Physician infertility: a structured literature review.

Physician infertility has become a growing concern because of the increasingly high rates of infertility physicians experience associated with their strenuous work schedules, environmental exposures, and delayed family planning due to their necessitated years of training. Fortunately, there has been an increase in awareness, advocacy, and urgency for institutional support alongside this suboptimal association. This awareness is reflected in the vast existing literature regarding physician infertility; in this scoping review, we aggregated and assessed the current data as well as identified gaps in the available research. Including 56 articles regarding various aspects of the current state of physician infertility, we compiled and synthesized the available data to understand the role of infertility in physician family planning, including specific analyses for surgeons and comparisons of male and female physicians. We discussed the utilization and downsides of artificial reproductive technologies for this population in terms of finances and logistics, contributing to this complex and, until recently, neglected issue. Lastly, we reported on a multitude of suggestions aimed at medical training programs to help combat the complex issue of physician infertility.

Long-Term Safety and Curvature Deformity Characterization in Patients Previously Treated with Collagenase clostridium Histolyticum for Peyronie's Disease.

PURPOSE: We assessed the long-term safety and immunogenicity profile of collagenase clostridium histolyticum and characterized penile curvature deformity over time in patients previously treated for Peyronie's disease. MATERIALS AND METHODS: This phase 4 study included men who received collagenase clostridium histolyticum in either 12-month, double-blind, placebo controlled clinical trials (IMPRESS I/II), or one of two 9-month open label studies. Eligible patients received no additional collagenase clostridium histolyticum treatment and were followed once yearly for up to 5 years to assess Peyronie's disease clinical symptoms, patient reported outcomes and safety. RESULTS: Of 280 patients enrolled 204 (73%) completed the study. At baseline 247 patients had already experienced a mean±SD penile curvature decrease from 51.8±15.0 to 31.0±16.1 degrees (improvement of 20.9±16.2 degrees or 39.5%). At year 5 in 180 patients, despite no additional treatment, there was an additional 9.1% improvement in mean penile curvature compared with reference data (4.3±13.4 degrees, 95% CI 2.3-6.2, p <0.02). At baseline 183 patients experienced mean Peyronie's Disease Questionnaire bother domain score improvement from 6.5±3.5 to 3.4±3.3. At year 5 there was additional score improvement to 2.4±2.9 (p=0.0003). Adverse events were reported in 17.5% (49) of patients but no adverse events were considered treatment related. No long-term safety issues were identified up to 5 years after treatment. Long-term immunogenicity profiling showed a decreasing trend in the number of anti-AUX-I and anti-AUX-II seropositive cases at years 4 and 5 after collagenase clostridium histolyticum treatment. CONCLUSIONS: Most patients treated with collagenase clostridium histolyticum continued to have penile curvature and Peyronie's Disease Questionnaire domain score improvements through year 5 without additional collagenase clostridium histolyticum treatment, and no additional safety signals were identified.

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 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.

Human Chorionic Gonadotropin monotherapy for the treatment of hypogonadal symptoms in men with total testosterone > 300 ng/dL.

PURPOSE: The 2018 American Urological Association guidelines on the Evaluation and Management of Testosterone Deficiency recommended that 300 ng/dL be used as the threshold for prescribing testosterone replacement therapy (TRT). However, it is not uncommon for men to present with signs and symptoms of testosterone deficiency, despite having testosterone levels greater than 300 ng/dL. There exists scant literature regarding the use of hCG monotherapy for the treatment of hypogonadism in men not interested in fertility. We sought to evaluate serum testosterone response and duration of therapy of hCG monotherapy for men with symptoms of hypogonadism, but total testosterone levels > 300 ng/dL. MATERIALS AND METHODS: We performed a multi-institutional retrospective case series of men receiving hCG monotherapy for symptomatic hypogonadism. We evaluated patient age, treatment indication, hCG dosage, past medical history, physical exam findings and serum testosterone and gonadotropins before and after therapy. Descriptive analysis was performed and Mann Whitney U Test was utilized for statistical analysis. RESULTS: Of the 20 men included in the study, treatment indications included low libido (45%), lack of energy (50%), and erectile dysfunction (45%). Mean testosterone improved by 49.9% from a baseline of 362 ng/dL (SD 158) to 519.8 ng/dL (SD 265.6), (p=0.006). Median duration of therapy was 8 months (SD 5 months). Fifty percent of patients reported symptom improvement. CONCLUSIONS: Treatment of hypogonadal symptoms with hCG for men who have a baseline testosterone level > 300 ng/dL appears to be safe and effi cacious with no adverse events.

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.

Male Fertility Preservation.

PURPOSE OF REVIEW: With improvements in cancer treatment outcomes and an increase in cancer survivorship, understanding the importance of fertility preservation options prior to undergoing cancer treatment is essential. Therefore, we review herein the effect of cancer and its treatment on male fertility, the rationale for sperm cryopreservation, options for sperm retrieval, ART outcomes, and experimental options. RECENT FINDINGS: Recent data update fertility outcomes with newer cancer therapies and provide longitudinal insight into survivor paternity with and without fertility preservation. Likewise, updated ART outcomes and future preservation options are discussed. The effect of cancer and its treatment on spermatogenesis is well established. Sperm cryopreservation is the best pre-treatment insurance for the opportunity of future fertility. Post-therapy patients may also achieve fertility restoration with ART, using cryopreserved or freshly obtained sperm. Meanwhile, utilization of cryopreserved testicular stem cells for future transfer or for in vitro maturation represents exciting alternatives on the horizon.

Infertility in the Aging Male.

PURPOSE OF REVIEW: In many countries, the average age of paternity is rising. The negative effect of older age on fertility in women is well documented; however, less is known about the impact of paternal age on fecundity. In this review, we summarize the current knowledge of how paternal age affects semen parameters, reproductive success, and offspring health. RECENT FINDINGS: Contemporary evidence confirms that aged men have worse semen parameters, including overall negative changes in sperm genetics. Reproductive outcomes with unassisted pregnancy tend to be worse with older fathers. While most current studies of assisted pregnancy do show a negative effect of paternal age, there are some conflicting results. Studies continue to show an overall increased risk of health problems, particularly neuropsychiatric conditions, in the offspring of older men. While men can often maintain fertility potential throughout a lifetime, increasing evidence indicates worsening of semen parameters, including sperm genetics, and potentially worse reproductive success. Older men should also be counseled on their offspring's possible increased risk of certain medical conditions.

Iron and a Man's Reproductive Health: the Good, the Bad, and the Ugly.

PURPOSE OF REVIEW: To discuss the physiologic and pathologic effects of iron on men's reproductive health. RECENT FINDINGS: Iron overload diseases are associated with hypogonadotropic hypogonadism, infertility, and sexual dysfunction in men. Recent findings have elucidated the roles by which iron may affect the male reproductive axis. Iron is requisite for life. Iron can also catalyze the production of reactive oxygen species. To maintain balance, the human body tightly regulates dietary iron absorption. Severe iron overload disorders-e.g., hereditary hemochromatosis and ß-thalassemia-occur when these regulatory mechanisms are deficient. While iron is necessary, the male reproductive system is particularly sensitive to iron overload. Hypogonadotropic hypogonadism, infertility, and sexual dysfunction commonly occur if excess iron from iron overload disorders is not removed. The average male in the USA consumes significantly more iron than needed to replace daily losses. How this degree of iron loading may affect one's reproductive health remains less clear, but there is evidence it may have adverse effects.

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.

Testosterone therapy improves well being and psychological health.

PURPOSE OF REVIEW: To ascertain whether testosterone therapy (TTh) improves psychological health and a sense of overall well being in a number of clinical domains. RECENT FINDINGS: Recent work suggests small but durable and replicable improvements in the components of male health and well being. SUMMARY: Symptomatic hypogonadism is frequently associated with decreased libido and fatigue that contributes to lowered overall quality-of-life and worsening psychological health. This manuscript will review the evidence behind the generalized benefits of TTh on overall male health as well as on depression and cognitive function in particular. Influence of TTh on body composition and its relationship to cardiovascular disease are also discussed in this overall context.

Testosterone versus clomiphene citrate in managing symptoms of hypogonadism in men.

INTRODUCTION: Both clomiphene citrate (CC) and testosterone supplementation therapy (TST) are effective treatments for men with hypogonadism. We sought to compare changes in symptoms and treatment efficacy in hypogonadal men before and after receiving CC and TST. PATIENTS AND METHODS: 52 men who received TST and 23 men who received CC for symptomatic hypogonadism were prospectively followed for change in hormone levels and symptoms after treatment. These men were also compared to eugonadal men who were not on CC or TST during the same period. Comparisons were made between baseline and posttreatment hormone levels and symptoms. Symptoms were evaluated using the androgen deficiency in aging male (ADAM) and quantitative ADAM (qADAM) questionnaires. RESULTS: Serum total testosterone increased from pretreatment levels in all men (P < 0.05), regardless of therapy type (TST: 281-541 ng/dL, CC: 235.5-438 ng/dL). Men taking TST reported fewer ADAM symptoms after treatment (5-2, P < 0.05). Similarly, men taking CC reported fewer ADAM symptoms after treatment (3.5-1.5, P < 0.05). Conversely, eugonadal men had similar T levels (352 vs. 364 ng/dL) and hypogonadal symptoms (1.5 vs. 1.4) before and after follow-up. When we evaluated individual symptoms, men treated with TST showed significant increases in qADAM scores in libido, erectile function, and sports performance. However, among the men who received CC, qADAM subscore for libido was lower following treatment (3.75-3.2, P = 0.04), indicating that CC could have an adverse effect on libido in hypogonadal men. CONCLUSIONS: Both TST and CC are effective medications in treating hypogonadism; however, our study indicates that TST is more effective in raising serum testosterone levels and improving hypogonadal symptoms. CC remains a viable treatment modality for hypogonadal men but its adverse effect on libido warrant further study.

Genetic counseling for men with recurrent pregnancy loss or recurrent implantation failure due to abnormal sperm chromosomal aneuploidy.

PURPOSE: The purpose of this study is to review recurrent pregnancy loss (RPL) due to sperm chromosomal abnormalities and discuss the genetic counseling that is required for men with sperm chromosomal abnormalities. METHOD: The literature was reviewed, and a genetic counselor lends her expertise as to how couples with RPL and sperm chromosomal abnormalities ought to be counseled. The review of the literature was performed using MEDLINE. RESULTS: Sperm fluorescence in situ hybridization (FISH) can be used to determine if disomy or unbalanced chromosomal translocations are present. In men with aneuploidy in sperm or who carry a chromosomal translocation, pre-implantation genetic screening (PGS) combined with in vitro fertilization (IVF) and intra-cytoplasmic sperm injection (ICSI) can increase chances of live birth. In men with abnormal sperm FISH results, the degree of increased risk of abnormal pregnancy remains unclear. Genetic counselors can provide information to couples about the risk for potential trisomies and sex chromosome aneuploidies and discuss their reproductive and testing options such as PGS, use of donor sperm, and adoption. The provision of genetic counseling also allows a couple to be educated about recommended prenatal testing since pregnancies conceived with a partner who has had abnormal sperm FISH are considered to be at increased risk for aneuploidy. CONCLUSION: We review the literature and discuss genetic counseling for couples with RPL or recurrent implantation failure due to increased sperm aneuploidy.

Elevated Dihydrotestosterone is Associated with Testosterone Induced Erythrocytosis.

PURPOSE: Erythrocytosis is the most common dose limiting adverse effect of testosterone therapy but the mechanisms of testosterone mediated erythropoiesis remain unclear. In this study we examine risk factors for erythrocytosis associated with testosterone therapy. MATERIALS AND METHODS: A retrospective review was performed of 179 hypogonadal men on testosterone therapy at a single andrology clinic. Demographic data, testosterone therapy formulation and duration of treatment, and 5α-reductase inhibitor use were assessed. Serum dihydrotestosterone, total testosterone, free testosterone, follicle-stimulating hormone, luteinizing hormone, hematocrit and lipid levels were extracted, and changes during treatment were determined. Spearman's rank correlation was used to identify relationships between change in hematocrit and study variables. RESULTS: Of 179 patients 49 (27%) experienced a 10% or greater change in hematocrit and erythrocytosis (hematocrit 50% or greater) developed in 36 (20.1%) at a median followup of 7 months. Topical gels were used by 41.3% of patients, injectable testosterone by 52.5% and subcutaneous pellets by 6.1%. More men who experienced a change in hematocrit of 10% or greater used injectable testosterone than men with a change in hematocrit of less than 10% (65% vs 48%, p=0.035), and were less likely to be on a 5α-reductase inhibitor (2% vs 15%, p=0.017). Men with a change in hematocrit of 10% or greater had higher posttreatment dihydrotestosterone levels (605.0 vs 436.0 ng/dl, p=0.017) and lower luteinizing hormone and follicle-stimulating hormone levels than men with a change in hematocrit of less than 10%. Spearman's rank correlations yielded relationships between change in hematocrit and posttreatment dihydrotestosterone ρ=0.258, p=0.001) and total testosterone (ρ=0.171, p=0.023). CONCLUSIONS: Dihydrotestosterone may have a role in testosterone therapy related erythrocytosis and monitoring dihydrotestosterone levels during testosterone therapy should be considered. In men in whom erythrocytosis develops, 5α-reductase inhibitors may be therapeutic.