The Evolving Landscape of Male Varicocele Pathophysiology in the Era of Multi-Omics: A Narrative Review of the Current Literature.

Male-factor infertility is implicated in over half of the millions of cases of infertility worldwide, and varicoceles are the most common correctable cause of male-factor infertility. The pathophysiologic mechanism for varicoceles is complex and next-generation technologies offer promising insights into the molecular underpinnings of this condition. In this narrative review, we highlight historical and contemporary paradigms associated with varicoceles, with an emphasis on the biological underpinnings of this disease. Specifically, we review the literature describing the underlying causes of varicoceles, discuss the molecular and cellular mechanisms causing pathological changes in some (but not all) men, and highlight key articles regarding the next-generation analyses (e.g., transcriptome, epigenome, proteome, and microbiome) being applied to better understand the condition and its treatment. These data demonstrate an ongoing evolution of the knowledge of varicoceles and the potential for improved personalized care in the future for men with this condition.

The natural history of benign prostatic hyperplasia-related voiding symptoms following penile prosthesis implantation.

Background: There is a rising prevalence of benign prostatic hyperplasia (BPH)-related urinary symptoms along with erectile dysfunction in the aging male population. Therefore, assessment of lower urinary tract symptoms (LUTS) is advised before penile prosthesis surgery with some men requiring preoperative transurethral surgical management to reduce the risk of post-procedure complications. However, less is known about the natural history of men with uncomplicated LUTS who do not require surgical management for BPH before penile prosthesis. Objective: We sought to assess the natural history of BPH-related uncomplicated LUTS in men following penile prosthesis surgery. Design: Single institution retrospective review. Methods: Following institutional review board approval, we performed a retrospective review of all adult males with a preoperative diagnosis of LUTS undergoing penile prosthesis surgery at our institution from January 2017 to November 2022. The primary outcome was progression to transurethral surgery. Results: From 2017 to 2022, 211 patients with preexisting LUTS underwent penile prosthesis surgery and met all criteria for inclusion including no history of transurethral surgery. The median (interquartile range, IQR) AUA symptom score (AUA-SS) was 12 (12). Post-void residual was below 200 cc in 96.2% of patients preoperatively and 99.1% of patients after surgery. At a median (IQR) follow-up duration of 9 (23) months after surgery, 5.7% (12/211) of patients had progressed to bladder outlet surgery and 35.5% of patients endorsed LUTS bother with a median (IQR) AUA-SS of 14.5 (11.8). Conclusion: The majority of patients with uncomplicated LUTS did not require bladder outlet surgery following penile prosthesis implantation and could be managed with conservative or pharmacologic measures alone. Prostate gland size was significantly larger in patients who progressed to bladder outlet surgery. While the results are overall reassuring, further study is needed to identify specific factors associated with pursuing bladder outlet surgery in this small subset of patients.

Early PSA decline after starting second-generation hormone therapy in the post-docetaxel setting predicts cancer-specific survival in metastatic castrate-resistant prostate cancer.

BACKGROUND: The objective of this study was to evaluate the prognostic value of early PSA decline following initiation of second-generation hormone therapy (2nd HT), namely abiraterone acetate or enzalutamide, in patients with taxane-refractory metastatic castrate-resistant prostate cancer (mCRPC) and evaluate utility of this metric in informing intensified surveillance/imaging protocols. METHODS: We retrospectively identified 75 mCRPC patients treated with 2nd HT following docetaxel failure (defined as PSA rise and radiographic progression). Patients were categorized patients into two cohorts based on the first PSA within 3 months after initiation of therapy: PSA reduction ≥50% (Group A) and PSA reduction <50% (Group B). The primary endpoint was cancer-specific mortality (CSM). The secondary endpoint was radiographic disease progression (rDP) on 2nd HT. In univariate and multivariate analyses, we investigated factors associated with rPD and CSM. RESULTS: We included 75 patients (52 in Group A, 23 in Group B) in the analytic cohort. Baseline clinico-demographic characteristics, including median age, primary Gleason score risk group, median pre-treatment PSA, disease burden, site of metastases, and pre-treatment ECOG score were not statistically different between the two groups. Median follow up time was 30 months and the median time to radiographic disease progression was 28.1 and 12.5 months (p = 0.002) in cohorts A and B, respectively. On univariate and multivariate analyses, both PSA reduction ≥50% and volume of metastatic disease were significantly associated with a decreased risk of radiographic disease progression (HR 0.41, 95% CI 0.21-0.80, p = 0.0113) as well as a decreased risk of cancer-specific mortality (HR 0.29, 95% CI 0.09-0.87, p = 0.0325). CONCLUSION: PSA reduction ≥50% within 3 months of starting 2nd HT was associated with significantly improved radiographic disease progression-free survival and 3-year cancer-specific mortality. This suggests using PSA 50%-decline metric in surveillance patients with on 2nd HT and identifies patients who require further evaluation with imaging.

Deafening Silence of Male Infertility.

Think about 6 loved ones of reproductive age in your life. Now imagine that 1 of these 6 individuals is suffering from infertility. Perhaps they feel alone and isolated, unable to discuss their heartbreak with their closest friends, family, and support network. Suffering in silence. In this editorial, we discuss the infertility journey through the lens of the patients, the providers, and the scientists who struggle with infertility each and every day. Our goal is to open a dialogue surrounding infertility, with an emphasis on dismantling the longstanding societal barriers to acknowledging male infertility as a disease. Through education, communication, compassion, and advocacy, together we can all begin to break the deafening silence of male infertility.

Expanded Utilization of Intralesional Therapies for Treatment of Peyronie's Disease.

Purpose: In this narrative review we explore additional indications for which intralesional collagenase Clostridium histolyticum (CCH) injection therapy may be used, in addition to those utilized in the IMPRESS trials. The goal is to provide updated assessment of available intralesional therapies and justify whether to expand clinical indications based on advancements over the last decade. Results: Patients receiving CCH in the acute phase of PD have shown significant improvement in penile curvature - which may be even more significant than reported due to progressive curvature over the longitudinal course of injection therapy. Across studies, patients with ventral plaques achieved the greatest curvature improvement (~30°) compared to PD patients with dorsal or lateral plaques. Patients with curvature > 90° have been minimally documented. However, the concept of patients with higher degree of curvature achieving more significant degrees of improvement prevails across studies. Studies including PD patients with volume loss deformities or indentation(s) focus on curvature improvement and do not gauge improvement in these girth loss or indentation features specifically. PD patients with calcification may benefit from CCH, however, critical analysis of included study designs and results compared to placebo do not lend for strong support of CCH in PD at this time. Conclusion: Based on the most recent research, the use of CCH in the acute phase of PD and patients with ventral penile plaques may be effective and safe. The limited available research on the efficacy of CCH on calcified plaque(s) and curvature greater than 90° is promising, however, more research is needed to ensure safety and success in this patient cohort. Finally, the current literature continues to show the use of CCH is not effective in PD patients with volume loss, indentation, or hourglass deformity. When expanding the use of CCH to patients not originally included in the IMPRESS trials, providers must prioritize minimizing chances of potential injury to urethral tissue. Finally, further investigation is required to determine whether CCH has utility for curvature greater than 90° or calcified plaques, although the limited available literature is promising.

Discordant Bilateral Testicular Pathology Does not Affect Sperm Retrieval Rate in Bilateral Microdissection Testicular Sperm Extraction (mTESE).

OBJECTIVE: To assess the incidence of discordant testicular pathology in men undergoing bilateral microdissection testicular sperm extraction (mTESE) and association with sperm retrieval rate. METHODS: We performed a retrospective single-institutional review of all patients undergoing mTESE from 2007 to 2021 and aggregated clinical history, physical exam, semen analysis, and operative findings. Specimens with discordant pathology were re-reviewed by an experienced genitourinary.ßpathologist and categorized in a standardized fashion. Data were analyzed using SPSS. RESULTS: One hundred fourteen non-obstructive azoospermia.ßmen undergoing 132 mTESEs were identified within the study period. Eighty-five percent (112/132) of cases had pathology specimens available, and within this specific cohort the success rate was 41.9% (47/112). A total of 206 pathological reports resulted including 52.4% Sertoli cell only, 4.9% Leydig cell hyperplasia, 8.7% fibrosis, 16.5% maturation arrest, and 17.5% hypospermatogenesis. Twelve percent of testicles had more than 1 pathologic diagnosis. Sixty-six men had synchronous bilateral testicular pathology, and 11/66 (16.6%) had at least partially discordant pathology on initial review. Focused re-review by a genitourinary pathologist confirmed exclusively discordant pathology in 7/66 (10.6%) cases, with a sperm retrieval rate of 57% (4/7). The sperm retrieval rate.ßin men with discordant pathology was not significantly different from those with concordant pathology. CONCLUSION: Over 1 in 10 men undergoing mTESE may have discordant pathology between testicles, though this may not affect sperm retrieval rate.ßat the time of procedure. Clinicians should consider submitting bilateral testicular specimens for pathology to (1) clarify their outcomes data, and (2) assist with clinical decision-making and surgical planning if a repeat mTESE is indicated.

A scoping review of ejaculatory dysfunction due to surgical treatments for benign prostatic hyperplasia: limitations of available tools for assessment and reporting.

INTRODUCTION: Clinicians primarily focus on the presence or absence of anterograde ejaculation following surgery for benign prostatic hyperplasia (BPH). Failing to assess dysfunctional ejaculation and associated bother in a granular fashion can underestimate the prevalence and significance of ejaculatory dysfunction in this population. OBJECTIVES: This scoping review provides critical appraisal of existing tools assessing ejaculatory function and associated bother, emphasizing the importance of adequate history-taking, preoperative counseling, and supplemental questions that should be used prior to and after treatment. METHODS: A literature review was conducted using pertinent keywords from 1946 to June 2022. Eligibility criteria included men developing ejaculatory dysfunction following BPH surgery. Measured outcomes included the assessment of patient bother related to ejaculatory function, pre- and postoperative scores from the Male Sexual Health Questionnaire (MSHQ). and Danish Prostate Symptom sexual function domain (DAN-PSSsex). RESULTS: Results of this study included only 10 documented patients' bother due to ejaculatory dysfunction following treatment. Pre- and postoperative MSHQ were used as the diagnostic tool in 43/49 studies, one study documented "preservation of anterograde ejaculation", and one used DAN-PSSsex. Q1-4 of the MSHQ were used in 33/43 studies, 3/43 used Q1, 3, 5-7, 1/43 used solely Q4, 1/43 used Q1-3 + Q6 and Q7, and 5/43 used the entire MSHQ. No studies used post-ejaculation urinalysis to diagnose retrograde ejaculation. Only four studies explicitly documented bother and found 25-35% of patients were bothered with a "lack of ejaculate" or "other ejaculation difficulties" during sexual activity after BPH surgery. CONCLUSIONS: There are currently no studies stratifying patient bother by various components of ejaculation (force, volume, consistency, sensation of seminal expulsion, painful ejaculation, etc.) after BPH surgery. Opportunities for improvement exist in reporting ejaculatory dysfunction related to BPH treatment. A comprehensive sexual health history is needed. Further investigation into effects of BPH surgical treatments on specific characteristics of the patient's experience of ejaculation is required.

Rising vasectomy volume following reversal of federal protections for abortion rights in the United States.

In June 2022 the United States Supreme Court issued a ruling in the case Dobbs v. Jackson that overturned Roe v. Wade, the 1973 ruling establishing a federally protected right to abortion in the United States. Anecdotal reports suggested increased vasectomy volume following this event; however, no published data exist. We sought to describe trends in vasectomy consultation before and after the Dobbs v. Jackson ruling (referred to as pre- and post-Dobbs herein). Following IRB approval, we reviewed charts of all adults seeking vasectomy consultation in July-August 2021 and July-August 2022 at a large healthcare organization. We then aggregated vasectomy procedural billing data from 2018 to present. The primary outcome was volume of vasectomy consultation appointments and the secondary outcome was number of vasectomies performed. In July-August 2021 (Pre-Dobbs), 116 men attended vasectomy consultation versus 142 men in July-August 2022 (Post-Dobbs). Median age Post-Dobbs was significantly younger than Pre-Dobbs (35 vs 38 years, respectively, p = 0.01) with a significant increase in Post-Dobbs men under 30 seeking vasectomy (p = 0.005). A total of 16.9% (24/142) of Post-Dobbs men were childless, compared to 8.6% (10/116) of Pre-Dobbs men (p = 0.05). Of those with children, median number of offspring was unchanged at 2. Billing data showed a significant increase in vasectomy procedural volumes Post-Dobbs. While overturning Roe v Wade directly impacted female reproductive rights, number of vasectomy consultations and procedures increased significantly following this decision. Younger men, especially those under 30, as well as childless men were significantly more likely to seek consultation Post-Dobbs compared to the prior reproductive legal climate. While longer-term data are needed, findings indicate that men are invested in maintaining reproductive autonomy for themselves and their partners.

The clinical significance of imperfection: is idiopathic corporal asymmetry related to curvature during penile prosthesis placement?

Patient satisfaction after inflatable penile prosthesis (IPP) has been linked to preexisting curvature; however the association with intraoperative asymmetric corporal measurements (ACM) has not been well described. We sought to identify incidence of ACM during IPP surgery, and relationship to penile curvature. A retrospective review of all patients undergoing primary IPP placement between 6/2019 and 6/2021 was performed. Logistic regression analysis was performed to identify factors associated with ACM and need for adjunct straightening techniques. A total of 273 patients underwent primary IPP. 27.8% had Peyronie's disease (PD) diagnosed preoperatively or detected intraoperatively. ACM was identified in 20.1% (55/273) patients. There was no significant difference in ACM in PD versus non-PD patients (p = 0.55). Most patients with ACM (78.2%, 43/55) underwent placement of asymmetric device. ACM did not predict need for invasive straightening maneuvers (p = 0.12). However ACM patients were significantly more likely to have mild residual curvature than those with symmetry (p < 0.0001). Our study is first to address management of idiopathic ACM and association with curvature, providing new insight into a common situation. While ACM was detected in 20%, it did not predict need for adjunct straightening techniques. Our findings may provide reassurance to urologists troubleshooting idiopathic ACM during corporal dilation during IPP surgery.

The Diversity of Vasectomy Reversal Providers and Their Web-based Advertising Habits in the United States.

OBJECTIVE: To better understand the internet advertising material published on clinician websites for the 30,000 men who undergo evaluation for vasectomy reversal (VR), which is a technically demanding procedure requiring microsurgical expertise. METHODS: Internet search trends for "vasectomy" and "vasectomy reversal" from 2004 to 2022 were assessed using Google Trends. Search engines were then queried on a state-by-state basis for physicians performing VR and the available information aggregated and analyzed using standard statistical approaches. RESULTS: VR search volume consistently represented roughly one-tenth of the search volume for vasectomy. One hundred and ninety reversal clinics were identified in 44 of 50 states with the highest number identified in the southeast region and an overall median price of $6500. Ninety percent of physicians were male and completed residencies in urology. Other specialties included obstetrics and gynecology, general surgery, family medicine and orthopedic surgery. Forty-two percent of urologists had completed infertility fellowships. Sixty percent of physicians utilized a microscope, and 4.7% of physicians explicitly stated they did not perform vasoepididymostomy even when indicated. Fifty two percent of clinics reported VR success rates as high as 100%, and 34% of clinics reported pregnancy outcomes. Twenty-five percent of clinics reported out-of-pocket VR pricing and 26% discussed possible complications. CONCLUSION: VR is a technically demanding cash-pay procedure being performed by physicians with a wide array of backgrounds and outcomes. Urologists should strive to lead by example and report their training, personal experiences, and expected outcomes to enable optimal medical decision making for each patient.

Current Landscape of Andrology Fellowship Programs and the Effect of Gender on Post-Fellowship Practice Patterns.

OBJECTIVE: To evaluate the current landscape of andrology fellowships, characteristics of past fellows, and post-fellowship career paths of fellowship graduates. MATERIAL AND METHODS: The websites of the American Urological Association (AUA), Society for the Study of Male Reproduction (SSMR), and Sexual Medicine Society of North America (SMSNA) were reviewed for sponsored fellowships. Program coordinators, institutional websites, and Google were queried for information about each program in a stepwise fashion. Descriptive statistics and t-tests were used to compare outcomes by gender. RESULTS: The SMSNA endorsed 73% of programs, and SSMR 48%, while only 45% of all programs participated in the 2021 AUA match. Nearly all programs (93%) were affiliated with an academic institution. Only 20% programs had any female andrology faculty. From 1982-2020, 324 andrology fellows were identified, 16.4% of whom were female. Of the fellows identified, 54.5% of women pursued academia versus 45.5% of men (P = .39). Men and women were equally likely to advertise an exclusive andrology practice, 65.4 and 61.4%, respectively (P = .78). There was an increase in the proportion of female fellows from 8.1%-20.7% when comparing fellows who began training prior to 2010 to those who began training in 2010 or later (P = .0038). CONCLUSION: National societies have taken steps towards standardizing andrology fellowship training, but much of the fellowship information is not readily available, restricting the interpretation of gender-based differences in practice environment. However, we found that there was no negative impact in female andrologists' ability to practice andrology or enter academic careers despite being in a male-dominated subspecialty.