Urine microbes and predictive metagenomic profiles associate with abnormalities in sperm parameters: implications for male subfertility.

OBJECTIVE: To explore the taxonomic and predicted functional relationship between the urine microbiome and alterations of semen analysis (SA) parameters. DESIGN: Cross-sectional study. SETTING: Academic medical center. PATIENT(S): Men presenting for fertility evaluation or men presenting for vasectomy consultation with proven biological paternity were recruited and stratified on the basis of alterations, or lack thereof, in SA parameters. MAIN OUTCOME MEASURE: Changes in the functional and taxonomic urine microbiome profiles of participants with or without alterations in SA parameters. RESULTS: Seventy-three participants were included in our study. Men with abnormal sperm motility (N = 27) showed a nearly 50-fold higher abundance of Dialister micraerophilus compared with those with normal sperm motility (N = 46). This relationship persisted on canonical correlational analysis (r = 0.439). Men with abnormal sperm concentration (N = 20) showed a lower abundance of Enterococcus faecalis and Staphylococcus aureus, compared with those with normal sperm concentration (N = 53). The urine of participants with impaired sperm motility demonstrated dramatic differences in predictive functional profiles in pathways involved in oxidation-reduction balance and cell longevity. CONCLUSIONS: Our findings underscore differences in the urinary microbiome and abnormalities in semen parameters, especially sperm motility. By incorporating predictive functional profiling, we also highlight possible mechanisms that may drive the observed differences in sperm parameters.

Semen microbiota are dramatically altered in men with abnormal sperm parameters.

There has recently been an explosion of studies implicating the human microbiome in playing a critical role in many disease and wellness states. The etiology of abnormal semen analysis (SA) parameters is not identified in 30% of cases; investigations involving the semen microbiome may bridge this gap. Here, we explore the relationship between the semen microbiome and alterations of sperm parameters. We recruited men presenting for fertility evaluation or vasectomy consultation with proven biological paternity. SA and next generation sequencing was performed. Differential abundance testing using Analysis of composition of Microbiota with Bias Correction (ANCOM-BC) was performed along with canonical correlational analysis for microbial community profiling. Men with abnormal (N = 27) sperm motility showed a higher abundance of Lactobacillus iners compared to those with normal (N = 46) sperm motility (mean proportion 9.4% versus 2.6%, p = 0.046). This relationship persisted on canonical correlational analysis (r = 0.392, p = 0.011). Men with abnormal sperm concentration (N = 20) showed a higher abundance of Pseudomonas stutzeri (2.1% versus 1.0%, p = 0.024) and Pseudomonas fluorescens (0.9% versus 0.7%, p = 0.010), but a lower abundance of Pseudomonas putida (0.5% versus 0.8%, p = 0.020), compared to those with normal sperm concentration (N = 53). Major limitations are related to study design (cross-sectional, observational). Our results suggest that a small group of microorganisms may play a critical role in observed perturbations of SA parameters. Some of these microbes, most notably Lactobacillus iners, have been described extensively within other, fertility-related, contexts, whereas for others, this is the first report where they have potentially been implicated. Advances in our understanding of the semen microbiome may contribute to potentially new therapeutic avenues for correcting impairments in sperm parameters and improving male fertility.

Multiple courses of intralesional collagenase injections for Peyronie disease: a retrospective analysis.

BACKGROUND: In the original clinical trials evaluating intralesional collagenase Clostridium histolyticum for Peyronie disease (PD), treatment protocols were limited to 8 injections. AIM: We sought to describe our single-center experience with the use of multiple rounds (>8 injections) of intralesional collagenase in patients with PD. METHODS: We conducted a retrospective analysis of all patients with PD receiving intralesional collagenase injections at our institution from October 2015 through December 2020. Some patients who completed 1 round of treatment elected to undergo additional rounds (16 or 24 injections) based on persistent curvature and presence of penile plaque. Clinical improvement was defined as a 20% reduction in penile curvature from the start of a given round of treatment to the end of that round of treatment. We measured erect penile curvature before and after each round and collected demographics, medical and surgical history, curvature outcomes, and treatment-related adverse events. OUTCOME: The primary outcome was the reduction in penile curvature after multiple rounds of treatment with intralesional collagenase injections in patients with PD. RESULTS: A total of 330 patients underwent intralesional collagenase injections for PD, of whom 229 completed at least 8 injections and underwent pre- and posttreatment erect penile goniometry. An overall 42.8% (98/229), 38.6% (22/57), and 12.5% (1/8) of patients achieved clinical improvement after 1 round of therapy (8 injections), 2 rounds (16 injections), and 3 rounds (24 injections), respectively. Mean degree and mean percentage improvement of penile curvature for the start and end of each round of treatment were 8.3° and 16.4% (after 1 round), 7.2° and 16.8% (after 2 rounds), and 3.3° and 8.1% (after 3 rounds). Bruising was the most common complication, with an incidence of at least 50% in each round. CLINICAL IMPLICATIONS: Knowledge of patient responses to multiple rounds of intralesional collagenase injections may help guide physicians in management and counseling of patients regarding PD treatment options. STRENGTHS AND LIMITATIONS: This is the first study to evaluate multiple rounds (>8 injections) of intralesional collagenase for PD. Limitations include retrospective analysis and smaller sample size among patients undergoing 3 rounds (24 injections). CONCLUSION: For patients who did not achieve clinical improvement after 1 round of treatment, an additional round may be beneficial. However, no real improvement was observed for patients undergoing a third round.

Cannabis and male sexual health: contemporary qualitative review and insight into perspectives of young men on the internet.

INTRODUCTION: Cannabis use is increasing across the United States, yet its short- and long-term effects on sexual function remain controversial. Currently, there is a paucity of studies exploring the relationship between cannabis and men's health. OBJECTIVES: To summarize the available literature on cannabis and men's health and provide insight into lay perceptions of this topic. METHODS: We performed a qualitative PubMed review of the existing literature on cannabis and men's health according to the PRISMA guidelines. Separately, we analyzed relevant themes in online men's health forums. We utilized a Google cloud-based platform (BigQuery) to extract relevant posts from 5 men's health Reddit forums from August 2018 to August 2019. We conducted a qualitative thematic analysis of the posts and quantitatively analyzed them using natural language processing and a meaning extraction method with principal component analysis. RESULTS: Our literature review revealed a mix of animal and human studies demonstrating the negative effects of cannabis on semen parameters and varying effects on erectile function and hormone levels. In our analysis of 372 686 Reddit posts, 1190 (0.3%) included relevant discussion on cannabis and men's health. An overall 272 posts were manually analyzed, showing that online discussions revolve around seeking answers and sharing the effects of cannabis on various aspects of sexual health and quality of life, often with conflicting experiences. Quantitative analysis revealed 1 thematic cluster related to cannabis, insecurity, and mental/physical health. CONCLUSIONS: There is a limited number of quality human studies investigating the effects of cannabis on men's health. Men online are uncertain about how cannabis affects their sexual health and seek more information. As the prevalence of cannabis use increases, so does the need for research in this area.

Temporal Changes of Clomiphene on Testosterone Levels and Semen Parameters in Subfertile Men.

PURPOSE: Clomiphene citrate (CC) is prescribed off-label in men to improve testosterone and sperm parameters, but the duration of treatment needed to reach maximal benefit remains unclear. Our objective was to examine temporal effects of CC on total testosterone (TT) and semen analysis (SA) using longitudinal follow-up data in treated men. MATERIALS AND METHODS: We analyzed an IRB-approved database of men treated with CC (25 mg q.d. or 50 mg q.o.d.) from January 2016 through May 2021. We identified patients with 3, 6, 9, and 12 month follow-up data for TT and 3, 6, and 9 month follow-up SA. Mean absolute changes in TT and sperm concentration compared to baseline were calculated, along with 95% confidence intervals. Men with prior genitourinary procedures or hormone therapy were excluded. Paired t-tests were used to compare TT and sperm concentration at each time point to baseline (alpha=0.05). RESULTS: One hundered thirty-four men received CC, mean age 37.7 years (SD 6.7, range 24-52). TT at all follow-ups (3, 6, 9, and 12 months) were available for 25 men, and SA at 3, 6, and 9 months for 26 men. Baseline TT was 358±145 ng/dL and sperm concentration was 13±17.2 M/mL. Significant improvement in TT was identified at 3 months (62.7 ng/dL, 95% CI: 0.49-125.0, p=0.048), additional benefit at 6 months (181.8 ng/dL, 95% CI: 114.1-249.5, p<0.01), and plateau at 9 and 12 months. Improvement in sperm concentration was first observed at 9 months (20.7 M/mL, 95% CI: 10.2-31.2, p<0.01). Semen volume and sperm motility did not change. CONCLUSIONS: Duration of treatment with clomiphene may impact testosterone and sperm concentration, and the historical 3 month milestone may be insufficient for clinical and research evaluation. Men taking CC may experience plateau in TT at 6 months and first benefit in sperm concentration at 9 months.

Intralesional collagenase Clostridium histolyticum for acute phase Peyronie's disease: a single-center, retrospective cohort study.

Background: Peyronie's disease (PD) can be subdivided into acute and chronic phases. Intralesional collagenase Clostridium histolyticum has been shown to improve curvature in the chronic phase. Initial clinical trials excluded patients in the acute phase from treatment. Recent studies show comparable results among men in the acute phase. The definition of acute phase varies among existing studies, but it is generally understood to last 12-18 months and is accompanied by penile pain and progression of deformity. We sought to evaluate the safety and efficacy of intralesional collagenase injection therapy during the acute phase of PD using multiple definitions of the acute phase. Methods: All men receiving intralesional collagenase for PD from October 2015 through December 2020 at a single academic institution were retrospectively assessed for patient demographics and comorbidities, pre- and post-treatment curvature, and adverse events. Two definitions of acute phase were used: (I) acute phase duration ≤6 months, chronic phase duration >6 months; and (II) acute phase duration ≤12 months with penile pain, chronic phase duration >12 or no penile pain. Results: Of 330 patients identified, 229 underwent intralesional collagenase treatment with pre- and post-treatment erect penile goniometry. 65 (28%) met criteria for definition 1 of acute phase, 37 (16%) met criteria for definition 2, and 76 (33%) met criteria for either. Percent change in penile curvature was not significantly different between acute and chronic phases using definition 1 (16.0% vs. 16.6%, P=0.89), definition 2 (19.9% vs. 15.7%, P=0.43), or either (16.5% vs. 16.3%, P=0.96). The rates of development of bruising, swelling, hematoma, or corporal rupture were not significantly different between the acute and chronic phases under either definition (all P>0.05). Conclusions: This single-center, retrospective cohort analysis suggests that intralesional collagenase is both safe and effective for the treatment of men with acute phase PD. Limitations exist inherent to retrospective review, since many men did not return for post-treatment goniometry, possibly skewing our cohort toward incomplete responders. Prospective, randomized studies will be required to confirm these findings.

Engagement With HIV and COVID-19 Prevention: Nationwide Cross-sectional Analysis of Users on a Geosocial Networking App.

BACKGROUND: Geosocial networking (GSN) apps play a pivotal role in catalyzing sexual partnering, especially among men who have sex with men. OBJECTIVE: To quantify the prevalence and disparities in disclosure of pre-exposure prophylaxis (PrEP) use and COVID-19 vaccination among GSN app users, mostly men who have sex with men, in the United States. METHODS: Web-based Grindr profiles from the top 50 metropolitan areas as well as the 50 most rural counties in the United States by population were randomly sampled. Grindr provides an option to disclose current PrEP use (HIV positive, HIV negative, or HIV negative with PrEP use). The free text in all profiles was analyzed, and any mention of COVID-19 vaccination was recorded. Multivariable logistic regression to assess independent associations with PrEP disclosure and COVID-19 vaccination was performed. Imputation analyses were used to test the robustness of the results. RESULTS: We evaluated 1889 urban and 384 rural profiles. Mean age among urban profiles was 32.9 (SD 9.6) years; mean age among rural profiles was 33.5 (SD 12.1) years (P=.41). Among the urban profiles, 16% reported being vaccinated against COVID-19 and 23% reported PrEP use compared to 10% and 8% in rural profiles, respectively (P=.002 and P<.001, respectively). Reporting COVID-19 vaccination (adjusted odds ratio [aOR] 1.7, 95% CI 1.2-2.4), living in an urban center (aOR 3.2, 95% CI 1.8-5.7), and showing a face picture as part of the Grindr profile (aOR 4.0, 95% CI 2.3-7.0) were positively associated with PrEP disclosure. Self-identified Black and Latino users were less likely to report PrEP use (aOR 0.6, 95% CI 0.4-0.9 and aOR 0.5, 95% CI 0.4-0.9, respectively). Reporting PrEP use (aOR 1.7, 95% CI 1.2-2.4), living in an urban center (aOR 2.5, 95% CI 1.4-4.5), having a "discreet" status (aOR 1.6, 95% CI 1.0-2.5), and showing a face picture (aOR 2.7, 95% CI 1.5-4.8) were positively associated with reporting COVID-19 vaccination on their profile. Users in the southern United States were less likely to report COVID-19 vaccination status than those in the northeast United States (aOR 0.6, 95% CI 0.3-0.9). CONCLUSIONS: Variations in PrEP disclosure are associated with race, whereas COVID-19 vaccination disclosure is associated with geographic area. However, rural GSN users were less likely to report both PrEP use and COVID-19 vaccination. The data demonstrate a need to expand health preventative services in the rural United States for sexual minorities. GSN platforms may be ideal for deployment of preventative interventions to improve access for this difficult-to-reach population.

Acute Lower Back Pain after Intralesional Injection of Collagenase Clostridium histolyticum for Peyronie's Disease.

PURPOSE: The safety label for collagenase Clostridium histolyticum was updated to include postinjection acute lower back pain as an adverse event observed with intralesional therapy for Peyronie's disease. Incidence and causality are unknown. We assessed frequencies and temporal associations for this adverse event in a large cohort. MATERIALS AND METHODS: Data on all men undergoing collagenase injections for Peyronie's disease at our institution from October 2015 through December 2020 were retrospectively assessed. The study included 330 patients, 300 completing at least 1 full course (8 injections). Measured outcomes included incidence and timing of back pain, and associations with demographics and comorbidities. RESULTS: Of 330 patients, 19 (5.8%) experienced at least 1 episode of postinjection acute lower back pain. Of 300 who completed at least 1 full course of 8 injections, 4 (1.3%) reported back pain within the 8-injection course. A subset underwent additional rounds (16 or 24 injections). Back pain increased to 8.7% (13/149) during a second round, 6.9% (3/43) during a third. No association was found with age, diabetes or back pain history. Most cases occurred shortly after injection; all were self-limited or resolved with a single dose of ketorolac. CONCLUSIONS: This single-center, retrospective analysis suggests that intralesional collagenase injections for Peyronie's disease may cause acute lower back pain in up to 6% of patients. Patients may benefit from counseling regarding this risk. Incidence rises with additional rounds of treatment. Prospective safety data regarding >8 injections do not exist. No patient had long-term sequelae of back pain.

Initial gonadotropin levels and sperm parameters differentiate the response to clomiphene citrate in subfertile men.

Background: Efficacy of clomiphene citrate (CC) in the treatment of male subfertility remains unclear, with inconsistent results in the literature and limited guidance from professional organizations. We sought to stratify the response to clomiphene in men based on their initial gonadotropins and semen parameters. Methods: We conducted a retrospective analysis of 234 patients from an academic center who took CC for subfertility. Patients with pre-treatment and 3 months follow-up total testosterone (TT) and semen analyses were included. Patients with previous hormone therapy, genitourinary surgery, prior success in conceiving pregnancy, or only one semen analysis were excluded. Primary outcomes were magnitudes of improvement in TT and semen parameters at 3 months. Student's t-test (alpha =0.05) was used for univariate analyses; multivariable linear regression was used for multivariate analysis. Results: One hundred and thirty-seven patients met inclusion criteria. Thirty-four percent of patients experienced improvement in sperm concentration after 3 months of CC treatment, 13% decreased, and 53% showed no change. Using a pre-treatment TT cutoff of 300 ng/dL and gonadotropin thresholds of 7 miU/mL, initial TT did not affect magnitude of improvement in semen parameters, while lower initial gonadotropins showed statistical improvement across all outcomes. Multivariate analysis showed pre-treatment follicle stimulating hormone (FSH) was inversely correlated with improvement in TT [odds ratio (OR): 2.64e-05, 95% confidence interval (CI): 1.32e-09 to 5.28e-01, P=0.04] and sperm concentration (OR: 0.22, 95% CI: 5.70e-02 to 8.48e-01, P=0.03). We also provide initial gonadotropin cutoffs that suggest statistical benefit from CC use. Conclusions: Men with lower gonadotropin levels may expect greater degree of improvement in both hormone and semen parameters with use of CC. Men with azoospermia do not benefit based on semen analyses alone. Degree of non-azoospermia does not affect magnitude of improvement. CC had decreasing efficacy at higher initial gonadotropin levels. These data may provide guidance in stratifying and counseling men for CC treatment.

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.

Increased Risk of Hypogonadal Symptoms in Shift Workers With Shift Work Sleep Disorder.

OBJECTIVE: To examine the association between shift work sleep disorder (SWSD), a primary circadian rhythm disorder characterized by excessive day-time sleepiness associated with shift work, and hypogonadal symptoms in shift workers. METHODS: Men presenting to an andrology clinic between July 2014 and June 2017 completed questionnaires assessing shift work schedule, SWSD risk, and hypogonadal symptoms ([quantitative] Androgen Deficiency in the Aging Male [qADAM, ADAM]). The impact of nonstandard shift work and SWSD on responses to qADAM and ADAM was assessed using ANOVA and linear regression. RESULTS: About 24.1% (619/2571) of men worked nonstandard shifts. Of those, 196 (31.7%) were considered to have SWSD. Controlling for age, comorbidities, and testosterone (T) levels, nonstandard shift workers had qADAM scores 1.12 points lower than day-time workers (P <.01). Subgroup analysis of nonstandard shift workers showed that those with SWSD had qADAM scores 5.47 points lower than men without SWSD (P <.01). In this same subgroup analysis, SWSD was independently associated with lower T levels (mean decrease 100.4 ng/dL, P <.01) when controlling for age, comorbidities, and prior T supplementation. CONCLUSION: Nonstandard shift workers with SWSD have even worse hypogonadal symptoms and lower T levels than day-time workers and nonstandard shift workers without SWSD. This suggests that poor sleep habits, as identified by SWSD, may contribute to the more severe hypogonadal symptoms seen in nonstandard shift workers.

Shift Workers With Shift Work Disorder Have Worse Lower Urinary Tract Symptoms.

OBJECTIVE: To examine the association between shift work or shift work disorder (SWD) and lower urinary tract symptoms (LUTS). Nonstandard shift workers are defined as those working shifts outside of a normal 7 AM-6 PM work day. METHODS: Men presenting to a single andrology clinic between July 2014 and June 2017 completed questionnaires that included questions about work schedules, shift work status, SWD[1][1], personal well-being via the Patient Health Questionnaire-9, and LUTS (International Prostate Symptom Score [IPSS]). Men who had previously undergone prostate surgery were excluded. Shift work and SWD on IPSS was assessed via multivariate linear regression. RESULTS: Of the 2571 men who completed all questionnaires, 619 (24.1%) reported working nonstandard shifts in the past month. Of these, 196 (31.7%) had high risk of SWD as determined by a questionnaire. When controlling for age, medications, surgical intervention for benign prostatic hyperplasia, comorbidities, and testosterone (T) levels, nonstandard shift work overall was not associated with worse LUTS (P = .82). However, nonstandard shift workers at high risk for SWD had IPSS scores that were clinically significantly higher (3.74 points ± 0.57 standard error) than nonstandard shift workers without SWD (P <.0001). CONCLUSION: Nonstandard shift workers at high risk for SWD have worse LUTS than those without SWD. However, no association between nonstandard shift work and LUTS was found.

Hypogonadism: Therapeutic Risks, Benefits, and Outcomes.

Hypogonadism is a common condition defined by the presence of low serum testosterone levels and hypogonadal symptoms, and most commonly treated using testosterone therapy (TTh). The accuracy of diagnosis and appropriateness of treatment, along with proper follow-up, are increasingly important given the large increase in testosterone prescriptions and the recent concern for cardiovascular (CV) risk associated with TTh. In March of 2015, the US Food and Drug Administration required that testosterone product labels disclose a potential CV risk, despite the evidence base for this association being weak and inconclusive. However, TTh may improve CV outcomes rather than increase risks.

The Safety and Efficacy of Growth Hormone Secretagogues.

INTRODUCTION: Growth hormone (GH) increases lean body mass, decreases fat mass, increases exercise tolerance and maximum oxygen uptake, enhances muscle strength, and improves linear growth. Long-term studies of GH administration offer conflicting results on its safety, which has led to strict Food and Drug Administration criteria for GH use. The potential drawbacks of exogenous GH use are believed to be due in part to impaired regulatory feedback. AIM: To review the literature on GH secretagogues (GHSs), which include GH-releasing peptides and the orally available small-molecule drug ibutamoren mesylate. METHODS: Review of clinical studies on the safety and efficacy of GHSs in human subjects. MAIN OUTCOME MEASURE: Report on the physiologic changes from GHS use in human subjects including its safety profile. RESULTS: GHSs promote pulsatile release of GH that is subject to negative feedback and can prevent supra-therapeutic levels of GH and their sequelae. To date, few long-term, rigorously controlled studies have examined the efficacy and safety of GHSs, although GHSs might improve growth velocity in children, stimulate appetite, improve lean mass in wasting states and in obese individuals, decrease bone turnover, increase fat-free mass, and improve sleep. Available studies indicate that GHSs are well tolerated, with some concern for increases in blood glucose because of decreases in insulin sensitivity. CONCLUSION: Further work is needed to better understand the long-term impact of GHSs on human anatomy and physiology and more specifically in the context of a diversity of clinical scenarios. Furthermore, the safety of these compounds with long-term use, including evaluation of cancer incidence and mortality, is needed. Sigalos JT, Pastuszak AW. The Safety and Efficacy of Growth Hormone Secretagogues. Sex Med Rev 2018;6:45-53.

Growth Hormone Secretagogue Treatment in Hypogonadal Men Raises Serum Insulin-Like Growth Factor-1 Levels.

Realizing the reported misuse of human growth hormone (GH), investigation of a safe alternative mechanism for increasing endogenous GH is needed. Several GH secretagogues are available, including GH-releasing peptides (GHRPs) GHRP-2 and GHRP-6, and the GH-releasing hormone analog, sermorelin (SERM). Insulin-like growth factor 1 (IGF-1) serves as a surrogate marker for GH. Here, the effect of GHRP/SERM therapy on IGF-1 levels is evaluated. A retrospective review of medical records was performed for 105 men on testosterone (T) therapy seeking increases in lean body mass and fat loss who were prescribed 100 mcg of GHRP-6, GHRP-2, and SERM three times daily. Compliance with therapy was assessed, and 14 men met strict inclusion criteria. Serum hormone levels of IGF-1, T, free T (FT), estradiol (E), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were evaluated. Mean (SD) age of the cohort was 33.2 (2.9) years, and baseline IGF-1 level was 159.5 (26.7) ng/mL. Mean (SD) duration of continuous GHRP/SERM treatment was 134 (88) days. Mean posttreatment IGF-1 level was 239.0 (54.6) ng/mL ( p < .0001). Three of the 14 men were on an aromatase inhibitor and/or tamoxifen prior to treatment and another 4 men were coadministered an aromatase inhibitor and/or tamoxifen during treatment. Inhibition of E production or estrogen receptor blockade resulted in smaller increases in IGF-1 levels. GHRP/SERM therapy increases serum IGF-1 levels with strict compliance to thrice-daily dosing. The results suggest that combination therapy may be beneficial in men with wasting conditions that can improve with increased GH secretion.

Chronic orchialgia: epidemiology, diagnosis and evaluation.

Chronic orchialgia is a vexing condition defined as chronic or intermittent scrotal pain lasting at least three months that significantly interferes with daily activities. There are currently no guidelines regarding the diagnosis and management of this condition despite it being the cause of 2.5-4.8% of urologic clinic visits. Men often present with chronic orchialgia in their mid to late 30s, although the condition can present at any age. A broad differential diagnosis of chronic orchialgia includes epididymitis, testicular torsion, tumors, obstruction, varicocele, epididymal cysts, hydrocele, iatrogenic injury following vasectomy or hernia repair, and referred pain from a variety of sources including mid-ureteral stone, indirect inguinal hernia, aortic or common iliac artery aneurysms, lower back disorders, interstitial cystitis, and nerve entrapment due to perineural fibrosis; approximately 25-50% of chronic orchialgia is idiopathic in nature. In such cases, it is reasonable to consider psychological and psychosocial factors that may be contributing to chronic pain. Invasive testing is not recommended in the work-up of chronic orchialgia.