Intra-individual changes in sperm parameters and total motile count with time among infertile men.

BACKGROUND: Paternal age association with sperm parameters has been previously studied, demonstrating a decrease in semen volume, sperm motility, and sperm morphology, but not in sperm concentration. However, scarce data exists on the individual intra-personal changes in semen parameters with time. STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To evaluate the changes in semen parameters and total motile count of infertile men over time. MATERIALS AND METHODS: In this retrospective cohort study, infertile men without known risk factors for sperm quality deterioration and at least two semen analyses done > 3 months apart, between 2005 and 2021, were evaluated. Allocation to groups was according to time between first and last semen analyses - 3-12 months, 1-3 years, 3-5 years, and > 5 years. Basic characteristics and first and last semen analyses were compared. The primary outcome was the change in sperm parameters and the secondary outcome was the occurrence of a total motile count < 5 million in men with an initial total motile count > 10 million. RESULTS: A total of 2018 men were included in the study. The median age at first semen analyses was 36.2 (interquartile range: 32.8-40.1) years and the median time between semen analyses was 323 days (range 90-5810 days). The overall trend demonstrated an increase in concentration in the 3-12 months and the 1-3 years groups, whereas volume, motility, and morphology remained similar in these time groups. Semen analyses done more than 5 years apart showed decreased volume (p < 0.05), motility (p < 0.05) morphology (p < 0.05), and steady sperm concentration. Significant declines in TMCs were found over time (p < 0.001), with 18% and 22% of infertile men with an initial total motile count > 10 million dropping to < 5 million after 3 and 5 years, respectively. The factors independently predictive of total motile count < 5 M in the last semen analyses in men with an initial total motile count of > 10 M in a multivariate logistic regression model were baseline volume (odds ratio 0.80, p = 0.03), baseline total motile count (odds ratio 0.98, p = 0.01) and time between semen analyses - 3-5 years (odds ratio 3.79, p < 0.001) and > 5 years (odds ratio 3.49, p = 0.04) DISCUSSION: Our study demonstrates, at the individual level, that while improvement in sperm concentration is observed in the first year and between 1 and 3 years, possibly due to fertility treatments, fertility-related counseling, and lifestyle changes, semen parameters decline with time over 3 years in individuals. Of significance, close to 22% of men with an initial total motile count > 10 million (a range where spontaneous pregnancy is attainable) declined to < 5 million (a range usually indicating a need for in-vitro fertilization/intracytoplasmic sperm injection) over 5 years. This data could contribute to individualized family planning for infertile men regarding the mode and timing of conception and the need for sperm banking, in order to minimize the need for future fertility treatments.

Temporal Trends in Semen Quality, Hormone Levels, and Substance Use Among Infertile Men in Pre- and Post-Cannabis Legalization Eras in Canada.

Background: The Cannabis Act (Bill C-45) was enacted in 2018, to legalize and regulate the use, production, and sale of nonmedical cannabis in Canada. While public health and safety implications of cannabis legalization have yet to be elucidated, the wide availability of cannabis necessitates health care providers to be knowledgeable about therapeutic potential and side effects of use. This study aimed to examine the temporal trends over two decades and the impact of the Cannabis Act in Canada, implemented in October 2018, on substance use, semen parameters, and testosterone levels of infertile men. Methods: We conducted a retrospective cohort study from a prospectively maintained database of a single infertility clinic. Demographic, fertility, and substance use history were correlated with semen and hormone assessments. Temporal trends in cannabis use and semen quality between 2001 and 2021 were investigated and compared between pre-cannabis legalization eras (PRCL) and post-cannabis legalization eras (POCL). Results: Our cohort included 11,630 patients (9411 PRCL and 2230 POCL). Cannabis use increased by 8.4% per year (p<0.001), while alcohol and tobacco consumption declined (0.8% and 1.5% per year, p<0.05 and p=0.004, respectively). Similar trends were noticed in the POCL, with higher rates of cannabis use (22.4% vs. 12.9%, p<0.001) and decreased tobacco and alcohol intake (15.2% vs. 17.7%, p=0.005 and 50.5% vs. 55.2%, p<0.001, respectively) compared to the PRCL group. Semen concentration was lower in the POCL group (24.8±44.8 vs. 28.7±48.3 million/mL, p=0.03). Testosterone did not differ between the cohorts. Comparison between cannabis users (n=1715) and nonusers (n=9924) demonstrated a slight increase in sperm motility (25.9%±15.3% vs. 23.9%±15.0%, p=0.002) and decreased sperm concentration among users (27.6±53.5 vs. 23.9±15.0 million/mL, p=0.03). Conclusion: A nearly 10% rise in cannabis use in the POCL era was observed among men being investigated for infertility. Our data suggest cannabis use may be associated with an increase in testosterone, slightly improved sperm motility, and decreased sperm concentration.

Improved sperm DNA fragmentation levels in infertile men following very short abstinence of 3-4 hours.

Background: Limited data exists on possible approaches to improve sperm DNA fragmentation index (DFI) when no identifiable cause is found. The effect of short abstinence on sperm parameters has been extensively studied, but rarely reported on the effect on DFI in infertile men. In this study, we aimed to determine whether a second ejaculate provided after very short abstinence demonstrates lower DFI rates in infertile men. Methods: This prospective cohort study was conducted at Mount Sinai Hospital, Toronto, Canada, a tertiary university affiliated hospital. All men having DFI testing in addition to the standard semen analysis were identified via a prospectively collected database. Infertile men were instructed to provide two semen samples 3-4 hours apart (the first sample was given after 2-5 days of abstinence) to test the effect on DFI levels. Data analysis was performed for the comparison of the change in sperm parameters and DFI between samples and between men with DFI above and under 30%. Results: A total of 52 men provided double ejaculates 3-4 hours apart. In the entire group, DFI decreased from 38.9%±21.4% to 35.1%±21.6% in the second sample (P<0.001). Semen volume was lower on the second sample (2.3±1.4 vs. 1.5±0.9 mL, P<0.001), while the remaining parameters did not change. Forty out of 52 patients (76.9%) had improved DFI (average of 6.0±4.0 percentage points). Change in DFI varied with 22/52 (42.3%) and 7/52 (13.5%) of patients found to have decreases in DFI >5% and >10% in the second ejaculate, respectively. For men with DFI of 30-40%, 64% (7/11) of DFIs reduced to the under 30% range. First DFI value was the only parameter associated with DFI decrease to under 30% in multivariate models [odds ratio (OR), 0.62; 95% confidence interval (CI): 0.39-0.98; P=0.04]. Conclusions: This study identified significant improvements in DFI in infertile men providing a second sample after 3-4 hours. Controlled trials are needed to determine if reproductive outcomes are improved using a second ejaculate for infertile men with high initial sperm DFI values.

Intra-individual changes in sperm DNA fragmentation levels over short and long time periods.

PURPOSE: We aimed to examine the longitudinal, intra-personal changes in DNA fragmentation index (DFI) over time. METHODS: Men who performed at least two DFI measurements (using sperm chromatin structure assay (SCSA) between 2003 and 2019 were included in this study and allocated to groups by time between DFI tests: < 1 year, 1-3 years, 3-5 years, and > 5 years. An analysis of DFI change over time according to age groups was additionally performed. Regression models were developed to predict changes in DFI with time. RESULTS: Overall, 225 patients had two or more DFI measurements done at least a month apart (mean of 586.7± 710.0 days). The < 1 year (n = 124) and 1-3 years (n = 68) groups demonstrated decreased DFI levels, while an increase in DFI was shown in 3-5 years (n = 21) and more than 5 years (n = 12) groups - 7.1 ± 14.9%, - 4.5 ± 13.4%, + 3.2 ± 8.4%, and + 10.8 ± 18.0%, respectively, p < 0.001). This trend was similarly shown in age subgroups of under 40 years and 40-50 years at baseline DFI. Linear regression models showed that the factors predictive of DFI increase are baseline DFI and > 3 years between DFI tests. CONCLUSION: This study shows that DFI, in men being investigated for infertility, initially decreases in the first 3 years of follow-up, and then increases over time with the highest increase occurring after 5 years interval (an average increase of 10.8%). Testing infertile men's DFI levels at first evaluation may contribute to personalized consult regarding future reproductive outcomes.

One size does not fit all: variations by ethnicity in demographic characteristics of men seeking fertility treatment across North America.

OBJECTIVE: To compare racial differences in male fertility history and treatment. DESIGN: Retrospective review of prospectively collected data. SETTING: North American reproductive urology centers. PATIENT(S): Males undergoing urologist fertility evaluation. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Demographic and reproductive Andrology Research Consortium data. RESULT(S): The racial breakdown of 6,462 men was: 51% White, 20% Asian/Indo-Canadian/Indo-American, 6% Black, 1% Indian/Native, <1% Native Hawaiian/Other Pacific Islander, and 21% "Other". White males sought evaluation sooner (3.5 ± 4.7 vs. 3.8 ± 4.2 years), had older partners (33.3 ± 4.9 vs. 32.9 ± 5.2 years), and more had undergone vasectomy (8.4% vs. 2.9%) vs. all other races. Black males were older (38.0 ± 8.1 vs. 36.5 ± 7.4 years), sought fertility evaluation later (4.8 ± 5.1 vs. 3.6 ± 4.4 years), fewer had undergone vasectomy (3.3% vs. 5.9%), and fewer had partners who underwent intrauterine insemination (8.2% vs. 12.6%) compared with all other races. Asian/Indo-Canadian/Indo-American patients were younger (36.1 ± 7.2 vs. 36.7 ± 7.6 years), fewer had undergone vasectomy (1.2% vs. 6.9%), and more had partners who underwent intrauterine insemination (14.2% vs. 11.9%). Indian/Native males sought evaluation later (5.1 ± 6.8 vs. 3.6 ± 4.4 years) and more had undergone vasectomy (13.4% vs. 5.7%). CONCLUSION(S): Racial differences exist for males undergoing fertility evaluation by a reproductive urologist. Better understanding of these differences in history in conjunction with societal and biologic factors can guide personalized care, as well as help to better understand and address disparities in access to fertility evaluation and treatment.

Microscopic evaluation of the vasal fluid for sperm at the time of vasectomy reversal: Do we really need to check?

INTRODUCTION: During vasectomy reversal, intraoperative microscopic evaluation of the vasal fluid for sperm presence/quality can inform of the possibility of epididymal obstruction and need for a vasoepididymostomy (VE). In an effort to validate the utility of microscopic vasal fluid evaluation, the current initiative correlates gross vasal fluid characteristics with sperm presence and quality in a large series of VRs. METHODS: A total of 1267 vasectomy reversals yielded a total of 2522 vasal-units (right/left sides) for analysis. During vasectomy reversal, vasal fluid was sampled from the testicular-end vas and the fluid was characterized (thick-paste/opaque/translucent/clear). Each aspirate underwent microscopic evaluation for sperm quality and was categorized as: motile sperm/intact-non-motile sperm/sperm parts/no sperm. The predictive utility of the gross vasal fluid characteristics with respect to microscopic sperm presence and quality was analyzed. RESULTS: Among the 2522 vasal units analyzed, the side-to-side (left-right) concordance of vasal fluid quality and microscopic vasal sperm quality was 72% and 52%, respectively. When thick-pasty fluid was observed, no sperm were seen in the samples in 53% of cases, and if present, only non-motile sperm were observed. Even in the setting of more favorable vasal fluid characteristics (clear, translucent, and opaque fluid), no sperm were seen in 6-11% of cases, suggesting the possibility of epididymal obstruction and the need for VE. CONCLUSIONS: Intraoperative microscopic evaluation of the vasal fluid for sperm is a necessary practice during vasectomy reversal to optimize surgical outcomes. Reliance on gross vasal fluid characteristics in isolation may lead to unrecognized epididymal obstruction, and the need for a VE, in approximately 11% of cases.

Non-conventional therapies for Peyronie's disease: what is the evidence for efficacy?

BACKGROUND: In recent years, there has been a surge in non-conventional therapies for Peyronie's disease (PD). With increasing interest in these novel therapies, we conducted a narrative review to explore the efficacy and safety of these treatments to provide clarity for patients and providers. METHODS: A literature search was conducted to find studies describing non-conventional treatments of PD. These treatments were defined as those within the standard of care, including intralesional therapies and surgical options. RESULTS: A total of 14 studies were found. Non-conventional therapies included platelet-rich plasma (PRP), hyaluronic acid (HA), combination therapy of PRP and HA, extracorporeal shockwave therapy (ESWT), stem cell therapy (SCT), mycophenolate mofetil (MMF), and H-100. Most studies were limited to animal models and reported modest improvements in angulation and erectile function. Complication rates and cost of each treatment were infrequently reported. CONCLUSIONS: There is limited evidence supporting non-conventional therapies for PD. As such, they are currently not recommended in clinical guidelines.

The effect of ethnicity on semen analysis and hormones in the infertile patient.

INTRODUCTION: We aimed to study the association of ethnicity on semen parameters and hormones in patients presenting with infertility. METHODS: Data from men presenting for infertility assessment were prospectively collected and retrospectively reviewed. Demographic and clinical history was self-reported. Semen analysis included volume, count, motility, morphology, and vitality. The 2010 World Health Organization cutoffs were used. Baseline total testosterone and follicle-stimulating hormone (FSH) levels were recorded. Ethnicity data was classified as Caucasian, African Canadian, Asian, Indo-Canadian, Native Canadian, Hispanic, and Middle Eastern. All patients with complete data were included and statistical analysis was performed. RESULTS: A total of 9079 patients were reviewed, of which 3956 patients had complete data. Of these, 839 (21.2%) were azoospermic. After adjusting for age, African Canadians (odds ratio [OR] 1.70; 95% confidence interval [CI] 1.28-2.25) and Asians (1.34; 95% CI 1.11-1.62) were more likely to be azoospermic compared to Caucasians. Similarly, African Canadians (OR 1.75; 95% CI 1.33-2.29) were more likely to be oligospermic and Asians (OR 0.82; 95% CI 0.70-0.97) less likely to be oligospermic. Low volume was found in African Canadian (OR 1.42; 95% CI 1.05-1.91), Asians (OR 1.23; 95% CI 1.01-1.51), and Indo-Canadians (OR 1.47; 95% CI 1.01-2.13). Furthermore, Asians (OR 0.73; 95% CI 0.57-0.93) and Hispanics (OR 0.58; 95% CI 034-0.99) were less likely to have asthenospermia. Asians (OR 0.73; 95% CI 0.57-0.94) and Indo-Canadians (OR 0.58; 95% CI 0.35-0.99) were less likely to have teratozospermia. No differences were seen for vitality. No differences were seen for FSH levels, however, Asians (p<0.01) and Indo-Canadians (p<0.01) were more likely to have lower testosterone. CONCLUSIONS: Our study illustrates that variations in semen analyses and hormones exist in men with infertility. This may provide insight into the workup and management for infertile men from different ethnicities.

Efficacy of Nasal Testosterone Gel (Natesto®) Stratified by Baseline Endogenous Testosterone Levels.

OBJECTIVE: Pharmacokinetic and efficacy data from a phase 3 testosterone nasal gel (TNG) study were stratified by baseline endogenous testosterone level in patients with testosterone deficiency. Total testosterone (TT), LH, and FSH levels, as well as erectile function, mood, and lean body mass for each group were compared. In a subset of patients with very low baseline endogenous testosterone levels (<100 ng/dL), we investigated whether TNG is a suitable treatment option. MATERIALS AND METHODS: Patients with testosterone deficiency (serum TT <300 ng/dL) were treated with TNG for 3 months, followed by safety extension periods of 90 and/or 180 days. Pharmacokinetic parameters were calculated from serum hormone levels on days 30 and 90, along with efficacy measurements, which were analyzed by comparison with baseline values. Baseline and/or predose TT values were used for patient stratification. RESULTS: Prestudy and predose endogenous testosterone concentrations correlated. The maximal concentration of TT was nearly identical across all cohorts at days 30 and 90, whereas the average concentration over 24 hours had a slight positive dependence relative to predose levels. LH levels remained in the normal range but were decreased more in patients with higher starting baseline levels. These findings indicate that TNG works with an active hypothalamic-pituitary-gonadal axis that responds to each dose of TNG throughout the treatment period. Patients with the lowest endogenous testosterone levels received maximum exposure impact from each TNG dose. Patients with severe testosterone deficiency had similar efficacy improvements as the remainder of the study population. CONCLUSION: All testosterone-deficient cohorts were successfully treated with TNG.

Reproductive endocrinologists are the gatekeepers for male infertility care in North America: results of a North American survey on the referral patterns and characteristics of men presenting to male infertility specialists for infertility investigations.

OBJECTIVE: To characterize the referral patterns and characteristics of men presenting for infertility evaluation using data obtained from the Andrology Research Consortium. DESIGN: Standardized male infertility questionnaire. SETTING: Male infertility centers. PATIENT(S): Men presenting for fertility evaluation. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Demographic, infertility history, and referral data. RESULT(S): The questionnaires were completed by 4,287 men, with a mean male age of 40 years ± 7.4 years and female partners age of 37 years ± 4.9 years. Most were Caucasian (54%) with other races being less commonly represented (Asian 18.6%, and African American 5.5%). The majority (59.7%) were referred by a reproductive gynecologist, 19.4% were referred by their primary care physician, 4.2% were self-referred, and 621 (14.5%) were referred by "other." Before the male infertility investigation, 12.1% of couples had undergone intrauterine insemination, and 4.9% of couples had undergone in vitro fertilization (up to six cycles). Among the male participants, 0.9% reported using finasteride (5α-reductase inhibitor) at a dose used for androgenic alopecia, and 1.6% reported exogenous testosterone use. CONCLUSION(S): This broad North American patient survey shows that reproductive gynecologists are the de facto gateway for most male infertility referrals, with most men being assessed in the male infertility service being referred by reproductive endocrinologists. Some of the couples with apparent male factor infertility are treated with assisted reproductive technologies before a male factor investigation. The survey also identified potentially reversible causes for the male infertility including lifestyle factors such as testosterone and 5α-reductase inhibitor use.

Peyronie's disease and testosterone deficiency: Is there a link?

INTRODUCTION: Peyronie's disease (PD) and testosterone deficiency (TD) impact men at the same stage of life and can ultimately contribute to erectile dysfunction. There is speculation that low levels of testosterone (T) may predispose men to penile fibrosis; however, there is no published, up-to-date review summarizing the current evidence. Therefore, we conducted a narrative review of the literature exploring the relationship between PD and TD. METHODS: A comprehensive systematic search of existing literature of five online databases from June 1990 to June 2018 examining the relationship between PD and TD was conducted. The Cochrane risk-of-bias tool for randomized trials and the risk-of-bias assessment tool for cohort studies were used to evaluate the quality of studies. RESULTS: Six studies were identified (n = 675). Overall, five studies supported the link between PD and TD by demonstrating relationships in PD patients with low total T, free T, bioavailable T, greater penile curvature, and plaque development. However, one study demonstrated no connection between the conditions. The literature is restricted by small studies with methodological flaws. CONCLUSION: There are a number of mechanisms to support the link between TD and PD. The literature on the topic is limited by small studies which are overall conflicting. The findings of this work suggest the need for larger, prospective studies to clarify the role of TD in the development, evaluation, and treatment of PD. Establishing such a relationship could change management of PD as a diagnosis of PD may encourage clinicians to evaluate a patient's testosterone levels.

Prevalence and Management of Incidental Small Testicular Masses Discovered on Ultrasonographic Evaluation of Male Infertility.

PURPOSE: We report the safety of surveillance of small testicular masses incidentally discovered during evaluation of male infertility. MATERIALS AND METHODS: We retrospectively reviewed a prospectively collected database to identify patients with male infertility found to have incidental small testicular masses (hypoechoic lesions less than 10 mm) on scrotal ultrasound. The men were offered close surveillance with interval imaging and office followup. Patient and imaging characteristics were collected to compare the surveillance and surgical groups with additional comparisons between benign and malignant pathologies to elucidate predictors of underlying malignancy. RESULTS: Of 4,088 men in whom scrotal ultrasound was completed for male infertility evaluation 120 (2.9%) were found to have a subcentimeter testicular mass. Average followup was 1.30 years (range 0.1 to 16.9). A total of 18 men (15%) proceeded to extirpative surgery while 102 remained on surveillance at last followup. In those with at least 1 month of followup the mean lesion growth rate was -0.01 mm per year. Reasons for surgery included testicular exploration for infertility, mass growth, positive tumor markers, history of testis cancer, concerning imaging characteristics and patient choice. Six of the 18 men who underwent surgery were found to have malignancy, which was seminoma in all. All malignant lesions were greater than 5 mm on initial imaging and demonstrated vascularity, although size and vascularity were not significantly different from those of benign lesions on final pathology findings. No patients demonstrated advanced or recurrent disease. CONCLUSIONS: Small testicular masses are not uncommon, especially in the infertile male population. Most of these masses do not show significant growth during long-term evaluation and can be safely surveilled with close followup.

Varicocelectomy to "upgrade" semen quality to allow couples to use less invasive forms of assisted reproductive technology.

OBJECTIVE: To determine the magnitude of improvement in semen parameters after a varicocelectomy and the fraction that have improvements such that couples needing IVF or IUI are "upgraded" to needing less invasive assisted reproductive technology (ART). DESIGN: Retrospective review of prospectively collected data. SETTING: Academic medical centers. PATIENT(S): Men presenting for a fertility evaluation with a clinical varicocele. INTERVENTION(S): Varicocele repair (surgical or embolization). MAIN OUTCOME MEASURE(S): Total motile sperm count (TMSC) before and after repair, and the proportion of men considered candidates for: natural pregnancy (NP) >9 million, IUI 5-9 million, or IVF < 5 million. RESULT(S): A total of 373 men underwent varicocele repair. The TMSC increased from 18.22 ± 38.32 to 46.72 ± 210.92 (P=.007). The most pronounced increase was with baseline TMSC <5 million, from 2.32 ± 1.50 to 15.97 ± 32.92 (P=.0000002); 58.8% of men were upgraded from IVF candidacy to IUI or NP. For baseline TMSC 5-9 million, the mean TMSC increased from 6.96 ± 1.16 to 24.29 ± 37.17 (P=.0004), allowing 64.9% of men to become candidates for NP. For baseline TMSC of >9 million, TMSC increased from 36.26 ± 52.08 to 81.80 ± 310.83 (P=.05). CONCLUSION(S): Varicocele repair has an important role in the treatment of infertility. Even for low TMSCs, a varicocelectomy may reduce the need for IVF. Varicocele repair (by embolization or microsurgery) potentially reduces the need for IVF and IUI.

Influence of increasing body mass index on semen and reproductive hormonal parameters in a multi-institutional cohort of subfertile men.

OBJECTIVE: To determine whether obesity affects serum and seminal measures of male reproductive potential among a multi-institutional cohort. DESIGN: Retrospective multi-institutional cohort study. SETTING: Infertility clinics. PATIENT(S): All men referred for male infertility evaluation from 2002 to 2014 (n = 4,440). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Collected reproductive parameters included hormonal (gonadotropins, T, E2, PRL) and semen analysis (ejaculate volume, sperm concentration, motility, normal morphology) data. Body mass index (BMI) was calculated for all patients with comparisons to reproductive parameters using univariate and multiparametric models. RESULT(S): Based on World Health Organization definitions, 30.9% of the cohort was normal weight (BMI 18.5-24.9), 45.1% overweight (25-29.9), and 23.3% obese (>30). Neither FSH nor LH demonstrated significant correlations with BMI on multivariate analysis. Total T (r = -0.27) and the T:E2 ratio (r = -0.29) inversely varied with BMI, whereas E2 (r = 0.13) had a direct correlation. On univariate analyses, BMI had weak but significant negative correlations with ejaculate volume (r = -0.04), sperm concentration (r = -0.08), motility (r = -0.07), and morphology (r = -0.04). All parameters remained significant on multivariate modeling with the exception of sperm motility. Rates of azoospermia and oligospermia were also more prevalent among obese (12.7% and 31.7%, respectively) compared with normal weight men (9.8% and 24.5%). CONCLUSION(S): In one of the largest cohorts of male fertility and obesity, serum hormone and semen parameters demonstrated mild but significant relationships with BMI, possibly contributing to subfertility in this population.

Cocaine Use in the Infertile Male Population: A Marker for Conditions Resulting in Subfertility.

INTRODUCTION: We sought to evaluate the incidence and effect of cocaine use in the infertile male population. MATERIALS AND METHODS: Men presenting for fertility evaluation reporting cocaine usage were identified via prospectively collected database. Data were analyzed for usage patterns, reproductive history, associated drug use and medical conditions, hormonal and semen parameters. RESULTS: Thirty-eight out of 4,400 (0.9%) men reported cocaine use. Most used cocaine every 3 months or less. Compared with non-cocaine using men, cocaine users reported more recreational drug use (89 vs. 9.2%), marijuana use (78.9 vs. 11.4%), chlamydia (10.5 vs. 3%), herpes (7.9 vs. 2.5%), and tobacco use (55.3 vs. 19.5%). After excluding men with causes for azoospermia, the mean semen parameters for cocaine users were: volume 2.47 ± 1.02 ml; concentration 53.55 ± 84.04 × 10(6)/ml; motility 15.72 ± 12.26%; total motile sperm count 76.67 ± 180.30 × 10(6). CONCLUSIONS: Few (< 1%) men in our infertile population reported the use of cocaine, and the frequency of use was low. Given the low use rates and limitations of reporting bias, it is difficult to determine the direct effect of cocaine use on male fertility. However, while infrequent cocaine use seems to have limited impact on semen parameters, men reporting cocaine use represent a different cohort of men than the overall infertile population, with higher rates of concurrent substance abuse, tobacco use and infections, all of which may negatively impact their fertility. Reported cocaine users should be screened for concurrent drug use and infections.

Accuracy of testosterone concentrations in compounded testosterone products.

OBJECTIVE: This study aims to evaluate the accuracy of the testosterone concentrations within testosterone gels and creams manufactured by compounding pharmacies. METHODS: Ten compounding pharmacies within Toronto area were included. Pharmacies were blinded as to the nature of the study. A standardized prescription for 50 mg of compounded testosterone gel/cream applied once daily was presented to each pharmacy. Two independently compounded batches were analyzed from each pharmacy 1 month apart. Testosterone concentrations in a 5-g sachet of Androgel® 1% (Abbott) and 5-g tube of Testim®1% (Auxilium) were evaluated as controls. Samples were analyzed independently and in a blinded fashion by the Laboratory Medicine Program at the University Health Network. Measurement of testosterone concentration was performed using a modified liquid chromatography tandem mass spectrometry validated for serum testosterone. RESULTS: Compounded formulations included seven gels and three creams with a volume/daily dose ranging from 0.2 mL to 1.25 mL. Product cost ranged from $57.32 to $160.71 for a 30-day supply. There was significant variability both within and between pharmacies with respect to the measured concentration of testosterone in the compounded products. In contrast, the concentration of testosterone within Androgel and Testim was consistent and accurate. Collectively, only 50% (batch 1) and 30% (batch 2) of the compounding pharmacies provided a product with a testosterone concentration within ± 20% of the prescribed dose. Two pharmacies compounded products with >20% of the prescribed dose. One pharmacy compounded a product with essentially no testosterone. CONCLUSIONS: Testosterone concentrations in compounded testosterone products can be variable and potentially compromise the efficacy and safety of treatment.