Disorders of Ejaculation: An AUA/SMSNA Guideline.

PURPOSE: Men who ejaculate before or shortly after penetration, without a sense of control, and who experience distress related to this condition may be diagnosed with premature ejaculation (PE), while men who experience difficulty achieving sexual climax may be diagnosed with delayed ejaculation (DE). The experience of many clinicians suggest that these problems are not rare and can be a source of considerable embarrassment and dissatisfaction for patients. The role of the clinician in managing PE and DE is to conduct appropriate investigation, to provide education, and to offer available treatments that are rational and based on sound scientific data. MATERIALS AND METHODS: The systematic review utilized to inform this guideline was conducted by a methodology team at the Pacific Northwest Evidence-based Practice Center. A research librarian conducted searches in Ovid MEDLINE (1946 to March 1, 2019), the Cochrane Central Register of Controlled Trials (through January 2019) and the Cochrane Database of Systematic Reviews (through March 1, 2019). An update search was conducted on September 5, 2019. Database searches resulted in 1,851 potentially relevant articles. After dual review of abstracts and titles, 223 systematic reviews and individual studies were selected for full-text dual review, and 8 systematic reviews and 59 individual studies were determined to meet inclusion criteria and were included in the review. RESULTS: Several psychological health, behavioral, and pharmacotherapy options exist for both PE and DE; however, none of these pharmacotherapy options have achieved approval from the United States Food and Drug Administration and their use in the treatment of PE and DE is considered off-label. CONCLUSION: Disturbances of the timing of ejaculation can pose a substantial impediment to sexual enjoyment for men and their partners. The Panel recommends shared decision-making as fundamental in the management of disorders of ejaculation; involvement of sexual partner(s) in decision making, when possible, may allow for optimization of outcomes.

Risk of Postoperative Thromboembolism in Men Undergoing Urological Prosthetic Surgery: An Assessment of 21,413 Men.

PURPOSE: We assessed venous thromboembolism (VTE) and associated risk factors following artificial urinary sphincter (AUS) and inflatable penile prosthesis (IPP) surgery. MATERIALS AND METHODS: Using IBM® MarketScan, a commercial claims database, patients undergoing AUS and IPP surgery were identified using CPT® and ICD (International Classification of Diseases)-10 procedure codes between 2008 and 2017. ICD-9 and -10 codes were used to identify health care visits associated with lower extremity deep vein thrombosis (DVT) and pulmonary embolism (PE) within 90 days of surgery. Covariates were assessed using a multivariable model to determine association with outcome of DVT and/or PE. RESULTS: A total of 21,413 men underwent AUS (4,870) or IPP (16,543) surgery between 2008 and 2017 with a median age of 62 years and 68 years, respectively. DVT and PE events following AUS and IPP surgery occurred in 1.54% and 1.04%, respectively. A history of varicose veins (HR 2.76; 95% CI 1.11-6.79), prior history of DVT (HR 13.65; 95% CI 7.4-25.19), or PE (HR 7.65; 95% CI 4.01-14.6) in those undergoing AUS surgery was highly associated with development of postoperative VTE. Likewise, prior history of DVT (HR 12.6; 95% CI 7.99-19.93) and PE (HR 8.9; 95% CI 5.6-14.13) was strongly associated with a VTE event following IPP surgery. CONCLUSIONS: In a large cohort of men undergoing AUS and IPP surgery, 1.54% and 1.04% of men experienced a VTE event within 90 days of surgery, respectively. Prior history of varicose veins, DVT, and PE was associated with an increased likelihood of developing a postoperative DVT or PE.

Seasonal variation in semen quality is not associated with fecundity in the Utah Population Database.

We determine whether a suspected seasonal variability in semen quality affect subsequent live birth rates. This is a retrospective, cohort analysis of men who provided semen analyses as part of fertility workup through a large andrology lab between 1996 and 2013 and corresponding birth rates using the Utah Population Database (UPDB). Semen parameters were analysed including total motile count (TMC), total sperm count, sperm concentration and progressive motility. Corresponding live births reflect those born in the state of Utah and were derived from birth certificate data available in the UPDB. Descriptive statistics were reported along with linear regression analysis with mixed effected models to test for an interaction between seasonal variation in semen quality and birth rates, accounting for age at the time of the semen analysis and abstinence time. A total of 11,929 patients and 14,765 semen samples were included. Only 3597 men (39% of men) had one or more values outside the World Health Organization reference range for their semen parameters. Linear regression demonstrated a consistent U-shaped relationship between TMC, total sperm count, and sperm concentration and season, with spring and winter yielding the highest values with a decline in the summer and fall. 7319 of these males had recorded live births for a total of 13,502 live births during the study period after a median follow-up of 7.2 years (IQR: 3.9-11.0). We did not find a significant interaction between specific semen parameters for a specific season and subsequent live births. Semen quality was the highest in the spring and winter, however there was no interaction between seasonal variability in semen quality and subsequent births. This is one of the largest studies describing seasonal variation in semen quality in humans.

Lower female partner live birth rate in male cancer survivors: An age-matched cohort analysis of the Utah Population Database.

We determine the time to first live birth for female partners of males after a cancer diagnosis. Our group performed a retrospective, population-based, age-matched cohort study of Utah male residents diagnosed with cancer at age 18 years or later between 1956 and 2013 (exposed) matched to male Utah residents without cancer diagnosis (unexposed). Using stratified Cox proportional hazard models, we adjusted for race, ethnicity and number of live births prior to cancer diagnosis, to estimate the effect of time to a partner live birth following cancer diagnosis. Our study cohort included 19,303 men diagnosed with cancer (exposed) and 93,608 age-matched men without cancer diagnoses (unexposed). Exposed men were less likely to have a live birth prior to first cancer diagnosis (60.7% vs. 65.4%, p < 0.001) and after first cancer diagnosis (10.9% vs. 12.2%, p < 0.001) compared to unexposed men. Exposed men had a fertility hazard rate that was 31% lower after cancer diagnosis date than unexposed men (HR: 0.69; 95% CI: 0.65-0.72). This was most profound for men aged 18-30 years (HR: 0.59, 95% CI: 0.55-0.63). Male cancer survivors have a 31% lower female partner live birth rate after cancer diagnosis. These findings are important for patient counselling regarding fertility preservation at the time of cancer diagnosis.

Semen parameter thresholds and time-to-conception in subfertile couples: how high is high enough?

STUDY QUESTION: What thresholds for total sperm count, sperm concentration, progressive motility, and total progressive motile sperm count (TPMC) are associated with earlier time-to-conception in couples undergoing fertility evaluation? SUMMARY ANSWER: Values well above the World Health Organization (WHO) references for total sperm count, concentration, and progressive motility, and values up to 100 million for TPMC were consistently associated with earlier time-to-conception and higher conception rates. WHAT IS KNOWN ALREADY: Although individual semen parameters are generally not able to distinguish between fertile and infertile men, they can provide clinically useful information on time-to-pregnancy for counseling patients seeking fertility treatment. Compared to the conventional semen parameters, TPMC might be a better index for evaluating the severity of male infertility. STUDY DESIGN, SIZE, DURATION: We used data from a longitudinal cohort study on subfertile men from 2002 to 2017 and included 6061 men with initial semen analysis (SA) in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Men from subfertile couples who underwent a SA within the study period were included, and 5-year follow-up data were collected to capture conception data. Couples were further categorized into two subgroups: natural conception (n = 5126), after separating those who achieved conception using ART or IUI; natural conception without major female factor (n = 3753), after separating those with severe female factor infertility diagnoses. TPMC was calculated by multiplying the semen volume (ml) by sperm concentration (million/ml) and the percentage of progressively motile sperm (%). Cox proportional hazard models were used to report hazard ratios (HRs) with 95% CIs before and after adjusting for male age, the number of previous children before the first SA, and income. Using the regression tree method, we calculated thresholds for total sperm count, sperm concentration, progressive motility, and TPMC to best differentiate those who were more likely to conceive within 5 years after first SA from those less likely to conceive. We also plotted continuous values of semen parameters in predicting 5-year conception rates and time-to-conception. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, the median time to conception was 22 months (95% CI: 21-23). A total of 3957 (65%) couples were known to have achieved conception within 5 years of the first SA. These patients were younger and had higher values of sperm concentration, progressive motility, and TPMC. In the overall cohort, a TPMC of 50 million best differentiated men who were more likely to father a child within 5 years. Partners of men with TPMC ≥50 million had a 45% greater chance of conception within 5 years in the adjusted model (HR: 1.45; 95% CI: 1.34-1.58) and achieved pregnancy earlier compared to those men with TPMC < 50 million (median 19 months (95% CI: 18-20) versus 36 months (95% CI: 32-41)). Similar results were observed in the natural conception cohort. For the natural conception cohort without major female factor, the TPMC cut-off was 20 million. In the visual assessment of the graphs for the continuous semen parameter values, 5-year conception rates and time-to-conception consistently plateaued at higher values of sperm concentration, total sperm count, progressive motility, and TPMC compared to the WHO reference levels and our calculated thresholds. For TPMC, values up to 100-150 million were still associated with a better conception rate and time-to-conception in the visual assessment of the curves. LIMITATIONS, REASONS FOR CAUTION: There was limited information on female partners and potential for inaccuracies in capturing less severe female infertility diagnoses. Also we lacked details on assisted pregnancies achieved outside of our healthcare network (with possible miscoding as 'natural conception' in our cohort). We only used the initial SA and sperm morphology, another potentially important parameter, was not included in the analyses. We had no information on continuity of pregnancy attempts/intention, which could affect the time-to-conception data. Finally, most couples had been attempting conception for >12 months prior to initiating fertility treatment, so it is likely that we are underestimating time to conception. Importantly, our data might lack the generalizability to other populations. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that a TPMC threshold of 50 million sperm provided the best predictive power to estimate earlier time-to-conception in couples evaluated for male factor infertility. Higher values of sperm count, concentration and progressive motility beyond the WHO references were still associated with better conception rates and time-to-conception. This provides an opportunity to optimize semen parameters in those with semen values that are low but not abnormal according to the WHO reference values. These data can be used to better inform patients regarding their chances of conception per year when SA results are used for patient counseling. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Testosterone Therapy and Cardiovascular Risk: A Critical Analysis of Studies Reporting Increased Risk.

BACKGROUND: Treatment of "adult-onset hypogonadism" (AOH) with exogenous testosterone therapy (TTh) to raise serum testosterone (T) levels may influence cardiovascular (CV) risk factors in patients with AOH, whereas low endogenous T levels are associated with an increased CV risk and mortality. AIM: To critically evaluate studies reporting increased CV risk associated with TTh and to provide an overview of the risks and benefits of restoring T levels through exogenous TTh. METHODS: A review of publications focusing on the association between TTh and increased CV risk was conducted, and the study methodologies and conclusions of each were critically evaluated. Further, recent clinical and epidemiological studies associating AOH or TTh with a change in CV risk, and pertinent hematologic and vascular effects noted in animal studies and in vitro, as well as in clinical practice were also reviewed. OUTCOMES: A review of the literature shows that untreated testosterone deficiency and/or low T is associated with an increase in CV risk and adverse outcomes, with numerous studies and meta-analyses to support a positive association between exogenous TTh and an improvement in CV risk factors in men with AOH. RESULTS: Numerous studies in the literature demonstrate the positive benefits of using TTh; however, since 2013, some publications have suggested a link to increased CV risk associated with TTh. A number of these studies retrospectively analyzed insurance claims databases using diagnosis codes, procedures codes, and prescription information. Many reviews published since have pointed out the methodological flaws and debatable conclusions of these studies. CLINICAL IMPLICATIONS: A careful assessment of the patient's current health status and CV risk factors should be weighed against the benefits and possible risks resulting from TTh, and consideration should be given to deferring treatment pending resolution or stabilization of CV disease or risk factors. STRENGTHS & LIMITATIONS: In this review, we provide an in-depth analysis of studies reporting increased CV risk with TTh. Many of the studies were not well-designed, randomized, double-blind, prospective clinical trials but rather post hoc analyses of cohort data. These studies may reflect bias in how treatment and nontreatment decisions are made or reflect conclusions based on widely cited methodological flaws. CONCLUSION: Appropriate patient selection supported by low pre-treatment T levels and monitoring T levels during treatment with the goal of achieving and maintaining physiologic levels all contribute to the safe and effective use of TTh in men with AOH. Khera M, Miner M, Jaffe J, et al. Testosterone Therapy and Cardiovascular Risk: A Critical Analysis of Studies Reporting Increased Risk. J Sex med 2021;18:83-98.

Lower total motile count is associated with smaller historic intergenerational family size: a pedigree analysis from the Utah Population Database.

PURPOSE: To describe the association between contemporary total motile count (TMC), a measure of male factor infertility, and historic intergenerational family size. METHODS: This is a retrospective, population-based, cohort study of men who underwent semen analysis for infertility workup at University of Utah, with at least a single measure of TMC, who were linked to extensive genealogical data. Two thousand one hundred eighty-two pedigree branches of men with a measure of TMC within the UPDB were identified. We identified the average number of generations and offspring within each generation. Conditional logistic regression models were used to assess the association between the risk of having a TMC in the 5th or 25th percentile and intergenerational family size. Generalized estimating equations (GEE) were used to assess the association between interval-level TMC and the number of ancestral offspring. RESULTS: We found no association between intergenerational size and TMC within the 5th percentile (TMC < 4 million; RR = 0.97, 95% CI 0.93-1.01) or the 25th percentile (TMC < 62 million; RR = 1.00, 95% CI 0.97-1.03). When TMC was analyzed as a continuous variable, we found that lower TMC is associated with smaller intergenerational family size. For every additional child in their ancestral pedigree, we observed an increase in TMC of 1.88 million (p = 0.03). Men in the top quartile for intergenerational family size had a TMC that was 48 million higher than men in the bottom quartile (p = 0.047). CONCLUSIONS: We found an association between TMC and ancestral family size, suggesting that lower TMC is associated with smaller intergenerational family size.

Shift Work Sleep Disorder and Night Shift Work Significantly Impair Erectile Function.

OBJECTIVES: Here we examine the association between shift work sleep disorder (SWSD) and erectile dysfunction (ED) in shift workers. METHODS: Men presenting to a single andrology clinic between January 2014 and July 2017 completed validated questionnaires: International Index of Erectile Function (IIEF), Patient Health Questionnaire-9 (PHQ-9), and the nonvalidated SWSD Questionnaire. Men were also asked about shift work schedule, comorbidities, phosphodiesterase 5 (PDE5) inhibitor use, and testosterone use. Serum total testosterone values were determined for each visit. Linear regression was performed controlling for testosterone use, testosterone levels, PDE5 inhibitor use, age, and comorbidities to determine the effect of SWSD on ED as assessed using the IIEF. RESULTS: Of the 754 men completing questionnaires, 204 reported nonstandard shift work (begins before 7 am or after 6 pm, regularly extends out of that frame, or rotates frequently) and 48 were found to have SWSD using a screening questionnaire. Nonstandard shift work alone did not result in worse IIEF-EF scores (P = .31), but those who worked nonstandard shifts and had SWSD demonstrated IIEF-EF scores 2.8 points lower than men without SWSD (P < .01). When assessing for the type of shift work performed, men who worked night shifts had IIEF-EF scores 7.6 points lower than men who worked during the day or evening (P < .01). Testosterone use improved IIEF-EF scores for men with SWSD by 2.9 points, ameliorating the effect of SWSD on ED. However, baseline testosterone levels were not associated with worse erectile function in this cohort. CONCLUSION: Men with SWSD have worse erectile function, with men who work night shifts having even poorer erectile function. These findings suggest that circadian rhythm disturbance may significantly impact erectile function. While testosterone therapy may partly reverse the effects of SWSD, shift work is a potential risk factor for ED and should be assessed for as part of the evaluation of men with ED. Rodriguez KM, Kohn TP, Kohn JR, et al. Shift Work Sleep Disorder and Night Shift Work Significantly Impair Erectile Function. J Sex Med 2020;17:1687-1693.

A review of inflammation and fibrosis: implications for the pathogenesis of Peyronie's disease.

Peyronie's disease (PD) is a superficial fibrosing disorder that causes penile deformity and can interfere with sexual intercourse and reproduction, as well as diminish quality of life. While the exact mechanism of PD is still being investigated, there is likely a genetic component to the predisposition to penile plaque formation. Ultimately, however, perturbations in normal wound healing and aberrant deposition of extracellular matrix components lead to fibrotic tissue deposition. Fibrosis in PD is regulated by a complex pathway of inflammatory and fibrotic mediators. Currently there are no treatments for PD that address an underlying cause or disease progression. In this review, we provide an overview of the known inflammatory and fibrotic mediators of PD and explore the pathophysiology of other human superficial fibrosing disorders to develop further insights into PD.

Cannabis and Male Fertility: A Systematic Review.

PURPOSE: With cannabis consumption on the rise and use prominent among males of reproductive age it is essential to understand the potential impact of cannabis on male fertility. We reviewed the literature regarding the effects of cannabis on male fertility. MATERIALS AND METHODS: We performed a literature search using PubMed®/MEDLINE® to identify relevant studies of the effects of cannabis on male fertility. Relevant studies were identified and reviewed. RESULTS: The strongest evidence of cannabis induced alterations in male fertility is in the category of semen parameters. Research supports a role for cannabis in reducing sperm count and concentration, inducing abnormalities in sperm morphology, reducing sperm motility and viability, and inhibiting capacitation and fertilizing capacity. Animal models demonstrate a role for cannabis in testicular atrophy, and reduced libido and sexual function but to our knowledge these results have not yet been replicated in human studies. Studies of hormonal changes suggest inconclusive effects on testosterone levels, lowered luteinizing hormone levels and unchanged follicle-stimulating hormone levels. CONCLUSIONS: Current research suggests that cannabis may negatively impact male fertility. Further studies are needed to validate that robust findings in animal models will carry over into human experience. Clinicians should be aware of these potential effects when prescribing medical marijuana therapies to men of reproductive age, and they should consider the degree of cannabis use as a possible component of a complete male infertility workup.

The risk of birth defects is not associated with semen parameters or mode of conception in offspring of men visiting a reproductive health clinic.

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.

Testosterone Imposters: An Analysis of Popular Online Testosterone Boosting Supplements.

INTRODUCTION: Testosterone-boosting supplements (T-Boosters) are prominently featured on Amazon.com, with numerous dedicated pages and claims that they "naturally" increase testosterone levels. AIM: To evaluate the highest rated and frequently reviewed T-Boosters on Amazon.com to facilitate patient counseling regarding marketing myths, T-Booster formulations, and evidence for efficacy and safety. METHODS: The Amazon marketplace was queried using the key words "testosterone" + "booster," with default search settings and ranking items based on relevance. The top 5 T-Boosters identified on July 22, 2018, were reviewed based on price, ratings, reviews, manufacturer details, and ingredients. Consumer reviews were categorized using core themes in the Androgen Deficiency in the Aging Male (ADAM) questionnaire as a proxy to understand T-Booster efficacy and reanalyzed after filtration of untrustworthy comments using ReviewMeta.com, a proprietary Amazon customer review analysis software. MAIN OUTCOME MEASURES: Quantitative and qualitative evaluation of T-Boosters on Amazon.com was performed. RESULTS: The top 5 T-Boosters had an average ± SD of 2,761 ± 5,112 reviews and a rating of 4.56 ± 0.25 stars. 19 unique ingredients were identified across these T-Boosters, and literature review revealed 191 studies involving the 10 most common ingredients, of which 19% involved human subjects, 53% animal models, 15% in vitro studies, and 12% case reports or review articles. Among 37 human studies, 30% observed an increase in T levels, 3% a decrease, 46% no effect, and 22% were indeterminate. Analysis of top customer reviews from the first 2 pages of reviews for each supplement revealed differences in the ADAM score before and after ReviewMeta.com filtration. After filtration, there was a 91% decrease in users reporting increased libido, a 59% decrease in reports of increased energy, a 93% decrease in reports of improved strength/endurance, a 60% decrease in reports of improved erections, an elimination of reports of improved work performance, a 67% decrease in reports of improved sleep, and an 89% decrease in reports of improved sports ability. CLINICAL IMPLICATIONS: Our study can serve as a guide for providers to counsel patients about the efficacy of popular online T-Boosters as well as the prevalence of disingenuous reviews associated with these products on online marketplaces like Amazon.com. STRENGTHS & LIMITATIONS: Strengths include the novel approach to assess consumers' perceptions and satisfaction of T-Boosters, as well as summary information that clinicians can provide patients. Limitations include selection bias, a small number of supplements analyzed, and the proprietary nature of the Amazon review analysis software. CONCLUSION: T-Boosters are easily available online. Our investigation revealed that limited human studies have evaluated T-Boosters, resulting in no definitive findings of efficacy. In the absence of additional human studies, patients should be cautioned before considering T-Boosters, given the availability of highly effective therapies approved by the Food and Drug Administration. Balasubramanian A, Thirumavalavan N, Srivatsav A, et al. Testosterone Imposters: An Analysis of Popular Online Testosterone Boosting Supplements. J Sex Med 2019;16:203-212.

An Analysis of Popular Online Erectile Dysfunction Supplements.

INTRODUCTION: Erectile dysfunction supplements (ED-Ss) are featured on online marketplaces like Amazon.com, with dedicated pages and claims that they naturally treat ED. However, their efficacy and safety are largely unknown, limiting the ability to counsel patients regarding their use. AIM: To evaluate the highest rated and most frequently reviewed ED-Ss on Amazon.com to facilitate patient counseling regarding marketing myths, ingredient profiles, and evidence for product efficacy and safety. METHODS: The Amazon marketplace was queried using the key term "erectile dysfunction" with default search settings and ranking items based on relevance. The top 6 ED-S products identified on September 29, 2018, were reviewed based on price, ratings, reviews, manufacturer, and ingredients. Consumer reviews were categorized using subtopics within the International Index of Erectile Function (IIEF) questionnaire to better understand ED-S efficacy and then reanalyzed following filtration of untrustworthy comments using ReviewMeta.com, a proprietary Amazon review analysis software. OUTCOMES: Quantitative and qualitative evaluation of ED-S products sold on Amazon.com. RESULTS: The top 6 ED-Ss had an average of 2,121 ± 1,282 reviews and a mean rating of 3.92 ± 0.42 stars. A total of 21 ingredients were identified in these ED-Ss. Ginseng, horny goat weed, L-arginine, and tongkat ali were the most popular ingredients included in the analyzed products. Our literature review identified 413 studies involving the 21 identified ingredients, of which 59 (16%) involved human subjects. Among these 69 human studies, only 12 (17%) investigated supplement ingredients individually and reported improvement in ED. Analysis of top-ranked customer reviews from the first 2 pages of reviews for each supplement revealed differences in IIEF scores before and after ReviewMeta.com filtration. After filtration, we observed a 77% decrease in reviews reporting improved erection strength, an 83% decrease in reviews reporting improved ability to maintain erection, a 90% decrease in reviews reporting increased sexual satisfaction, an 88% decrease in reviews reporting increased enjoyment with intercourse, and an 89% decrease in reviews reporting increased erection confidence. STRENGTHS & LIMITATIONS: Study strengths include a novel approach to ascertaining consumers' perceptions and satisfaction with ED-Ss and practical summary information that clinicians can provide to patients. Limitations include selection bias, the small number of supplements analyzed, and the proprietary nature of the Amazon review analysis software. CONCLUSIONS: Our investigation revealed that human studies evaluating the efficacy of ED-S ingredients are limited and have yielded no definitive findings of the effects on ED. Patients considering ED-S use should receive appropriate counseling, given the prevalence of disingenuous reviews and the ready availability of Food and Drug Administration-approved drug therapies. Balasubramanian A, Thirumavalavan N, Srivatsav A, et al. An Analysis of Popular Online Erectile Dysfunction Supplements. J Sex Med 2019;16:843-852.

Emerging Treatments for Erectile Dysfunction: a Review of Novel, Non-surgical Options.

PURPOSE OF REVIEW: To review novel, non-surgical therapies for erectile dysfunction (ED). RECENT FINDINGS: Recently, a landmark study identified the SIM1 locus, involved in the leptin-melanocortin pathway, as an independent risk factor for ED and a potential target for novel therapies. The recent literature otherwise has focused on low-intensity shock wave therapy (LiSWT), with several randomized trials and meta-analyses suggesting therapeutic efficacy. There are few novel oral agents for ED. There is growing evidence suggesting efficacy of intracavernosal stem cells therapy and low-intensity shock wave therapy (LiSWT), although these therapies are still investigational. A better understanding of the pathophysiologic spectrum of ED will offer new opportunities for novel, non-surgical therapies for ED.

Biomechanical Comparison of Inflatable Penile Implants: A Cadaveric Pilot Study.

BACKGROUND: Throughout the last decade there has been a growing interest in the biomechanical differences between inflatable penile prostheses (IPPs) and their significance with regard to the patient experience. AIM: To present our findings assessing the biomechanical properties of IPPs with and without rear tip extenders (RTEs). METHODS: This is a biomechanical study of the 3 most commonly used IPPs (AMS CX, AMS LGX, and Coloplast Titan) as assessed by column compression, modified cantilever deflection, and 3-point bending methods. The IPPs were surgically placed into 3 fresh cadavers via an infrapubic technique by a single large-volume implanter. A biomechanical evaluation of the properties of each IPP inside the fibroelastic tunica albuginea was assessed in blinded testing, and analyses were based on industry standard methods for assessment. OUTCOMES: Maximum axial load; kink formation; horizontal stiffness; and resistance to 3-point flexure testing were measured. RESULTS: At maximum inflation, all 3 implants had similar performance. Differences appear to be most affected by fill pressures. In fact, only the AMS LGX at less than maximum inflation (LTMI) was unable to consistently withstand the roughly 0.9 kg (2 lbs) of pressure for column load testing mimicking vaginal intromission. The Coloplast Titan showed slightly better rigidity than the AMS LGX and CX devices in horizontal load testing, and, with 3-point flexure testing, the CX showed the best rigidity in the shortest phallus (A). Overall, the Titan showed slightly better rigidity in the longest phallus (C) and the phallus with mild Peyronie's disease (B). CLINICAL TRANSLATIONS: Penile implants with circumferential expansion had higher rigidity on biomechanical testing and should be considered in a patient's decision during selection of a penile implant. STRENGTHS AND LIMITATIONS: Strengths include blinding of the biomechanical testing and analyses, surgical procedures performed by a highly experienced surgeon, and that this is the "closest to" in vivo evaluation (inside the tunica albuginea) of penile implant function and properties to date. Weaknesses are that this study was performed in cadavers and not in live patients. It also has a small sample size, including the use of only 3 cadavers, and there was no correlation of performance to patient satisfaction. CONCLUSION: The results of this study support the conclusion that all devices are capable of functionally restoring erectile capacity. However, we observed that, in general, the 2 circumferentially expanding penile prosthesis showed greater resistance in biomechanical testing when compared with longitudinal and circumferential expanding devices. This should be considered as a guide during device selection for a patient undergoing penile prosthesis. Wallen JJ, Barrera EV, Ge L, et al. Biomechanical Comparison of Inflatable Penile Implants: A Cadaveric Pilot Study. J Sex Med 2018;15:1034-1040.

Increased Risk of Incident Disease in Men with Peyronie's Disease: Analysis of U.S. Claims Data.

BACKGROUND: The subsequent health risks associated with Peyronie's disease (PD) are unknown. AIM: 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. METHODS: 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. OUTCOMES: 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. RESULTS: 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. CLINICAL IMPLICATIONS: Clinicians should have heightened awareness for these relevant co-morbidities when treating men with PD. STRENGTHS & LIMITATIONS: 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. CONCLUSION: 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.

The Role of Testosterone Therapy in the Setting of Prostate Cancer.

PURPOSE OF REVIEW: The role of testosterone in the development of prostate cancer and the safety of testosterone therapy (TTh) after prostate cancer treatment, or in the setting of active surveillance, remains controversial. There are many concerns about using TTh in men, particularly those with a history of prostate cancer, ranging from a possible increased risk of cardiovascular disease to cancer progression or recurrence. With many prostate cancer patients living longer, and hypogonadism having significant morbidity, much care must go into the decision to treat. Here, we review the literature investigating the effects of testosterone on the prostate as well as the efficacy and safety of exogenous testosterone in men with a history of prostate cancer. RECENT FINDINGS: The improvement in quality of life with TTh is well studied and understood, while the argument for significantly increased risk of cancer or other adverse effects is much less robust. Neither increased rates of prostate cancer, cancer recurrence, or cardiovascular risk have been well established. In men with high-risk prostate cancer, evidence in the setting of TTh is very limited, and TTh should be used with caution. The fears of TTh causing or worsening prostate cancer do not appear to be well supported by available data. Though more studies are needed to definitively determine the safety of TTh in men with prostate cancer, consideration should be given to treatment of hypogonadal men with a history of CaP.

The Effect of Shift Work on Urogenital Disease: a Systematic Review.

PURPOSE OF REVIEW: Non-standard shift work schedules negatively impact the overall health of shift workers, and several studies have shown that shift work, specifically, is detrimental to urogenital health. The aims of this study are to systematically review the literature and determine the effect of shift work on the outcomes of hypogonadism, male infertility, lower urinary tract symptoms, and urogenital cancers. RECENT FINDINGS: Recent evidence supports associations between non-standard shift work and an increase in the frequency of prostate cancer and the severity of erectile dysfunction, lower urinary tract symptoms, and hypogonadal symptoms, as well as worsening of semen parameters and fertility. These associations are strengthened by the presence of shift work sleep disorder (SWSD) which affects up to 20% of shift workers. No studies have assessed the impact of shift work on the frequency or severity of nephrolithiasis, interstitial cystitis, pelvic pain, prostatitis, or urinary tract infections. Non-standard shift work has been associated with a variety of negative health outcomes and urologic complications, especially with concurrent shift work sleep disorder. Recognition of these elevated risks among shift workers can aid in more effective screening for urologic conditions.

The Effect of Subclinical Varicocele on Pregnancy Rates and Semen Parameters: a Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: Current guidelines recommend against surgical repair of subclinical varicoceles (SCVs) for infertility; several studies demonstrate mixed fertility results after SCV correction. To determine whether surgical correction of SCV improves semen parameters and/or reproductive outcomes, we performed a systematic review and meta-analysis. Seven biomedical literature databases were searched through January 2018 for studies that assessed reproductive outcomes and/or change in semen parameters in men with corrected SCV compared to either (1) uncorrected SCV or (2) corrected clinical varicocele. Estimates were pooled using random-effects meta-analysis. RECENT FINDINGS: Data were extracted from 13 studies involving 1357 men. Overall, the risk of bias for included studies was high and without a consistent SCV definition across studies. Surgical correction of SCV was associated with a minor increase in sperm density and total motile sperm count (TMSC) compared to uncorrected SCV. This increase in semen parameters is not clinically significant, as men prior to varicocelectomy were on average normospermic nor was correction of a SCV associated with an increase in pregnancy rates when compared to men with uncorrected SCV. Comparing corrected SCV to corrected clinical varicocele, SCV correction resulted in a smaller increase in TMSC but no difference in average annual pregnancy rate. The risk of bias within and heterogeneity between studies assessing SCV correction are high, yet overall very little clinical benefit is derived from SCV correction.