Metformin and testosterone replacement therapy inversely associated with hormone-associated cancers (prostate, colorectal and male breast cancers) among older White and Black men.

BACKGROUND: The independent and joint association of metformin and testosterone replacement therapy (TTh) with the incidence of prostate, colorectal, and male breast cancers remain poorly understood, including the investigation of the risk of these cancers combined (HRCs, hormone-associated cancers) among men of different racial and ethnic background. METHODS: In 143,035 men (≥ 65 yrs old) of SEER-Medicare 2007-2015, we identified White (N = 110,430), Black (N = 13,520) and Other Race (N = 19,085) men diagnosed with incident HRC. Pre-diagnostic prescription of metformin and TTh was ascertained for this analysis. Weighted multivariable-adjusted conditional logistic and Cox proportional hazards models were conducted. RESULTS: We found independent and joint associations of metformin and TTh with incident prostate (odds ratio [OR]joint = 0.44, 95% confidence interval [CI]: 0.36-0.54) and colorectal cancers (ORjoint = 0.47, 95% CI: 0.34-0.64), but not with male breast cancer. There were also inversed joint associations of metformin and TTh with HRCs (ORjoint = 0.45, 95% CI: 0.38-0.54). Similar reduced associations with HRCs were identified among White, Black, and Other Race men. CONCLUSION: Pre-diagnostic use of metformin and TTh were, independently and jointly, inversely associated with incident prostate and colorectal cancers. The risk of HRCs was also reduced among White, Black and Other Race men. Greatest reduced associations of prostate and colorectal cancers and HRCs were mainly observed in combination of metformin and TTh. Larger studies are needed to confirm the independent and joint association of metformin plus TTh with these cancers in understudied and underserved populations.

Ethnic Minority Representation in Female Sexual Dysfunction Questionnaire Validation: A Scoping Review.

BACKGROUND: Female sexual dysfunction (FSD) is a significant cause of distress for an estimated 12-24% of women, and over the past 5 decades several questionnaires have been developed for clinical practice. AIM: The purpose of this scoping review is to evaluate the ethnic representation of sample populations used in the studies to validate FSD questionnaires. METHODS: A scoping review was performed using electronic databases, including PubMed and Scopus, to identify FSD questionnaires validated between 1976 and 2021. Weighted averages from the combined ethnicity data were compared to population data from 2019 US census data and 2018 healthcare workforce reports to evaluate epidemiologic diversity. Ethnicity data from each questionnaire were also investigated longitudinally to evaluate trends in representation over the past 50 years. OUTCOMES: Our outcome of interest was comparison of the weighted averages for ethnicity categories from validation populations to the US female general population, US female health care workforce, and US census data. RESULTS: 48 validation studies were reviewed and showed that the average ethnic representation of the study populations relative to the US general population and US female health care workforce, respectively, was: Caucasian (83.7% vs 62.7% and 68.5%), Black (7.8% vs 13.3% and 8.3%), Hispanic (3.6% vs 16.0% and 9.6%), Native American (0.1% vs 0.8% and 0.3%), Asian (0.6% vs 6.4% and 6.2%), and Other (3.1% vs 0.7% and 1.4%). CLINICAL IMPLICATIONS: FSD questionnaires are relied upon in research and clinical settings, so lack of diversity in validation populations could lead to under recognition and undertreatment in ethnic minority women. STRENGTHS & LIMITATIONS: Our results are dependent on the quality of data available from previously published validation studies. We attempted to account for biases in lack of data and size of validation populations by using weighted averages for making comparisons. We chose the US general population and female healthcare workforce for comparison and analyzed validation populations across multiple decades and geographic locations. Many of the validation studies were performed at least 10 years ago and may not reflect the current state of FSD and potential of questionnaire responses of ethnic minority women. This manuscript raises critical awareness regarding the lack of validated instruments for FSD in ethnically diverse women. CONCLUSION: Study populations used to validate FSD questionnaires demonstrate a trend of ethnic minority underrepresentation relative to the US female general and healthcare workforce populations. Battle CR, Rubin RS, Kingsberg SA, et al. Ethnic Minority Representation in Female Sexual Dysfunction Questionnaire Validation: A Scoping Review. J Sex Med 2022;19:1824-1838.

Ivabradine, the hyperpolarization-activated cyclic nucleotide-gated channel blocker, elicits relaxation of the human corpus cavernosum: a potential option for erectile dysfunction treatment.

OBJECTIVE: To evaluate the effect of the If channel inhibitor, ivabradine on human corpus cavernosum (HCC) smooth muscle tone. METHODS: HCC samples were obtained from erectile dysfunction(ED) patients (n = 12) undergoing penile prosthesis surgery. Concentration-response curves for ivabradine were exposed to various inhibitory and stimulatory agents. The relaxant and contractile responses to electrical field stimulation (EFS, 10 Hz and 80 Hz) were examined in the presence or absence of ivabradine (10 µM). HCN3 and HCN4 channel expression and localization were determined by Western blot and immunohistochemical analyses of HCC tissues. RESULTS: Increasing ivabradine concentrations dependently reduced the maximal contractile responses of isolated HCC strips induced by KCl (59.5 ± 2.5%) and phenylephrine (84.0 ± 9.8%), which was not affected by nitric oxide synthase and soluble guanylyl cyclase inhibitors after phenylephrine-induced contraction. Nifedipine and tetraethylammonium inhibited the maximum relaxation to ivabradine by 75% and 39.3%, respectively. Fasudil and sildenafil increased the relaxation response to ivabradine without altering the maximum response. Pre-incubation with ivabradine significantly increased relaxant responses to EFS (p < 0.01) and reduced the contractile tension evoked by EFS (72.3%) (p < 0.001). Ivabradine incubation did not affect the expression and localization of HCN3 and HCN4 channels in the HCC smooth muscle cells. CONCLUSIONS: Ivabradine exhibits a relaxant effect on HCC tissues, which is likely to be attributed to the blocking of L-type Ca2+ channels and the opening of K+ channels, independent of changes in the activation of the nitric oxide/cyclic guanosine monophosphate system. Inhibition of HCN channels localized in cavernosal smooth muscle cells may offer pharmacological benefits for patients with cardiovascular risk factors.

Intralesional Collagenase Clostridium histolyticum Causes Meaningful Improvement in Men with Peyronie's Disease: Results of a Multi-Institutional Analysis.

PURPOSE: In a multi-institutional setting we studied the efficacy and safety outcomes at multiple high volume centers where collagenase Clostridium histolyticum is used to treat Peyronie's disease. MATERIALS AND METHODS: We collected retrospective data on consecutive patients with Peyronie's disease who underwent treatment with collagenase C. histolyticum between April 2014 and March 2018 at a total of 5 institutions. Included in the study were 918 patients. Main outcomes of interest included the change in curvature after receiving collagenase C. histolyticum therapy and the frequency of serious treatment related adverse events. The 2-tailed paired Student t-test was used to compare continuous variables. Univariate and multivariate regression analyses were performed to assess predictors of the success of collagenase C. histolyticum therapy to improve curvature. RESULTS: In the cohort of 918 patients curvature improved from a mean of 48.2 degrees before treatment to 32.9 degrees after treatment, a 30.1% improvement from baseline (p <0.0001). Of the men 68.7% had a 20% or greater improvement in curvature. In the 502 patients who completed 4 or more cycles curvature improved from a mean of 49.7 degrees before to 32.7 degrees after treatment, a 33% improvement from baseline (p <0.0001). Of these men 74.4% experienced a 20% or greater improvement in curvature. A complication of treatment developed in 9% of patients. The number of cycles of collagenase C. histolyticum received was predictive of curvature improvement (p <0.0001). CONCLUSIONS: This large multi-institutional analysis confirms the safety and efficacy of collagenase C. histolyticum therapy in men with Peyronie's disease. Intralesional collagenase C. histolyticum for Peyronie's disease according to the IMPRESS (Investigation of Maximal Peyronie's Reduction Efficacy and Safety Studies) trial protocol produced an improvement in penile curvature in men with Peyronie's disease with a low rate of complications.

Andrianne Mini-Jupette Graft at the Time of Inflatable Penile Prosthesis Placement for the Management of Post-Prostatectomy Climacturia and Minimal Urinary Incontinence.

BACKGROUND: After radical prostatectomy (RP), erectile dysfunction, often necessitating the need for inflatable penile prosthesis (IPP) insertion, and urinary incontinence and climacturia can ensue. AIM: To assess the efficacy and safety of the mini-jupette, a mesh used to approximate the medial aspects of the 2 corporotomies at the time of IPP insertion, for the management of climacturia and urine leakage in patients with minimal incontinence. METHODS: We conducted a pilot multicenter study of patients with post-RP erectile dysfunction and climacturia and/or mild urinary incontinence (≤2 pads/day [ppd]) undergoing IPP insertion with concomitant placement of a mini-jupette graft. OUTCOMES: Pre- and postoperative erectile function, continence and climacturia, and overall surgical outcomes were assessed. RESULTS: 38 patients underwent the mini-jupette procedure. The mean age of the population was 65.3 years (SD = 7.7). 30 had post-RP climacturia and 32 patients had post-RP incontinence (mean = 1.3 ppd, SD = 0.8). 31 patients received Coloplast Titan, 4 received AMS 700 LGX, and 3 received AMS 700 CX IPPs. Mean corporotomy size was 2.9 cm (SD = 1.0). Mean graft measurements were 3.2 cm (SD = 0.9) for width, 3.3 cm (SD = 1.3) for length, and 11.0 cm2 (SD = 5.1) for surface area. At a mean follow-up of 5.1 months (SD = 6.9), there were 5 postoperative complications (13.2%) of which 4 required explantation. Climacturia and incontinence were subjectively improved in 92.8% and 85.7%, respectively. Mean ppd decreased by 1.3 postoperatively. CLINICAL IMPLICATIONS: The Andrianne mini-jupette is a feasible adjunct to IPP placement that can be used for subsets of patients with post-RP climacturia and/or minimal incontinence. STRENGTHS AND LIMITATIONS: Strengths of this study include the novel nature of this intervention, the multi-institutional nature of the study, and the promising results demonstrated. Limitations include the retrospective nature of the study and the heterogeneity of the techniques and grafts used by different surgeons involved. CONCLUSION: Longer follow-up and larger patient cohorts are needed to confirm the long-term safety and benefits of this intervention. Yafi FA, Andrianne R, Alzweri L, et al. Andrianne Mini-Jupette Graft at the Time of Inflatable Penile Prosthesis Placement for the Management of Post-Prostatectomy Climacturia and Minimal Urinary Incontinence. J Sex Med 2018;15:789-796.

A propensity score-matched analysis of intra- and postoperative penile prosthetic complications in the solid organ transplant population.

INTRODUCTION: Solid organ transplant (SOT) has an anticipated higher risk of penile prosthesis (PP) complications related to immunosuppression and surgical approach post-SOT. It is still not determined if PP surgery in the SOT population incurs these same higher risks. OBJECTIVES: To observe differences in intra- and postoperative PP complications between SOT and non-SOT cases from the TriNetX US Collaborative Network, a large real-world database of deidentified patient data from 56 health care organizations within the United States. METHODS: We used the TriNetX database to perform a propensity score-matched cohort study comparing 10-year outcomes between patients with and without a SOT (kidney, heart, lung, liver, pancreas, and intestine) who underwent a PP procedure. Cohorts were matched on age, race/ethnicity, history of pelvic and abdominal surgery, overweight and obesity status, type 2 diabetes mellitus, atherosclerosis, substance use disorders, socioeconomic difficulties, anticoagulant/antiplatelet medications, and spinal cord injury. Outcomes included intra- and perioperative complications as well as prosthetic complications (mechanical malfunction, fibrosis, displacement, hemorrhage, pain, stenosis, removal with or without replacement, and complex [all postoperative complications]). RESULTS: There were 233 patients in each group after matching (SOT and non-SOT). The mean ± SD age at the prosthesis procedure was 59.7 ± 9.89 years, and 44% of patients were White (P > .05). There was no significant difference for incidence of intra- and perioperative complications (2.62% vs 2.19%, P = .76). The SOT group did not have a higher 10-year incidence of complex complications (30.58% vs 27.51%, P = .11) or mechanical malfunction (10.35% vs 11.62%, P = .25) when compared with the non-SOT group. No difference was found for other prosthetic-related complications (P > .05). CONCLUSION: In our analysis, patients with a SOT were not more likely to experience long-term complications related to PP. Surgeons performing PP surgery in the SOT population may consider this procedure a potentially safe and viable option for restoring erectile function.

Analysis of sexual dysfunction development among male and female living kidney donors.

INTRODUCTION: Living kidney donations (LKDs) face a persistent demand for patients with end-stage renal disease, emphasizing the importance of LKDs' growth and success. Although living kidney donors generally exhibit excellent survival rates, little research has explored the development of long-term sexual dysfunction following LKD. OBJECTIVES: This study aimed to analyze differences in 5-year sexual dysfunction outcomes between male and female living kidney donors, utilizing the TriNetX database, a federated network of electronic medical records from multiple U.S. healthcare organizations. METHODS: A propensity score-matched cohort study compared 45-year sexual dysfunction outcomes in adult male and female living kidney donors from December 2013 to December 2022. Cohorts were matched on age; sex; race and ethnicity; diabetes, cardiovascular, genitourinary, and psychiatric comorbidities; lifestyle-related factors; and medications that may impact normal sexual functioning. Primary outcomes included hazard ratio (HR) for decreased libido, sexual dysfunction (composite of male erectile dysfunction, ejaculatory disorders, vaginismus/dyspareunia, infertility, orgasmic disorders, arousal/desire disorders), and sexually transmitted diseases. Secondary outcomes assessed sex counseling and interpersonal relationship issues with spouses or partners. RESULTS: The matched cohorts included 2315 patients each (male, female), and the mean age was 42.3 ± 12.5 years. At 5 years, male donors had a significantly higher HR for sexual dysfunction (HR, 3.768; 95% confidence interval, 1.929-7.358). Erectile dysfunction occurred in 1% of male patients, while vaginismus/dyspareunia affected <1% of female patients. Other sexual disorders, decreased libido, sexually transmitted diseases, and incidences of sexual and interspousal counseling were not significantly different. CONCLUSION: Male living kidney donors faced a higher risk of developing sexual dysfunction 5 years after donation. While LKD remains a safe and viable alternative, clinicians and donors should be mindful of the potential association with sexual dysfunction postdonation. Further research may enhance support for the well-being of living kidney donors.

Association of serum testosterone with chronic obstructive pulmonary disease (COPD) in a nationally representative sample of White, Black, and Hispanic men.

BACKGROUND: The association between total testosterone (T) and chronic obstructive pulmonary disease (COPD), remains poorly understood. We aim to investigate this association and how it varies by smoking status, body fatness, and race/ethnicity in a nationally representative sample of American men. METHODS: Data included a full sample (NHANES 1988-1991, 1999-2004, 2011-2012) and subset sample (excluding 2011-2012, no estradiol and SHBG levels available) of 2748 and 906 men (≥20 years), respectively. COPD was measured by self-report or spirometry test. Total T (ng/mL) was measured among men who participated in a morning examination session. Weighted multivariable-adjusted logistic regression models were conducted. RESULTS: Low T was positively associated with self-reported COPD in the full sample (OR = 2.10, 95% CI = 1.18-3.74, Ptrend = 0.010), and when stratified by current smokers and body fatness. When examined across race and ethnicity strata, this association persisted among White men (OR = 2.50, 95% CI = 1.30-4.79, Ptrend = 0.002) but not among Hispanic or Black men. In the subset sample, low T was positively associated with self-reported COPD (OR = 1.42, 95% CI, 0.57,3.55, Ptrend = 0.04), including among smokers and White men, but not body fatness. No significant associations were observed with COPD defined with spirometry plus self-report. CONCLUSION: Low levels of T were associated with an increased prevalence of self-reported COPD in the full and subset samples. Similar associations were observed after stratifying by smoking status, body fatness, and race/ethnicity in the full sample and subset sample. Prospective studies are warranted to confirm these significant associations among understudied and underserved populations.

Evaluating the impact of pre-diagnostic use of statins and testosterone replacement therapy on mortality outcomes in older men with hormone-related cancers: Surveillance, Epidemiology, and End Results-Medicare 2007-2015.

BACKGROUND: The link between the pre-diagnostic use of statins and testosterone replacement therapy and their impact on hormone-related cancers, prostate cancer, colorectal cancer, and male breast cancer survival remains a topic of controversy. Further, there is a knowledge gap concerning the joint effects of statins and testosterone replacement therapy on hormone-related cancer survival outcomes. OBJECTIVE: To examine the independent and joint effects of pre-diagnostic use of statins and testosterone replacement therapy on the risk of all-cause and cause-specific mortality among older men diagnosed with hormone-related cancers, including prostate cancer, colorectal cancer, and male breast cancer. METHODS: In 41,707 men (≥65 years) of Surveillance, Epidemiology, and End Results-Medicare 2007-2015, we identified 31,097 prostate cancer, 10,315 colorectal cancer, and 295 male breast cancer cases. Pre-diagnostic prescription of statins and testosterone replacement therapy was ascertained and categorized into four groups (Neither users, statins alone, testosterone replacement therapy alone, and Dual users). Multivariable-adjusted Cox proportional hazards and competing-risks (Fine-Gray subdistribution hazard) models were conducted. RESULTS: No significant associations were found in Cox-proportional hazard models for hormone-related cancers. However, in the Fine-Gray competing risk models among high-grade hormone-related cancers, statins alone had an 11% reduced risk of hormone-related cancer-specific death (hazard ratio: 0.89; 95% confidence interval: 0.81-0.99; p 0.0451). In the prostate cancer cohort with both statistical models, the use of testosterone replacement therapy alone had a 24% lower risk of all-cause death (hazard ratio: 0.76; 95% confidence interval: 0.59-0.97; p 0.0325) and a 57% lower risk of prostate cancer-specific death (hazard ratio: 0.43; 95% confidence interval: 0.24-0.75; p 0.0029). Similar inverse associations were found among aggressive prostate cancer cases with testosterone replacement therapy alone and statins alone. No significant associations were found in the colorectal cancer and male breast cancer sub-groups. CONCLUSION: Pre-diagnostic use of statins and testosterone replacement therapy showed a survival benefit with reduced mortality in high-grade hormone-related cancer patients (only statins) and aggressive prostate cancer patients in both statistical models. Findings of testosterone replacement therapy use in aggressive prostate cancer settings could facilitate clinical trials. Further studies with extended follow-up periods are needed to substantiate these findings.

Hard-Flaccid syndrome: a survey of sexual medicine practitioners' knowledge and experience.

Hard-flaccid syndrome (HFS) is a poorly understood condition of male sexual dysfunction (MSD) that has more recently become a new topic of discussion in online forums and sexual medicine conferences. There has been limited research looking into HFS and consequently there are no evidence-based guidelines for its work-up and management. In order to identify the current level of understanding of HFS in the sexual medicine community, a survey was distributed at a national urologic conference focusing on pertinent management strategies employed by practitioners, and their own thoughts on HFS. This showed that nearly one-third of those surveyed had never seen HFS in their practice. Of those that had, diagnosis was mainly made via clinical history as well as patient self-diagnosis. Additionally, only about half of the respondents who had seen HFS were confident in its legitimacy as a real medical syndrome. This analysis is one of the first of its kind, and highlights the ongoing lack of familiarity of HFS among the sexual medicine community. There were limitations, most notably its survey format as well as low sample size, however, it importantly emphasizes the critical need for continued education and research into HFS to improve diagnostic accuracy, enhance patient care, and develop effective treatment strategies.

A population analysis of delayed ejaculation using a claims database: characteristics and national trends in prevalence, incidence, and pharmacotherapy.

We investigated the prevalence, incidence, and rates of pharmacological treatment of delayed ejaculation using the TriNetX Diamond Network. We included all men evaluated in the inpatient, outpatient, and emergency settings. Prevalence was determined by comparing the number of men diagnosed with delayed ejaculation to the entire population. Incidence was determined by comparing the number of men diagnosed with delayed ejaculation without a prior diagnosis to the overall population without a prior diagnosis. Rates of pharmacologic treatment were calculated by comparing the number of men who received a prescription to the total number of men with delayed ejaculation. Trends in prevalence and incidence were compared using six-month intervals, while trends in pharmacologic treatment were compared using one-year intervals. A total of 23,164 adult males were diagnosed with delayed ejaculation from 2013 to 2019. During the final six-month interval (July to December 2019), 2,747 of 16,496,744 men received a delayed ejaculation diagnosis, and 1,375 of 16,488,270 men without a prior diagnosis were diagnosed with delayed ejaculation. In 2019, only 916 of 4,733 (19.4%) men diagnosed with delayed ejaculation received any prescription, with the most common being testosterone (9.5%), bupropion (6.6%), and buspirone (2.3%). Prevalence, incidence and pharmacologic treatment all had increasing trends.

Prescribing semaglutide for weight loss in non-diabetic, obese patients is associated with an increased risk of erectile dysfunction: a TriNetX database study.

Semaglutide was approved in June 2021 for weight loss in non-diabetic, obese patients. While package inserts include sexual dysfunction as a side effect, no study has assessed the degree of this risk. The objective of our study is to assess the risk of developing erectile dysfunction after semaglutide is prescribed for weight loss in obese, non-diabetic men. The TriNetX Research database was used to identify men without a diagnosis of diabetes ages 18 to 50 with BMI > 30 who were prescribed semaglutide after June 1st, 2021. Men were excluded if they had a prior erectile dysfunction diagnosis, any phosphodiesterase-5 inhibitors prescription, intracavernosal injections, penile prosthesis placement, history of testosterone deficiency, testosterone prescription, pelvic radiation, radical prostatectomy, pulmonary hypertension, or were deceased. We further restricted our cohort to non-diabetic, obese men by excluding men with a prior diabetes mellitus diagnosis, a hemoglobin A1c > 6.5%, or having ever received insulin or metformin. Men were then stratified into cohorts of those that did and did not receive a semaglutide prescription. The primary outcome was the risk of new ED diagnosis and/or new prescription of phosphodiesterase type 5 inhibitors at least one month after prescription of semaglutide. The secondary outcome was risk of testosterone deficiency diagnosis. Risk was reported using risk ratios with 95% confidence intervals (95% CI). 3,094 non-diabetic, obese men ages 18-50 who received a prescription of semaglutide were identified and subsequently matched to an equal number cohort of non-diabetic, obese men who never received a prescription of semaglutide. After matching, average age at index prescription for non-diabetic, obese men was 37.8 ± 7.8 and average BMI at index prescription was 38.6 ± 5.6. Non-diabetic men prescribed semaglutide were significantly more likely to develop erectile dysfunction and/or were prescribed phosphodiesterase type 5 inhibitors (1.47% vs 0.32%; RR: 4.5; 95% CI [2.3, 9.0]) and testosterone deficiency (1.53% vs 0.80%; RR: 1.9; 95% CI [1.2, 3.1]) when compared to the control cohort of non-diabetic men who never received a semaglutide prescription.

Robotic management of a large mullerian duct cyst: a case report and review of surgical options.

Introduction: Mullerian duct cysts (MDCs) are a rare diagnosis in adulthood, primarily found in men aged 20 to 40 due to reproductive or urinary symptoms. Asymptomatic patients are generally observed. Treatment of symptomatic patients varies widely based on the presentation. Small cysts can be treated with transurethral and percutaneous methods due to a lower risk of damage to surrounding structures. However, larger and more complicated cysts are often treated using open or laparoscopic approaches. Case Description: Our case presents a 38-year-old male with worsening obstructive lower urinary tract symptoms and recurrent episodes of acute urinary retention. Preliminary diagnosis of a MDC was made using CT and MRI. After failing initial minimally invasive therapy, the patient was treated with definitive robotic-assisted laparoscopic surgical excision of the cyst. At the one-month follow-up, the patient reported no complications and resolution of symptoms. As shown by this case, robotic surgical methods may be used as a more precise approach, reducing the risk of damage to vessels, nerves, and structures within the abdomen and pelvis. Conclusions: Asymptomatic patients can be observed. Treatment of symptomatic patients varies widely based on the presentation. Small cysts can be treated with transurethral and percutaneous methods due to a lower risk of damage to surrounding structures. Larger, more complicated cysts are often treated using open, laparoscopic, or robotic surgical methods. More precise approaches, including robotic methods, can reduce the risk of damage to vessels, nerves, and structures within the abdomen and pelvis.

Association of total and free testosterone with cardiovascular disease in a nationally representative sample of white, black, and Mexican American men.

Associations of total testosterone (T) and calculated free T with cardiovascular disease (CVD) remain poorly understood. Particularly how these associations vary according to race and ethnicity in a nationally representative sample of men. Data included 7058 men (≥20 years) from NHANES. CVD was defined as any reported diagnosis of heart failure (HF), coronary artery disease (CAD), myocardial infarction (MI), and stroke. Total T (ng/mL) was obtained among males who participated in the morning examination. Weighted multivariable-adjusted logistic regression models were conducted. We found associations of low T (OR = 1.57, 95% CI = 1.17-2.11), low calculated free T (OR = 1.53, 95% CI = 1.10-2.17), total T (Q1 vs Q5), and calculated free T (Q1 vs Q5) with CVD after adjusting for estradiol and SHBG. In disease specific analysis, low T increased prevalence of MI (OR = 1.72, 95% CI = 1.08-2.75) and HF (OR = 1.74, 95% CI = 1.08-2.82), but a continuous increment of total T reduced the prevalence of CAD. Similar inverse associations were identified among White and Mexican Americans, but not Blacks (OR = 0.93, 95% CI = 0.49-1.76). Low levels of T and calculated free T were associated with an increased prevalence of overall CVD and among White and Mexican Americans. Associations remained in the same direction with specific CVD outcomes in the overall population.

Peyronie's disease - outcomes of collagenase clostridium histolyticum injection: A systematic review.

OBJECTIVE: To review recent literature pertaining to collagenase clostridium histolyticum (CCh)and other intralesional (IL) therapies for the treatment of Peyronie's disease (PD). METHODS: A systematic search of literature was performed using MEDLINE and PubMed.'Peyronie's Disease Clostridium Histolyticum', 'Peyronie's Disease Intralesional', 'Peyronie'sDisease Causes', and 'Atypical Peyronie's Disease' were used as query entries. Inclusion criteriarequired English text from 1980 onwards and have a full text available. Records were reviewed for study power, accuracy, and relevance to our research topic. The review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. RESULTS: Recent literature supports the notion that CCh is the most effective IL treatment forpatients with typical and atypical PD. The capstone CCh study was the IMPRESS trial thatshowed a 34% reduction in curvature with a mean (SD) - 17.0 (14.8)° reduction with IL CCh,while men in the placebo saw an average 18.2% decrease in penile bend with a mean (SD) - 9.3 (13.6)° per person (P < 0.001). A shortened protocol for IL CCh treatment offered a 31.4%reduction in curvature, while decreasing cost and office visits, potentially increasing patientcompliance. Lastly, literature shows CCh is used most in atypical cases, with ~64.8% of patients being treated with CCh, probably because of the high efficacy and safetyprofile that it offers. Serious complications associated with CCh include urethralinjury, corporal rupture, and penile fracture. CONCLUSION: Since the approval of CCh by the United States Food and Drug Administration in2013, it has been a staple in the treatment of PD, and here we report the continuedsuperiority of this therapy. CCh is an effective, minimally invasive option in most PDpopulations; however, recent changes have made CCh unavailable for commercial use outside the United States, impacting many patients who have previously benefited.

Testosterone positively regulates functional responses and nitric oxide expression in the isolated human corpus cavernosum.

BACKGROUND: Testosterone (T) deficiency is associated with erectile dysfunction (ED). The relaxant response of T on the corporal smooth muscle through a non-genomic pathway has been reported; however, the in vitro modulating effects of T on human corpus cavernosum (HCC) have not been studied. OBJECTIVES: To compare the effects of various concentrations of T on nitric oxide (NO)-dependent and nitric oxide-independent relaxation in organ bath studies and elucidate its mode of action, specifically targeting the cavernous NO/cyclic guanosine monophosphate (cGMP) pathway. MATERIALS AND METHODS: Human corpus cavernosum (HCC) samples were obtained from men undergoing penile prosthesis implantation (n = 9). After phenylephrine (Phe) precontraction, the effects of various relaxant drugs of HCC strips were performed using organ bath at low (150 ng/dL), eugonadal (400 ng/dL), and hypergonadal (600 ng/dL) T concentrations. The penile tissue measurements of endothelial nitric oxide synthase (eNOS), neuronal (n)NOS, and phosphodiesterase type 5 (PDE5) were evaluated via immunostaining, Western blot, cGMP and nitrite/nitrate (NOx) assays. RESULTS: Relaxation responses to ACh and EFS in isolated HCC strips were significantly increased at all T levels compared with untreated tissues. The sildenafil-induced relaxant response was significantly increased at both eugonadal and hypergonadal T levels. Normal and high levels of T are accompanied by increased eNOS, nNOS, cGMP, and NOx levels, along with reduced PDE5 protein expression. CONCLUSION: This study reveals an important role of short-term and modulatory effects of different concentrations of T in HCC. T positively regulates functional activities, inhibition of PDE5 expression, and formation of cGMP and NOx in HCC. These results demonstrate that T indirectly contributes to HCC relaxation via downstream effects on nNOS, eNOS, and cGMP and by inhibiting PDE5. This action provides a rationale for normalizing T levels in hypogonadal men with ED, especially when PDE5 inhibitors are ineffective. T replacement therapy may improve erectile function by modulating endothelial function in hypogonadal men.

Penile Prosthesis Complications: Planning, Prevention, and Decision Making.

INTRODUCTION: Inflatable penile prosthesis (IPP) is an established treatment option for men with erectile dysfunction (ED) refractory to medical therapy. Standardization of surgical technique and improvements in device construction have reduced all-cause complication rates to less than 5% in recent reports. Nonetheless, complications do exist, and can strongly impact morbidity and the quality of life of patients. Prosthetic urologists must be aware of the constellation of complications that can arise during or after IPP placement. AIM: To provide a comprehensive review of penile prosthesis complications and discuss preventative strategies, as well as proper preoperative, intraoperative, and postoperative decision making. METHODS: A review of the available literature from 1973 to 2018 was performed using PubMed with regard to IPP complications. MAIN OUTCOME MEASURES: We reviewed publications that outlined preoperative planning strategies and the following IPP complications: hematoma, floppy glans, corporal fibrosis, corporal perforation and crossover, urethral injury, infection, impending erosion, and glandular ischemia. RESULTS: Careful patient and device selection, setting realistic expectations of postsurgical outcomes, and adherence to a perioperative checklist is essential in the preoperative period. Intraoperatively, anticipate corporal fibrosis situations and always dilate laterally during corporal passage to reduce the risk of crossover and urethral injury. Limit perioperative antiplatelet therapy, apply compressive dressing, use a closed suction drain if indicated, and leave the device partially inflated postoperatively to reduce risk of hematoma. After surgery, monitor patients for potential complications that may warrant device explantation or salvage: IPP infection, glans ischemia, and impending erosion. CONCLUSIONS: By using evidence and expert opinion-based decision-making strategies in the preoperative, intraoperative, and postoperative period of IPP placement, surgeons can reduce the risk of complications and dissatisfaction, even in ED patients with multiple comorbid conditions. Scherzer ND, Dick B, Gabrielson AT, et al. Penile Prosthesis Complications: Planning, Prevention, and Decision Making. Sex Med Rev 2019;7:349-359.

Male Orgasmic Dysfunction Post-Radical Pelvic Surgery.

BACKGROUND: Pelvic surgeries are recognized to cause dysfunction of the male sexual response, which consists of erection, emission, expulsion, and orgasm. However, the least attention has been paid to male orgasmic dysfunction after invasive pelvic surgery. AIM: To describe the available literature on post-pelvic surgery orgasmic dysfunction disorders. METHODS: A literature search was performed on PubMed using the search strings related to dysfunction of the male sexual cycle and orgasm after pelvic surgery. OUTCOMES: Orgasmic dysfunction after pelvic procedures in urologic, colorectal, and vascular surgeries was assessed. RESULTS: Radical prostatectomy was the most common procedure where orgasmic dysfunction was quantified. Anorgasmia post-operatively occurred in patients in a range of 5-70%. Dysorgasmia occurred less frequently from 7-14%. The prevalence of climacturia was highly variable occurring in 20-93% of patients. Radical cystectomy resulted in anorgasmia 33-62% of the time and climacturia ranged from 6-45%. Studies involving colorectal surgeries were less likely to assess for dysorgasmia and climacturia, but anorgasmia rates ranged from 0-52%. Most current studies do not differentiate between ejaculatory and orgasmic dysfunction. However, more recent studies have started to distinguish between the 2 disorders and publish more specific data on what components of the male sexual response has been affected by the specific surgery. CONCLUSIONS: The male sexual response, specifically the male orgasm, is difficult to quantify in a non-obtrusive setting and can exhibit variability between patients and between sexual encounters in the same patient. Data involving the outcome of male orgasmic dysfunction after pelvic surgery are sparse, limiting health professionals' ability to appropriately counsel patients. Future work needs to standardize outcome assessment for orgasmic disorders, which, in turn, can be used across all surgical specialties. Haney NM, Alzweri LM, Hellstrom WJG. Male Orgasmic Dysfunction Post-Radical Pelvic Surgery. Sex Med Rev 2018;6:429-437.

Role of Penile Prosthesis in Priapism: A Review.

Ischemic priapism is a urological emergency that has been associated with long-standing and irreversible adverse effects on erectile function. Studies have demonstrated a linear relationship between the duration of critically ischemic episodes and the subsequent development of corporal fibrosis and irreversible erectile function loss. Placement of a penile prosthesis is a well-established therapeutic option for the management of erectile dysfunction secondary to ischemic priapism, and will be the focus of this review. Review of the current literature demonstrates a growing utilization of penile prostheses in the treatment of erectile dysfunction secondary to ischemic priapism. Unfortunately, there is a paucity of randomized-controlled trials describing the use of prosthesis in ischemic priapism. As a result, there is a lack of consensus regarding the type of prosthesis (malleable vs. inflatable), timing of surgery (acute vs. delayed), and anticipated complications for each approach. Both types of prostheses yielded comparable complication rates, but the inflatable penile prosthesis have higher satisfaction rates. Acute treatment of priapism was associated with increased risk of prosthetic infection, and could potentially cause psychological trauma, whereas delayed implantation was associated with greater corporal fibrosis, loss of penile length, and increased technical difficulty of implantation. The paucity of high-level evidence fuels the ongoing discussion of optimal use and timing of penile prosthesis implantation. Current guidance is based on consensus expert opinion derived from small, retrospective studies. Until more robust data is available, a patient-centered approach and joint decision-making between the patient and his urologist is recommended.