Semen parameters are unaffected by statin use in men evaluated for infertility.

The effects of statin use on conventional semen parameters in humans are largely unknown and have not been previously studied in subfertile men. We retrospectively reviewed data from 10,140 patients seen at our fertility clinic between 2002 and 2013 to assess the effects of statin use on semen parameters. Men who used any statins for >3 months before semen sample collection were included as cases. Data were gathered on patient age, medication use and conventional semen parameters. A total of 118 patients (126 samples) used statins for at least 3 months before semen sample collection. Data from 7698 patients (8,760 samples), who were not using any medications, were used as controls. In age-adjusted regression models, statin use was not associated with statistically significant changes in semen parameters. When used in combination with other nonspermatotoxic medications, it was associated with 0.3 ml decrease in semen volume (95% confidence interval: 0.02 to 0.58 ml, p-value = .04). In conclusion, statin use was not adversely associated with semen parameters other than semen volume in subfertile patients. These findings from our large-scale retrospective study suggest that there are no clinically relevant deleterious effects from statin use on conventional semen parameters.

Cigarette smoking significantly alters sperm DNA methylation patterns.

Numerous health consequences of tobacco smoke exposure have been characterized, and the effects of smoking on traditional measures of male fertility are well described. However, a growing body of data indicates that pre-conception paternal smoking also confers increased risk for a number of morbidities on offspring. The mechanism for this increased risk has not been elucidated, but it is likely mediated, at least in part, through epigenetic modifications transmitted through spermatozoa. In this study, we investigated the impact of cigarette smoke exposure on sperm DNA methylation patterns in 78 men who smoke and 78 never-smokers using the Infinium Human Methylation 450 beadchip. We investigated two models of DNA methylation alterations: (i) consistently altered methylation at specific CpGs or within specific genomic regions and (ii) stochastic DNA methylation alterations manifest as increased variability in genome-wide methylation patterns in men who smoke. We identified 141 significantly differentially methylated CpGs associated with smoking. In addition, we identified a trend toward increased variance in methylation patterns genome-wide in sperm DNA from men who smoke compared with never-smokers. These findings of widespread DNA methylation alterations are consistent with the broad range of offspring heath disparities associated with pre-conception paternal smoke exposure and warrant further investigation to identify the specific mechanism by which sperm DNA methylation perturbation confers risk to offspring health and whether these changes can be transmitted to offspring and transgenerationally.

Teratozoospermia and asthenozoospermia are associated with specific epigenetic signatures.

Semen analysis is commonly used as a tool to assess the fertility potential of a male, despite its relatively low predictive power. In this study, we have assessed associations between semen analysis findings (low count, low motility, low viability, poor sperm penetration assay results, poor morphology, and increased DNA damage) and DNA methylation patterns in mature spermatozoa. DNA methylation patterns in the mature spermatozoa are thought to be indicative of patterns in the adult germline stem cells and may offer insight into potential perturbations to cellular pathways involved in spermatogenesis. In this study, sperm DNA methylation at >480,000 CpGs was assessed in 94 men using the Illumina 450k HumanMethylation Array and compared to standard measures of sperm quality. We did not identify any global changes to methylation profiles that were associated with reduced semen parameters. Similarly, we found no significant difference in methylation variability that was associated with any abnormal semen analysis parameter, although sperm displaying abnormal parameters tended to have an increased coefficient of variability, suggesting that, in some samples, this may be a contributing factor. Analysis of methylation at single CpGs and genomic regions did identify associations for low viability and low motility, and to a smaller extent, low count. Interestingly, based on GO Term analysis, differentially methylated regions associated with low viability were over-represented in regions important in meiosis, spermatogenesis, and genomic imprinting. These results suggest that while there are not global alterations to the sperm methylome associated with semen abnormalites, some viability associated regional alterations do exist that may be indicative of perturbed cellular pathways during spermatogenesis.

Glycaemic control and risk of incident urinary incontinence in women with Type 1 diabetes: results from the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study.

AIMS: To study the impact of glycaemic control on urinary incontinence in women who participated in the Diabetes Control and Complications Trial (DCCT; 1983-1993) and its observational follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC; 1994-present). METHODS: Study participants were women who completed, at both years 10 (2003) and 17 (2010) of the EDIC follow-up, the urological assessment questionnaire (UroEDIC). Urinary incontinence was defined as self-reported involuntary leakage of urine that occurred at least weekly. Incident urinary incontinence was defined as weekly urinary incontinence present at EDIC year 17 but not at EDIC year 10. Multivariable regression models were used to examine the association of incident urinary incontinence with comorbid prevalent conditions and glycaemic control (mean HbA1c over the first 10 years of EDIC). RESULTS: A total of 64 (15.3%) women with Type 1 diabetes (mean age 43.6 ± 6.3 years at EDIC year 10) reported incident urinary incontinence at EDIC year 17. When adjusted for clinical covariates (including age, DCCT cohort assignment, DCCT treatment arm, BMI, insulin dosage, parity, hysterectomy, autonomic neuropathy and urinary tract infection in the last year), the mean EDIC HbA1c was associated with increased odds of incident urinary incontinence (odds ratio 1.03, 95% CI 1.01-1.06 per mmol/mol increase; odds ratio 1.41, 95% CI 1.07-1.89 per % HbA1c increase). CONCLUSIONS: Incident urinary incontinence was associated with higher HbA1c levels in women with Type 1 diabetes, independent of other recognized risk factors. These results suggest the potential for women to modify their risk of urinary incontinence with improved glycaemic control. (Clinical Trials Registry no: NCT00360815 and NCT00360893).

The safety and efficacy of clomiphene citrate in hypoandrogenic and subfertile men.

Our objective was to evaluate the safety and efficacy of clomiphene citrate (CC) in infertile and hypoandrogenic men through a retrospective study between September 2013 and May 2014. We identified 47 men between 18 and 55 years placed on 50 mg CC every other day. We evaluated the effect of CC on testosterone after 2 weeks, rates of adverse effects and predictors of CC response. Mean baseline testosterone, bioavailable testosterone and estradiol were 246.8 ng dl(-1), 125.5 ng dl(-1) and 20.8 pg dl(-1), respectively. At 2 weeks, mean testosterone, bioavailable testosterone and estradiol increased to 527.6 ng dl(-1), 281.8 ng dl(-1) and 32.0 pg dl(-1) (all P<0.001). Two patients at 2 weeks and one patient at 3 months had a paradoxical decrease in testosterone. Mean total motile count (TMC) and concentration increased from 59.7 million (s.e.m.: 16.5) and 50.7 millions ml(-1) (s.e.m.: 11.1) at baseline to 90.9 million (s.e.m.: 25.9) and 72.5 millions ml(-1) (s.e.m.: 17.5), respectively, at 3 months, although this was nonsignificant (P=0.09, 0.09). No patient on CC experienced a paradoxical decrease in TMC or sperm concentration. On age-adjusted regression analysis, age, BMI, longitudinal testis axis, baseline follicle-stimulating hormone, LH and estradiol did not correlate with improvement in bioavailable testosterone at 2 weeks. CC improves testosterone and may improve semen parameters, although a small percentage of men may not demonstrate improvement in testosterone.

Men with diabetes may require more aggressive treatment for erectile dysfunction.

Diabetes mellitus (DM) and erectile dysfunction (ED) are common health problems that markedly increase in prevalence and incidence with advancing age. DM is a known risk factor for developing ED; however, among men with ED it is unknown if DM alters the need for more invasive therapies. We sought to determine whether DM is associated with increased ED severity, reduced effectiveness of first-line (oral) therapies, and therefore higher utilization of second- and third-line therapies. The Inovus I3 database was queried to identify men with ED. Claims were followed for 48 months. Men with incomplete follow-up data and those diagnosed with DM after ED diagnosis were excluded from analysis. Rates of second-line (penile suppositories or injectables) and third-line (penile prostheses) ED therapies were compared between men with and without preexisting DM. Risk of progressing to second- and third-line therapies associated with DM was assessed with logistic regression and Kaplan-Meier analysis. From 1 January 2002 to 31 December 2006, 136 306 men were identified with prevalent and incident ED. Among this group, 19 236 men had DM that preceded their ED diagnosis. Men with DM were more than 50% more likely to be prescribed secondary ED treatments over the 2-year observation period, and more than twice as likely to undergo penile prosthesis surgery. Among a large population-based cohort of men with ED, those with DM are more likely to require more aggressive treatments. These data suggest that ED among men with diabetes may be less responsive to first-line treatments (oral agents), worsen more rapidly, or both.

How curved is too curved? The severity of penile deformity may predict sexual disability among men with Peyronie's disease.

Peyronie's disease (PD) is caused by progressive fibrotic scarring of the tunica albuginea resulting in curvature or other deformities of the erect penis. The severity of penile curvature or other deformity may contribute to a man's inability to have intercourse (sexual disability), due to difficulty with penetration, partner pain or emotional stress. To determine whether the degree of curvature or type of penile deformity predicts sexual disability among men with PD. This cross-sectional analysis of consecutive men evaluated for PD at a single tertiary referral center used a PD-specific questionnaire to evaluate risk factors for sexual disability in men with PD, who did not have erectile dysfunction (ED). Multivariate logistic regression was used to determine the clinical predictors of sexual disability. Sexual disability as defined by the inability to have penetrative intercourse. A total of 202 men were evaluated and 88 men with ED were excluded. Sexual disability was associated with relationship problems, penile curvature and penile length loss in bivariate, but not multivariate analysis. We found that although many of the demographic, medical and sexual function domains were significant predictors of inability to have sex, the only significant predictor of sexual disability in multivariate analysis was curvature>60° (odds ratio 3.23 95%CI 1.08-9.67). PD can be sexually disabling in many men without ED. Severe penile curvature is a robust independent predictor of the ability to have intercourse. Other penile deformities fail to predict sexual disability. This is important for counseling patients with newly diagnosed PD and those who are considering medical or surgical intervention.