Rises in Hematocrit Are Associated With an Increased Risk of Major Adverse Cardiovascular Events in Men Starting Testosterone Therapy: A Retrospective Cohort Claims Database Analysis.

PURPOSE: Elevated hematocrit (Hct) can result in increased risk of major adverse cardiovascular events (MACE) in men receiving testosterone therapy (TTh). However, the impact of the magnitude of the change in Hct from baseline after starting TTh has never been assessed. MATERIALS AND METHODS: To assess whether an increase in Hct after initiating TTh is associated with an increased risk of MACE within 3 and 24 months of initiating TTh, we queried the TriNetX Research network database for men over the age of 18 with Hct values obtained within 6 months before starting TTh, and who had follow-up Hct measurements within 3 and 24 months after beginning TTh from 2010 to 2021. Men with and without a subsequent increase in Hct after initiating TTh were propensity matched. MACE was defined as myocardial infarction, stroke, or death. RESULTS: After matching, 10,511 men who experienced an any increase in Hct after initiating TTh and an equal number of controls who did have an increase in Hct were included. Compared to controls who did not have an increase in Hct after starting TTh, the men who had an increase in subsequent Hct had a significantly increased risk of MACE compared to men with no change in Hct. CONCLUSIONS: We demonstrate that increases in Hct from baseline are associated with increased risk of MACE, compared to men whose Hct remains stable while receiving TTh.

Testosterone therapy in females is not associated with increased cardiovascular or breast cancer risk: a claims database analysis.

BACKGROUND: Testosterone therapy (TTh) has been shown to improve libido in women with sexual dysfunction, but its utilization has been limited due to concern for cardiovascular events and past studies reporting highly variable results. AIM: To assess the association of TTh in women with major adverse cardiac events (MACEs), including heart attack, stroke, or death, using a large database. METHODS: The TriNetX Diamond Network was queried from 2009 to 2022. Our study cohort included adult females with ≥3 systemic testosterone prescriptions within a year. Our control cohort excluded females with any testosterone prescriptions, polycystic ovary syndrome, or androgen excess. Both cohorts excluded females with prior heart failure, unstable angina, intersex surgery (female to male), personal history of sex reassignment, or gender identity disorders. Propensity matching between the cohorts was performed. A subanalysis by age was conducted (18-55 and >55 years). OUTCOMES: We evaluated the association of TTh to the following: MACE, upper or lower emboli or deep vein thrombosis (DVT), pulmonary embolism (PE), breast neoplasm, and hirsutism within 3 years of TTh. RESULTS: When compared with propensity-matched controls, adult females with TTh had a lower risk of MACE (risk ratio [RR], 0.64; 95% CI, 0.51-0.81), DVT (RR, 0.61; 95% CI, 0.42-0.90), PE (RR, 0.48; 95% CI, 0.28-0.82), and malignant breast neoplasm (RR, 0.48; 95% CI, 0.37-0.62). Similarly, females aged 18 to 55 years with TTh had a lower risk of MACE (RR, 0.49; 95% CI, 0.28-0.85) and DVT (RR, 0.48; 95% CI, 0.25-0.93) and a similar risk of malignant breast neoplasm (RR, 0.62; 95% CI, 0.34-1.12). Females aged ≥56 years with TTh had a similar risk of MACE (RR, 0.84; 95% CI, 0.64-1.10), DVT (RR, 0.82; 95% CI, 0.50-1.36), and PE (RR, 0.52; 95% CI, 0.26-1.05) and a significantly lower risk of malignant breast neoplasm (RR, 0.51; 95% CI, 0.38-0.68). Risk of hirsutism was consistently higher in those with TTh as compared with propensity-matched controls. CLINICAL IMPLICATIONS: Our results contribute to safety data on TTh, a therapy for sexual dysfunction in women. STRENGTHS AND LIMITATIONS: The TriNetX Diamond Network allows for significant generalizability but has insufficient information for some factors. CONCLUSIONS: We found a decreased risk of MACE among women with TTh as compared with matched controls and a similar risk of MACE in postmenopausal women while demonstrating a similar or significantly lower risk of breast cancer on age-based subanalysis.

Antidepressant nonadherence and sexual dysfunction among young adult males: the cross-sectional YAMAN study.

PURPOSE: Selective serotonin reuptake inhibitors are associated with high rates of nonadherence and sexual dysfunction, yet the correlation between these findings in young adult men is poorly characterized. We aimed to evaluate if young adult men are less willing to adhere to antidepressant treatment due to intolerable side effects, such as sexual dysfunction. METHODS: Deidentified, compensated survey that assessed baseline demographics, PHQ-8 and GAD-7 scores, attitudes towards antidepressant medication side effects, and perceptions of antidepressant medications including selective serotonin reuptake inhibitors, bupropion, and mirtazapine. RESULTS: From 665 delivered surveys, 505 respondents completed their survey (response rate: 76%), of which 486 were included for final analysis. After seeing common side effect profiles, our sample's willingness to take sexual function-sparing agents, such as bupropion or mirtazapine, was significantly greater than selective serotonin reuptake inhibitors (p < 0.001), with no significant difference between bupropion and mirtazapine (p = 0.263). The negative influence of erectile dysfunction and anorgasmia scored significantly higher than other common antidepressant side effects like weight gain, nausea, and dry mouth (range: p < 0.001, p = 0.043). With the exception of insomnia, participants indicated that experiencing sexual dysfunction while taking an antidepressant medication would lead to nonadherence at a significantly higher frequency than any other side effect assessed (range: p < 0.001, p = 0.005). CONCLUSION: The risk of experiencing sexual side effects when taking antidepressants could lead young adult men to become nonadherent to these medications. Strategies to augment the effectiveness of antidepressants, such as shared decision-making and the use of sexual function-sparing agents, are critical.

Surgically Extracted Epididymal Sperm from Men with Obstructive Azoospermia Results in Similar In Vitro Fertilization/Intracytoplasmic Sperm Injection Outcomes Compared with Normal Ejaculated Sperm.

PURPOSE: Controversy exists around the use of epididymal sperm for in vitro fertilization and intracytoplasmic sperm injection for couples with obstructive azoospermia, and the ability to reliably predict fertility outcomes with surgically extracted epididymal sperm remains limited. To provide additional clinical context, we sought to compare in vitro fertilization/intracytoplasmic sperm injection outcomes of epididymal sperm from couples with obstructive azoospermia to outcomes of couples using normal, ejaculated sperm. MATERIALS AND METHODS: We performed a case-control analysis of 40 couples who underwent office based epididymal sperm retrieval for obstructive azoospermia followed by in vitro fertilization/intracytoplasmic sperm injection compared with a control group of 38 female, age matched couples with no evidence of female factor infertility who underwent in vitro fertilization/intracytoplasmic sperm injection with normal, ejaculated sperm. Primary outcome was live birth on the initial embryo transfer. RESULTS: Epididymal samples yielded a median total motile sperm count of 9.1 million, compared to 81 million for ejaculated sperm. On the primary embryo transfer fertilization rate (71% vs 77%, p=0.2), blastulation rate (48% vs 59%, p=0.09), clinical pregnancy rate (70% vs 58%, p=0.4), and live birth rate (58% vs 47%, p=0.4) did not differ between epididymal and ejaculated sperm groups. CONCLUSIONS: For couples with a male partner with obstructive azoospermia epididymal sperm in vitro fertilization/intracytoplasmic sperm injection outcomes compare similarly with age matched controls undergoing in vitro fertilization/intracytoplasmic sperm injection using normal, ejaculated sperm. These results may help reproductive surgeons provide reassurance about the use of obstructed epididymal sperm as well as help guide discussions about anticipated outcomes of in vitro fertilization/intracytoplasmic sperm injection.

Access to male fertility preservation information and referrals at National Cancer Institute Cancer Centers.

Cancer treatment can lead to infertility, which is a significant source of financial and emotional distress for cancer patients and survivors. Given that future fertility and sexual function are critical quality of life issues, we hypothesise that access to subspecialist care is not uniformly distributed. Therefore, we sought to identify access gaps in male sexual health and infertility care at NCI cancer centres across US Census Regions. All 64 clinical NCI cancer centre websites were examined for language related to male sexual health and fertility. A phone-based survey was used to establish cancer centre referral patterns to andrologists and sperm banks. We utilised the Society for the Study of Male Reproduction member directory to determine geographic locations for andrologists relative to each centre. We found that the presence of information regarding male sexual health information was not associated with region. The presence of andrologists within 5-miles of a CC was significantly higher in the Northeast compared to all other census regions. Our work describes the access gap in fertility services at NCI cancer centres and how this differs by region of the country. These data can inform patients, and encourage centres to provide improved access to oncofertility care.

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.

The effect of tetrahydrocannabinol on testosterone among men in the United States: results from the National Health and Nutrition Examination Survey.

PURPOSE: To determine the association between tetrahydrocannabinol (THC) use and testosterone (T) levels among men in the United States. METHODS: Using the National Health and Nutrition Examination Survey (NHANES) data from the years 2011-2016, we identified all men 18 years and older who answered the substance use questionnaire and underwent laboratory testing for T. Regular THC users were defined as those who use THC at least one time per month, every month for at least 1 year. Multivariable linear regressions controlling for confounders were then used to determine the relationship between THC use and T levels. RESULTS: Among the 5146 men who met inclusion, 3027 endorsed using THC at least once in their life (ever-user). Nearly half of the THC ever-users (49.3%) were considered regular THC users. Multivariate analysis controlling for age, comorbidities, tobacco use, alcohol use, body mass index (BMI), exercise level, and race revealed a small but statistically significant increase in T among regular THC users at any measured level of use, compared to non-regular THC users (non-users). This increase was characterized by an inverse U-shaped trend with Regular THC users using two-three times per month demonstrating the greatest increase in T (+ 66.77 ng/dL) over non-users. CONCLUSION: THC use is associated with small increases in testosterone. This increase in T appears to decline as THC use increases, but nevertheless, T is still higher with any amount of regular use when compared to T in non-users. Prospective work is needed to validate the observed increase and to better elucidate the mechanism of impact THC use has on T levels.

Genetic testing in male infertility - reassessing screening thresholds.

PURPOSE OF REVIEW: Genetic testing in male infertility is an essential part of the process of diagnosis. Genetic abnormalities, such as Y-chromosome microdeletion, chromosomal abnormalities and mutations for cystic fibrosis, can all negatively impact a male's fertility and can be tested for during a fertility evaluation. Both Y-chromosome microdeletion and chromosomal abnormalities increase in prevalence as sperm concentrations decrease, and azoospermic men have the greatest frequency of genetic abnormalities. RECENT FINDINGS: These genetic abnormalities can also be found in oligospermic men; however, on the basis of several recent studies, the prevalence of genetic abnormalities is lower in oligospermic men than previously thought. SUMMARY: The current screening thresholds are devised from the previously determined prevalences and have not been revised based on the emerging data; thus, in this review of the literature, we will discuss this new evidence and whether screening thresholds should be changed.

Inflatable penile prosthesis outcomes after pelvic radiation.

INTRODUCTION Few studies have compared surgical outcomes after 3-piece inflatable penile prosthesis (IPP) surgery in patients exposed to pelvic radiation therapy (RT) compared to a radiation naïve control group. MATERIALS AND METHODS: A total of 715 consecutive patients underwent 3-piece IPP placement between 2007-2018. There were 101 men exposed to pelvic RT before or after IPP for a variety of malignancies and 153 men met inclusion criteria for the control group, which included men undergoing IPP surgery with a history of radical prostatectomy but no exposure to pelvic RT. RESULTS: Patients in the RT group had a higher body mass index (kg/m²) (28.7 versus 27.8, p = 0.003) and higher Charlson co-morbidity index score (6 versus 5; p < 0.001). At a median follow up of 5 years (IQR 2-8 years), there was an 18.4% surgical complication rate in the radiation group compared to 11.5% in the control group, though this was not statistically significant (p = 0.141). Timing of radiation, prior artificial urinary sphincter (AUS) status, co-implantation of an AUS, and brand of prosthesis were not associated with increased rate of complications. On multivariable logistic regression analysis, exposure to RT was not significantly associated with increased risks of complications (OR: 1.31; CI 0.55-3.12). CONCLUSIONS: This study shows no significant increase in risk of surgical complication in patients exposed to pelvic RT and supports the use of IPP in men with a history of RT and refractory erectile dysfunction.

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.

Impaired sleep is associated with low testosterone in US adult males: results from the National Health and Nutrition Examination Survey.

PURPOSE: Testosterone deficiency has been linked to several adverse health outcomes and recent data have suggested that abnormal sleep quality may result in lower testosterone levels. We assessed the effect of self-reported sleep patterns on serum testosterone while controlling for co-morbidities, and baseline demographics. MATERIALS AND METHODS: Using data collected from the 2011-2012 National Health and Nutrition Examination Survey (NHANES), we extracted serum total testosterone level, sleep duration, demographic, and co-morbidities for men aged 16 years and older. Univariate and multivariate linear regression was used to estimate the association of number of hours slept, co-morbidities, and demographics with serum testosterone. RESULTS: Among the 9756 individuals in the NHANES dataset, 2295 (23.5%) were males 16 years and older with a median (interquartile range) age of 46 years (29-62) who also had serum testosterone levels drawn. Median serum testosterone level was 377 ng/dL (IQR: 279-492 ng/dL). Median number of hours slept was 7 h (IQR: 6-8 h). On multivariate linear regression, we found serum testosterone decreased by 0.49 ng/dL per year of age (p = 0.04), 5.85 ng/dL per hour loss of sleep (p < 0.01) and 6.18 ng/dL per unit of body mass index (BMI) increase (p < 0.01). CONCLUSIONS: Among men aged 16-80 in the United States, we found increasing age, impaired sleep and elevated BMI is associated with low testosterone. It is important, therefore, that evaluation and treatment of reduced serum testosterone should also include improving sleep duration in combination with weight management.

Advanced paternal age does not affect embryo aneuploidy following blastocyst biopsy in egg donor cycles.

PURPOSE: To study the impact of advanced paternal age on embryo aneuploidy. METHODS: This is a multicenter international retrospective case series of couples undergoing assisted reproduction via in vitro fertilization using donor eggs to control for maternal factors and preimplantation genetic testing for aneuploidy via next-generation sequencing at Igenomix reproductive testing centers. The main outcome measure was the prevalence of embryo aneuploidy in egg donor cycles. Semen analysis data was retrieved for a small subset of the male patients. RESULTS: Data from 1202 IVF/ICSI egg donor cycles using ejaculated sperm (total 6934 embryos) evaluated using PGT-A between January 2016 and April 2018 in a global population across all Igenomix centers were included. No significant association was identified between advancing paternal age and the prevalence of embryo aneuploidy overall and when analyzing for each chromosome. There was also no significant association between advancing paternal age and specific aneuploid conditions (monosomy, trisomy, partial deletion/duplication) for all chromosomes in the genome. CONCLUSIONS: This is the largest study of its kind in an international patient population to evaluate the impact of advancing paternal age on embryo aneuploidy. We conclude there is no specific effect of paternal age on the prevalence of embryo aneuploidy in the context of embryo biopsies from egg donor cycles.

Effect of Sperm Morphology on Pregnancy Success via Intrauterine Insemination: A Systematic Review and Meta-Analysis.

PURPOSE: Men with abnormal sperm morphology are often counseled that natural conception and intrauterine insemination are ineffective, and in vitro fertilization is the only option. Our objective was to determine the effect of sperm morphology on the pregnancy success of intrauterine insemination. MATERIALS AND METHODS: We systematically searched for studies published prior to January 2017 that 1) reported ultrasound verified clinical pregnancies per intrauterine insemination cycle, 2) assessed sperm morphology using the Kruger strict criteria and 3) described morphology at the greater than 4% and 4% or less and/or the 1% or greater and less than 1% thresholds. In all studies mean female age was between 25 and 40 years and mean total motile sperm count was greater than 10 million. Estimates were pooled using random effects meta-analysis. RESULTS: Data were extracted from 20 observational studies involving a total of 41,018 cycles. When comparing men at the greater than 4% and 4% or less thresholds, the rate of ultrasound verified pregnancy per intrauterine insemination cycle was not statistically or clinically different (14.2% vs 12.1%, p = 0.06) and the risk difference was 3.0% (95% CI 1.4-4.6), indicating 3.0 additional pregnancies per 100 intrauterine insemination cycles. When comparing men at the 1% or greater and the less than 1% thresholds, there were no statistical or clinical differences in the rate of ultrasound verified pregnancy per cycle of intrauterine insemination (14.0% vs 13.9%, p = 0.97) or in the risk difference (1.6%, 95% CI -4.5-7.6). CONCLUSIONS: There appears to be no clinical difference in intrauterine insemination pregnancy success among men with normal and abnormal sperm morphology when accounting for total motile sperm count and female age. Abnormal sperm morphology alone should not exclude couples from attempting intrauterine insemination.

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 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.

Low Plasma Testosterone Is Associated With Elevated Cardiovascular Disease Biomarkers.

BACKGROUND: The relation between testosterone (T) plasma concentration and cardiovascular (CV) risk is unclear, with evidence supporting increased risk in men with low and high T levels. Few studies have assessed CV risk as a function of plasma T levels using objective biomarkers. AIM: To determine the relation between T levels and high-sensitivity CV risk biomarkers. METHODS: Ten thousand forty-one male patients were identified in the database of a commercial clinical laboratory performing biomarker testing. Patients were grouped by total T concentration and associations with the following biomarkers were determined: cardiac troponin I (cTnI), endothelin-1 (ET-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-17A, N-terminal pro-B-type natriuretic peptide (NTproBNP), high-density lipoprotein (HDL) cholesterol, high-sensitivity C-reactive protein (hs-CRP), hemoglobin A1c (HbA1c), and leptin. OUTCOMES: Association of CV risk markers with levels of T in men. RESULTS: The median age of the cohort was 58 years (interquartile range = 48-68), and the median plasma T level was 420 ng/dL (interquartile range = 304-565); T levels did not vary with patient age. An inverse relation between plasma T levels and CV risk was observed for 9 of 10 CV markers: cTnI, ET-1, IL-6, TNF-α, NTproBNP, HDL cholesterol, hs-CRP, HbA1c, and leptin. Even after adjusting for age, body mass index, HbA1c, hs-CRP, and HDL cholesterol levels, the CV markers IL-6, ET-1, NTproBNP, and leptin were significantly associated with a T level lower than 250 ng/dL. CLINICAL IMPLICATIONS: Men with low T levels could be at increased risk for increased CV disease as seen by increased CV risk markers. STRENGTH AND LIMITATIONS: This study was performed in a group of 10,041 men and is the first study to examine CV risk associated with circulating T levels using a large panel of 10 objective biomarkers. This study is limited by an absence of clinical data indicating whether men had pre-existing CV disease or other CV risk factors. CONCLUSION: Men with low plasma T levels exhibit increases in CV risk markers, consistent with a potential increased risk of CV disease. Pastuszak AW, Kohn TP, Estis J, Lipshultz LI. Low Plasma Testosterone Is Associated With Elevated Cardiovascular Disease Biomarkers. J Sex Med 2017;14:1095-1103.

Effects of Low-Intensity Extracorporeal Shockwave Therapy on Erectile Dysfunction: A Systematic Review and Meta-Analysis.

INTRODUCTION: Low-intensity extracorporeal shock wave therapy (Li-ESWT) has been proposed as an effective non-invasive treatment option for erectile dysfunction (ED). AIM: To use systematic review and meta-analysis to assess the efficacy of Li-ESWT by comparing change in erectile function as assessed by the erectile function domain of the International Index of Erectile Function (IIEF-EF) in men undergoing Li-ESWT vs sham therapy for the treatment of ED. METHODS: Systematic search was conducted of MEDLINE, EMBASE, and ClinicalTrials.gov for randomized controlled trials that were published in peer-reviewed journals or presented in abstract form of Li-ESWT used for the treatment of ED from January 2010 through March 2016. Randomized controlled trials were eligible for inclusion if they were published in the peer-reviewed literature and assessed erectile function outcomes using the IIEF-EF score. Estimates were pooled using random-effects meta-analysis. MAIN OUTCOME MEASURES: Change in IIEF-EF score after treatment with Li-ESWT in patients treated with active treatment vs sham Li-ESWT probes. RESULTS: Data were extracted from seven trials involving 602 participants. The average age was 60.7 years and the average follow-up was 19.8 weeks. There was a statistically significant improvement in pooled change in IIEF-EF score from baseline to follow-up in men undergoing Li-ESWT vs those undergoing sham therapy (6.40 points; 95% CI = 1.78-11.02; I2 = 98.7%; P < .0001 vs 1.65 points; 95% CI = 0.92-2.39; I2 = 64.6%; P < .0001; between-group difference, P = .047). Significant between-group differences were found for total treatment shocks received by patients (P < .0001). CONCLUSION: In this meta-analysis of seven randomized controlled trials, treatment of ED with Li-ESWT resulted in a significant increase in IIEF-EF scores.