CDK2 kinase activity is a regulator of male germ cell fate.

The ability of men to remain fertile throughout their lives depends upon establishment of a spermatogonial stem cell (SSC) pool from gonocyte progenitors, and thereafter balancing SSC renewal versus terminal differentiation. Here, we report that precise regulation of the cell cycle is crucial for this balance. Whereas cyclin-dependent kinase 2 (Cdk2) is not necessary for mouse viability or gametogenesis stages prior to meiotic prophase I, mice bearing a deregulated allele (Cdk2Y15S ) are severely deficient in spermatogonial differentiation. This allele disrupts an inhibitory phosphorylation site (Tyr15) for the kinase WEE1. Remarkably, Cdk2Y15S/Y15S mice possess abnormal clusters of mitotically active SSC-like cells, but these are eventually removed by apoptosis after failing to differentiate properly. Analyses of lineage markers, germ cell proliferation over time, and single cell RNA-seq data revealed delayed and defective differentiation of gonocytes into SSCs. Biochemical and genetic data demonstrated that Cdk2Y15S is a gain-of-function allele causing elevated kinase activity, which underlies these differentiation defects. Our results demonstrate that precise regulation of CDK2 kinase activity in male germ cell development is crucial for the gonocyte-to-spermatogonia transition and long-term spermatogenic homeostasis.

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.

Effects of valganciclovir on spermatogenesis in renal transplant patients - results of a multicenter prospective nonrandomized study.

Ganciclovir (GCV) inhibits spermatogenesis in preclinical studies but long-term effects on fertility in renal transplant patients are unknown. In a prospective, multicenter, open-label, nonrandomized study, male patients were assigned to Cohort A [valganciclovir (VGCV), a prodrug of GCV] (n = 38) or B (no VGCV) (n = 21) by cytomegalovirus prophylaxis requirement. Changes in semen parameters and DNA fragmentation were assessed via a mixed-effects linear regression model accounting for baseline differences. Sperm concentration increased post-transplant, but between baseline and treatment end (mean 164 days Cohort A, 211 days Cohort B), the model-based change was lower in Cohort A (difference: 43.82 × 106 /ml; P = 0.0038). Post-treatment, sperm concentration increased in Cohort A so that by end of follow-up (6 months post-treatment) changes were comparable between cohorts (difference: 2.09 × 106 /ml; P = 0.92). Most patients' sperm concentration improved by end of follow-up; none with normal baseline concentrations (≥20 × 106 /ml) were abnormal at end of follow-up. Changes in seminal volume, sperm motility/morphology, DNA fragmentation, and hormone levels were comparable between cohorts at end of follow-up. Improvement in semen parameters after renal transplant was delayed in men receiving VCGV, but 6 months post-treatment parameters were comparable between cohorts.

Functional Magnetic Resonance Imaging Detects Between-Group Differences in Neural Activation Among Men with Delayed Orgasm Compared with Normal Controls: Preliminary Report.

BACKGROUND: Mechanisms underlying delayed orgasm (DO) are poorly understood; however, known effects of psychotropic medications on sexual function provides a rationale for aberrant central nervous system signaling as a cause. AIM: To compare brain activation between men with normal orgasm and those with lifelong DO during sexual stimulation using brain fMRI algorithms. METHODS: 3 subjects with self-reported life-long DO and 6 normal controls were included in this study. The International Index of Erectile Function, Male Sexual Health Questionnaire, and self-reported time to orgasm were used to assess sexual function. Subjects underwent a 3-T fMRI study while viewing 3 video clips: a neutral control (NC), a positive emotional control (EC), and a sexual condition (SC). Each video sequence was repeated 5 times, with 50-second clips presented in a randomized fashion. fMRI data were analyzed in a block design manner to determine areas of differential brain activation between groups. The Allen Brain Atlas of gene expression in the human brain was used to identify signaling pathways in the areas of differential fMRI activation between the DO and control groups. OUTCOMES: The primary outcome was differential activation of fMRI neural activation between groups. RESULTS: Analysis of differential activation in the SC compared with the NC and EC revealed increased activation in the right frontal operculum (P = .003), right prefrontal gyrus (P = .003), and inferior occipital gyrus (P = .003). Increased activation in the right fusiform gyrus of the occipital lobe and the right hippocampus (P = .0004) was seen in the DO group compared with controls. Using the Allen Atlas of Human Brain Expression, we identified corresponding neurotransmitter receptors to this region, including adenosine receptors, muscarinic and nicotinic cholinergic receptors, cannabinoid receptors, and dopamine receptors, among others. CLINICAL IMPLICATIONS: Lifelong DO in men may be due to abnormal neurotransmitter signaling leading to poor progression of arousal due to aberrant processing of sexual cues. Identification of neurotransmitter pathways by fMRI will aid the development of pharmacotherapeutic agents. STRENGTHS & LIMITATIONS: Strengths of this study include the novel application of functional neuroimaging to investigate the pathogenesis of DO. Limitations include the small sample size, making this study exploratory in nature. CONCLUSION: This study revealed differences in brain activation on visualization of sexual stimuli in men with a history of DO compared with controls. Identified regions are rich in numerous neurotransmitter receptor subtypes and may be amenable to pharmacologic targeting to identify novel therapies for these men. Flannigan R, Heier L, Voss H, et al. Functional Magnetic Resonance Imaging Detects Between-Group Differences in Neural Activation Among Men with Delayed Orgasm Compared with Normal Controls: Preliminary Report. J Sex Med 2019:16;1246-1254.

Impact of Testosterone Solution 2% on Ejaculatory Dysfunction in Hypogonadal Men.

INTRODUCTION: Hypogonadism is defined as decreased testosterone levels in men. Hypogonadism can be accompanied by erectile, orgasmic, and ejaculatory dysfunction. AIMS: To evaluate whether treatment with testosterone solution 2% (testosterone) could improve ejaculatory function in a cohort of hypogonadal men. METHODS: Sexually active, hypogonadal men at least 18 years old (total testosterone < 300 ng/dL) were randomized to receive testosterone or placebo for 12 weeks. MAIN OUTCOME MEASURES: Effects of testosterone on primary outcomes were evaluated using the International Index of Erectile Function (IIEF) and the Men's Sexual Health Questionnaire, Ejaculatory Dysfunction, Short Form (MSHQ-EjD-SF) questionnaires. Treatment differences were calculated using analysis of covariance. RESULTS: In total, 715 men (mean age = 55 years) were randomized to placebo (n = 357) or testosterone (n = 358). Most sexually active men who reported IIEF scores had some degree of erectile dysfunction (IIEF erectile function score < 26). Although ejaculatory function score (MSHQ-EjD-SF) improved in the testosterone group compared with placebo (P < .001), improvement on the "bother" item did not reach statistical significance. Treatment-related adverse events in the testosterone group affecting at least 1% of patients were increased hematocrit, upper respiratory tract infection, arthralgia, burning sensation, fatigue, increased prostate-specific antigen, erythema, and cough. Few patients in either treatment group developed at least one adverse event leading to discontinuation (testosterone = 1.98% vs placebo = 3.09%; P = .475). CONCLUSION: Hypogonadal men receiving testosterone solution 2% therapy experience significantly greater improvement in ejaculatory function, compared with placebo, as assessed by the MSHQ-EjD-SF. However, improvement in "bother" was not statistically different between the two groups. Testosterone therapy was generally well tolerated.

Human spermatogenic failure purges deleterious mutation load from the autosomes and both sex chromosomes, including the gene DMRT1.

Gonadal failure, along with early pregnancy loss and perinatal death, may be an important filter that limits the propagation of harmful mutations in the human population. We hypothesized that men with spermatogenic impairment, a disease with unknown genetic architecture and a common cause of male infertility, are enriched for rare deleterious mutations compared to men with normal spermatogenesis. After assaying genomewide SNPs and CNVs in 323 Caucasian men with idiopathic spermatogenic impairment and more than 1,100 controls, we estimate that each rare autosomal deletion detected in our study multiplicatively changes a man's risk of disease by 10% (OR 1.10 [1.04-1.16], p<2 × 10(-3)), rare X-linked CNVs by 29%, (OR 1.29 [1.11-1.50], p<1 × 10(-3)), and rare Y-linked duplications by 88% (OR 1.88 [1.13-3.13], p<0.03). By contrasting the properties of our case-specific CNVs with those of CNV callsets from cases of autism, schizophrenia, bipolar disorder, and intellectual disability, we propose that the CNV burden in spermatogenic impairment is distinct from the burden of large, dominant mutations described for neurodevelopmental disorders. We identified two patients with deletions of DMRT1, a gene on chromosome 9p24.3 orthologous to the putative sex determination locus of the avian ZW chromosome system. In an independent sample of Han Chinese men, we identified 3 more DMRT1 deletions in 979 cases of idiopathic azoospermia and none in 1,734 controls, and found none in an additional 4,519 controls from public databases. The combined results indicate that DMRT1 loss-of-function mutations are a risk factor and potential genetic cause of human spermatogenic failure (frequency of 0.38% in 1306 cases and 0% in 7,754 controls, p = 6.2 × 10(-5)). Our study identifies other recurrent CNVs as potential causes of idiopathic azoospermia and generates hypotheses for directing future studies on the genetic basis of male infertility and IVF outcomes.

The effect of hypogonadism and testosterone-enhancing therapy on alkaline phosphatase and bone mineral density.

OBJECTIVE: To evaluate the relationship of testosterone-enhancing therapy on alkaline phosphatase (AP) in relation to bone mineral density (BMD) in hypogonadal men. PATIENTS AND METHODS: Retrospective review of 140 men with testosterone levels of <350 ng/dL undergoing testosterone-enhancing therapy and followed for 2 years. Follicle-stimulating hormone, luteinising hormone, free testosterone, total testosterone, sex hormone binding globulin, calcium, AP, vitamin D, parathyroid hormone, and dual-energy X-ray absorptiometry (DEXA) scans were analysed. A subgroup of 36 men with one DEXA scan before and one DEXA 2 years after initiating treatment was performed. RESULTS: Analysis of the relationship between testosterone and AP at initiation of therapy using stiff linear splines suggested that bone turnover occurs at total testosterone levels of <250 ng/dL. In men with testosterone levels of <250 ng/dL, there was a negative correlation between testosterone and AP (R(2) = -0.347, P < 0.001), and no correlation when testosterone levels were between 250 and 350 ng/dL. In the subgroup analysis, the mean (sd) testosterone level was 264 (103) ng/dL initially and 701 (245), 539 (292), and 338 (189) ng/dL at 6, 12, and 24 months, respectively. AP decreased from a mean (sd) of 87 (38) U/L to 57 (12) U/L (P = 0.015), 60 (17) U/L (P < 0.001), and 55 (10) U/L (P = 0.03) at 6, 12, and 24 months, respectively. The BMD increased by a mean (sd) of 20 (39)% (P = 0.003) on DEXA. CONCLUSION: In hypogonadal men, the decrease in AP is associated with an increase in BMD on DEXA testing. This result suggests the use of AP as a marker of response to therapy.

Clinical and Demographic Correlates of Ejaculatory Dysfunctions Other Than Premature Ejaculation: A Prospective, Observational Study.

INTRODUCTION: Ejaculatory dysfunctions other than premature ejaculation are commonly encountered in specialized clinics; however, their characterization in community-dwelling men is lacking. AIM: The aim of this study was to evaluate the prevalence, severity, and associated distress of four ejaculatory dysfunctions: delayed ejaculation (DE), anejaculation (AE), perceived ejaculate volume reduction (PEVR) and/or decreased force of ejaculation (DFE) as a function of demographic and clinical characteristics in men. METHODS: Observational analysis of 988 subjects presenting with one or more types of ejaculatory dysfunctions other than premature ejaculation who screened for a randomized clinical trial assessing the efficacy of testosterone replacement on ejaculatory dysfunction. Demographic and clinical characteristics were assessed as potential risk factors using regression analysis. MAIN OUTCOME MEASURES: The main outcome measures used were ejaculatory dysfunction prevalence and scores (3-item Men's Sexual Health Questionnaire Ejaculatory Dysfunction-Short Form [MSHQ-EjD-SF]), and bother (MSHQ-EjD-SF Bother item) and sexual satisfaction/enjoyment (International Index of Erectile Function Questionnaire Q7, Q8) as a function of subject's age, race, body mass index (BMI) and serum testosterone levels (measured by liquid chromatography tandem mass spectrometry). RESULTS: Mean (standard deviation [SD]) age of the participants was 52 years (11). Eighty-eight percent of the men experienced more than one type of ejaculatory dysfunction and 68% considered their symptoms to be bothersome. Prevalence of the ejaculatory dysfunctions was substantial across a range of age, race, BMI, and serum testosterone categories. Prevalence of PEVR and DFE were positively associated with age (<40 years vs. 60-70 years: PEVR: odds ratio [OR], 3.05; 95% confidence interval [CI], 1.32-7.06; DFE: OR, 2.78; 95% CI, 1.46-5.28) while DFE was associated with BMI (≥30 kg/m(2) vs. < 25 kg/m(2) : OR, 1.80; 95% CI, 1.062-3.05). All ejaculatory dysfunctions were more prevalent in black men. CONCLUSION: The majority of the participants experienced multiple ejaculatory dysfunctions and found them to be highly bothersome. Ejaculatory dysfunctions were prevalent across a wide range of demographic and clinical characteristics.

Trends in the Utilization of Penile Prostheses in the Treatment of Erectile Dysfunction in the United States.

BACKGROUND: The utilization of penile prosthesis (PP) insertion in the general population for medically refractory erectile dysfunction (ED) has not been well-characterized. This study assessed the national temporal trends in the surgical management of ED utilizing PP. MATERIALS AND METHODS: An analysis of the 5% Medicare Public Use Files from 2001 to 2010 was performed to assess the use of PP. Regression analysis was performed to identify factors associated with PP placement, type of PP utilized, and factors associated with revisions. RESULTS: A total of 1,763,260 men were diagnosed with ED, 3% (53,180) of whom underwent PP insertion. The utilization of PP for ED decreased from 4.6% in 2002 to 2.3% in 2010 (P < 0.01). This temporal decline in utilization was significant across all demographic factors including age, ethnicity, and geographic location. Men aged 65-74, from the U.S. South and West, and those with Charlson comorbidity scores >1 were more likely to have a PP inserted for ED (P < 0.01). African American men were more likely to have a semirigid PP placed compared with a multicomponent inflatable PP, and were more likely to undergo a revision or removal of the PP compared with Caucasian men (P < 0.01). CONCLUSIONS: The surgical management of ED with PP changed significantly between 2001 and 2010. The overall utilization of PP decreased, but its use in patients with significant medical comorbidities increased. Age >65, ethnicity, and geography influenced the likelihood of PP placement, prosthesis type, as well as the likelihood of prosthesis removal or revision.

Safety and efficacy of testosterone replacement therapy in adolescents with Klinefelter syndrome.

PURPOSE: We investigated the safety and tolerability of testosterone replacement therapy in adolescents with Klinefelter syndrome. MATERIALS AND METHODS: We reviewed the medical records of all consecutive adolescents with Klinefelter syndrome evaluated between 2007 and 2012. Patients receiving testosterone replacement and aromatase inhibitor therapy were identified. Data on demographics, physical characteristics, medical history and serum hormone concentrations were collected for each patient. We evaluated longitudinal changes in serum testosterone, luteinizing hormone and follicle-stimulating hormone as well as changes in body mass index after the initiation of testosterone replacement therapy. RESULTS: We identified 151 adolescents with Klinefelter syndrome. Mean age at presentation was 11.6 years. Testosterone replacement therapy and aromatase inhibitors were initiated in 110 and 75 patients, respectively, at an average age of 13 to 14 years. Topical testosterone replacement therapy was used in 95% of patients with good clinical efficacy and compliance based on serial serum testosterone values. After the initiation of testosterone replacement therapy average serum testosterone improved from 240 to 650 ng/ml. Serum luteinizing hormone and follicle-stimulating hormone increased with the progression of puberty from 2.6 to 16.6 and 7 to 42 mIU/ml, respectively. No adverse outcomes related to testosterone replacement therapy were reported. CONCLUSIONS: Hormone supplementation with testosterone and aromatase inhibitors in adolescents with Klinefelter syndrome appears to be safe and effective for maintaining serum testosterone within the normal range. Compliance with topical formulations is high. Topical testosterone replacement therapy is not associated with the suppression of endogenous serum luteinizing hormone or follicle-stimulating hormone.

Endocrinological issues and hormonal manipulation in children and men with Klinefelter syndrome.

47, XXY or Klinefelter syndrome (KS), the most common chromosomal aberration in males, is characterized by either absolute or relative hypogonadism with frequent decline in serum testosterone (T) following the onset of puberty. Decreased T levels are the result of testicular dysfunction with decrease in size of Leydig cells, and loss of germs and Sertoli cells leading to tubular hyalinization. Increase in estradiol results from over-expression of aromatase CYP19. Deficient androgen production and observed varied response of end-organs to T leads to delayed progression of puberty with decreased facial/body hair, poor muscle development, osteoporosis, and gynecomastia. It is possible that hypogonadism and excessive estradiol production contribute to emotional and social immaturity, and specific learning disabilities in KS. Based on the authors' experience and literature review, early fertility preservation and hormonal supplementation may normalize pubertal development, prevent metabolic sequelae of hypogonadism, and have a positive effect on academic and social development. No randomized clinical trials are available studying the effects of T supplementation on reproductive or cognitive issues in KS. Aggressive T supplementation (topical gel) and selective use of aromatase inhibitors may be considered at the onset of puberty with careful follow-up and titration to reach age-specific high-normal physiologic serum values. The decision to institute hormonal therapy should be part of a multidisciplinary approach including physical, speech, behavioral, and occupational therapy. © 2013 Wiley Periodicals, Inc.

Flow cytometric characterization of apoptosis and chromatin damage in spermatozoa.

Apoptosis has been implicated in sperm chromatin damage; it is unclear whether apoptosis occurs through cytoplasmic or mitochondrial pathways. Sperm has minimal volume of cytoplasm but prominent mitochondria. Propidium iodide (PI), annexin V (AV), DiIC1(5) and proprietary fluorochrome (PF-1) were used to investigate apoptosis activation in human sperm using multichannel flow cytometry. There was a time-dependent increase in staining of spermatozoa with both AV and PF-1 and decrease in mitochondrial staining with DiIC1(5). These results strongly suggest that the drop in mitochondrial potential precedes changes in membrane phospholipids, and thus suggest apoptotic activation through mitochondrial pathway in human spermatozoa.

Effects of 12 weeks of tadalafil treatment on ejaculatory and orgasmic dysfunction and sexual satisfaction in patients with mild to severe erectile dysfunction: integrated analysis of 17 placebo-controlled studies.

OBJECTIVES: To compare effects of tadalafil on ejaculatory and orgasmic function in patients presenting with erectile dysfunction (ED). To determine the effects of post-treatment ejaculatory dysfunction (EjD) and orgasmic dysfunction (OD) on measures of sexual satisfaction. PATIENTS AND METHODS: Data from 17 placebo-controlled 12-week trials of tadalafil (5, 10, 20 mg) as needed in patients with ED were integrated. EjD and OD severities were defined by patient responses to the International Index of Erectile Function, question 9 (IIEF-Q9; ejaculation) and IIEF-Q10 (orgasm), respectively. Satisfaction was evaluated using the intercourse and overall satisfaction domains of the IIEF and Sexual Encounter Profile question 5. Analyses of covariance were performed to compare mean ejaculatory function and orgasmic function, and chi-squared tests evaluated differences in endpoint responses to IIEF-Q9 and IIEF-Q10. RESULTS: A total of 3581 randomized subjects were studied. Treatment with tadalafil 10 or 20 mg was associated with significant increases in ejaculatory and orgasmic function (vs placebo) across all baseline ED, EjD, and OD severity strata. In the tadalafil group, 66% of subjects with severe EjD reported improved ejaculatory function compared with 36% in the placebo group (P < 0.001). Similarly, 66% of the tadalafil-treated subjects (vs 35% for placebo; P < 0.001) with severe OD reported improvement. Residual severe EjD and OD after treatment had negative impacts on sexual satisfaction. Limitations of the analysis include its retrospective nature and the use of an instrument (IIEF) with as yet unknown performance in measuring treatment responses for EjD and OD. CONCLUSIONS: Tadalafil treatment was associated with significant improvements in ejaculatory function, orgasmic function and sexual satisfaction. Proportions of subjects reporting improved ejaculatory or orgasmic function were ≈ twofold higher with tadalafil than with placebo. These findings warrant corroboration in prospective trials of patients with EjD or OD (without ED).

Exploring the relationship between socioeconomic status and erectile dysfunction: an analysis of the National Health and Nutrition Examination Survey.

The aim of this study was to investigate the association between socioeconomic status and erectile dysfunction. Data were obtained from the National Health and Nutrition Examination Survey, a nationally representative survey of the United States population. Socioeconomic status was estimated using the poverty income ratio, a ratio of family income to established poverty levels. Erectile function was assessed from a single survey question and was divided into two groups: normal (always and usually able to maintain an erection) and erectile dysfunction (sometimes or never able to maintain an erection). Multivariable logistic regression, using a multi-model approach, was used to characterize the interplay between well-established risk factors for erectile dysfunction and socioeconomic status. Our final cohort included 3679 respondents, representative of 81,255,155 subjects with a mean age of 44.4 [SE, 0.365]. Multivariable logistic regression showed that low-income respondents were significantly more likely to report erectile dysfunction [adjusted odds ratio (AOR) = 1.95, 95% CI 1.28-2.96; p = 0.003] compared to higher-income respondents. This study suggests that low socioeconomic status may be associated with erectile dysfunction in a large, nationally representative sample.

Factors associated with ejaculatory and orgasmic dysfunction in men with erectile dysfunction: analysis of clinical trials involving the phosphodiesterase type 5 inhibitor tadalafil.

OBJECTIVE: To determine frequencies of, and risk factors for, ejaculatory dysfunction (EjD) and orgasmic dysfunction (OD) in men with different degrees of erectile dysfunction (ED). PATIENTS AND METHODS: Baseline data from 28 ED trials were integrated and analysed. The International Index of Erectile Function Question 9 (IIEF-Q9; 'When you had sexual stimulation or intercourse, how often did you ejaculate?') and IIEF-Q10 ('How often did you have the feeling of orgasm with or without ejaculation?') were used to evaluate ejaculatory and orgasmic functions. Responses of 'almost never or never' or 'a few times (much less than half the time)' were taken as evidence of EjD or OD, respectively, whereas responses of 'almost always or always' or 'most times (much more than half the time)' were taken as evidence of normal function. Estimates of the relative risks (RRs) of EjD or OD were determined for multiple patient characteristics. RESULTS: Among 12,130 study participants with available data, only 5117 (42.2%) reported normal ejaculatory function, and 4321 (35.6%) normal orgasm, regardless of ED severity. Among subjects with poor ejaculatory function, 16.7% had mild ED, and among subjects with poor sensation of orgasm, 21.9% had mild ED. Frequencies of EjD and OD increased with increasing ED severity. Of the 5117 individuals with normal ejaculatory function, 796 (15.6%) had poor sensation of orgasm. Of the 4321 subjects with normal orgasm, 226 (5.2%) had poor ejaculatory function. Men with (vs without) EjD or OD tended to be younger: 53.7 vs 56.9 years and 54.2 vs 56.2 years, respectively. Factors associated with increased RRs of EjD and OD included cardiomyopathy (RR for EjD 1.74; RR for OD 1.59); cardiac failure (RR 1.40; 1.22); and baseline use (or history of use) of antipsychotics (RR 1.45; 1.30), selective serotonin reuptake inhibitors (RR 1.31; 1.27), and tricyclic antidepressants (RR 1.34; 1.28). CONCLUSIONS: EjD and OD occurred at baseline in more than one in three men enrolled in tadalafil trials. Even men with mild ED reported EjD or OD. Further studies are warranted to better understand the impacts of EjD and OD on male sexuality and quality of life.

Nerve sparing can preserve orgasmic function in most men after robotic-assisted laparoscopic radical prostatectomy.

OBJECTIVE: • To investigate orgasmic outcomes in patients undergoing robotic-assisted laparoscopic radical prostatectomy (RALP) and the effects of age and nerve sparing on these outcomes. PATIENTS AND METHODS: • Between January 2005 and June 2007, 708 patients underwent RALP at our institution. • We analysed postoperative potency and orgasmic outcomes in the 408 men, of the 708, who were potent, able to achieve orgasm preoperatively and available for follow-up. RESULTS: • Of men aged ≤60 years, 88.4% (198/224) were able to achieve orgasm postoperatively in comparison to 82.6% (152/184) of older men (P < 0.001). • Of patients who received bilateral nerve sparing (BNS) during surgery, 273/301 (90.7%) were able to achieve orgasm postoperatively compared with 46/56 (82.1%) patients who received unilateral nerve sparing and 31/51 (60.8%) men who received non-nerve-sparing surgery (P < 0.001). • In men ≤60 years who also underwent BNS, decreased sensation of orgasm was present in 3.2% of men, and postoperative orgasmic rates were significantly better than men ≤60 years who underwent unilateral or no nerve sparing (92.9% vs 83.3% vs 65.4%, respectively; P < 0.001). • Potency rates were also significantly higher in men ≤60 years and in those who underwent BNS. CONCLUSIONS: • Age and nerve sparing influence recovery of orgasm and erectile function after RALP. • Men ≤60 years old and those who undergo BNS are most likely to maintain normal sexual function.

[Male sexual dysfunction and obesity]. / Troubles sexuels masculins et obésité.

Obesity concerns more than 200 million people in the world, with an increasing prevalence in western countries. It is closely related to multiple medical conditions, such as diabetes and hypertension. It was recently shown that testosterone deficiency syndrome and erectile dysfunction (ED) are also linked to male obesity. In this group of patients, ED may be due to defects in corpus cavernosum relaxation, endocrine modifications and nerve signal alterations. Weight loss and increased physical activities can improve erectile function in 30% of obese patients. Additional medical treatments of ED enhance erectile function in more than 80% of patients. Self image improvement associated with appropriate erectile dysfunction medical treatment allow better sexual life and potentially increased motivation for weight loss.

Race and Ethnicity Have a Significant Effect on the Disclosure of Erectile Function: An Analysis of NHANES Response Patterns.

OBJECTIVES: To determine if race/ethnicity impacts disclosure of erectile function. METHODS: Data on age, education, erectile function, and past medical history were obtained from the National Health and Nutrition Examination Survey. Response rates to a single survey question regarding erectile function were calculated and compared between race/ethnicity groups. Two subgroups were created by excluding non-responders to questions about hypertension and prostate disease to control for overall non-responsiveness and urologic health literacy. RESULTS: Our final cohort consisted of 4,694 men. Overall, 3,898 (83.0%) responded to the erectile function survey question. Race/ethnicity was a significant factor in overall response rates to the Erectile function question: 85.2% in non-hispanic white, 82.3% in non-hispanic black, 81.2% in hispanic, and 64.8% in other subjects (P<.001). Race/ethnicity remained significantly associated with responses rates among both subgroups. Multivariate logistic regression using the prostate disease subgroup showed that non-hispanic black (AOR = 2.02, 95% CI 1.01-4.03, P = .047) and hispanic (AOR = 2.18, 95% CI 1.19-4.00, P = .012) participants were significantly more likely to not disclose their erectile function compared to non-hispanic white participants after controlling for age and education. CONCLUSION: Non-hispanic black and hispanic men were significantly less likely to disclose their erectile function than non-hispanic white men in an anonymous, nationally representative survey. A better understanding of how cultural differences affect reporting of erectile function is important in improving patient care and accurately studying outcomes of urological procedures.

Diagnosis of the gr/gr Y chromosome microdeletion does not help in the treatment of infertile American men.

PURPOSE: The phenotypic effects of the gr/gr partial azoospermia factor c deletion vary geographically and to our knowledge have not been reported in the American population. We evaluated the clinical characteristics of infertile American men with the gr/gr deletion. MATERIALS AND METHODS: We retrospectively reviewed clinical data on 1,410 infertile men tested for the gr/gr deletion. We analyzed sperm concentration and the outcome of microdissection testicular sperm extraction with respect to gr/gr status. RESULTS: We identified 73 men with gr/gr deletions, including 43 of 989 (4.3%) with azoospermia, 18 of 317 (5.7%) with severe oligospermia (less than 5 million sperm per ml), 6 of 61 (9.8%) with oligospermia (5 to less than 20 million sperm per ml) and 6 of 43 (14%) infertile men with normospermia (greater than 20 million sperm per ml). A gr/gr deletion correlated with higher sperm production. The gr/gr deletion rate was higher in men with normospermia than in those with a sperm concentration of less than 20 million and less than 5 million per ml (p = 0.021 and 0.006, respectively). Microdissection testicular sperm extraction was done in 22 azoospermic men with gr/gr deletions and sperm were retrieved in 14 (64%). This retrieval rate was similar to that at our center in men with idiopathic nonobstructive azoospermia (p = 0.13). CONCLUSIONS: Diagnosis of the gr/gr deletion did not predict impaired sperm production in our patient population and did not appear to alter the prognosis for surgical sperm retrieval. Despite the established modulatory impact of the gr/gr deletion on sperm production in some populations at this time the clinical value of testing infertile American men for the gr/gr deletion is not clear.

Prolactin in men's health and disease.

PURPOSE OF REVIEW: To review physiology of prolactin (PRL), cause and managment of hyperprolactinemia, and discuss evolving diverse roles of PRL in men's health. RECENT FINDINGS: Hyperprolactinemia can be physiologically found after sexual activities, exercise, lactation, during pregnancy, and after stressful venipuncture. Elevated PRL can be caused by medications use, renal failure, hypothyroidism, and by prolactinoma - PRL secreting tumors. Symptomatic hyperprolactinemia and prolactinomas should be treated to lower PRL levels, decrease tumor size, and restore gonadal function. Three modes of treatment are typically utilized: pharmacological, radiosurgery with gamma radiation, and external beam radiation. Pharmacological treatment of prolactinomas is mainly based on dopamine agonists. The most frequently used dopamine agonists are bromocriptine and cabergoline. Cabergoline becoming the preferred drug in the treatment of prolactinomas because of higher response rate and less side-effects. Bromocriptine has been recently approved to improve glycemic control in diabetes mellitus. SUMMARY: PRL plays a diverse role in men's reproduction and health. Detecting and treating elevated PRL may not only improve infertility and hypogonadism but also have a positive effect on the metabolic profile of patient and control of glycemic control and metabolic profile - an important advantage considering dramatic and worldwide increase in obesity and diabetes.