men's health clinic. Anogenital distance (the distance from the posterior aspect of the scrotum to the anal verge) and penile length (PL) were measured using digital callipers. anova and linear regression were used to determine correlations between AGD, fatherhood status and age. In all, 473 men were included in the analysis with a mean age of 43 ± 13 years. The mean AGD for the group was 39 ± 13 mm. Anogenital distance did not vary between age categories for the entire group, for fathers, and for childless men. Moreover, penile length also remained constant across age categories. On adjusted analyses stratified by fatherhood status, there was no relationship between AGDp and age. The current cross-sectional study demonstrates that anogenital distance, defined as the distance from the posterior scrotum to the anal verge, is similar for men of different ages. As such, AGD may provide a measure for genital development and function throughout adult life. However, confirmation with longitudinal studies is needed.

  View details for DOI 10.1111/j.2047-2927.2012.00019.x

  View details for Web of Science ID 000315461700013

  View details for PubMedID 23258635

• Paternal aging and increased risk of congenital disease, psychiatric disorders, and cancer PATERNAL INFLUENCES ON HUMAN REPRODUCTIVE SUCCESS Conti, S. L., Eisenberg, M. L., Carrell, D. 2013: 93–102

  View details for Web of Science ID 000323554200011

• Increased cancer risk and azoospermia. Fertility and sterility Eisenberg, M. L., Betts, P. n., Herder, D. n., Lamb, D. J., Lipshultz, L. I. 2013

  View details for DOI 10.1016/j.fertnstert.2013.06.025

  View details for PubMedID 23850299

• Anogenital distance and the risk of prostate cancer. BJU international Eisenberg, M. L. 2012; 110 (11): E711-?

  View details for DOI 10.1111/j.1464-410X.2012.11524.x

  View details for PubMedID 22984939

• The relationship between anogenital distance and the efficacy of varicocele repair. BJU international Eisenberg, M. L., Shy, M., Herder, D., Walters, R. C., Lipshultz, L. I. 2012; 110 (11): E927-30

  Abstract

  Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Anogenital distance (AGD) is a marker of genital development and adult testicular function. To date, there is no data on the clinical utility of using such an anthropomorphic variable. About 30% of men will have no improvement in semen parameters after varicocele repair. It is currently difficult to assess which patients are most likely to benefit from surgical repair. The present study showed that men with a longer AGD had a higher likelihood of improvement after varicocelectomy. As such, AGD may allow clinicians to better counsel men on the efficacy of varicocele repair.• To investigate whether anogenital distance (AGD) can identify men most likely to show improved semen parameters after varicocele ligation, as AGD has been shown to correlate with intrinsic adult testicular function.• Men with varicoceles who were evaluated at a men's reproductive health clinic in Houston were recruited. • AGD (the distance from the posterior aspect of the scrotum to the anal verge) was measured using digital callipers. • Logistic regression was used to compare outcomes after stratifying men based on AGD.• In all, 46 men with a mean (sd) age of 33.1 (6.3) years with postoperative semen data were recruited. • Semen concentration, motility, and total motile sperm count all showed significant improvement postoperatively (P < 0.01). • While 48% of men with a shorter AGD had improvements in sperm concentration postoperatively, 84% of men with a longer AGD improved (P = 0.01). • There was a trend toward a lower percentage of men (62% vs 84%) with shorter AGDs showing improvements in total motile sperm count (P = 0.09).• AGD may provide a novel metric to assess intrinsic testicular function and predict efficacy of varicocele repair.

  View details for DOI 10.1111/j.1464-410X.2012.11154.x

  View details for PubMedID 22520827

• The relationship between anogenital distance and the efficacy of varicocele repair BJU INTERNATIONAL Eisenberg, M. L., Shy, M., Herder, D., Walters, R. C., Lipshultz, L. I. 2012; 110 (11C): E927-E930

  Abstract

  Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Anogenital distance (AGD) is a marker of genital development and adult testicular function. To date, there is no data on the clinical utility of using such an anthropomorphic variable. About 30% of men will have no improvement in semen parameters after varicocele repair. It is currently difficult to assess which patients are most likely to benefit from surgical repair. The present study showed that men with a longer AGD had a higher likelihood of improvement after varicocelectomy. As such, AGD may allow clinicians to better counsel men on the efficacy of varicocele repair.• To investigate whether anogenital distance (AGD) can identify men most likely to show improved semen parameters after varicocele ligation, as AGD has been shown to correlate with intrinsic adult testicular function.• Men with varicoceles who were evaluated at a men's reproductive health clinic in Houston were recruited. • AGD (the distance from the posterior aspect of the scrotum to the anal verge) was measured using digital callipers. • Logistic regression was used to compare outcomes after stratifying men based on AGD.• In all, 46 men with a mean (sd) age of 33.1 (6.3) years with postoperative semen data were recruited. • Semen concentration, motility, and total motile sperm count all showed significant improvement postoperatively (P < 0.01). • While 48% of men with a shorter AGD had improvements in sperm concentration postoperatively, 84% of men with a longer AGD improved (P = 0.01). • There was a trend toward a lower percentage of men (62% vs 84%) with shorter AGDs showing improvements in total motile sperm count (P = 0.09).• AGD may provide a novel metric to assess intrinsic testicular function and predict efficacy of varicocele repair.

  View details for DOI 10.1111/j.1464-410X.2012.11154.x

  View details for Web of Science ID 000315029700025

• PARENTHOOD, HOST RESISTANCE TO THE COMMON COLD, AND IMPAIRED FERTILITY PSYCHOSOMATIC MEDICINE Eisenberg, M. L. 2012; 74 (9): 988-988

  View details for DOI 10.1097/PSY.0b013e318273880f

  View details for Web of Science ID 000311131800017

  View details for PubMedID 23107840

• Seasonal Fluctuations in Testosterone-Estrogen Ratio in Men From the Southwest United States JOURNAL OF ANDROLOGY Moskovic, D. J., Eisenberg, M. L., Lipshultz, L. I. 2012; 33 (6): 1298-1304

  Abstract

  Although controversial, seasonal variations in testosterone have been observed in several populations of men throughout the world. This finding might have an impact on screening and treatment of hypogonadism. We examined the circannual patterns of sex hormones in the Southwest United States. A prospectively assembled database of almost 11 000 patients in a men's health practice was used to collect data on testosterone, estradiol, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and dehydroepiandrosterone-sulfate (DHEA-S). Patient age, address, and date of visit were recorded. Of note, testosterone-estrogen ratio (T/E ratio) and free testosterone were calculated values. The data were grouped by month and by season (3-month intervals beginning with June, July, and August as summer). Analysis of variance was used to compare hormone levels between seasonal and monthly data sets, with P < .05 regarded as statistical significance. Statistically significant differences in estradiol (P = .02), T/E ratio (P < .01), FSH (P = .02), and SHBG (P < .01) were observed between seasons. Peak-to-trough variations were as follows: 6% for estradiol, 16.5% for T/E ratio, 11.0% for FSH, and 11.6% for SHBG. The T/E ratio peaked in the spring and was at its nadir in the fall. No differences in testosterone (P = .21), LH (P = .25), free testosterone (P = .08), and DHEA-S (P = .11) were observed. Statistically significant evidence of variation in estradiol and T/E ratio were identified in the men included in this study. Although this is consistent with seasonal body habitus changes, physical activity levels, and hypothesized hormonal patterns, the variability reported in the literature makes further trials covering a broader geographic region important to confirm the findings.

  View details for DOI 10.2164/jandrol.112.016386

  View details for Web of Science ID 000312113200032

  View details for PubMedID 22790643

• The relationship between anogenital distance and azoospermia in adult men INTERNATIONAL JOURNAL OF ANDROLOGY Eisenberg, M. L., Shy, M., Walters, R. C., Lipshultz, L. I. 2012; 35 (5): 726-730

  Abstract

  Anogenital distance (AGD) is a marker for endocrine disruption in animal studies in which decreased male AGD has been associated with testicular dysfunction. The objective of the study was to investigate whether anogenital distance could distinguish men with obstructive azoospermia (OA) from those with nonobstructive azoospermia (NOA). To accomplish this, azoospermic men were recruited and evaluated at a men's reproductive health clinic in Houston, TX. Anogenital distance (the distance from the posterior aspect of the scrotum to the anal verge) and penile length (PL) were measured using digital calipers. Testis size was estimated by physical examination. Logistic regression was used to compare AGD lengths in men with OA and men with NOA. A total of 69 OA men (mean age: 44.2 ± 9.2) and 29 NOA men (mean age: 32.8 ± 4.8) were recruited. The NOA men possessed significantly shorter mean AGD than the men with OA (AGD: 36.3 vs. 41.9 mm, p = 0.01). An AGD of less than 30 mm, had a 91% specificity in accurately classifying NOA. Moreover, after adjustment for age, race, and BMI, an AGD of less than 30 mm yielded a significantly increased odds of NOA compared to OA (OR 5.6, 95% CI 1.0, 30.7). In summary, AGD may provide a novel metric for assessing testicular function in men and in distinguishing OA from NOA.

  View details for DOI 10.1111/j.1365-2605.2012.01275.x

  View details for Web of Science ID 000308642100014

  View details for PubMedID 22519659

• Sperm counts and sperm sex ratio in male infertility patients ASIAN JOURNAL OF ANDROLOGY Eisenberg, M. L., Murthy, L., Hwang, K., Lamb, D. J., Lipshultz, L. I. 2012; 14 (5): 683-686

  Abstract

  In recent years, investigators have noted a trend toward a declining proportion of male births in many industrialized nations. While men bear the sex-determining chromosome, the role of the female partner as it pertains to fertilization or miscarriage may also alter the gender ratio. We attempted to determine a man's secondary sex ratio (F1 generation) by directly examining the sex chromosomes of his sperm. We examined our male infertility clinic database for all men who had undergone a semen fluorescence in situ hybridization (FISH). Patient demographic and semen parameters were recorded. Chi-squared analysis was used to compare gender ratios (Y chromosomes/total chromosomes). Multivariable logistic regression was used to predict the odds of possessing a Y-bearing sperm after accounting for demographic and semen parameters. A total of 185 men underwent sperm FISH. For the entire cohort, the proportion of Y chromosome-bearing sperm was 51.5%. Men with less than five million motile sperm had a significantly lower proportion of Y chromosome-bearing sperm (50.8%) compared to men with higher sperm counts (51.6%; P=0.02). After multivariable adjustment, a higher sperm concentration, total motile sperm count and semen volume significantly increased the odds of having a Y chromosome-bearing sperm (P<0.01). As a man's sperm production declines, so does the proportion of Y chromosome-bearing sperm. Thus, a man's reproductive potential may predict his ability to sire male offspring.

  View details for DOI 10.1038/aja.2012.58

  View details for Web of Science ID 000308666400009

  View details for PubMedID 22842703

• Caucasian male infants and boys with hypospadias exhibit reduced anogenital distance HUMAN REPRODUCTION Hsieh, M. H., Eisenberg, M. L., Hittelman, A. B., Wilson, J. M., Tasian, G. E., Baskin, L. S. 2012; 27 (6): 1577-1580

  Abstract

  Animal models of endocrine dysfunction have associated male genital defects with reduced anogenital distance (AGD). Human studies have correlated shorter AGD with exposure to putative endocrine disruptors in the environment but have not examined AGD in hypospadiac boys. We measured AGD in boys with hypospadias and those with normal genitals.Data were collected prospectively on boys undergoing urologic procedures at the University of California San Francisco and the Children's Hospital of Oakland, CA, USA. Data included age, race, height, weight, BMI, urologic diagnoses and AGD. To minimize any potential effects of race on observed AGD, we examined only Caucasian boys. Differences between boys with hypospadias and those with normal genitals were examined through two-tailed Student's t-tests.One hundred and nineteen Caucasian boys ranging in age from 4 to 86 months underwent AGD measurement, of which 42 and 77 were boys with normal genitals and hypospadias, respectively. The mean (±SD) AGD of boys with hypospadias was 67 ± 1.2 versus 73 ± 1 mm for boys with normal genitals (P = 0.002). In these age-unmatched patient groups, there were also differences in age, height and weight (P = 0.0001, 0.0002 and 0.0004, respectively). After age matching (all <2 years of age), boys with hypospadias (n= 26) still featured a shorter AGD than boys with normal genitals (n= 26; 62 ± 2 versus 68 ± 2 mm respectively, P = 0.033) but the differences in age, height and weight were no longer significant.In humans, hypospadias may indeed be associated with reduced AGD. Additional studies are needed to corroborate these preliminary findings and to determine their etiology.

  View details for DOI 10.1093/humrep/des087

  View details for Web of Science ID 000304530900004

  View details for PubMedID 22434852

  View details for PubMedCentralID PMC3357195

• IS VITAMIN D ASSOCIATED WITH ED? A REVIEW OF A COMPUTERIZED MEDICAL RECORD SYSTEM AT A TERTIARY CARE MEDICAL CENTER Shindel, A., Smith, J., Eisenberg, M., Breyer, B. WILEY-BLACKWELL. 2012: 7–7

  View details for Web of Science ID 000299826700016

• THE RELATIONSHIP BETWEEN ANOGENITAL DISTANCE AND REPRODUCTIVE HORMONE LEVELS IN ADULT MEN Eisenberg, M., Jensen, T., Walters, R., Skakkebaek, N., Lipshultz, L. WILEY-BLACKWELL. 2012: 17–17

  View details for Web of Science ID 000299826700051

• The Relationship Between Anogenital Distance and Reproductive Hormone Levels in Adult Men JOURNAL OF UROLOGY Eisenberg, M. L., Jensen, T. K., Walters, R. C., Skakkebaek, N. E., Lipshultz, L. I. 2012; 187 (2): 594-598

  Abstract

  Anogenital distance is a marker for endocrine disruption in animal studies in which decreased distance has been associated with testicular dysfunction. In this study we investigated whether anogenital distance was associated with reproductive hormone levels in adult men.A total of 116 men (mean age 36.1 ± 8.0 years) were evaluated at an andrology clinic in Houston. Anogenital distance (the distance from the posterior aspect of the scrotum to the anal verge) and penile length were measured using digital calipers. Testis size was estimated by physical examination. Linear regression was used to determine correlations between genital measurements and hormone levels.Anogenital distance (r = 0.20, p = 0.03) and penile length (r = 0.20, p = 0.03) were significantly associated with serum testosterone levels while total testis size was not (r = 0.17, p = 0.07). No relationship between genital length and luteinizing hormone, follicle-stimulating hormone or estradiol was identified. After adjusting for age the serum testosterone increased by 20.1 ng/dl (95% CI 1.8, 38.4; p = 0.03) for each 1 cm increase in anogenital distance. On multivariable models no statistically significant relationship existed between penile length and testosterone levels. Moreover men with hypogonadal testosterone levels (less than 300 ng/dl) had a significantly shorter anogenital distance compared to men with higher testosterone levels (31.6 vs 37.3 mm, p = 0.02).Anogenital distance may provide a novel metric to assess testicular function in men. Assuming that anogenital distance at birth predicts adult anogenital distance, our findings suggest a fetal origin for adult testicular function.

  View details for DOI 10.1016/j.juro.2011.10.041

  View details for Web of Science ID 000299070400082

  View details for PubMedID 22177168

• Men Who Seek Infertility Care May Not Represent the General US Population: Data From the National Survey of Family Growth UROLOGY Hotaling, J. M., Davenport, M. T., Eisenberg, M. L., Vandeneeden, S. K., Walsh, T. J. 2012; 79 (1): 123-127

  Abstract

  To examine the National Survey of Family Growth to identify differences in the characteristics of men who did and did not seek infertility care to determine whether such men are representative of the U.S. population.We analyzed the data from the 2002 (cycle 6) National Survey of Family Growth. In-home interviews were conducted from March 2002 to February 2003. A total of 4928 men were surveyed, with underrepresented groups sampled at greater rates to provide an adequate sample size for meaningful statistical analyses. The use of infertility services was queried by a single question: "Have you been to a doctor to talk about ways to help have a baby together?" The demographic and socioeconomic variables, including age, marital status, number of children, race, religion, income, education, and insurance status were analyzed for the 2161 men surveyed who were aged 30-45 years. We performed bivariate and multivariate logistic regression analyses to determine the predictors of infertility service use.Marital status and education level were strongly associated with infertility care seeking. In the adjusted analysis, married men were 9 times (odds ratio 9.3, 95% confidence interval 4.1-20.9) more likely to seek care than unmarried men, and men with a college degree and those with an advanced degree were 3 times (odds ratio 2.7, 95% confidence interval 1.4-5.0) and 5 times (odds ratio 4.7, 95% confidence interval 2.1-10.5) more likely to seek care, respectively.Men seeking infertility care in the United States tend to be married, older, and more educated than those not seeking care. Given these findings, some results of male infertility studies from cohorts of men from infertility referral centers might not apply to the U.S. population.

  View details for DOI 10.1016/j.urology.2011.09.021

  View details for Web of Science ID 000298671000031

  View details for PubMedID 22119258

• Fatherhood and the risk of cardiovascular mortality in the NIH-AARP Diet and Health Study HUMAN REPRODUCTION Eisenberg, M. L., Park, Y., Hollenbeck, A. R., Lipshultz, L. I., Schatzkin, A., Pletcher, M. J. 2011; 26 (12): 3479-3485

  Abstract

  Fertility potential and reproductive fitness may reflect a man's future health, given that over one-third of the male human genome is involved in reproduction. We sought to determine if offspring number predicts cardiovascular death in the US men.Using data from the NIH-AARP Diet and Health Study, 137,903 men (aged 50-71) without prior cardiovascular disease were followed-up for an average of 10.2 years. International Classification of Diseases, ninth edition, codes were used to establish the cause of death, and multivariable Cox proportional hazards modeling was used to estimate the association between offspring number and cardiovascular death while accounting for sociodemographic and lifestyle characteristics.Almost all (92%) participants had fathered at least one child and 50% had three or more offspring. A total of 3082 men died of cardiovascular causes during follow-up for an age-adjusted incidence rate of 2.70 per 1000 person-years. Compared with fathers, after adjusting for sociodemographic and lifestyle factors, childless men had a 17% [hazard ratio (HR): 1.17; 95% confidence interval (CI): 1.03-1.32] increased risk of death from cardiovascular disease contracted in the study period, and this elevated risk appeared to extend also to men with only one child. In comparison with fathers of five or more children, adjusted relative hazards for cardiovascular mortality of this sort were 1.06 (95% CI: 0.92-1.22) for four children, 1.02 (0.90-1.16) for three children, 1.02 (0.90-1.16) for two children, 1.11 (0.95-1.30) for one child and 1.21 (1.03-1.41) for no children.Married men who have no children have a higher risk of dying from cardiovascular disease contracted after the age of 50 than men with two or more children.

  View details for DOI 10.1093/humrep/der305

  View details for Web of Science ID 000297058000033

  View details for PubMedID 21946940

  View details for PubMedCentralID PMC3212876

• Fecundity and sex ratio of offspring in an infertile cohort FERTILITY AND STERILITY Eisenberg, M. L., Schembri, M., Croughan, M. S., Walsh, T. J. 2011; 96 (4): 833-836

  Abstract

  To determine whether male and female subfecundity is associated with the gender ratio.Retrospective cohort study.Reproductive endocrinology clinics in California.A cohort of 30,448 women who sought infertility treatment or evaluation in California between 1990 and 1998 was identified. A fertile comparison group was assembled after matching data from vital statistics records.Not applicable.Multivariate logistic regression was used to determine the odds of a male birth based on fertility status.We identified 5,293 infertile women and 6,730 fertile matched women in the live-birth and fetal death records. There were 6,178 children born to women evaluated and/or treated for infertility, compared with 9,131 born to fertile women, for a total of 15,309 births. There was no significant difference in the secondary sex ratio between births in the infertile cohort and the fertile cohort or on the basis of male factor infertility versus female factor infertility. After controlling for confounding factors, there was no difference in sex ratio based on the use of advanced reproductive technologies, duration of infertility treatment, or the type of infertility.This study found no statistical evidence to support an association between infertility and secondary sex ratio.

  View details for DOI 10.1016/j.fertnstert.2011.07.1141

  View details for Web of Science ID 000295938800015

  View details for PubMedID 21864839

• Use of Google Insights for Search to Track Seasonal and Geographic Kidney Stone Incidence in the United States UROLOGY Breyer, B. N., Sen, S., Aaronson, D. S., Stoller, M. L., Erickson, B. A., Eisenberg, M. L. 2011; 78 (2): 267-271

  Abstract

  To determine whether Internet search volume for kidney stones has seasonal and geographic distributions similar to known kidney stone incidence.Google Insights for Search analyzes a portion of Google web searches from all Google domains to compute how many searches are performed for a given term relative to the total number of searches done over a specific time interval and geographic region. Selected terms related to kidney stones were examined to determine which most closely tracked kidney stone incidence. Google Insights for Search data were correlated with hospital admissions for the emergent treatment of nephrolithiasis found through the Nationwide Inpatient Sample. Ambient temperature in Seattle and New York were compared with search volume for these regions to display qualitative relationships.The term "kidney stones" had the highest seasonal correlation of terms examined (r = .81, P = .0014). Google Insights for Search output and national Inpatient Sample admissions also correlated when regions were compared (r = .90, P = .005). Qualitative relationships between ambient temperatures and kidney stone search volume do exist.Internet search volume activity for kidney stones correlates with temporal and regional kidney stone insurance claims data. In the future, with improved modeling of search detection algorithms and increased Internet usage, search volume has the potential to serve as a surrogate for kidney stone incidence.

  View details for DOI 10.1016/j.urology.2011.01.010

  View details for Web of Science ID 000293577100010

  View details for PubMedID 21459414

• Words of wisdom: Re: Does varicocele repair improve male infertility? An evidence-based perspective from a randomized, controlled trial. European urology Eisenberg, M. L., Lipshultz, L. I. 2011; 60 (2): 395-?

  View details for DOI 10.1016/j.eururo.2011.05.025

  View details for PubMedID 21703969

• Socioeconomic disparities in the use and success of fertility treatments: analysis of data from a prospective cohort in the United States FERTILITY AND STERILITY Smith, J. F., Eisenberg, M. L., Glidden, D., Millstein, S. G., Cedars, M., Walsh, T. J., Showstack, J., Pasch, L. A., Adler, N., Katz, P. P. 2011; 96 (1): 95-101

  Abstract

  To determine the effect of income, education, and race on the use and outcomes of infertility care.Prospective cohort.Eight community and academic infertility practices.Three hundred ninety-one women presenting for an infertility evaluation.Face-to-face and telephone interviews and questionnaires.Use of infertility services and odds of pregnancy. Linear and logistic regression used to assess relationship between racial and socioeconomic characteristics, use of infertility services, and infertility outcomes.After adjustment for age and demographic and fertility characteristics, college-educated couples (β = $5,786) and households earning $100,000-$150,000 (β = $6,465) and ≥$150,000 (β = $8,602) spent significantly more on infertility care than their non-college-educated, lower-income counterparts. Higher income and college-educated couples were much more likely to use more cycles of higher-intensity fertility treatment. The increased cost of infertility care was primarily explained by these differences in number and type of infertility treatment. Even after adjustment for these factors and total amount spent on fertility care, having a college degree was associated with persistently higher odds of achieving a pregnancy (OR = 1.9).Education and household income were independently associated with the amount of money spent on fertility care. This relationship was primarily explained by types and intensity of infertility treatments used. Having at least a college degree was independently associated with improved odds of pregnancy.

  View details for DOI 10.1016/j.fertnstert.2011.04.054

  View details for Web of Science ID 000292283000039

  View details for PubMedID 21616487

• The Relationship between Anogenital Distance, Fatherhood, and Fertility in Adult Men PLOS ONE Eisenberg, M. L., Hsieh, M. H., Walters, R. C., Krasnow, R., Lipshultz, L. I. 2011; 6 (5)

  Abstract

  Anogenital distance (AGD), a sexually dimorphic measure of genital development, is a marker for endocrine disruption in animal studies and may be shorter in infant males with genital anomalies. Given the correlation between anogenital distance and genital development, we sought to determine if anogenital distance varied in fertile compared to infertile adult men.A cross sectional study of consecutive men being evaluated for infertility and men with proven fertility was recruited from an andrology clinic. Anogenital distance (the distance from the posterior aspect of the scrotum to the anal verge) and penile length (PL) were measured using digital calipers. ANOVA and linear regression were used to determine correlations between AGD, fatherhood status, and semen analysis parameters (sperm density, motility, and total motile sperm count).A total of 117 infertile men (mean age: 35.3±17.4) and 56 fertile men (mean age: 44.8±9.7) were recruited. The infertile men possessed significantly shorter mean AGD and PL compared to the fertile controls (AGD: 31.8 vs 44.6 mm, PL: 107.1 vs 119.5 mm, p<0.01). The difference in AGD persisted even after accounting for ethnic and anthropomorphic differences. In addition to fatherhood, on both unadjusted and adjusted linear regression, AGD was significantly correlated with sperm density and total motile sperm count. After adjusting for demographic and reproductive variables, for each 1 cm increase in a man's AGD, the sperm density increases by 4.3 million sperm per mL (95% CI 0.53, 8.09, p = 0.03) and the total motile sperm count increases by 6.0 million sperm (95% CI 1.34, 10.58, p = 0.01). On adjusted analyses, no correlation was seen between penile length and semen parameters.A longer anogenital distance is associated with fatherhood and may predict normal male reproductive potential. Thus, AGD may provide a novel metric to assess reproductive potential in men.

  View details for DOI 10.1371/journal.pone.0018973

  View details for Web of Science ID 000290483600004

  View details for PubMedID 21589916

  View details for PubMedCentralID PMC3092750

• Contraceptive usage patterns in North American medical students CONTRACEPTION Rowen, T. S., Smith, J. F., Eisenberg, M. L., Breyer, B. N., Drey, E. A., Shindel, A. W. 2011; 83 (5): 459-465

  Abstract

  Previous studies indicate that the sexual beliefs and mores of students in medical professions may influence their capacity to care for patients' sexuality and contraception issues. Students also represent a large sample of reproductive-age individuals. In this study, we examined contraceptive usage patterns in North American medical students.Students using online medical student social and information networks enrolled in allopathic and osteopathic medical schools in North America between February and July of 2008 were invited to participate via email and published announcements in an Internet-based survey consisting of a questionnaire that assessed ethnodemographic factors, year in school and sexual history. We also collected information about current use of contraceptive and barrier methods. Descriptive statistics and logistic regression were utilized to analyze responses.Among our 2269 complete responses, at least one form of contraception was being utilized by 71% of men and 76% of women. Condoms were the most popular form of contraceptive, utilized by 1011 respondents (50% of men and 40% of women). Oral contraceptive pills were the contraceptive of choice for 34% of men and 41% of women. Decreased rates of contraception use were associated with being black or Asian, not being in a relationship and having more sexual dysfunction in female respondents. Students who reported comfort discussing sexual issues with patients were more likely to use effective contraceptive methods themselves. Ten percent of this of sexually active medical students was not currently using contraception.There are significant differences in contraceptive use based on demographics, even at the highest education levels. The personal contraception choices of medical students may influence their ability to accurately convey information about contraception to their patients. In addition, medical students may personally benefit from improved knowledge of effective contraceptive practices.

  View details for DOI 10.1016/j.contraception.2010.09.011

  View details for Web of Science ID 000289821600013

  View details for PubMedID 21477690

• HIV Status is An Independent Risk Factor for Reporting Lower Urinary Tract Symptoms JOURNAL OF UROLOGY Breyer, B. N., Van Den Eeden, S. K., Horberg, M. A., Eisenberg, M. L., Deng, D. Y., Smith, J. F., Shindel, A. W. 2011; 185 (5): 1710-1715

  Abstract

  HIV/AIDS is a worldwide epidemic. Limited evidence suggests that men infected with HIV/AIDS are at increased risk for lower urinary tract symptoms. We determined whether HIV/AIDS status is an independent risk factor for self-reported bothersome lower urinary tract symptoms in a large contemporary cohort.We performed a cross-sectional, Internet based survey of urinary quality of life outcomes in adult HIV infected and HIV uninfected men who have sex with men. The main outcome measure was International Prostate Symptom Score.Of respondents with complete data 1,507 were HIV uninfected (median age 42 years, mean 43) and 323 HIV infected (median age 45 years, mean 45.1). Of the HIV infected respondents 148 were nonAIDS defining HIV infected and 175 were AIDS defining HIV infected. After adjusting for age and other comorbid conditions, nonAIDS defining HIV infected and AIDS defining HIV infected status increased the odds of severe lower urinary tract symptoms by 2.07 (95% CI 1.04-3.79) and 2.49 (95% CI 1.43-4.33), respectively. HIV infected men had a worse total International Prostate Symptom Score for all domains including quality of life compared to HIV uninfected men. Within the population of men with HIV, those with AIDS had worse mean total International Prostate Symptom Score and all individual International Prostate Symptom Score components relative to nonAIDS defining HIV infected men.HIV status is an independent risk factor for bothersome lower urinary tract symptoms. The odds of severe lower urinary tract symptoms are greater in HIV infected men with a history of AIDS.

  View details for DOI 10.1016/j.juro.2010.12.043

  View details for Web of Science ID 000289279600050

  View details for PubMedID 21420120

• Fatherhood and incident prostate cancer in a prospective US cohort INTERNATIONAL JOURNAL OF EPIDEMIOLOGY Eisenberg, M. L., Park, Y., Brinton, L. A., Hollenbeck, A. R., Schatzkin, A. 2011; 40 (2): 480-487

  Abstract

  Fatherhood status has been hypothesized to affect prostate cancer risk but the current evidence is limited and contradictory.We prospectively evaluated the relationship between offspring number and the risk of prostate cancer in 161,823 men enrolled in the National Institues of Health - American Association of Retired Persons Diet and Health Study. Participants were aged 50-71 years without a cancer diagnosis at baseline in 1995. Analysing 8134 cases of prostate cancer, Cox regression was used to estimate the association between offspring number and prostate cancer incidence while accounting for socio-demographic and lifestyle characteristics.When examining the entire cohort, there was no relationship between fatherhood and incident prostate cancer [hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.86-1.02]. However, after stratifying for prostate cancer screening, prostate-specific antigen (PSA) unscreened childless men had a lower risk of prostate cancer (HR 0.73, 95% CI 0.58-0.91) compared with fathers due to the interaction between PSA screening and fatherhood (P for interaction < 0.01). A trend for the lower risk of prostate cancer among unscreened fathers compared with childless men was seen for low-grade prostate cancer (HR 0.78, 95% CI 0.61-1.01), high-grade prostate cancer (HR 0.62, 95% CI 0.37-1.04) and even fatal prostate cancer (HR 0.28, 95% CI 0.07-1.12). The number of children fathered was not related to prostate cancer (P(trend) = 0.17). In addition, men's inability to sire female offspring showed a weak positive association with prostate cancer in the PSA unscreened study subjects.Our findings suggest fatherhood status and offspring gender is associated with a man's prostate cancer risk.

  View details for DOI 10.1093/ije/dyq163

  View details for Web of Science ID 000289165800028

  View details for PubMedID 20959354

• Re: Estimating the Number of Vasectomies Performed Annually in the United States: Data From the National Survey of Family Growth JOURNAL OF UROLOGY Eisenberg, M. L., Lipshultz, L. I. 2011; 185 (4): 1541-1542

  View details for Web of Science ID 000288430200141

  View details for PubMedID 21345456

• Costs of infertility treatment: results from an 18-month prospective cohort study FERTILITY AND STERILITY Katz, P., Showstack, J., Smith, J. F., Nachtigall, R. D., Millstein, S. G., Wing, H., Eisenberg, M. L., Pasch, L. A., Croughan, M. S., Adler, N. 2011; 95 (3): 915-921

  Abstract

  To examine resource use (costs) by women presenting for infertility evaluation and treatment over 18 months, regardless of treatment pursued.Prospective cohort study in which women were followed for 18 months.Eight infertility practices.Three hundred ninety-eight women recruited from infertility practices.Women completed interviews and questionnaires at baseline and after 4, 10, and 18 months of follow-up. Medical records were abstracted after 18 months to obtain details of services used.Per-person and per-successful-outcome costs.Treatment groups were defined as highest intensity treatment use. Twenty percent of women did not pursue cycle-based treatment; approximately half pursued IVF. Median per-person costs ranged from $1,182 for medications only to $24,373 and $38,015 for IVF and IVF-donor egg groups, respectively. Estimates of costs of successful outcomes (delivery or ongoing pregnancy by 18 months) were higher--$61,377 for IVF, for example--reflecting treatment success rates. Within the time frame of the study, costs were not significantly different for women whose outcomes were successful and women whose outcomes were not.Although individual patient costs vary, these cost estimates developed from actual patient treatment experiences may provide patients with realistic estimates to consider when initiating infertility treatment.

  View details for DOI 10.1016/j.fertnstert.2010.11.026

  View details for Web of Science ID 000287480300014

  View details for PubMedID 21130988

• Pentoxifylline treatment and penile calcifications in men with Peyronie's disease ASIAN JOURNAL OF ANDROLOGY Smith, J. F., Shindel, A. W., Huang, Y., Clavijo, R. I., Flechner, L., Breyer, B. N., Eisenberg, M. L., Lue, T. F. 2011; 13 (2): 322-325

  Abstract

  This retrospective cohort study from a single clinical practice enrolled patients with evidence of calcified Peyronie's disease (PD) plaques detected on penile ultrasound at the time of initial presentation. The primary objective was to describe the effect of pentoxifylline (PTX) treatment on subtunical calcifications in men with PD. A PD-specific questionnaire was administered and sonographic evaluations were performed at baseline and follow-up visits. Descriptive statistics and χ(2) analysis were used to characterize the effect of PTX on calcified tunical plaques. In all, 71 men (mean age: 51.9 years) with PD and sonographic evidence of calcification were identified. Of them, 62 of these men were treated with PTX for a mean duration of 1 year, and nine with vitamin E or no treatment. Improvement or stabilization in calcium burden at follow-up was noted in 57 (91.9%) of men treated with PTX versus four (44.4%) of those not treated with PTX (P<0.001). PTX users were much less likely to have a subjective worsening of their clinical condition (25.0% versus 78.3%, P=0.002). Treatment with PTX appeared to stabilize or reduce calcium content in PD plaques. A randomized controlled trial is warranted to further explore this effect.

  View details for DOI 10.1038/aja.2010.117

  View details for Web of Science ID 000288074400035

  View details for PubMedID 21102473

• The importance of tumor palpability and transrectal ultrasonographic appearance in the contemporary clinical staging of prostate cancer UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS Eisenberg, M. L., Cowan, J. E., Davies, B. J., Carroll, P. R., Shinohara, K. 2011; 29 (2): 171-176

  Abstract

  An accurate assessment of the clinical stage of prostate cancer is important to determine the most appropriate treatments for patients. Most centers rely on digital rectal examination, given conflicting results in the literature regarding the role of transrectal ultrasonography (TRUS).Since ultrasound technologies as well as physician experience have improved, the contemporary impact of TRUS on the clinical staging of prostate cancer was assessed.In 2002, a standardized form to evaluate TRUS findings in order to rank the clinical suspicion of extracapsular extension (ECE) was used for all prostate cancer patients evaluated at UCSF. Preoperative clinical findings were compared with pathological staging as assessed by analysis of radical prostatectomy specimens from 2002 to 2007 (n = 620).Mean patient age was 58 ± 6.6 years with a mean PSA of 7.0 ± 4.5; 157/620 (25.3%) had pathologic ECE. Evidence of ECE by TRUS was associated with higher pathologic stage (P < 0.00001) and higher rates of biochemical failure after prostatectomy (P = 0.0006). Overall, TRUS had a 31% sensitivity, 92% specificity, 58% positive predictive value, and 80% negative predictive value with an area under the curve of 0.77 for the detection of ECE. TRUS alone was significantly more accurate in predicting ECE than commonly used nomograms or tables (P < 0.001) when examining patients with impalpable tumors.In the current era, TRUS provides an accurate method to assess a cancer stage.

  View details for DOI 10.1016/j.urolonc.2009.01.005

  View details for Web of Science ID 000288342700012

  View details for PubMedID 19362864

• Tunica-sparing ossified Peyronie's plaque excision BJU INTERNATIONAL Eisenberg, M. L., Smith, J. F., Shindel, A. W., Lue, T. F. 2011; 107 (4): 622-625

  Abstract

  Ossified Peyronie's plaques may require surgical excision because of the palpable problems and penile curvature that result. As tunical excision can result in impotence and decrease penile sensation, we describe a novel method of tunical preserving excision of such lesions.We evaluated 12 men with dorsal penile curvature between 10° and 90°. Penile plaque size ranged from 1 to 5 cm. 80% had painful erections. An artificial erection was induced with intracavernous injection of papaverine to assess penile deformity. Via a circumcising or ventral incision, plication sutures were placed to correct penile curvature. A lateral longitudinal corporotomy was made and the calcified/ossified portion was dissected free from the tunica albuginea/plaque of the corpora cavernosa. Watertight tunical closure was then performed.Postoperatively, 80% of men reported erections always adequate for intercourse and normal sensation with a mean follow-up of 7 months (range 2.1-14.5 months). All patients required simultaneous penile plication to ensure a straight phallus. Pathologic evaluation of plaque specimens all showed bone fragments.Tunica-sparing excision of the ossified/calcified portion of Peyronie's plaques shows a durable benefit for large, ossified lesions and maintains potency and penile sensation.

  View details for DOI 10.1111/j.1464-410X.2010.09546.x

  View details for Web of Science ID 000286767300016

  View details for PubMedID 20804484

• Sexual Function and Depressive Symptoms Among Female North American Medical Students JOURNAL OF SEXUAL MEDICINE Shindel, A. W., Eisenberg, M. L., Breyer, B. N., Sharlip, I. D., Smith, J. F. 2011; 8 (2): 391-399

  Abstract

  Depression and sexual dysfunction are often comorbid.We explored the relationship between sexuality, sexual dysfunction, and depressive symptoms in female medical students in North America.Female North American medical students were invited to participate in an internet survey. The CES-D was utilized to screen for depressive symptoms and an abbreviated Spielberger State-Trait Anxiety Index (STAI) was used to quantify anxiety symptoms.Subjects completed an ethnodemographic survey, a sexuality survey, and modified instruments for the quantification of sexual function (the Female Sexual Function Index [FSFI] and the Index of Sexual Life [ISL]). Multivariable logistic regression was used to explore the relationship between sexuality and depressive symptoms.There were 1,241 female subjects with complete data on CES-D and STAI. Mean age was 25.4 years. Depressive symptoms (CES-D>16) were present in 46% of respondents and were more common in subjects with anxiety symptoms. Subjects who were Caucasian, younger than 28, heterosexual, and in a relationship were least likely to report depressive symptoms. High risk of female sexual dysfunction (HRFSD) was significantly associated with greater likelihood of depressive symptoms (odds ratio [OR] 2.25, P<0.001). After adjusting for ethnodemographic and sexual history factors, HRFSD remained significantly positively associated with depressive symptoms (OR 1.85, P<0.001). Analysis of FSFI and ISL domains indicated that depressive symptoms were most directly associated with worse orgasmic function, interference in sex life from stress and lack of partner, and lower general life satisfaction (P<0.05). Interestingly, greater ISL-sexual satisfaction was associated with greater odds of depressive symptoms (OR 1.40, P=0.01).Depressive symptoms are common in female medical students. HRFSD is associated with depressive symptoms, although the relationship is complex when psychosocial factors are included in the multivariate model. Attention to sexuality factors from student health providers may enhance quality-of-life, academic achievement, and patient care.

  View details for DOI 10.1111/j.1743-6109.2010.02085.x

  View details for Web of Science ID 000286838900008

  View details for PubMedID 21054793

• Management for Prostate Cancer Treatment Related Posterior Urethral and Bladder Neck Stenosis With Stents JOURNAL OF UROLOGY Erickson, B. A., McAninch, J. W., Eisenberg, M. L., Washington, S. L., Breyer, B. N. 2011; 185 (1): 198-203

  Abstract

  Prostate cancer treatment has the potential to lead to posterior urethral stricture. These strictures are sometimes recalcitrant to dilation and urethrotomy alone. We present our experience with the Urolume® stent for prostate cancer treatment related stricture.A total of 38 men with posterior urethral stricture secondary to prostate cancer treatment were treated with Urolume stenting. Stents were placed in all men after aggressive urethrotomy over the entire stricture. A successfully managed stricture was defined as open and stable for greater than 6 months after any necessary secondary procedures.The initial success rate was 47%. After a total of 31 secondary procedures in 19 men, including additional stent placement in 8 (18%), the final success rate was 89% at a mean ± SD followup of 2.3 ± 2.5 years. Four cases (11%) in which treatment failed ultimately requiring urinary diversion (3) or salvage prostatectomy (1). Incontinence was noted in 30 men (82%), of whom 19 (63%) received an artificial urinary sphincter a mean of 7.2 ± 2.4 months after the stent. Subanalysis revealed that irradiated men had longer strictures (3.6 vs 2.0 cm, p = 0.003) and a higher post-stent incontinence rate (96% vs 50%, p < 0.001) than men who underwent prostatectomy alone but the initial failure rate was similar (54% vs 50%, p = 0.4).Urolume stenting is a reasonable option for severe post-prostate cancer treatment stricture when patients are unwilling or unable to undergo open reconstructive surgery. Incontinence should be expected. The need for additional procedures is common and in some men may be required periodically for the lifetime of the stent.

  View details for DOI 10.1016/j.juro.2010.09.020

  View details for Web of Science ID 000285141900064

  View details for PubMedID 21074796

• Varicocele-induced infertility: Newer insights into its pathophysiology. Indian journal of urology : IJU : journal of the Urological Society of India Eisenberg, M. L., Lipshultz, L. I. 2011; 27 (1): 58-64

  Abstract

  The association between varicoceles and male infertility has been known since the 1950s; however, the pathophysiology of the process remains uncertain. The primary proposed hypotheses involve hyperthermia, venous pressure, testicular blood flow, hormonal imbalance, toxic substances, and reactive oxygen species. It is difficult to identify a single or dominant factor, and it is likely that many of these factors contribute to the infertile phenotype seen in clinical practice. Moreover, patient lifestyle and genetic factors likely affect patient susceptibilities to the varicocele insult. While the current studies have weaknesses, they provide building blocks for futures studies into the pathophysiology of the varicocele.

  View details for DOI 10.4103/0970-1591.78428

  View details for PubMedID 21716891

• Fertility treatments and outcomes among couples seeking fertility care: data from a prospective fertility cohort in the United States FERTILITY AND STERILITY Smith, J. F., Eisenberg, M. L., Millstein, S. G., Nachtigall, R. D., Sadetsky, N., Cedars, M. I., Katz, P. P. 2011; 95 (1): 79-84

  Abstract

  To determine the relationship between number of fertility treatment cycles and pregnancy rates.Prospective cohort study.Eight community and academic infertility practices.Four hundred eight (408) couples presenting for an infertility evaluation.Face-to-face and telephone interviews and questionnaires.Incidence of pregnancy. Cox regression analysis compared the efficacy of cycle-based fertility treatments with no cycle-based fertility treatment after multivariable adjustment.Couples using one to two medications-only cycles had a significantly higher pregnancy rate (hazard ratio [HR] 4.7 [95% confidence interval 1.3-16.6]), a benefit that did not persist after three or more cycles (HR 0.6 [0.1-3.2]). Couples using IUI for one (HR 2.9 [1.4-5.8]), two (HR 2.0 [0.9-4.5]), and three cycles (HR 4.5 [1.8-10.9]) were more likely to achieve a pregnancy. No additional benefit was seen for couples using four or more IUI cycles (HR 1.0 [0.4-2.6]). In vitro fertilization was associated with significant benefit for couples using one (HR 2.8 [1.5-5.2]) and two cycles (HR 2.2 [1.2-4.1]). Couples using three or more IVF cycles had a non-statistically significant higher likelihood of pregnancy (HR 1.3 [0.7-2.4]).Cycle-based fertility treatments may offer a point of diminishing returns for infertile couples: two cycles of medications only, three cycles of IUI, and two cycles of IVF.

  View details for DOI 10.1016/j.fertnstert.2010.06.043

  View details for Web of Science ID 000285411600021

  View details for PubMedID 20659733

• Sexual Function and Depressive Symptoms among Male North American Medical Students JOURNAL OF SEXUAL MEDICINE Smith, J. F., Breyer, B. N., Eisenberg, M. L., Sharlip, I. D., Shindel, A. W. 2010; 7 (12): 3909-3917

  Abstract

  The role of sexuality as an association of medical student well-being has not been extensively studied.We explored the relationship between depressive symptoms, sexuality, and sexual dysfunction in male North American medical students.North American medical students were invited to participate in an Internet-based survey. The Center for Epidemiological Studies Depression Scale (CES-D) was utilized to screen for depressive symptoms.Subjects completed an ethnodemographic survey, a sexuality survey, and instruments for the quantification of anxiety, sexuality, and psychosocial function. Descriptive statistics, odds ratios (ORs), and logistic regression were used to analyze our data.There were 844 male subjects with complete data on the CES-D and the Spielberger State-Trait Anxiety Index. Depressive symptoms (CES-D ≥ 16) were present in 37% of respondents and were more common in subjects with greater levels of anxiety. Subjects who were in sexual relationships and/or had frequent sexual activity were less likely to be depressed compared to other subjects. Erectile dysfunction (ED) was associated with significantly greater likelihood of depressive symptoms (OR 2.90 and 9.27 for depressive symptoms in men with mild or moderate/severe ED relative to men without ED, P < 0.01). After adjusting for ethnodemographic and sexual history factors, ED remained significantly positively associated with depressive symptoms (OR 2.87 and 6.59 for depressive symptoms in men with mild or moderate/severe ED relative to men without ED after adjustment, P ≤ 0.01). Inclusion of data related to psychosocial/relationship factors in the multivariate model eliminated the significant association between ED and depressive symptoms (OR 1.59 and 2.29 for depressive symptoms in men with mild or moderate/severe ED relative to men without ED after adjustment with the Self-Esteem and Relationship quality instrument, P > 0.05), suggesting that psychosocial factors were more strongly associated with depressive symptoms than erectile function.Healthy sexuality and relationships may be protective against depressive symptoms in medical students. Attention to these factors may enhance medical student well-being.

  View details for DOI 10.1111/j.1743-6109.2010.02033.x

  View details for Web of Science ID 000284850800011

  View details for PubMedID 21059174

• Estimating the Number of Vasectomies Performed Annually in the United States: Data From the National Survey of Family Growth JOURNAL OF UROLOGY Eisenberg, M. L., Lipshultz, L. I. 2010; 184 (5): 2068-2072

  Abstract

  While hospital discharge and ambulatory surgery registries provide accurate estimates of female sterilization procedures, current estimates of male sterilization rates are lacking since these procedures are done in many settings. Population based data are used to estimate annual sterilization numbers.We analyzed data on 4,928 men and 7,643 women from the 2002 National Survey of Family Growth. We determined the year of vasectomy in men and the year of tubal ligation in women who reported a history of surgical sterilization. After accounting for the complex survey design of the National Survey of Family Growth we calculated the estimated number of individuals who underwent surgical sterilization in the United States.A total of 141 men reported vasectomy, representing an overall 6% prevalence in National Survey of Family Growth survey population, while 1,173 women (16%) reported tubal ligation. Using National Survey of Family Growth data an estimated 175,000 to 354,000 vasectomies were done yearly from 1998 to 2002. In the same period the National Survey of Family Growth estimated that 546,000 to 789,000 tubal ligations were done annually in the United States. This compares closely to the 596,000 to 687,000 tubal ligations calculated using ambulatory surgery and hospital discharge data from a similar period.The estimated annual number of tubal ligations from the National Survey of Family Growth is in line with the current literature using hospital discharge and ambulatory surgery registries, suggesting the accuracy of the method of estimating surgical sterilization numbers. This suggests that the National Survey of Family Growth may be used to provide an estimate of vasectomy use in the United States.

  View details for DOI 10.1016/j.juro.2010.06.117

  View details for Web of Science ID 000282679200086

  View details for PubMedID 20850832

• Predictors of not pursuing infertility treatment after an infertility diagnosis: examination of a prospective US cohort FERTILITY AND STERILITY Eisenberg, M. L., Smith, J. F., Millstein, S. G., Nachtigall, R. D., Adler, N. E., Pasch, L. A., Katz, P. P. 2010; 94 (6): 2369-2371

  Abstract

  We studied a prospective cohort of 434 couples in Northern California and found that 13% did not pursue any form of infertility treatment after their initial consultation. Although age, education, and financial concerns remain important for patients in choosing whether to pursue infertility treatment, depressive symptoms may also be a barrier to achieving reproductive goals.

  View details for DOI 10.1016/j.fertnstert.2010.03.068

  View details for Web of Science ID 000283441400097

  View details for PubMedID 20471010

• The impact of infertility on family size in the USA: data from the National Survey of Family Growth HUMAN REPRODUCTION Breyer, B. N., Smith, J. F., Shindel, A. W., Sharlip, I. D., Eisenberg, M. L. 2010; 25 (9): 2360-2365

  Abstract

  Investigators have postulated that family size may be influenced by biologic fertility potential in addition to sociodemographic factors. The aim of the current study is to determine if a diagnosis of infertility is associated with family size in the USA.We analyzed data from the male and female samples of the 2002 National Survey of Family Growth using multivariable logistic regression models to determine the relationship between infertility and family size while adjusting for sociodemographic and reproductive characteristics.In the survey, 4409 women and 1739 men met the inclusion criteria, of whom 10.2% and 9.7%, respectively, were classified as infertile, on the basis of having sought reproductive assistance. Infertile females had a 34% reduced odds of having an additional child compared with women who did not seek reproductive assistance. For each additional 6 months it took a woman to conceive her first child, the odds of having a larger family fell by 9% and the odds of having a second child were reduced by 11%. A diagnosis of male infertility reduced the odds of having a larger family more than a diagnosis of female infertility.A diagnosis of infertility, especially male factor, is associated with reduced odds of having a larger family, implicating a biologic role in the determination of family size in the USA.

  View details for DOI 10.1093/humrep/deq152

  View details for Web of Science ID 000281343700026

  View details for PubMedID 20601679

• Perceived negative consequences of donor gametes from male and female members of infertile couples FERTILITY AND STERILITY Eisenberg, M. L., Smith, J. F., Millstein, S. G., Walsh, T. J., Breyer, B. N., Katz, P. P. 2010; 94 (3): 921-926

  Abstract

  To determine the views toward donor sperm and eggs of both men and women. The use of donor sperm or ova becomes an option for some infertile couples.Prospective cohort of infertile couples.Eight California reproductive endocrinology practices.Infertile couples (n=377) were recruited after an initial infertility clinic visit.From questionnaires administered at recruitment, ratings concerning the impact of the use of donor gametes were assessed. Differences between men and women in attitudes toward donor gametes were compared with analysis of variance (ANOVA). Linear regression was used to identify independent predictors of attitudes toward gametes.Women's attitudes toward donor sperm were significantly more negative than their attitudes toward donor eggs (5.1+/-1.4 vs. 4.7+/-1.6). Similarly, male donor gamete attitude scores were higher for donor sperm compared with donor eggs (4.9+/-1.6 vs. 4.1+/-1.6). Both men and women agreed that the use of donor sperm was more likely to have negative effects on their relationship and negative societal ramifications. Female donor gamete attitude scores were predicted by marital status, race, and education, whereas men's scores were independent of all measured factors.Both men and women view the use of donor sperm with more skepticism compared with the use of donor eggs, suggesting a unique underlying perception regarding the use of male donor gametes.

  View details for DOI 10.1016/j.fertnstert.2009.04.049

  View details for Web of Science ID 000280407900016

  View details for PubMedID 19523614

• Use of Google in Study of Noninfectious Medical Conditions EPIDEMIOLOGY Breyer, B. N., Eisenberg, M. L. 2010; 21 (4): 584-585

  View details for DOI 10.1097/EDE.0b013e3181e080cd

  View details for Web of Science ID 000279038600024

  View details for PubMedID 20539114

• The Impact of Sexual Orientation on Sexuality and Sexual Practices in North American Medical Students JOURNAL OF SEXUAL MEDICINE Breyer, B. N., Smith, J. F., Eisenberg, M. L., Ando, K. A., Rowen, T. S., Shindel, A. W. 2010; 7 (7): 2391-2400

  Abstract

  There has been limited investigation of the sexuality and sexual dysfunction in non-heterosexual subjects by the sexual medicine community. Additional research in these populations is needed.To investigate and compare sexuality and sexual function in students of varying sexual orientations.An internet-based survey on sexuality was administered to medical students in North American between the months of February and July of 2008.All subjects provided information on their ethnodemographic characteristics, sexual orientation, and sexual history. Subjects also completed a series of widely-utilized instruments for the assessment of human sexuality (International Index of Erectile Function [IIEF], Female Sexual Function Index [FSFI], Premature Ejaculation Diagnostic Tool [PEDT], Index of Sex Life [ISL]).There were 2,276 completed responses to the question on sexual orientation. 13.2% of male respondents and 4.7% of female respondents reported a homosexual orientation; 2.5% of male and 5.7% of female respondents reported a bisexual orientation. Many heterosexual males and females reported same-sex sexual experiences (4% and 10%, respectively). Opposite-sex experiences were very common in the male and female homosexual population (37% and 44%, respectively). The prevalence of premature ejaculation (PEDT > 8) was similar among heterosexual and homosexual men (16% and 17%, P = 0.7, respectively). Erectile dysfunction (IIEF-EF < 26) was more common in homosexual men relative to heterosexual men (24% vs. 12%, P = 0.02). High risk for female sexual dysfunction (FSFI < 26.55) was more common in heterosexual and bisexual women compared with lesbians (51%, 45%, and 29%, respectively, P = 0.005).In this survey of highly educated young professionals, numerous similarities and some important differences in sexuality and sexual function were noted based on sexual orientation. It is unclear whether the dissimilarities represent differing relative prevalence of sexual problems or discrepancies in patterns of sex behavior and interpretation of the survey questions.

  View details for DOI 10.1111/j.1743-6109.2010.01794.x

  View details for Web of Science ID 000279620100010

  View details for PubMedID 20384941

• Relationship Between Body Mass Index and Quantitative 24-Hour Urine Chemistries in Patients With Nephrolithiasis UROLOGY Eisner, B. H., Eisenberg, M. L., Stoller, M. L. 2010; 75 (6): 1289-1293

  Abstract

  To examine the relationship between body mass index and 24-hour urine constituents in a population of stone-forming patients.A total of 880 patients who presented to a metabolic stone clinic for initial evaluation were analyzed. Patients were stratified by gender and divided into quartiles of body mass index. Associations between body mass index (BMI) and urine parameters were explored using bivariate and multivariate linear regression.On bivariate analysis, increasing body mass index was associated with a significant increase in sodium, calcium, citrate, uric acid, magnesium, calcium oxalate, uric acid, and a decrease in pH in men. In women, it was associated with a significant increase in sodium, uric acid, oxalate, uric acid, and decreasing pH. On multivariate analysis, BMI was associated only with increases in sodium and calcium oxalate and decrease in pH in men. In women, multivariate analysis demonstrated positive association between BMI and urine sodium, creatinine, and phosphate and a negative relationship with urine citrate and sulfate.Increasing body mass index was related to several risk factors for urinary stone disease in this study, including increasing urine sodium and decreasing pH in men and increasing urine uric acid, sodium, and decreasing urine citrate in women. Just as general recommendations for patients with nephrolithiasis include high voided volumes, low dietary sodium, and low animal protein intake, perhaps weight reduction should be included as part of the counseling of stone-formers to optimize 24-hour urine parameters.

  View details for DOI 10.1016/j.urology.2009.09.024

  View details for Web of Science ID 000278221100015

  View details for PubMedID 20018350

• Selective arterial embolization of angiomyolipoma leading to pulmonary hypertension CANADIAN JOURNAL OF UROLOGY Lee, F., Aaronson, D. S., Blaschko, S., Barbosa, P., Wu, A. K., Eisenberg, M., Erickson, B. A., McAninch, J. W. 2010; 17 (3): 5232-5235

  Abstract

  To report two cases of secondary pulmonary hypertension resulting from microsphere extravasation following selective arterial embolization of renal angiomyolipoma, its diagnosis, and management.We reviewed the cases of two patients at the University of California, San Francisco, treated with selective arterial embolization for management of their angiomyolipoma (AML) using Tris-Acryl Gelatin Microspheres.Both patients were women, ages 51 and 77. Indications for treatment were the following: Patient 1 was treated for a large asymptomatic AML. Patient 2 was treated for a symptomatic, bleeding AML. Both patients developed progressive hypoxia following selective arterial embolization using Tris-Acryl Gelatin Microspheres. Each patient underwent a subsequent work up including a CT chest, echocardiogram, and chest x-ray. Both demonstrated significant pulmonary hypertension following their procedure and were discharged with supplemental oxygen.Selective arterial embolization of AML with microsphere extravasation into the pulmonary vasculature can lead to pulmonary hypertension and hypoxemia.

  View details for Web of Science ID 000279294100020

  View details for PubMedID 20566024

• Increased Risk of High-Grade Prostate Cancer Among Infertile Men CANCER Walsh, T. J., Schembri, M., Turek, P. J., Chan, J. M., Carroll, P. R., Smith, J. F., Eisenberg, M. L., Van Den Eeden, S. K., Croughan, M. S. 2010; 116 (9): 2140-2147

  Abstract

  It has been reported that fatherhood status may be a risk factor for prostate cancer. In the current study, the authors examined the subsequent occurrence of prostate cancer in a cohort of men evaluated for infertility to determine whether male infertility is a risk factor for prostate cancer.A total of 22,562 men who were evaluated for infertility from 1967 to 1998 were identified from 15 California infertility centers and linked to the California Cancer Registry. The incidence of prostate cancer was compared with the incidence in an age-matched and geography-matched sample of men from the general population. The risk of prostate cancer in men with and those without male factor infertility was modeled using a Cox proportional hazards regression model.A total of 168 cases of prostate cancer that developed after infertility were identified. Men evaluated for infertility but not necessarily with male factors were not found to have an increased risk of cancer compared with the general population (standardized incidence ratio [SIR], 0.9; 95% confidence interval [95% CI], 0.8-1.1). This risk was found to be highest for men with male factor infertility who developed high-grade prostate cancer (SIR, 2.0; 95% CI, 1.2-3.0). On multivariate analyses, men with male factor infertility were found to be 2.6 times more likely to be diagnosed with high-grade prostate cancer (hazard ratio, 2.6; 95% CI, 1.4-4.8).Men with male factor infertility were found to have an increased risk of subsequently developing high-grade prostate cancer. Male infertility may be an early and identifiable risk factor for the development of clinically significant prostate cancer.

  View details for DOI 10.1002/cncr.25075

  View details for Web of Science ID 000277111900012

  View details for PubMedID 20309846

  View details for PubMedCentralID PMC2893877

• The adjunctive use of power Doppler imaging in the preoperative assessment of prostate cancer BJU INTERNATIONAL Eisenberg, M. L., Cowan, J. E., Carroll, P. R., Shinohara, K. 2010; 105 (9): 1237-1240

  Abstract

  To determine if the adjunctive use of power Doppler imaging (PDI) could provide prognostic utility in the treatment of prostate cancer, as an accurate prediction of the clinical behaviour of prostate cancer is important to determine appropriate treatment.Most centres rely on a digital rectal examination or transrectal ultrasonography (TRUS) to assess the clinical stage of patients. In 2002, we began using a standardized form to evaluate TRUS findings and PDI findings. We compared preoperative clinical findings with those from pathological analysis of 620 radical prostatectomy specimens from 2002 to 2007.The mean (sd) patient age was 58 (6.6) years with a mean prostate-specific antigen (PSA) level of 7.0 (4.5) ng/mL. Of the 620 specimens 157 (25.3%) had evidence of extracapsular extension on pathological evaluation; 443 (71.5%) men had a hypervascular lesion seen on TRUS, while 177 (28.5%) patients had none. There was no difference in preoperative PSA level, grade or stage of tumour. Furthermore, rates of biochemical recurrence or secondary treatment did not differ based on PDI findings. As a tool to help locate prostate tumours, PDI improved the specificity of TRUS but did not improve the overall accuracy or sensitivity.PDI provides little prognostic utility to assess risk in prostate cancer. However, PDI might improve the specificity of TRUS in identifying prostate tumours and could have a role in image guidance for focal therapy of prostate cancer.

  View details for DOI 10.1111/j.1464-410X.2009.08958.x

  View details for Web of Science ID 000276486900008

  View details for PubMedID 19888980

• The use of complementary and alternative fertility treatment in couples seeking fertility care: data from a prospective cohort in the United States FERTILITY AND STERILITY Smith, J. F., Eisenberg, M. L., Millstein, S. G., Nachtigall, R. D., Shindel, A. W., Wing, H., Cedars, M., Pasch, L., Katz, P. P. 2010; 93 (7): 2169-2174

  Abstract

  To determine the prevalence of complementary and alternative medicine (CAM) use among couples seeking fertility care and to identify the predictors of CAM use in this population.Prospective cohort study.Eight community and academic infertility practices.A total of 428 couples presenting for an infertility evaluation.Interviews and questionnaires.Prevalence of complementary and alternative medicine therapy.After 18 months of observation, 29% of the couples had utilized a CAM modality for treatment of infertility; 22% had tried acupuncture, 17% herbal therapy, 5% a form of body work, and 1% meditation. An annual household income of > or = $200,000 (odds ratio 2.8, relative to couples earning <$100,000), not achieving a pregnancy (odds ratio 2.3), and a positive attitude toward CAM use at baseline were independently associated with CAM use.A substantial minority of infertile couples use CAM treatments. CAM was chosen most commonly by wealthier couples, those not achieving a pregnancy, and those with a baseline belief in the effectiveness of CAM treatments.

  View details for DOI 10.1016/j.fertnstert.2010.02.054

  View details for Web of Science ID 000277608200012

  View details for PubMedID 20338559

• Prognostic Implications of an Undetectable Ultrasensitive Prostate-Specific Antigen Level after Radical Prostatectomy EUROPEAN UROLOGY Eisenberg, M. L., Davies, B. J., Cooperberg, M. R., Cowan, J. E., Carroll, P. R. 2010; 57 (4): 622-629

  Abstract

  The prognostic meaning of an undetectable ultrasensitive prostate-specific antigen (USPSA) level after prostatectomy remains unclear.To determine whether an undetectable USPSA level obtained after surgery is a predictor of biochemical recurrence (BCR)-free survival.From the Urologic Oncology Database at the University of California San Francisco, 525 men were identified who had a USPSA measurement 1-3 mo postoperatively with at least 2 yr of follow-up. All preoperative and pathologic criteria were recorded.Patients were stratified based on their initial USPSA level. We defined an undetectable USPSA level at ≤0.05 ng/ml. Recurrence was defined as two consecutive prostate-specific antigen (PSA) levels ≥0.2 ng/ml or secondary treatment.We found that 456 patients (87%) had undetectable USPSA and 69 patients (13%) had detectable USPSA immediately postprostatectomy. A 5-yr recurrence-free rate of 86% was found in the undetectable USPSA group compared with 67% in the detectable USPSA group (p<0.01). For patients with pT3 disease, men with an undetectable USPSA had a 5-yr BCR-free survival rate of 78% compared with 40% for men with a detectable USPSA (p<0.01). A multivariable analysis confirmed that patients with an undetectable USPSA were 67% less likely to recur (hazard ratio: 0.33; 95% confidence interval: 0.20-0.55). As the detection level of PSA is lowered, the false-positive rate of BCR necessarily increases. A limitation of the study is its retrospective nature.An undetectable USPSA after radical prostatectomy is a prognostic indicator of BCR-free survival at 5 yr and may aid in predicting outcome in higher risk patients.

  View details for DOI 10.1016/j.eururo.2009.03.077

  View details for Web of Science ID 000275739300017

  View details for PubMedID 19375843

• Are Sonographic Characteristics Associated With Progression to Surgery in Men With Peyronie's Disease? JOURNAL OF UROLOGY Breyer, B. N., Shindel, A. W., Huang, Y., Eisenberg, M. L., Weiss, D. A., Lue, T. F., Smith, J. F. 2010; 183 (4): 1484-1488

  Abstract

  Traditionally, diagnosis and treatment plans for Peyronie's disease have been based on history and physical examination. Penile ultrasound provides rapid, anatomical information to establish disease severity, and to monitor progression and response to medical therapy. We determined the relationship between ultrasound characteristics and progression to surgical intervention in men with Peyronie's disease.We conducted a retrospective cohort study of 518 patients with Peyronie's disease. Patients completed a Peyronie's disease specific questionnaire detailing medical history, health related behaviors and Peyronie's disease characteristics, and underwent sonographic evaluation of the penis. Measurements of subtunical calcifications, septal fibrosis, tunical thickening (tunica thickness greater than 2 mm) and intracavernous fibrosis were made. Progression to surgery was determined from the medical record.In this cohort (mean patient age 53.8 years, range 20 to 78) 31% of patients had calcifications, 50% had tunical thickening, 20% had septal fibrosis and 15% had intracavernous fibrosis. Overall 25% of the cohort progressed to surgical intervention after an average followup of 1.25 years (range 0 to 7.6). Patients who underwent surgery were more likely to have subtunical calcifications present at the first clinic visit (OR 1.75, 95% CI 1.16-2.62). No other sonographic characteristics were associated with progression to surgery. After adjustment for age, marital status, degree of curvature, additional penile deformity, difficulty with penetration, ability to have intercourse and prior treatment for Peyronie's disease, calcifications were strongly associated with progression to surgery (OR 2.75, 95% CI 1.25-3.45).In a large cohort of patients with Peyronie's disease the presence of sonographically detected sub-tunical calcifications during the initial office evaluation was independently associated with subsequent surgical intervention.

  View details for DOI 10.1016/j.juro.2009.12.026

  View details for Web of Science ID 000275968200081

  View details for PubMedID 20171694

• Multivariate Analysis of Risk Factors for Long-Term Urethroplasty Outcome JOURNAL OF UROLOGY Breyer, B. N., McAninch, J. W., Whitson, J. M., Eisenberg, M. L., Mehdizadeh, J. F., Myers, J. B., Voelzke, B. B. 2010; 183 (2): 613-617

  Abstract

  We studied the patient risk factors that promote urethroplasty failure.Records of patients who underwent urethroplasty at the University of California, San Francisco Medical Center between 1995 and 2004 were reviewed. Cox proportional hazards regression analysis was used to identify multivariate predictors of urethroplasty outcome.Between 1995 and 2004, 443 patients of 495 who underwent urethroplasty had complete comorbidity data and were included in analysis. Median patient age was 41 years (range 18 to 90). Median followup was 5.8 years (range 1 month to 10 years). Stricture recurred in 93 patients (21%). Primary estimated stricture-free survival at 1, 3 and 5 years was 88%, 82% and 79%. After multivariate analysis smoking (HR 1.8, 95% CI 1.0-3.1, p = 0.05), prior direct vision internal urethrotomy (HR 1.7, 95% CI 1.0-3.0, p = 0.04) and prior urethroplasty (HR 1.8, 95% CI 1.1-3.1, p = 0.03) were predictive of treatment failure. On multivariate analysis diabetes mellitus showed a trend toward prediction of urethroplasty failure (HR 2.0, 95% CI 0.8-4.9, p = 0.14).Length of urethral stricture (greater than 4 cm), prior urethroplasty and failed endoscopic therapy are predictive of failure after urethroplasty. Smoking and diabetes mellitus also may predict failure potentially secondary to microvascular damage.

  View details for DOI 10.1016/j.juro.2009.10.018

  View details for Web of Science ID 000273540600079

  View details for PubMedID 20018318

• Socioeconomic, Anthropomorphic, and Demographic Predictors of Adult Sexual Activity in the United States: Data from the National Survey of Family Growth JOURNAL OF SEXUAL MEDICINE Eisenberg, M. L., Shindel, A. W., Smith, J. F., Breyer, B. N., Lipshultz, L. I. 2010; 7 (1): 50-58

  Abstract

  Individuals who engage in regular sexual intercourse are more likely to report good overall quality of life. Studies of sexuality in adolescents have focused on high-risk behaviors whereas similar studies in older adults have focused on sexual dysfunction. Given a paucity of data on the sexual behaviors of young adults and the possibility of important relationships between sexuality and overall health, we sought to determine factors that influence the frequency of intercourse in adult men and women in the United States.To identify factors related to coital frequency in young and middle-aged adults.We analyzed data from the male and female sample of the 2002 National Survey of Family Growth to examine frequency of sexual intercourse among Americans aged 25-45 years (men: N = 2,469; women: N = 5,120).Multivariable negative binomial regression modeling was used to test for independent associations between the frequency of sexual intercourse and demographic, socioeconomic, and anthropometric variables.In this study, men and women between the ages of 25 and 45 have sex a mean 5.7 and 6.4 times per month, respectively. Being married significantly increased coital frequency for women but has no effect on male coital frequency. Increased height, less than high school education, and younger age were predictive of increased sexual frequency in men. Pregnancy was associated with significantly lower coital frequency for both men and women. No association was shown between self-reported health status and coital frequency on multivariable analysis.Among young male adults, coital frequency is associated with specific socioeconomic, demographic, and anthropomorphic characteristics. Sexual frequency in women does not appear to be influenced by such factors. Self-reported health is not predictive of sexual activity in this age group.

  View details for DOI 10.1111/j.1743-6109.2009.01522.x

  View details for Web of Science ID 000273313600006

  View details for PubMedID 19796014

• Racial Differences in Vasectomy Utilization in the United States: Data From the National Survey of Family Growth UROLOGY Eisenberg, M. L., Henderson, J. T., Amory, J. K., Smith, J. F., Walsh, T. J. 2009; 74 (5): 1020-1024

  Abstract

  To explore whether health care, socioeconomic, or personal characteristics account for disparities observed in the utilization of vasectomy. More than 500,000 vasectomies are performed annually in the United States. The safety and efficacy of vasectomy make it a good family planning option, yet the factors related to use of male surgical sterilization are not well understood. In this analysis, we examined differences in vasectomy rates according to factors such as race and socioeconomic status.We analyzed data from the male sample of the 2002 National Survey of Family Growth to examine the use of vasectomy among the sample of men aged 30-45 (n = 2161). Demographic, socioeconomic, and reproductive characteristics were analyzed to assess associations with vasectomy.About 11.4% of men aged 30-45 years reported having a vasectomy, representing approximately 3.6 million American men. Although 14.1% of white men had a vasectomy, only 3.7% of black and 4.5% of Hispanic men reported undergoing vasectomy. On multivariate analysis, a significant difference in the odds of vasectomy by race/ethnicity remained, with black (odds ratio = 0.20, 0.09-0.45) and Hispanic men (odds ratio = 0.41, 0.18-0.95) having a significantly lower rate of vasectomy independent of demographic, partner, and socioeconomic factors. Having ever been married, fathering 2 or more children, older age, and higher income were the factors associated with vasectomy.After accounting for reproductive history, partner, and demographic characteristics, black and Hispanic men were less likely to rely on vasectomy for contraception. Further research is needed to identify the reasons for these race/ethnic differences and to identify factors that impede minority men's reliance on this means of fertility control.

  View details for DOI 10.1016/j.urology.2009.06.042

  View details for Web of Science ID 000271992400021

  View details for PubMedID 19773036

• Impact of Urine Sodium on Urine Risk Factors for Calcium Oxalate Nephrolithiasis JOURNAL OF UROLOGY Eisner, B. H., Eisenberg, M. L., Stoller, M. L. 2009; 182 (5): 2330-2333

  Abstract

  Increased sodium intake is thought to promote nephrolithiasis by dietary sodium hypercalciuric effects. However, equivocal data exist on whether increased urine sodium actually increases the nephrolithiasis risk. We examined the relationship between urine sodium and urine risk factors for nephrolithiasis.We retrospectively reviewed the records of 880 patients evaluated at a metabolic stone clinic to determine the relationship between urine sodium and urine calcium, volume and calcium oxalate supersaturation. Patients were separated into sodium excretion quintiles. Tests of linear trend were performed by examining the linear contrast in coefficients and using Cuzick's nonparametric linear trend test. Multivariate linear regression with urine sodium as a continuous variable was done to assess the relationship between urine sodium and other urine variables.Tests of linear trend showed that urine calcium and volume increased with increasing urine sodium (each p <0.01) but urine calcium oxalate supersaturation decreased with increasing urine sodium (p <0.01). Multivariate linear regression was adjusted for age, sex, body mass index and urine constituents. Urine sodium was positively associated with urine calcium (beta = 0.28, 95% CI 0.15 to 0.41, p <0.001) but negatively associated with urine calcium oxalate supersaturation (beta = -0.013, 95% CI -0.016 to -0.011, p <0.001). There was a trend toward a positive association of urine sodium and volume (beta = 0.001, 95% CI -0.00019 to 0.002, p = 0.10).Increasing urine sodium does not appear to increase the risk of calcium oxalate nephrolithiasis. Global sodium restriction may not necessarily alter the risk of stone formation, ie cause changes in calcium oxalate urine supersaturation, in patients with a history of nephrolithiasis.

  View details for DOI 10.1016/j.juro.2009.07.014

  View details for Web of Science ID 000270756900082

  View details for PubMedID 19758639

• Influence of Body Mass Index on Quantitative 24-Hour Urine Chemistry Studies in Children With Nephrolithiasis JOURNAL OF UROLOGY Eisner, B. H., Eisenberg, M. L., Stoller, M. L. 2009; 182 (3): 1142-1145

  Abstract

  A high body mass index increases the risk of nephrolithiasis in adults. Despite the growing problem of pediatric obesity, little is known about the relationship between body mass index and risk of nephrolithiasis in children. We examined the association between body mass index and 24-hour urine chemistry studies in children with a history of nephrolithiasis.A total of 43 children were included in the study. We retrospectively reviewed a database of 24-hour urine chemistry studies. We calculated body mass index for each individual and cases were then stratified by percentile. The 24-hour urine chemistry studies were adjusted for daily creatinine excretion, urine volume was adjusted for age, and pH and urine supersaturations were unadjusted.Body mass index percentile was below the 25th percentile in 8 cases, 25th to 49th percentile in 7, 50th to 74th percentile in 5 and 75th percentile or above in 14. On multivariate analysis the only 24-hour urine parameters with a significant relationship to body mass index were urine oxalate (negative relationship) and supersaturation of calcium phosphate (positive). As body mass index increased, urine oxalate excretion decreased and supersaturation of calcium phosphate increased.A high body mass index is associated with decreased urine oxalate and increased supersaturation of calcium phosphate. Given the increasing prevalence of obesity in younger patients, our findings have important clinical implications. Pediatricians and pediatric subspecialists should be aware of these findings when evaluating children with nephrolithiasis.

  View details for DOI 10.1016/j.juro.2009.05.052

  View details for Web of Science ID 000268899300120

  View details for PubMedID 19625057

• Who is the 40-Year-Old Virgin and Where Did He/She Come From? Data from the National Survey of Family Growth JOURNAL OF SEXUAL MEDICINE Eisenberg, M. L., Shindel, A. W., Smith, J. F., Lue, T. F., Walsh, T. J. 2009; 6 (8): 2154-2161

  Abstract

  Little is known about young and middle aged adults who have never engaged in sexual intercourse. Individuals who have not engaged in sexual activity may theoretically have diminished overall quality of life, as recent evidence suggests that sexual activity may be related to overall health status in adults.We sought to identify factors related to sexual abstinence in young and middle-aged adults.We analyzed data from the male and female sample of the 2002 National Survey of Family Growth to examine sexual abstinence among unmarried participants aged 25-45 (men: N = 2,469; women: N = 5,120). Main Outcome Measures. Multivariable logistic regression modeling was used to test for independent associations between demographic, medical, and anthropometric variables and abstinence while adjusting for confounding and mediating variables.A total of 122 (13.9%) men aged 25-45 reported never having had sex, representing approximately 1.1 million American men in this age cohort. Among female participants, a total of 104 (8.9%) women aged 25-45 reported never having sex, representing approximately 800,000 American women in this age cohort. Both men and women who reported that they attend religious services one or more times per week were more likely to be sexually abstinent, independent of their specific religious beliefs. Virgin status was also significantly associated with drinking alcohol within the past year. While a college degree in women predicted virginity, education was not associated with virginity in men. Men showed lower rates of sexual abstinence if they reported having spent time in prison or serving in the military.Amongst young adults, sexual abstinence does not appear to be mediated by health status, anthropometric measures, or age. Attending religious services and avoidance of alcohol consumption are associated with virginity in adults. Other factors associated with abstinence differ between genders and merit further study.

  View details for DOI 10.1111/j.1743-6109.2009.01327.x

  View details for Web of Science ID 000268466800010

  View details for PubMedID 19493289

• Endoscopic Management of Retained Renal Foreign Bodies UROLOGY Eisenberg, M. L., Lee, K. L., Stoller, M. L. 2009; 73 (6): 1189-1194

  Abstract

  To review our experience with endoscopic extraction of renal foreign bodies. We assessed the preoperative factors associated with renal failure, operative planning and technique, and postoperative outcomes. Retained foreign bodies in the kidney from previous endoscopic and/or percutaneous manipulation can be technically challenging.We retrospectively reviewed our database from November 1992 through April 2008 for patients who had undergone extraction of a renal foreign body.A total of 21 patients were identified who met the selection criteria (11 men and 10 women), with a mean age of 41 +/- 22 years. The renal foreign bodies included indwelling ureteral stents (n = 15), nephrostomy tubes (n = 3), the inner core of a guidewire (n = 1), a nephrostomy tube pull string (n = 1), and a laser fiber (n = 1). Of the 21 patients, 15 (71%) required antegrade instrumentation by way of a percutaneous tract to remove the foreign body. Extraction of the nephrostomy pull string, fragmented guidewire, and laser fiber remnant were approached percutaneously. In the case of a retained ureteral stent, all but 2 required a combined antegrade and retrograde approach for extraction. Patients presenting with renal insufficiency (n = 5), defined by a creatinine >1.5 mg/dL, had obstruction resulting from a forgotten ureteral stent that had been left in place for among the longest periods in our cohort (range 1.5-10 years). Two fifths of these patients had improvement in renal function after endoscopic extraction.Patients with retained renal foreign bodies benefit from extraction by way of retrograde and/or antegrade endoscopic techniques. In patients presenting with renal failure, improvement in renal function is often seen after extraction of a retained renal foreign body.

  View details for DOI 10.1016/j.urology.2008.09.010

  View details for Web of Science ID 000266972100009

  View details for PubMedID 19362355

• Effect of Obesity on Urethroplasty Outcome UROLOGY Breyer, B. N., McAninch, J. W., Whitson, J. M., Eisenberg, M. L., Master, V. A., Voelzke, B. B., Elliott, S. P. 2009; 73 (6): 1352-1355

  Abstract

  To determine whether obesity increases the risk of urethroplasty failure.A total of 381 patients underwent urethroplasty and had complete body mass index (BMI) data. Stricture recurrence-free survival was defined as subjective and objective improvement in urinary flow, an absence of radiographic evidence of stricture, and no further need for urethral instrumentation. Cox proportional hazards regression analysis was used to identify both univariate and multivariate predictors of urethroplasty outcome.The median patient age was 40 years (range 18-90). The median follow-up was 5.9 years (range 1 month to 10 years). Of the 381 patients, 60 developed recurrent stricture (15.7%). Overweight (BMI 25-30 kg/m(2)) and obese (BMI 30-35 kg/m(2)) patients were more likely to have urethroplasty failure, reaching significance and near significance on univariate and multivariate analysis, respectively (P = .03 and P = .07, respectively). Patients who were severely (BMI 35-40 kg/m(2)) or morbidly obese (BMI >40 kg/m(2)) did not have an increased risk of urethroplasty failure.Although obesity's relationship with urethroplasty failure is not linear, it does appear to affect outcomes after urethroplasty.

  View details for DOI 10.1016/j.urology.2008.12.073

  View details for Web of Science ID 000266972100058

  View details for PubMedID 19371937

• Use of Viscoelastic Solution to Improve Visualization During Urologic Microsurgery: Evaluation of Patency After Vasovasostomy UROLOGY Eisenberg, M. L., Walsh, T. J., Turek, P. J. 2009; 73 (1): 134-136

  Abstract

  Viscoat is a nonpyrogenic, sterile, viscoelastic solution used to protect the endothelium and enhance visualization during cataract and corneal surgery. Commonly used in ophthalmic surgery, we evaluated whether it could improve the optics during urologic microsurgery without adversely affecting outcomes.We retrospectively compared consecutive vasovasostomies performed by a single surgeon with (n = 23) and without (n = 50) the bilateral use of Viscoat. The examined parameters included patient age, vasectomy duration, intraoperative sperm characteristics, patency (ejaculation of motile sperm), time to patency, and postoperative semen characteristics. The comparisons of the sample mean values and proportions were assessed with analysis of variance, Wilcoxon, and chi(2) tests.Subjectively, Viscoat improved visualization of the vasal lumen and suture placement and aided in resident and fellow instruction. The vasovasostomy cases performed with and without the use of Viscoat were similar with regard to the patient and intraoperative characteristics. The overall patency rates were similar between the two groups (91% vs 92%, P = .92) with a median follow-up of 7 months. In addition, the best total motile sperm count and the durability of the patency achieved were similar between the two groups.Viscoat is a dispersive agent that does not adversely affect surgical patency after vasovasostomy. Subjectively, it helped with visualizing the lumen of the vas deferens during urologic microsurgery.

  View details for DOI 10.1016/j.urology.2008.03.006

  View details for Web of Science ID 000262379700036

  View details for PubMedID 18977020

• Differences in quantitative urine composition in stone-forming versus unaffected mate kidneys. Open access journal of urology Eisenberg, M. L., Lee, K. L., Breyer, B. N., Walsh, T. J., Konety, B. R., Stoller, M. L. 2009; 1: 9-13

  Abstract

  Many patients present with bilateral stones. There is a unique group of patients, however, that presents with stones exclusively on one side. We hypothesize that in such situations, 24-hour urine collections may not reveal specific defects on the affected stone-bearing kidney. We therefore evaluated selective 12-hour urine collections after percutaneous nephrolithotomy (PNL) to help determine if there is differential renal excretion.We collected urine specimens from patients with nephrolithiasis who underwent unilateral PNL. Urine samples were collected and analyzed from nephrostomy tubes, representing the affected kidneys, and from Foley bladder catheters, representing the contralateral mate kidney.Thirty-one patients were studied (14 with unilateral nephrolithiasis and 17 with bilateral). Treated kidneys from patients with unilateral nephrolithiasis displayed lowered urine excretion of uric acid, sodium, chloride, calcium, and total osmoles when compared to patients with bilateral nephrolithiasis. Stone size and length of procedure were not predictive of urine composition after PNL.Treated kidneys from patients with a history of unilateral stone disease revealed marked differences in urine excretion compared to those with bilateral nephrolithiasis after unilateral PNL. These findings could be secondary to the surgical insult, urinary stone disease, or could be a responsible factor for stone pathogenesis.

  View details for PubMedID 24198607

• Partial Salvage Cryoablation of the Prostate for Recurrent Prostate Cancer After Radiotherapy Failure UROLOGY Eisenberg, M. L., Shinohara, K. 2008; 72 (6): 1315-1318

  Abstract

  To determine the efficacy of partial cryoablation of the prostate in the salvage setting.All patients who were treated between April 2004 and September 2007 for recurrent prostate adenocarcinoma after failure of primary radiotherapy by means of partial cryoablation were identified.Nineteen patients met inclusion criteria; 15 had >6 months' follow-up. Mean age was 71 years. Men received salvage therapy a mean of 6 years after primary radiotherapy. Median follow-up was 18 months (range, 6-33 months). The biochemical recurrence-free survival rate (according to the American Society for Therapeutic Radiology and Oncology definition) was 89%, 67%, and 50% at 1, 2, and 3 years, respectively. One of 10 patients harbored residual carcinoma on routine follow-up biopsy at 1 year, whereas 50% harbored residual benign prostate tissue. Complications included incontinence (1), urethral stricture (1), and urethral ulcer (1).In properly selected patients with a unilateral focus of disease recurrence after radiotherapy, acceptable oncologic results can be achieved with partial cryoablation of the prostate, with low morbidity.

  View details for DOI 10.1016/j.urology.2008.03.040

  View details for Web of Science ID 000262121500032

  View details for PubMedID 18597824

• Ejaculatory duct manometry in normal men and in patients with ejaculatory duct obstruction JOURNAL OF UROLOGY Eisenberg, M. L., Walsh, T. J., Garcia, M. M., Shinohara, K., Turek, P. J. 2008; 180 (1): 255-260

  Abstract

  Ejaculatory duct obstruction is a treatable cause of male infertility but the diagnosis can be difficult to make. Transrectal ultrasound is valuable but not specific for ejaculatory duct obstruction. Adjunctive procedures, such as chromotubation and seminal vesicle aspiration, are more sensitive but not definitive, especially for partial obstruction. We describe what is to our knowledge a new hydraulic test and report its ability to identify physical and functional ejaculatory duct obstruction.Two groups of men were studied, including patients with infertility or ejaculatory pain in whom ejaculatory duct obstruction was suspected and fertile men undergoing vasectomy reversal (controls). In each cohort ejaculatory duct injection and manometry were performed. Patients with ejaculatory duct obstruction underwent transurethral ejaculatory duct resection based on routine criteria. Pressure was reassessed after resection. Manometry pressures were compared between controls and patients with ejaculatory duct obstruction, and correlated with the response to transurethral ejaculatory duct resection.In the 7 controls (14 sides) mean ejaculatory duct opening pressure was 33.2 cm H(2)O. In the 9 patients (17 sides) with suspected ejaculatory duct obstruction mean ejaculatory duct opening pressure before transurethral ejaculatory duct resection was 116 cm H(2)O. In the 6 patients who underwent resection, which was unilateral and bilateral in 3 each, mean ejaculatory duct opening pressure decreased from 118 to 53 cm H(2)O. Of the 5 patients who underwent semen analyses before and after resection 80% showed an increase in ejaculate volume and/or at least 100% improvement in TMC (volume x concentration x motile fraction).Ejaculatory duct manometry with baseline values defined in fertile men demonstrates that men with clinically suspected ejaculatory duct obstruction have higher ejaculatory duct opening pressure than fertile men and ejaculatory duct pressure decreases after transurethral ejaculatory duct resection.

  View details for DOI 10.1016/j.juro.2008.03.019

  View details for Web of Science ID 000256643900064

  View details for PubMedID 18499178

• First-stage urethroplasty: Utility in the modern era UROLOGY Elliott, S. P., Eisenberg, M. L., McAninch, J. W. 2008; 71 (5): 889-892

  Abstract

  To describe the current role of first-stage urethroplasty and its success as a management option in patients with complex anterior urethral stricture disease.We reviewed our urethral stricture database to identify patients managed with a staged urethral reconstruction or permanent first-stage urethroplasty. We noted patient age, etiology of stricture disease, location and length of stricture, location of neomeatus, indication for a staged approach, follow-up, and failure rate.A total of 38 men with a median age of 53 years met the inclusion criteria. The etiology of stricture disease varied, most commonly prior hypospadias repair (n = 9 [24%]) and lichen sclerosis (n = 6 [16%]). Location of stricture disease varied throughout the anterior urethra. Median stricture length was 5 cm. First-stage urethroplasty was accomplished with a penile shaft neomeatus in 13 patients (34%) and a perineal neomeatus in 25 (66%). Median follow-up was 22 months. Postoperative urethral dilation was required in 7 patients (18%). No patient has required an indwelling urethral catheter, suprapubic cystostomy, or urinary diversion. Of 38 patients, 9 (24%) have undergone a second-stage urethroplasty.The first-stage urethroplasty produces unobstructed voiding with few complications in high-risk patients. Few patients elect to have a second-stage urethroplasty performed. This is an old but not obsolete concept. We have presented modifications in technique to optimize success.

  View details for DOI 10.1016/j.urology.2007.11.051

  View details for Web of Science ID 000255992000042

  View details for PubMedID 18279942

• Management of restenosis after urethral stent placement JOURNAL OF UROLOGY Eisenberg, M. L., Elliott, S. P., McAnincht, J. W. 2008; 179 (3): 991-995

  Abstract

  We describe our experience with the management of restricture after urethral stent placement, including endoscopic and open surgical treatment.We surveyed our prospectively collected database for patients with restenosis after urethral stent insertion. We reviewed patient age, comorbidities, indications for stent placement, restricture length, management of restricture, postoperative complications and the further restenosis rate.Overall we have treated 22 patients with failed urethral stents with a median followup of 30 months (range 1 to 96). All stents were initially placed for urethral stricture management. Stricture etiology included prostate cancer therapy in 9 cases, idiopathic causes in 6, urethral instrumentation in 2, trauma in 2, simple prostatectomy in 2 and gender reassignment/phalloplasty in 1. Ten patients had anterior urethral stricture, 11 had posterior stricture and 1 patient had each type. Of the 22 patients with stenosis after stent placement 13 underwent urethroplasty. Of the 18 patients with indwelling stents at treatment the stent was removed in 8 intraoperatively and in 10 the stent was left in situ. Ten of the 11 anterior strictures were treated with urethroplasty. Only 4 of the 12 posterior strictures were treated with urethroplasty, while 8 were managed endoscopically. Our overall success rate for treatment after stent failure was 67% (8 of 12 cases) for posterior urethral strictures and 82% (9 of 11) for anterior strictures.Urethral stent failure requires complex intervention. A failed posterior urethral stent can often be managed endoscopically. Conversely we have managed failed anterior urethral stents by urethroplasty.

  View details for DOI 10.1016/j.juro.2007.10.047

  View details for Web of Science ID 000253176000058

  View details for PubMedID 18206915

• Associations among hypospadias, cryptorchidism, anogenital distance, and endocrine disruption. Current urology reports Hsieh, M. H., Breyer, B. N., Eisenberg, M. L., Baskin, L. S. 2008; 9 (2): 137-142

  Abstract

  Endocrine disruptors, such as environmental compounds with endocrine-altering properties, may cause hypospadias and cryptorchidism in several species, including humans. Anogenital distance is sexually dimorphic in many mammals, with males having longer anogenital distance on average than females. Animal models of proposed endocrine disruptors have associated prenatal exposure with hypospadias, cryptorchidism, and reduced anogenital distance. Human studies have correlated shorter anogenital distance to in utero exposure to putative endocrine disruptors. We review preliminary data suggesting that anogenital distance is reduced in boys with hypospadia and cryptorchidism. Hence, human hypospadias and cryptorchidism may be associated with reduced anogenital distance as a result of endocrine disruption.

  View details for PubMedID 18419998

• Long-term outcomes and late complications of laparoscopic nephrectomy with renal autotransplantation JOURNAL OF UROLOGY Eisenberg, M. L., Lee, K. L., Zumrutbas, A. E., Meng, M. V., Freise, C. E., Stoller, M. L. 2008; 179 (1): 240-243

  Abstract

  We report long-term outcomes and late complications after laparoscopic nephrectomy with autotransplantation.We retrospectively reviewed clinical data on all patients who underwent laparoscopic nephrectomy with autotransplantation between July 2000 and March 2007. Late complications, ie greater than 6 months, that required surgical intervention were analyzed. Clinical outcomes in patients with primary ureteral stricture disease and oncological outcomes in patients with renal tumors were examined.Indications for autotransplantation included complex ureteral stricture disease in 15 patients and renal malignancy in 4. Median age at surgery was 48 years (range 25 to 68). Median followup was 29 months. Of the 17 patients with greater than 6 months of followup late complications requiring surgical intervention occurred in 4. Transplant nephrectomy was required in 2 patients in the stricture group. Indications for nephrectomy were nonfunction complicated by pseudoaneurysm in 1 case and chronic loin pain in 1. Another patient had recurrent nephrolithiasis requiring percutaneous nephrolithotomy and in 1 a pseudoaneurysm was managed successfully by endovascular techniques. Two patients in the tumor group had disease progression, which was managed medically.Given the complexity and severity of disease that necessitates renal autotransplantation, it is not surprising that additional treatments are required. Patients with primary stricture disease may be at increased risk for vascular aneurysm due to infection and/or inflammation. Tumor progression is possible after ex vivo tumor excision and autotransplantation, especially in patients requiring heroic measures to avoid or delay dialysis. Thus, careful patient selection and vigilant followup are mandatory.

  View details for DOI 10.1016/j.juro.2007.08.135

  View details for Web of Science ID 000251650200062

  View details for PubMedID 18001789

• Preservation of lower urinary tract function in posterior urethral stenosis: Selection of appropriate patients for urethral Stents JOURNAL OF UROLOGY Eisenberg, M. L., Elliott, S. P., McAninch, J. W. 2007; 178 (6): 2456-2460

  Abstract

  We describe our experience with urethral stents to manage iatrogenic posterior urethral stenosis.We surveyed our retrospective database for patients in whom we placed a urethral stent for posterior urethral stricture disease. We reviewed patient age, comorbidities, indications for stent placement, stricture length, postoperative complications and the repeat stenosis rate.Overall we placed urethral stents in 13 patients, of whom 12 presented with posterior urethral stenosis and 1 presented with anterior and posterior stricture. The etiology of urethral stricture was prostate cancer therapy in 11 of 13 cases and simple prostatectomy in 2. Urethral stenting was chosen instead of urethral reconstruction largely due to prior radiation for prostate cancer and avoidance of the morbidity of surgery. Overall 6 of 13 patients required additional procedures for stricture recurrence, including 5 in previously irradiated patients. Two patients had stents removed due to migration or pain. Genitourinary infections developed in 5 of 13 patients. Eight of 13 patients with a posterior urethral stricture were incontinent, as expected after stent placement. Incontinence was managed by an artificial urinary sphincter in willing patients with 9 of 13 continent.Urethral stents provide reasonable treatment for patients with posterior urethral stenosis when attempting to preserve lower urinary tract function caused by stricture disease after prostate cancer therapy. Prior radiation seems to increase the failure rate. Continence can be maintained after posterior urethral stenting in select patients.

  View details for DOI 10.1016/j.juro.2007.08.013

  View details for Web of Science ID 000250847900062

  View details for PubMedID 17937962

• Complications in ureterosigmoidostomy endoscopic management of obstructive UROLOGY Eisenberg, M. L., Lee, K. L., Stoller, M. L. 2007; 70 (6): 1048-1052

  View details for DOI 10.1016/j.urology.2007.07.014

  View details for Web of Science ID 000253194400004

• Endoscopic management of obstructive complications in ureterosigmoidostomy. Urology Eisenberg, M. L., Lee, K. L., Stoller, M. L. 2007; 70 (6): 1048-1052

  Abstract

  Although rarely used today for supravesical urinary diversion, ureterosigmoidostomy remains useful in patients with bladder exstrophy. However, management of ureteral stricture and ureteral urolithiasis is challenging because of the lack of anatomic landmarks.We reviewed our prospectively collected database from 1994 to 2006 for all patients requiring surgical treatment for obstructive complications associated with ureterosigmoidostomy.Our analysis revealed 3 patients (mean age 46 years; 2 men and 1 woman). All 3 patients had undergone ureterosigmoidostomy as a component of bladder exstrophy management. All patients presented with renal failure due to obstruction and required antegrade endoscopic management. Two patients had anastomotic strictures and one had obstructive urolithiasis. One patient in whom the stricture was judged to be chronic was treated with an endoureterotomy and Acucise balloon. The second patient, who had an acute obstruction after colonoscopic biopsy of his anastomosis, was treated with antegrade balloon dilation. Both patients had stents placed across the anastomosis for 6 weeks postoperatively. Despite reflux of stool into the collecting system, neither patient manifested with local or systemic signs of infection. The patient with urolithiasis required antegrade basket stone extraction.Obstructive complications after ureterosigmoidostomy should be managed using antegrade endoscopic techniques.

  View details for PubMedID 18158011

• Posthumous sperm retrieval: analysis of time interval to harvest sperm HUMAN REPRODUCTION Shefi, S., Raviv, G., Eisenberg, M. L., Weissenberg, R., Jalalian, L., Levron, J., Band, G., Turek, P. J., Madgar, I. 2006; 21 (11): 2890-2893

  Abstract

  Current recommendations regarding posthumous sperm retrieval (PSR) are based on a small number of cases. Our purpose was to determine the time interval from death to a successful procedure.Seventeen consecutive PSR procedures in 14 deceased and 3 neurologically brain-dead patients at two male infertility centres [Sheba Medical Center (SMC), Tel-Hashomer, Israel and University of California San Francisco (UCSF), San Francisco, CA, USA] were analysed. Main outcome measures were retrieval of vital sperm, pregnancies and births.PSR methods included resection of testis and epididymis (n = 8), en-block excision of testis, epididymis and proximal vas deferens with vasal irrigation (n = 6), electroejaculation (EEJ) (n = 2) and epididymectomy (n = 1). PSR was performed 7.5-36 h after death. Sperm was retrieved in all cases and was motile in 14 cases. In two cases, testicular and epididymal tissues were cryopreserved without sperm evaluation, and in one case, no motility was detected. IVF and ICSI were performed in two cases in which sperm had been retrieved 30 h after death, and both resulted in pregnancies and live births.Viable sperm is obtainable with PSR well after the currently recommended 24-h time interval. PSR should be considered up to 36 h after death, following appropriate evaluation. No correlation was found between cause of death and chance for successful sperm retrieval.

  View details for DOI 10.1093/humrep/del232

  View details for Web of Science ID 000241272700024

  View details for PubMedID 16959804

• Insulin receptor (IR) and glucose transporter 2 (GLUT2) proteins form a complex on the rat hepatocyte membrane CELLULAR PHYSIOLOGY AND BIOCHEMISTRY Eisenberg, M. L., Maker, A. V., Slezak, L. A., Nathan, J. D., Sritharan, K. C., Jena, B. P., Geibel, J. P., Andersen, D. K. 2005; 15 (1-4): 51-58

  Abstract

  The hepatic glucose transporter, GLUT2, facilitates bidirectional glucose transport across the hepatocyte plasma membrane under insulin regulation. We studied the interactions of IR and GLUT2 proteins to determine whether they are physically coupled in a receptor-transporter complex. By comparing endosome and plasma membrane IR and GLUT2 ratios before and after feeding, it was determined that IR and GLUT2 are internalized in a fixed ratio. When solubilized hepatocytes were immunoprecipitated with antibodies against either IR or GLUT2, both proteins co-precipitated. The association of IR and GLUT2 was further assessed by confocal microscopy. Sections of fed liver were incubated with fluorescein-tagged anti-GLUT2 or Texas Red-tagged anti-IR. Colocalization was observed both at the plasma membrane and in the cytosol. Fluorescence-resonance energy transfer studies further confirmed this association. We conclude that IR and GLUT2 form a receptor-transporter complex in hepatocytes, which forms a mechanism of insulin-mediated hepatic glucose regulation.

  View details for DOI 10.1159/000083638

  View details for Web of Science ID 000226588000005

  View details for PubMedID 15665515