Publications by authors named "Michael L Eisenberg"

212 Publications

Consumption of cruciferous vegetables and the risk of bladder cancer in a prospective US cohort: data from the NIH-AARP diet and health study.

Am J Clin Exp Urol 2021 15;9(3):229-238. Epub 2021 Jun 15.

Department of Urology, Stanford University School of Medicine Stanford, California.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: Our study shows no association between dietary consumption of cruciferous vegetables and incident bladder cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303025PMC
June 2021

The association between work hours, shift work, and job latitude with fecundability: A preconception cohort study.

J Occup Health Psychol 2021 Jul 29. Epub 2021 Jul 29.

Department of Epidemiology.

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. Total hours worked was not associated with time to pregnancy. 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).
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http://dx.doi.org/10.1037/ocp0000279DOI Listing
July 2021

Trends in Testosterone Therapy use in Prostate Cancer Survivors in the United States.

J Sex Med 2021 Jul 21. Epub 2021 Jul 21.

Stanford University School of Medicine, Stanford, CA, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jsxm.2021.06.007DOI Listing
July 2021

Peyronie's Disease as a marker of inflammation -is there hope on the horizon?

Am J Med 2021 Jul 14. Epub 2021 Jul 14.

Department of Urology, Stanford University School of Medicine, Stanford, CA 94304.

While the description of Peyronie's disease, a connective tissue disorder involving the growth of fibrous plaques in the soft tissue of the penis, 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.
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http://dx.doi.org/10.1016/j.amjmed.2021.06.015DOI Listing
July 2021

Female Sexual Function During the COVID-19 Pandemic in the United States.

Sex Med 2021 Apr 17;9(4):100355. Epub 2021 Apr 17.

Department of Urology, Stanford University Medical Center, Stanford, CA, USA.

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, et al. Female Sexual Function During the COVID-19 Pandemic in the United States. Sex Med 2021;9:100355.
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http://dx.doi.org/10.1016/j.esxm.2021.100355DOI Listing
April 2021

RUBIC (ReproUnion Biobank and Infertility Cohort): A binational clinical foundation to study risk factors, life course, and treatment of infertility and infertility-related morbidity.

Andrology 2021 Jun 10. Epub 2021 Jun 10.

Departments of Environmental Health and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

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 Skåne 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 biospecimens (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.
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http://dx.doi.org/10.1111/andr.13063DOI Listing
June 2021

Testosterone target therapy: focus on immune response, controversies and clinical implications in patients with COVID-19 infection.

Ther Adv Endocrinol Metab 2021 22;12:20420188211010105. Epub 2021 Apr 22.

Department of Maternal-Infant and Urological Sciences, Prostate Cancer Unit, "Sapienza" Rome University, Policlinico Umberto I Hospital, Rome, Italy.

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.
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http://dx.doi.org/10.1177/20420188211010105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072920PMC
April 2021

The Association Between Hemoglobin A1c Levels and Inflatable Penile Prosthesis Infection: Analysis of US Insurance Claims Data.

J Sex Med 2021 06 6;18(6):1104-1109. Epub 2021 Jun 6.

Department of Urology, Stanford University School of Medicine, Stanford, CA, USA.

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.
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http://dx.doi.org/10.1016/j.jsxm.2021.03.077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253516PMC
June 2021

Does semen analysis testing reveal disparities?

Nat Rev Urol 2021 Jun 1. Epub 2021 Jun 1.

Department of Urology, Stanford University School of Medicine, Stanford, CA, USA.

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http://dx.doi.org/10.1038/s41585-021-00485-xDOI Listing
June 2021

Association of Bicycle-Related Genital Numbness and Female Sexual Dysfunction: Results From a Large, Multinational, Cross-Sectional Study.

Sex Med 2021 Jun 25;9(3):100365. Epub 2021 May 25.

Department of Urology, University California, San Francisco, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA. Electronic address:

Introduction: Cycling can lead to microtrauma due to increased perineal pressure, possibly contributing to genital numbness and sexual dysfunction in female cyclists.

Aim: We aim to explore the associations between cycling characteristics, female genital numbness, and female sexual dysfunction.

Methods: 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.

Outcome Measures: The outcome measures were cycling characteristics, questions regarding numbness (intensity, duration, location), and the FSFI score.

Results: 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).

Conclusions: 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;9:100365.
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http://dx.doi.org/10.1016/j.esxm.2021.100365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240355PMC
June 2021

Trends in time-to-pregnancy in the USA: 2002 to 2017.

Hum Reprod 2021 Jul;36(8):2331-2338

Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA.

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.
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http://dx.doi.org/10.1093/humrep/deab107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289323PMC
July 2021

A North American prospective study of depression, psychotropic medication use, and semen quality.

Fertil Steril 2021 May 6. Epub 2021 May 6.

Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts.

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.
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http://dx.doi.org/10.1016/j.fertnstert.2021.03.052DOI Listing
May 2021

Association of preconception paternal health and adverse maternal outcomes among healthy mothers.

Am J Obstet Gynecol MFM 2021 Apr 23;3(5):100384. Epub 2021 Apr 23.

Department of Obstetrics and Gynecology, Stanford University, Stanford, CA; Department of Urology, Stanford University, Stanford, CA (Ms Li and Dr Eisenberg).

Background: Maternal morbidity continues to be an issue of national and global concern. Paternal preconception health may play a significant role in pregnancy outcomes and has received less attention than maternal health.

Objective: This study aimed to examine the association between preconception paternal health and the risk for adverse maternal outcomes among healthy mothers.

Study Design: This was a retrospective analysis of live births from 2009 through 2016 to healthy women aged 20 to 45 years recorded 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 component diagnoses and the most common individual chronic disease diagnoses (hypertension, diabetes mellitus, obesity, hyperlipidemia, chronic obstructive pulmonary disease, cancer, and depression). Women with metabolic syndrome components were excluded to avoid potential confounding of maternal and paternal factors. Adverse maternal outcomes that were assessed included (1) abnormal placentation including placenta accreta spectrum, placenta previa, and placental abruption; (2) preeclampsia with and without severe features including eclampsia; and (3) severe maternal morbidity, identified as any indicator from the Centers for Disease Control and Prevention Index of life-threatening complications at the time of delivery to 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 with maternal outcomes was also determined using generalized estimating equations models, accounting for some mothers who contributed multiple births during the study period, and by 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 between all adverse maternal outcomes and worsening preconception paternal health defined either as the number of metabolic syndrome diagnoses or number of chronic disease diagnoses (P<.001; Cochran-Armitage Trend test). In the generalized estimating equations model, the odds for preeclampsia without severe features increased in a dose-dependent fashion and were 21% higher (95% confidence interval, 1.17-1.26) among women whose partners had ≥2 metabolic syndrome diagnoses than among women whose partners had no metabolic syndrome diagnosis. The odds for preeclampsia with severe features and eclampsia increased in a dose-dependent fashion and were 19% higher (95% confidence interval, 1.09-1.30) among women whose partners had ≥2 metabolic syndrome diagnoses than among women whose partners had no metabolic syndrome diagnosis. The odds for severe maternal morbidity were 9% higher (95% confidence interval, 1.002-1.19) among women whose partners had ≥2 metabolic syndrome diagnoses than among women whose partners had no metabolic syndrome diagnosis. The odds for abnormal placentation were similar between the groups (adjusted odds ratio, 0.96; 95% confidence interval, 0.89-1.03).

Conclusion: Among healthy mothers, we report that preconception paternal health is significantly associated with increased odds of preeclampsia with and without severe features and weakly associated with increased odds of severe maternal morbidity. 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 obstetrical complications.
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http://dx.doi.org/10.1016/j.ajogmf.2021.100384DOI Listing
April 2021

The Association between Mortality and Male Infertility: Systematic Review and Meta-analysis.

Urology 2021 Apr 2. Epub 2021 Apr 2.

Department of Urology, Stanford University School of Medicine, Stanford, CA; Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA. Electronic address:

Objective: 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.

Methods: 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.

Results: Six studies from 2006 to 2020 met inclusion criteria. Three studies examined male infertility and mortality (n = 202,456; n = 1396), while four studies examined survival in relation to semen parameters (n = 59,291; n = 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).

Conclusion: 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.
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http://dx.doi.org/10.1016/j.urology.2021.02.041DOI Listing
April 2021

A biofeedback-guided programme or pelvic floor muscle electric stimulation can improve early recovery of urinary continence after radical prostatectomy: A meta-analysis and systematic review.

Int J Clin Pract 2021 Apr 2:e14208. Epub 2021 Apr 2.

Department of Maternal-Infant and Urologic Sciences, 'Sapienza' University of Rome, Policlinico Umberto I Hospital, Rome, Italy.

Purpose: Urinary incontinence (UI) after radical prostatectomy (RP) is an early side effect after catheter removal. This systematic review and meta-analysis were conducted to compare different forms of non-invasive treatments for post-RP UI and to analyse 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-months follow-up.

Results: Twenty-six articles were selected. At baseline after RP and catheter removal, mean pad weight varied extremely. At 1- and 3-months intervals, mean difference in pad weight recovery from baseline was significantly higher using guided programs (BF, PFES or both) than using PFME alone (3-months: 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 < .01), while at 6- and 12-months differences were similar (P > .04). At 1- and 3-months intervals, event rate (ER) of continence recovery was significantly higher using guided programs than using PFME alone (3-months: 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 < .01), while at 6- and 12-months 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-month interval, when compared with the use of PFME alone.
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http://dx.doi.org/10.1111/ijcp.14208DOI Listing
April 2021

Modeling the Contribution of Male Testosterone Levels to the Duration of Positive COVID Testing among Hospitalized Male COVID-19 Patients.

Diagnostics (Basel) 2021 Mar 24;11(4). Epub 2021 Mar 24.

Department of Maternal-Infant and Urological Sciences, "Sapienza" University of Rome, Policlinico Umberto I Hospital, 00161 Rome, Italy.

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. 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. 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). 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.
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http://dx.doi.org/10.3390/diagnostics11040581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063957PMC
March 2021

The Association of the COVID-19 Pandemic on Male Sexual Function in the United States: A Survey Study of Male Cannabis Users.

Sex Med 2021 Jun 18;9(3):100340. Epub 2021 Feb 18.

Stanford University School of Medicine, Stanford, CA, USA.

Introduction: 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.

Aim: To examine changes in male sexual function during the COVID-19 pandemic and to evaluate associated demographic variables.

Methods: 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.

Main Outcome Measures: 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).

Conclusion: 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. Chen T, Bhambhvani HP, Kasman AM, 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;9:100340.
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http://dx.doi.org/10.1016/j.esxm.2021.100340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240149PMC
June 2021

A global approach to addressing the policy, research and social challenges of male reproductive health.

Hum Reprod Open 2021 21;2021(1):hoab009. Epub 2021 Mar 21.

Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.

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.
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http://dx.doi.org/10.1093/hropen/hoab009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982782PMC
March 2021

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.

J Cancer Res Clin Oncol 2021 Mar 6. Epub 2021 Mar 6.

Department of Maternal-Infant and Urological Sciences, Policlinico Umberto I Hospital, "Sapienza" University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.

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-naïve 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 (HR: 0.63; 95% CI 0.46-0.86; HR: 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 (HR: 0.58, 95% CI 0.39-0.86; HR: 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.
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http://dx.doi.org/10.1007/s00432-021-03571-0DOI Listing
March 2021

The association between testosterone, estradiol and their ratio and mortality among US men.

Andrologia 2021 May 5;53(4):e13993. Epub 2021 Mar 5.

Department of Urology, School of Medicine, Stanford University, Stanford, CA, USA.

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.
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http://dx.doi.org/10.1111/and.13993DOI Listing
May 2021

Primary malignancies of the epididymis: clinical characteristics and prognostic factors.

Can J Urol 2021 02;28(1):10522-10529

Department of Urology, Stanford University Medical Center, Stanford, California, USA.

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.
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February 2021

Association of daily step count and serum testosterone among men in the United States.

Endocrine 2021 06 12;72(3):874-881. Epub 2021 Feb 12.

Department of Urology, Stanford University School of Medicine, Stanford, CA, USA.

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 < 350 ng/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 7 ng/dL for each additional 1000 steps taken daily (β-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.
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http://dx.doi.org/10.1007/s12020-021-02631-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159788PMC
June 2021

Association between infertility and all-cause mortality: analysis of US claims data.

Am J Obstet Gynecol 2021 07 10;225(1):57.e1-57.e11. Epub 2021 Feb 10.

Department of Urology, Stanford University Medical Center, Stanford, CA.

Background: The consequences of an infertility diagnosis extend beyond the pursuit of family building, because women with infertility also face increased risks for severe maternal morbidity, cancer, and chronic disease.

Objective: This study aimed to examine the association between female infertility and all-cause mortality.

Study Design: This retrospective analysis compared 72,786 women with infertility, identified in the Optum Clinformatics Datamart from 2003 to 2019 by infertility diagnosis, testing, and treatment codes, with 3,845,790 women without infertility seeking routine gynecologic care. The baseline comorbidities were assessed using the presence of ≥1 metabolic syndrome diagnoses and the Charlson Comorbidity Index. The primary outcome, which was all-cause mortality, was identified by linkage to the Social Security Administration Death Master File outcomes and medical claims. The association between infertility and mortality was examined using a Cox proportional hazard regression by adjusting for age, hypertension, hyperlipidemia, type II diabetes, year of evaluation, smoking, number of visits per year, nulliparity, obesity, region of the country, and race.

Results: Among 16,473,458 person-years of follow-ups, 13,934 women died. Women with infertility had a 32% higher relative risk for death from any cause (0.42% vs 0.35%, adjusted hazard ratio, 1.32; 95% confidence interval, 1.18-1.48) than women without infertility. The mean follow-up time per patient was 4.0±3.7 years vs 4.2±3.8 years for women with and without infertility, respectively. When stratified by age of <35 or ≥35 years or baseline medical comorbidity, the association between infertility and mortality remained. Women with infertility who delivered a child during the follow-up period faced a similar increased risk for mortality than the overall infertile group. Finally, receiving fertility treatment was not associated with a higher risk for death than receiving an infertility diagnosis or testing alone.

Conclusion: Although the absolute risk for death was low in both groups, women with infertility faced a higher relative risk for mortality than women without infertility. The association remained across all age, race and ethnicity groups, morbidities, and delivery strata. Importantly, infertility treatment was not associated with an increased risk for death. These findings reinforce the disease burden associated with infertility and its potential for long-term sequelae.
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http://dx.doi.org/10.1016/j.ajog.2021.02.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254745PMC
July 2021

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.

J Assist Reprod Genet 2021 Apr 5;38(4):835-846. Epub 2021 Feb 5.

Epidemiology Program, Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, TX, USA.

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.
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http://dx.doi.org/10.1007/s10815-021-02095-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079460PMC
April 2021

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 2021 Jul 20;153:28-34. Epub 2021 Jan 20.

Department of Urology, University of California San Francisco, San Francisco, CA.

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 the 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 that we hope urologists and administrators can use when creating productivity plans for male infertility practices.
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http://dx.doi.org/10.1016/j.urology.2021.01.016DOI Listing
July 2021

The quality of systematic reviews and meta-analyses assessing the treatment and management of male infertility.

Andrology 2021 05 9;9(3):801-809. Epub 2021 Feb 9.

Department of Urology, Stanford University School of Medicine, Stanford, CA, USA.

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: Of 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.
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http://dx.doi.org/10.1111/andr.12972DOI Listing
May 2021

Racial and socioeconomic disparities in retroperitoneal lymph node dissection and survival in nonseminomatous germ cell tumor: A population-based study.

Urol Oncol 2021 03 7;39(3):197.e1-197.e8. Epub 2021 Jan 7.

Division of Oncology, Stanford University Medical Center, Stanford, CA.

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.
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http://dx.doi.org/10.1016/j.urolonc.2020.12.016DOI Listing
March 2021

AUTHOR REPLY.

Urology 2021 Jan;147:148-149

Department of Urology, Stanford University School of Medicine, Stanford, CA; Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA.

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http://dx.doi.org/10.1016/j.urology.2020.07.089DOI Listing
January 2021

Modeling the contribution of the obesity epidemic to the temporal decline in sperm counts.

Arch Ital Urol Androl 2020 Dec 21;92(4). Epub 2020 Dec 21.

Department of Urology, Stanford University School of Medicine, Stanford; Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California.

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.
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http://dx.doi.org/10.4081/aiua.2020.4.357DOI Listing
December 2020

Association between preconception paternal health and pregnancy loss in the USA: an analysis of US claims data.

Hum Reprod 2021 02;36(3):785-793

Department of Urology, Stanford University School of Medicine, Stanford, CA 94305-5118, USA.

Study Question: Is preconception paternal health associated with pregnancy loss?

Summary Answer: Poor preconception paternal health is associated with a higher risk of pregnancy loss as confirmed in sensitivity analyses accounting for maternal age and health.

What Is Known Already: Preconception paternal health can negatively impact perinatal outcomes.

Study Design, Size, Duration: Retrospective cohort study of US insurance claims database from 2009 to 2016 covering 958 804 pregnancies.

Participants/materials, Setting, Methods: 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).

Main Results And The Role Of Chance: 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.

Limitations, Reasons For Caution: Retrospective study design covering only employer insured individuals may limit generalizability.

Wider Implications Of The Findings: Optimization of a father's health may improve pregnancy outcomes.

Study Funding/competing Interests: 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.

Trial Registration Number: N/A.
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http://dx.doi.org/10.1093/humrep/deaa332DOI Listing
February 2021
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