Impact of Post-Hospital Syndrome on Penile Prosthesis Outcomes: A Period of Global Health Risk.

PURPOSE: Post-hospital syndrome is an acquired transient period of health vulnerability following inpatient admission. We assessed the impact of a preoperative hospitalization on outcomes following penile prosthesis surgery and sought to optimize surgical timing after inpatient admission. MATERIALS AND METHODS: We used the Healthcare Cost and Utilization Project State Inpatient Databases and State Ambulatory Surgery Database for California from 2007 to 2011 and for Florida from 2009 to 2014. Patients were identified as having undergone prosthesis placement by ICD-9 and CPT codes. The primary exposure was post-hospital syndrome, defined as any inpatient admission 90 days or less before prosthesis placement. Patients were further categorized by how recently the inpatient hospitalization occurred. The primary study outcome was 30-day hospital readmission. Secondary outcomes were length of stay, and device and postoperative complications. RESULTS: We identified 16,923 patients who received a penile prosthesis, of whom 477 (3%) had post-hospital syndrome exposure 90 days or less before prosthesis placement. After risk adjustment patients with post-hospital syndrome had higher odds of 30-day readmission (OR 3.0, 95% CI 2.2-4.1), length of stay 2 days or longer (OR 1.7, 95% CI 1.3-2.3) and device complications (OR 1.7, 95% CI 1.2-2.5). When categorizing patients by 30-day intervals, we found a linear decrease in the risk of 30-day readmission as the interval increased between post-hospital syndrome exposure and prosthesis surgery. CONCLUSIONS: Post-hospital syndrome exposure is a risk adjusted predictor of 30-day readmissions, prolonged length of stay and device complications. Medical optimization and delayed surgery can help combat the adverse effects associated with post-hospital syndrome exposure and may improve surgical outcomes.

Sonic hedgehog regulation of human rhabdosphincter muscle:Potential implications for treatment of stress urinary incontinence.

AIMS: Rhabdosphincter (RS) muscle injury occurs during prostatectomy, and is a leading cause of stress urinary incontinence (SUI). Current SUI treatments engender significant side effects, which negatively impact patient quality of life. Thus an unmet need exists to develop novel RS regeneration methods. We have shown that Sonic hedgehog (SHH) is a critical regulator of penile smooth muscle, and we have developed novel peptide amphiphile nanofiber hydrogel delivery of SHH protein to the penis to regenerate smooth muscle after prostatectomy induced injury. If similar SHH signaling mechanisms regulate RS muscle homeostasis, this innovative technology may be adapted for RS regeneration post-prostatectomy. We examine the SHH pathway in human RS muscle. METHODS: Human RS obtained during radical cystoprostatectomy (n = 13), underwent SHH pathway analysis. Primary cultures were established (n = 5), and RS cells were treated with SHH protein, SHH inhibitor, or PBS (control). Immunohistochemical analysis for SHH pathway, skeletal muscle actin, and trichrome stain were performed. RS growth was quantified at 3 and 6 days. RESULTS: SHH, it is receptors patched and smoothened, and transcriptional activators, GLI proteins, were identified in human RS muscle. At 3 and 6 days, RS cells increased 62% and 78% (P = 0.0001) with SHH treatment and decreased 40% (P = 0.0001) and 18% (P = 0.039) with SHH inhibition. CONCLUSIONS: The SHH pathway was identified in human RS. RS growth increased with SHH treatment, indicating intervention may be possible to enhance RS regeneration, and impact SUI. Peptide amphiphile delivery of SHH may be applicable for RS regeneration and SUI prevention.

Examining Online Traffic Patterns to Popular Direct-To-Consumer Websites for Evaluation and Treatment of Erectile Dysfunction.

BACKGROUND: Direct-to-consumer (DTC) Internet-based prescription and pharmacy platforms offer electronic consultation for evaluation and pharmacologic treatment of erectile dysfunction (ED) without a physical exam or in-person visit, presenting a potentially dramatic shift in care for this condition. AIM: To characterize the extent to which DTC prescribing sites for ED generate traffic and attract individual users. METHODS: Using SEMRush, a marketing software platform that provides analytics regarding website traffic, we examined online site visits to 6 major DTC prescribing websites offering ED evaluation and treatment from October 2017 through December 2019. OUTCOMES: We recorded trends in the number of unique visitors over time, visitor referral patterns, and the proportion of overall visitors to individual sites. RESULTS: During the study period, the total number of unique, quarterly visitors increased by 1,688% from 655,733 in the 4th quarter (Q4) 2017 to over 11 million in Q4 2019. In 2019, there were on average 4,971,674 visits to all sites combined each month. For the 2 largest sites (Hims and Roman), visitors predominantly reached the site via direct web address (27.3%) or search engine referral (27.3%). CLINICAL IMPLICATIONS: An increasingly large number of potential patients are utilizing DTC prescribing platforms for the diagnosis and treatment of ED, which do not require physical exams or treatment of other comorbid conditions. STRENGTH & LIMITATIONS: Demonstrates high demand for ED DTC prescribing services using independent market research software and characterizes the number of visits for the first time. Limitations include the lack of individual demographics and lack of information regarding what proportion of unique visits lead to evaluation and treatment using the services. CONCLUSION: The dramatic increase in visits to DTC prescribing sites that treat ED represents a paradigm shift in ED care, and it is imperative that clinicians and researchers work to understand how patients utilize online telemedicine, the safety and efficacy of online management of ED, and the potential downstream implications of its widespread use. Wackerbarth JJ, Fantus RJ, Darves-Bornoz A, et al. Examining Online Traffic Patterns to Popular Direct-To-Consumer Websites for Evaluation and Treatment of Erectile Dysfunction. Sex Med 2021;9:100289.

Evaluation of the impact of marijuana use on semen quality: a prospective analysis.

AIMS: To assess if marijuana consumption - prevalent among men of reproductive age and becoming widespread due to decriminalization - is associated with changes in semen parameters. Marijuana's active metabolite, tetrahydrocannabinol, can alter signaling pathways within spermatozoa, affecting spermatogenesis and fertility. METHODS: We prospectively evaluated semen analyses (SA) from men presenting for infertility evaluation at one institution from July 2017 to April 2018. Participants completed a reproductive health questionnaire including items regarding marijuana consumption. SA was performed in accordance with World Health Organization (WHO) 5th Edition criteria. SA parameters included volume (ml), concentration (million/ml), motility (%), progressive motility (%), and Tygerberg strict morphology (%). RESULTS: A total of 409 patients completed the questionnaire; 174 (43%) men reported marijuana use (ever-users). Current and past users comprised 71 (17%) and 103 (25%), respectively. Compared with never-users, current and past users had a significantly higher likelihood of abnormal sperm strict morphology (33.1% versus 50.7% and 53.4%, respectively; p < 0.001). However, sperm motility was more likely to be less than WHO reference values in never-users than current and past-users (38.3% versus 21.1% and 27.2%, respectively; p = 0.01). In multivariate logistic regression analyses, current use was associated with increased odds of abnormal strict morphology [odds ratio (OR) 2.15, 95% confidence interval (CI): 1.21-3.79] and semen volume less than WHO reference value (OR 2.76, 95%CI: 1.19-6.42), while odds of less than WHO reference value sperm motility were reduced (OR 0.47, 95%CI: 0.25-0.91). CONCLUSION: Marijuana use is common among men presenting for fertility evaluation, and may have a detrimental effect on semen quality, particularly morphology and volume, but may be protective against abnormal sperm motility. Large, prospective studies of both semen quality and fertility in this growing, at-risk population are warranted.

The association between guideline-based exercise thresholds and low testosterone among men in the United States.

BACKGROUND: Exercise and weight loss have been shown to improve serum testosterone (T) in obese individuals. However, the association between low T levels and guideline-based exercise thresholds has not been determined. OBJECTIVE: Using the recently updated Physical Activity Guidelines Advisory Committee (PAGAC) recommendations, we sought to investigate the relationship between recommended activity levels and the prevalence of low T levels. MATERIALS AND METHODS: The2011-2016 National Health and Nutrition Examination Survey (NHANES) was used to identify men ages 18 to 80 years who answered the physical activity questionnaire and underwent serum T testing. Men were categorized based on PAGAC activity level: less than recommended, recommended and greater than recommended. Multivariable logistic regressions were used to determine the association between low T (<300 ng/dL) and activity level across body mass index (BMI) categories while adjusting for potential confounders. RESULTS: Of the 7372 men who met the inclusion criteria, the majority (4372, 59.3%) exceeded the recommended amount of activity, whereas only 2326 (31.6%) exercised less than the recommended amount. On multivariable analysis, obese men whose activity exceeded the recommended amount were less likely to have low T (OR 0.523, 95% CI 0.409-0.669, P < .001) compared with men who did not meet the recommended activity level. DISCUSSION AND CONCLUSIONS: Using a large, nationally representative cohort, we demonstrated that obese men whose activity exceeded PAGAC recommendations had a decreased likelihood of having low T levels. Given the numerous benefits of exercise, these data provide a basis for counseling obese patients regarding the association between exercise and decreased prevalence of low T.

Orchiectomy as Bridge or Alternative to Vaginoplasty.

Simple orchiectomy for gender affirmation is a low-risk, minimally invasive, generalizable procedure that eliminates circulating endogenous testosterone, allowing reduced hormonal supplementation. This article describes a technique that serves as a step in definitive phenotypic transition while maximally preserving healthy tissue for future sex reassignment surgery. Orchiectomy should be offered routinely as a bridge or alternative to vaginoplasty, particularly in the setting of limited access to specialized centers for transgender surgery.

Penile Girth Enlargement Strategies: What's the Evidence?

INTRODUCTION: Most men seeking penile girth augmentation have physiologically normal penises but may suffer from severe preoccupation with penis size known as penile dysmorphophobic disorder. AIM: To describe the medical, procedural, and reconstructive techniques available for penile girth enhancement and to review the success and complications of each modality. METHODS: A comprehensive review of peer-reviewed publications on the topic was performed through a PubMed search. Key search terms included penis, enhancement, enlargement, phalloplasty, reconstruction, girth, and augmentation. MAIN OUTCOME MEASURE: We wanted to summarize the motivations behind penile girth enhancement and review the outcomes for girth augmentation treatments. RESULTS: Various medical, traction, injection, prosthetic, and reconstructive modalities have been studied for penile girth enhancement, with increases in girth ranging from 0-4.9 cm. Complications were reported in a minority of patients, but they may be devastating and include penile fibrosis, sexual dysfunction, device infection, and death. CONCLUSION: A variety of penile girth augmentation techniques have been studied. Clinical guidelines are lacking, and complications of penile girth enhancement are likely underreported. Until more rigorous investigation with accurate reporting of complications is achieved, penile girth augmentation procedures should be considered experimental. Hehemann MC, Towe M, Huynh LM, et al. Penile Girth Enlargement Strategies: What's the Evidence? Sex Med 2019;7:535-547.

Risk factors for hypogonadism in young men with erectile dysfunction.

BACKGROUND: The objective of this study is to evaluate the hormone profile of young men with the chief complaint of erectile dysfunction (ED) and determine the comorbidities in this population. METHODS: A retrospective chart review of men aged 18 to 40 years who presented with ED and had a hormone evaluation but without prior medication for hormone manipulation from 2002 to 2016 was performed at a tertiary care institution. Data were obtained on demographics, comorbidities, medications, and hormonal evaluations. RESULTS: A total of 2292 men with ED were identified and 2130 of them received testosterone level evaluation. The most common comorbidities that men were actively being treated for were depression (22.3%), anxiety (16.1%), hypertension (15.6%), diabetes (7.2%), cancer (6.2%), and cardiovascular disease (3.3%). The average total testosterone level was 368 ± 160 ng/dL; 10.7% of men had hypogonadism. Multivariate analysis demonstrated age, body mass index (BMI), depression, and cancer predicted a hypogonadal status. Patients with BMI > 28.2 kg/m, age > 34 years, cancer diagnosis, or depression were 3.350-fold, 1.447-fold, 2.317-fold, or 1.420-fold more likely to be diagnosed hypogonadal than nonoverweight, age ≤ 34 years, noncancer, or nondepressive patients. CONCLUSION: The majority of men under the age of 40 with ED exhibit a normal hormonal milieu. Young ED men with BMI > 28.2 kg/m, age >34 years, cancer diagnosis, or depression are at risk for hypogonadism.

Inconsistent Adoption of World Health Organization V (2010) Semen Analysis Reference Ranges in the United States Eight Years After Publication.

OBJECTIVE: To determine the percentage of laboratories in the United States that have adopted the World Health Organization 2010 (WHO 5) semen analysis (SA) reference values 6years after their publication. METHODS: Laboratories were identified via 3 approaches: using the Clinical Laboratory Improvement Amendments (CLIA) website, the CDC's 2015 Assisted Reproductive Technology Fertility Clinical Success Rate Report, and automated web searches. Laboratories were contacted by phone or email to obtain de-identified SA reports and reference ranges. RESULTS: We contacted 617 laboratories in 46 states, of which 208 (26.7%) laboratories in 45 states were included in our analysis. 132 (63.5%) laboratories used WHO 5 criteria, 57 (27.4%) used WHO 4 criteria, and 19 (9.1%) used other criteria. WHO 5 criteria adoption rates varied by geographic region, ranging from 87.5% (35/40) in the Midwest to 50.0% (33/66) in the West. There was a greater adoption rate of WHO 5 reference values in academic affiliated (23/26, 88.5%) compared to non-academic affiliated laboratories (110/182, 60.4%) (P = .028). CONCLUSION: While the majority of laboratories have adopted WHO 5 criteria following its release 6years ago, a large percentage (36.5%) use what is now considered outdated criteria. This variability could result in the characterization of a male's semen values as being "within reference range" at one center and "outside of reference range" at another. This inconsistency in classification may result in confusion for the both patient and physician and potentially shift the burden of infertility evaluation and treatment to the female partner.

Pelvic and hypogastric nerves are injured in a rat prostatectomy model, contributing to development of stress urinary incontinence.

Urinary incontinence affects 40% of elderly men, is common in diabetic patients and in men treated for prostate cancer, with a prevalence of up to 44%. Seventy-two percent of prostatectomy patients develop stress urinary incontinence (SUI) in the first week after surgery and individuals who do not recover within 6 months generally do no regain function without intervention. Incontinence has a profound impact on patient quality of life and a critical unmet need exists to develop novel and less invasive SUI treatments. During prostatectomy, the cavernous nerve (CN), which provides innervation to the penis, undergoes crush, tension, and resection injury, resulting in downstream penile remodeling and erectile dysfunction in up to 85% of patients. There are other nerves that form part of the major pelvic ganglion (MPG), including the hypogastric (HYG, sympathetic) and pelvic (PN, parasympathetic) nerves, which provide innervation to the bladder and urethra. We examine if HYG and PNs are injured during prostatectomy contributing to SUI, and if Sonic hedgehog (SHH) regulatory mechanisms are active in the PN and HYG nerves. CN, PN, HYG and ancillary (ANC) of uninjured, sham and CN crush/MPG tension injured (prostatectomy model) adult Sprague Dawley rats (n = 37) were examined for apoptosis, sonic hedgehog (SHH) pathway, and intrinsic and extrinsic apoptotic mechanisms. Fluorogold tracing from the urethra/bladder was performed. PN and HYG response to SHH protein was examined in organ culture. TUNEL, immunohistochemical analysis for caspase-3 cleaved, -8, -9, SHH, Patched and Smoothened (SHH receptors), and neurite formation, were examined. Florogold positive neurons in the MPG were reduced with CN crush. Apoptosis increased in glial cells of the PN and HYG after CN crush. Caspase 9 was abundant in glial cells (intrinsic), while caspase-8 was not observed. SHH and its receptors were abundant in neurons and glia of the PN and HYG. SHH treatment increased neurite formation. PN and HYG injury occur concomitant with CN injury during prostatectomy, likely contributing to SUI. PN and HYG response to SHH treatment indicates an avenue for intervention to promote regeneration and prevent SUI.

Scrotal Ultrasound for Pain: Low Frequency of Absolute Surgical Indications.

OBJECTIVE: To examine the results of scrotal ultrasounds (US) conducted for scrotal or testicular pain and review the pathologic findings of orchiectomies done for lesions that were suspicious for malignancy on US. MATERIALS AND METHODS: We retrospectively reviewed the indications and findings of all scrotal US completed at our institution from 2002 to 2014. If a patient underwent an orchiectomy for an intratesticular lesion that was concerning for malignancy on US, the pathology report was also reviewed. RESULTS: There were 18,593 scrotal US performed, with 7,668 (41.2%) conducted for scrotal pain. Of the US performed for pain, 80.4% revealed benign or normal findings, and only 2.2% demonstrated a finding that is an absolute indication for surgery (intratesticular lesion suspicious for malignancy 0.8%, abscess 0.7%, torsion 0.6%, infiltrative process such as lymphoma 0.1%). For those patients undergoing an orchiectomy, 75% had malignancy on pathologic analysis. CONCLUSION: The majority of the 7668 US performed to evaluate scrotal or testicular pain reveal normal or benign findings. A low percentage demonstrates a finding that necessitates urgent or emergent surgery.

Can lifestyle modification affect men's erectile function?

Erectile dysfunction (ED) is a common condition affecting millions of men worldwide. The pathophysiology and epidemiologic links between ED and risk factors for cardiovascular disease (CVD) are well-established. Lifestyle modifications such as smoking cessation, weight reduction, dietary modification, physical activity, and psychological stress reduction have been increasingly recognized as foundational to the prevention and treatment of ED. The aim of this review is to outline behavioral choices which may increase ones risk of developing ED, to present relevant studies addressing lifestyle factors correlated with ED, and to highlight proposed mechanisms for intervention aimed at improving erectile function in men with ED. These recommendations can provide a framework for counseling patients with ED about lifestyle modification.