IsoPSA Performance Characteristics are Unaffected by 5-Alpha Reductase Inhibitors or Alpha-Blockers: Results From the IsoPSA Validation Study.

OBJECTIVE: To. determine the impact of 5-α reductase inhibitors or α-blockers on IsoPSA performance for the detection of actionable prostate cancer. MATERIALS AND METHODS: This is a secondary analysis of data from an institutional review board approved, prospective, multicenter(8-sites) study evaluating IsoPSA in men ≥ 50 years of age with a total PSA ≥ 4 ng/mL with planned prostate biopsy who met previously described inclusion and exclusion criteria. Analytic groups included (i)all subjects, (ii-iii)+/- 5-ARI use, (iv-v)+/- α-blocker use. The performance characteristics of IsoPSA in these groups were assessed by ROC curve, sensitivity, and specificity (SP) analysis. RESULTS: A total of 1385 men were recruited with 888 men included in final analysis. Actionable prostate cancer, defined as GG2+, was identified in a total of 316 patients with 40 and 217 patients reporting 5-ARI and α-blocker use respectively. Sensitivity to detect both prostate cancer and actionable cancer was similar between patient subsets (P >.05). SP was similar between patients regardless of 5-ARI(P >.05). Increased SP was noted in patients on α-blockers(GG1+: No-α-blocker: 0.360 vs α-blocker: 0.529, P <.05; GG2+: No-α-blocker: 0.40 vs α-blocker: 0.61, P <.05). ROC analysis demonstrates that IsoPSA performance is unaffected by 5-ARI or α-blocker use for prostate cancer and actionable cancer (GG2+) detection. CONCLUSION: The performance of IsoPSA for detecting any prostate cancer and clinically actionable prostate cancer is unaffected by commonly used medications (5-ARI and α-blockers) for symptoms of benign prostatic hyperplasia.

Color Doppler ultrasound imaging in varicoceles: Is the difference in venous diameter encountered during Valsalva predictive of palpable varicocele grade?

Objective: The clinical grading system for varicoceles is subjective and dependent on clinician experience. Color Doppler ultrasound (US) has not been standardized in the diagnosis of varicoceles. We aimed to determine if US measurement of varicocele could be predictive of World Health Organization (WHO) varicocele grade. Methods: Men who presented for either scrotal pain or infertility to a tertiary men's health clinic underwent physical examination, and varicoceles were graded following WHO criteria (0=subclinical, 1, 2, 3). US was used to measure largest venous diameter in the pampiniform plexus bilaterally at rest and during Valsalva maneuver. Receiver operator characteristic curve analysis was used to determine if resting diameter, diameter during Valsalva, or change in diameter between at rest and during Valsalva provided the highest sensitivity and specificity for determining clinical grade. Threshold values for diameter were determined from these receiver operator characteristic curves. Results: A total of 102 men (50 with clinical varicocele and 52 with subclinical varicocele) were included. Diameter at rest was the best ultrasonographic discriminator between subclinical and clinical varicoceles (area under the curve [AUC]=0.67) with a diameter threshold of 3.0 mm (sensitivity 79%, specificity 42%). Diameter during Valsalva had the greatest AUC for determining clinical Grades 1 versus 2 (AUC=0.57) with diameter threshold of 5.7 mm (sensitivity 71%, specificity 33%). For differentiating between Grades 2 and 3, diameter at rest had the greatest AUC of 0.65 with a threshold of 3.6 mm (sensitivity 71%, specificity 58%). Conclusion: Our results corroborate other studies that have shown a weak correlation between US and clinical grading. The use of diameter during Valsalva was less predictive than diameter at rest and was only clinically significant in differentiating between Grade 1 and 2 varicocele. A standardized method for determining clinically relevant varicoceles on US would allow for improved patient counseling and clinical decision-making.

The Microbiome and Urolithiasis: Current Advancements and Future Challenges.

PURPOSE OF REVIEW: The aim of this review is to explore the effect of the microbiome on urolithiasis and explore recent advances and challenges in microbiome research for urolithiasis. RECENT FINDINGS: Lack of standardization and shortcomings in study design for urinary microbiome research on urolithiasis has hampered the generalizability of results and weakened the impact of findings on clinical practice. Important study limitations include sample heterogenicity, specimen contamination, poor culture yields, and lack of shared datasets for meta-analysis. Contrary to traditional teaching, the genitourinary tract is not a sterile environment. This urinary microbiome may influence the pathogenesis of urolithiasis, although the specific mechanisms are still currently being explored. Successful investigation will depend on consistency in study design and analysis, as well as sharing data and protocols across institutions. Developing an understanding of the relationship between the urinary microbiome and urolithiasis may lead to novel approaches to mitigate stone risk.

IsoPSA® Reduces Provider Recommendations for Biopsy and Magnetic Resonance Imaging in Men with Total Prostate Specific Antigen ≥4 ng/ml: A Real-World Observational Clinical Utility Study.

INTRODUCTION: We assessed the impact of the IsoPSA® test for prostate cancer risk assessment on provider patient management decisions in a real-world clinical setting. METHODS: A total of 38 providers, including advanced practice providers, fellowship trained oncologists and general urologists in the Cleveland Clinic health system including both community-based practices and academic locations, enrolled 900 men being evaluated for prostate cancer; 734 met inclusion criteria (age ≥50 years, total serum prostate specific antigen [PSA] ≥4 and <100 ng/ml and no history of prostate cancer) and IsoPSA indication for use. A standard template was used to document biopsy recommendation prior to and after receiving IsoPSA results. The primary outcome was the number of biopsy and magnetic resonance imaging recommendation changes occurring after IsoPSA testing. RESULTS: IsoPSA testing resulted in a 55% (284 vs 638) net reduction in recommendations for prostate biopsy for men with total PSA ≥4 ng/ml. Additionally, a 9% reduction in recommendations for magnetic resonance imaging was observed. There was strong concordance between IsoPSA results and provider recommendations for prostate biopsy, with 87% of patients with an IsoPSA index above the threshold recommended for biopsy and 92% of patients with an IsoPSA index below the threshold not recommended for biopsy. CONCLUSIONS: In a real-world clinical setting, providers from diverse training backgrounds and practice settings readily adopted IsoPSA with substantial reductions in the rate of recommended prostate biopsies in patients with elevated PSA values (≥4 ng/ml). There was a high concordance between recommendation for or against prostate biopsy and the IsoPSA result.

Is treatment of hypogonadism safe for men after a solid organ transplant? Results from a retrospective controlled cohort study.

Male solid organ transplant patients are at increased risk of hypogonadism and the safety of treating these patients for hypogonadism is unknown. We sought to evaluate the safety of treating hypogonadism in the solid organ transplant recipient. To accomplish this, we performed a retrospective review between 2009 and 2017 of patients treated at a single academic urology clinic. Men who underwent a solid organ transplant with a diagnosis of hypogonadism (Testosterone <350 ng/dl) were included. In total, 87 hypogonadal transplant recipients were included (29 no treatment; 58 treated). Treatment modalities included non-testosterone therapies (human chorionic gonadotropin, clomiphene), topical, injectable, and subcutaneous T preparations. There was no difference between groups for baseline characteristics including age, length of follow-up since transplant, baseline testosterone, and transplant type. There was no difference in prostate cancer diagnoses, erythrocytosis, rejection, infections, number of unplanned admissions per patient. While there was no difference in the proportion of deaths in untreated (21%; n = 6) and treated transplant recipients (7%; n = 4; p = 0.08), the median survival was longer in men treated with T (p = 0.03). Treatment of hypogonadism in solid organ recipients did not increase the risk for adverse effects related to treatment of hypogonadism or solid organ transplant.

PRSS50 is a testis protease responsible for proper sperm tail formation and function.

Multiple morphological abnormalities of the sperm flagella (MMAF) are a major cause of asthenoteratozoospermia. We have identified protease serine 50 (PRSS50) as having a crucial role in sperm development, because Prss50-null mice presented with impaired fertility and sperm tail abnormalities. PRSS50 could also be involved in centrosome function because these mice showed a threefold increase in acephalic sperm (head-tail junction defect), sperm with multiple heads (spermatid division defect) and sperm with multiple tails, including novel two conjoined sperm (complete or partial parts of several flagellum on the same plasma membrane). Our data support that, in the testis, as in tumorigenesis, PRSS50 activates NFκB target genes, such as the centromere protein leucine-rich repeats and WD repeat domain-containing protein 1 (LRWD1), which is required for heterochromatin maintenance. Prss50-null testes have increased IκκB, and reduced LRWD1 and histone expression. Low levels of de-repressed histone markers, such as H3K9me3, in the Prss50-null mouse testis may cause increases in post-meiosis proteins, such as AKAP4, affecting sperm formation. We provide important insights into the complex mechanisms of sperm development, the importance of testis proteases in fertility and a novel mechanism for MMAF.

Twenty-First Century Viral Pandemics: A Literature Review of Sexual Transmission and Fertility Implications in Men.

INTRODUCTION: The 21st century has seen a series of viral pandemics that have collectively infected millions of individuals. To understand factors that may contribute to viral spread and address long-term health sequelae for survivors, it is important to review evidence regarding viral presence in semen, sexual transmission potential, and possible effects on fertility. AIM: To review the current literature regarding the sexual transmissibility of recent viral pandemics and their effects on semen parameters and fertility. We review evidence for the following viruses: Ebola, Zika, West Nile, pandemic influenza, severe acute respiratory syndrome (SARS), and SARS-corona virus-2 (SARS-CoV-2). METHODS: A literature search was conducted to identify relevant studies. Titles and abstracts were reviewed for relevance. References from identified articles were searched and included, if appropriate. MAIN OUTCOME MEASURES: The main outcome measure of this study was reviewing of peer-reviewed literature. RESULTS: Both the Ebola virus and Zika virus are present in semen, but only the Zika virus shows consistent evidence of sexual transmission. Current evidence does not support the presence of the West Nile virus, pandemic influenza, SARS, and SARS-CoV-2 in semen. The Zika virus appears to alter semen parameters in a way that diminishes fertility, but the effect is likely time limited. The West Nile virus and SARS have been associated with orchitis in a small number of case reports. Viruses that cause febrile illness, such as pandemic influenza, SARS, and SARS-CoV-2, are associated with decreased sperm count and motility and abnormal morphology. SARS and SARS-CoV-2 may interact with angiotensin-converting enzyme 2 receptors present in the testes, which could impact spermatogenesis. CONCLUSIONS: We have reported the presence in semen, sexual transmission potential, and fertility side effects of recent viral pandemics. Overall, semen studies and fertility effects are highly understudied in viral pandemics, and rigorous study on these topics should be undertaken as novel pandemics emerge. Payne K, Kenny P, Scovell JM, et al. Twenty-First Century Viral Pandemics: A Literature Review of Sexual Transmission and Fertility Implications for Men. Sex Med Rev 2020;8:518-530.

Testosterone therapy and other treatment modalities for female sexual dysfunction.

PURPOSE OF REVIEW: Recently in October 2019 a Global Consensus Position on the use of Testosterone Therapy for Women was published. The use of testosterone and other agents for female sexual dysfunction (FSD) is an important topic for the urologist focusing on sexual health. This review describes the known causes for FSD, and discusses the role of androgens in this disorder, the evidence for using testosterone treatment, and other current and emerging therapies. RECENT FINDINGS: A recent meta-analysis, published in The Lancet Diabetes & Endocrinology evaluated a total of 36 randomized control trials spanning 1990-2018 and includes a total of 8480 patients. The primary findings were that testosterone therapy (TTh) increased sexual function including satisfactory sexual event frequency, sexual desire, pleasure, arousal, orgasm, responsiveness, and self-image when compared with either a placebo or drug-control (e.g., estrogen ±â€Šprogestogen). In addition, TTh reduced sexual concerns and distress in postmenopausal women. Side effects included an increase in weight, acne, and hair growth, but there was no increase in serious adverse events. Importantly, TTh duration was greater than 12 weeks in all randomized control trials included in this meta-analysis. SUMMARY: TTh is effective to treat FSD in postmenopausal women. More data is required to evaluate the long-term safety data on the effects of TTh on cardiovascular health, breast health, cognitive function, and the musculoskeletal system in women.

An Infertile Couple's Long and Expensive Path to Varicocele Repair.

OBJECTIVE: To characterize the pathways to care that infertile couples requiring varicocele repair (VR) pursue prior to presenting to a male fertility clinic. METHODS: An IRB-approved single center retrospective review of patients undergoing VR after presentation to an academic male fertility clinic was performed. Patients whose charts included partner histories were assessed for duration of attempting conception, prior workup, and assisted reproductive technology (ART) use. RESULTS: A total of 405 couples were included. At presentation, mean age was 34.4 (SD ± 6.5) years for men and 31.1 (SD ± 4.3) years for women (P < .0001). A couple's first visit to a physician was a gynecologist in 59% (198/334) of couples, a reproductive endocrinologist (REI) in 25% (83/334) of cases, with 14% (47/334) presenting without a previous female workup and were self-referred, and 2% (6/334) seeing both a gynecologist and REI prior to presentation. On average, couples attempted pregnancy for 22.3 (SD ± 21.1, range 0-120) months prior to presentation. Eighteen percent of couples underwent ART prior to presentation. Couples who had undergone ART had lower pre-VR total motile sperm counts compared to couples not pursuing ART prior to presentation (P = 0.031). The majority (70.4%) of females had no abnormality in their workup, making varicocele the only correctable factor for infertility in the couple. CONCLUSIONS: Our findings show a significant delay in referral of infertile men requiring VR. Eighteen percent of couples underwent costly ART prior to an inexpensive male workup. In an era of medical cost containment, early referral to a male infertility specialist is imperative.

Does Solid Organ Transplantation Affect Male Reproduction?

Patients undergoing solid organ transplantation have experienced increased graft survival rates over the past several decades. With increased longevity making fatherhood a viable option, many patients desire to pursue this path. However, many patients and practitioners are likely unaware of the feasibility and safety for a man on a transplant immunosuppression regimen to safely pursue fatherhood. In this review, we discuss effects of organ transplantation and post-transplantation treatment on male hormones, fertility, and the risk to potential offspring. Briefly, providers should be aware that organ transplant recipients may be at an increased risk for hypogonadism and erectile dysfunction, but fathering a child is a realistic and safe aspiration. PATIENT SUMMARY: In this mini-review, we discuss the effects of solid organ transplantation (such as lung, heart, kidney, and liver) on a man's sexual health, and his ability to have children. We focus on the most common problems encountered by patients after their transplant, and the effects of medications.

Testosterone Replacement Therapy Versus Clomiphene Citrate in the Young Hypogonadal Male.

The use of testosterone to treat hypogonadal symptoms has increased during the past decade. Consequently, one clinical challenge that has arisen is how to approach the young and treatment-naïve hypogonadal patient who is still within his reproductive years and may desire children in the future. Testosterone is known to suppress the hypothalamic-pituitary-gonadal axis resulting in suppressed spermatogenesis. There is a concern that, in some men, prolonged testosterone use may result in permanent spermatogenic failure. PATIENT SUMMARY: In this review, we discuss the risks and benefits of available treatment options for the young hypogonadal patient for whom future fertility is an important consideration. Fortunately, alternatives such as clomiphene citrate and human chorionic gonadotropin have been shown to increase endogenous testosterone production. However, their efficacy as treatments for hypogonadal symptoms is still under debate.

Patient-specific Virtual Simulation-A State of the Art Approach to Teach Renal Tumor Localization.

OBJECTIVE: To test whether a novel visuospatial testing platform improves trainee ability to convert two-dimensional to three-dimensional (3D) space. METHODS: Medical students were recruited from Baylor College of Medicine and McGovern Medical School (Houston, TX). We 3D reconstructed 3 partial nephrectomy cases using a novel, rapid, and highly accurate edge-detection algorithm. Patient-specific reconstructions were imported into the dV-Trainer (Mimics Technologies, Seattle, WA) as well as used to generate custom 3D printed physical models. Tumor location was altered digitally to generate 9 physical models for each case, 1 with the correct tumor location and 8 with sham locations. Subjects were randomized 1:1 into the dV-Trainer (intervention) and No-dV-Trainer (control) groups. Each subject completed the following steps: (1) visualization of computed-tomographic images, (2) visualization of the reconstructed kidney and tumor in the dV-Trainer (intervention group only), and (3) selection of the correct tumor location on the 3D printed models (primary outcome). Normalized distances from the correct tumor location were quantified and compared between groups. RESULTS: A total of 100 subjects were randomized for this study. dV-Trainer use significantly improved subjects ability to localize tumor position (tumor localization score: 0.24 vs 0.38, P < .001). However, subjects in the No-dV-Trainer group more accurately assigned R.E.N.A.L. scores. CONCLUSION: Even brief exposure to interactive patient-specific renal tumor models improves a novice's ability to localize tumor location. Virtual reality simulation prior to surgery could benefit trainees learning to localize renal masses for minimally invasive partial nephrectomy.

The Impact of Microsurgical Repair of Subclinical and Clinical Varicoceles on Total Motile Sperm Count: Is There a Difference?

OBJECTIVE: To determine if subclinical varicocele repair produces similar results to palpable varicocele repair. METHODS: Retrospective review was performed on 190 infertile men who underwent a microsurgical varicocele repair by two surgeons from 2009 to 2017. Improvement in total motile sperm count (TMC) that enables men limited to in vitro fertilization (IVF) or intrauterine insemination (IUI) to undergo IUI or natural conception (upgrade) is clinically meaningful. Using TMC, men were grouped into three pre- and postoperative categories: IVF, (TMC < 5 million), IUI (TMC 5-9 million), or natural pregnancy (TMC > 9 million). Changes in category after varicocele repair were assessed. We compared the proportion of men in each category with clinical varicoceles to those with subclinical varicoceles. RESULTS: Men with clinical and subclinical varicoceles had improvements in TMC after surgery (change in TMC of 9.3 ± 19.5, 7.7 ± 22.6 million, P < 0.001 for both, respectively). There was no difference in TMC improvement between men with clinical and subclinical varicoceles (P = 0.66). Of men initially limited to IVF, 11% improved to IUI, and 38% to natural pregnancy. Of patients starting in IUI category, 22% transitioned to natural pregnancy category. No difference exists in the proportion of men who "upgraded" between palpable or subclinical varicoceles. CONCLUSION: Men with subclinical varicoceles have similar, clinically meaningful improvement in TMC after varicocele repair compared with men with palpable varicoceles.

Percent of Tracer Clearance at 40 Minutes in MAG3 Renal Scans Is More Sensitive Than T1/2 for Symptomatic Ureteropelvic Junction Obstruction.

OBJECTIVE: To increase the diagnostic sensitivity of standard MAG3 diuretic renal scans for ureteropelvic junction obstruction (UPJO) by exploring the utility of an alternative measurement P40, the percentage of maximal tracer counts present at 40 minutes. MATERIALS AND METHODS: Patients with strong clinical and anatomic evidence for UPJO may have a normal T1/2, making definitive diagnosis difficult. We reviewed the charts of 142 consecutive patients who underwent successful laparoscopic or robotic-assisted laparoscopic pyeloplasty for UPJO between 2005 and 2015. Both pre- and postoperative renal scan images were available for 37 symptomatic patients with primary unilateral UPJO and 2 kidneys. We defined P40 as the percentage of maximal tracer counts present at 40 minutes. We identified the upper limit of normal (97.5th percentile, +2SD) for P40 using the preoperative renal scans from the unaffected kidney. We compared the sensitivity of P40 to T1/2 to identify symptomatic UPJO. RESULTS: In our cohort, 51% of symptomatic patients (n = 19) had a normal T1/2 (median 8.9 minutes; interquartile range: 7.5 minutes) and 49% (n = 18) had an abnormal T1/2 (median: 40 minutes; interquartile range: 0 minute). None of the patients had an abnormal P40 on their unaffected kidney. All patients with an abnormal T1/2 also had an abnormal P40. P40 increased the sensitivity of the renal scan from 49% (n = 18 of 37) to 73% (n = 27 of 37) when compared to T1/2. The majority of patients (95%) demonstrated an improvement in P40 after pyeloplasty. CONCLUSION: P40 markedly increases the sensitivity of a renal scan for diagnosing symptomatic UPJO and may be another valuable marker in addition to T1/2 to document functional improvement in drainage after pyeloplasty.