Cardiovascular Safety of Testosterone-Replacement Therapy.

BACKGROUND: The cardiovascular safety of testosterone-replacement therapy in middle-aged and older men with hypogonadism has not been determined. METHODS: In a multicenter, randomized, double-blind, placebo-controlled, noninferiority trial, we enrolled 5246 men 45 to 80 years of age who had preexisting or a high risk of cardiovascular disease and who reported symptoms of hypogonadism and had two fasting testosterone levels of less than 300 ng per deciliter. Patients were randomly assigned to receive daily transdermal 1.62% testosterone gel (dose adjusted to maintain testosterone levels between 350 and 750 ng per deciliter) or placebo gel. The primary cardiovascular safety end point was the first occurrence of any component of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, assessed in a time-to-event analysis. A secondary cardiovascular end point was the first occurrence of any component of the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization, assessed in a time-to-event analysis. Noninferiority required an upper limit of less than 1.5 for the 95% confidence interval of the hazard ratio among patients receiving at least one dose of testosterone or placebo. RESULTS: The mean (±SD) duration of treatment was 21.7±14.1 months, and the mean follow-up was 33.0±12.1 months. A primary cardiovascular end-point event occurred in 182 patients (7.0%) in the testosterone group and in 190 patients (7.3%) in the placebo group (hazard ratio, 0.96; 95% confidence interval, 0.78 to 1.17; P<0.001 for noninferiority). Similar findings were observed in sensitivity analyses in which data on events were censored at various times after discontinuation of testosterone or placebo. The incidence of secondary end-point events or of each of the events of the composite primary cardiovascular end point appeared to be similar in the two groups. A higher incidence of atrial fibrillation, of acute kidney injury, and of pulmonary embolism was observed in the testosterone group. CONCLUSIONS: In men with hypogonadism and preexisting or a high risk of cardiovascular disease, testosterone-replacement therapy was noninferior to placebo with respect to the incidence of major adverse cardiac events. (Funded by AbbVie and others; TRAVERSE ClinicalTrials.gov number, NCT03518034.).

Cosmetic penile enhancement procedures: an SMSNA position statement.

BACKGROUND: Penile cosmetic enhancement procedures have been performed for many years with varying success. However, they have historically been relegated to niche areas of sexual medicine, with limited data, and have not achieved mainstream adoption. More recently, the topic has been increasingly discussed within academic congresses due to availability of novel techniques, therapies, and procedures. Given their distinctive nature, the Sexual Medicine Society of North America (SMSNA) felt that it was pertinent to develop formal position statements to help guide both patients and sexual medicine providers on the current state of the scientific literature and to give recommendations for future research. AIM: The study sought to provide an evidence-based set of recommendations for injection and surgical procedures designed to lengthen, augment, or otherwise cosmetically enhance the penis. METHODS: A review was performed of all scientific literature listed in PubMed from inception through December 2023 relating to penile cosmetic enhancement procedures. Only invasive (injection/surgery) therapies were included due to their distinct risk-benefit profile compared with more conservative treatments (eg, vacuum erection devices, penile traction devices). Similar therapies were categorized, with pertinent data summarized and used to help create relevant position statements. All statements were expert opinion only and were based on analyses of the potential risks and benefits of the specific therapies. OUTCOMES: A total of 6 position statements were issued relating to 5 distinct sexual medicine cosmetic enhancement procedures. RESULTS: A consensus opinion was reached by SMSNA leadership on the state of injection/surgical penile cosmetic enhancement procedures as of 2024. Key topic areas addressed included injectable soft tissue fillers, suspensory ligament division, graft-and-flap procedures, silicone sleeve implants, and sliding/slicing techniques. Distinct recommendations were tailored to each therapy and were based solely on the current state of the literature. It is anticipated that future studies will further inform position statements and will lead to ongoing modifications. CLINICAL IMPLICATIONS: The current position statements provide both patients and clinicians evidence-based, expert recommendations on best practices relating to penile cosmetic enhancement procedures. STRENGTHS AND LIMITATIONS: Strengths include the use of an expert panel of sexual medicine clinicians, consensus design, and summary of existing literature. Limitations include expert opinion and limited research on the topic. CONCLUSION: The current SMSNA position statements provide evidence-based, consensus opinions on the appropriate role for penile augmentation and cosmetic procedures in 2024.

Sexual Medicine Society of North America (SMSNA)/American Urological Association (AUA) telemedicine and men's health white paper.

PURPOSE: The purpose of this white paper is to educate health care professionals about the evolution of telemedicine (TM) and to propose a hybrid model that leverages the strengths of traditional in-person medicine as well as virtual medicine while maximizing the safety and quality of men's sexual health care. LITERATURE SEARCH STRATEGY: A literature search focused on the use of TM in urology and men's health was performed through PubMed/MEDLINE, Embase, and Web of Science (January 1, 2012-April 26, 2022). Keywords included all known permutations of the terminology used to refer to virtual health, care as well as the terminology used to refer to urologic diseases, issues specific to men's health, and men's sexual health concerns. Publications that emerged after the literature search that met this criterion also were incorporated. Opinion pieces, letters to the editor, meeting abstracts, and conference proceedings were excluded. Additional resources were retrieved, such as governmental technical reports, legislative updates and reviews, and blogs. This search strategy yielded 1684 records across databases after removal of duplicates. Abstracts from the retrieved records were reviewed for relevance. Relevant publications were defined as those that reported data on any aspect of TM use specific to urology, men's health, and/or men's sexual health. If relevance was unclear from the abstract, then the full text of the article was retrieved for a more detailed review. In addition, the published evidence-based practice guidelines relevant to care for erectile dysfunction, Peyronie's disease, ejaculatory dysfunction, and hypogonadism were retrieved. The most common reasons for article exclusions were a focus on TM use in disciplines other than urology and the absence of data (ie, opinion pieces). After exclusions, a total of 91 publications remained and constituted the evidence base for this paper.

Effect of aerobic exercise on erectile function: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The health benefits of regular aerobic exercise are well established, although there is limited high-quality evidence regarding its impact on erectile function. AIM: To determine the effect of aerobic exercise on erectile function in men and to identify factors that may influence this effect. METHODS: This systematic review and meta-analysis included randomized controlled trials that evaluated the effects of aerobic exercise on erectile function via the Erectile Function domain of the International Index of Erectile Function (IIEF-EF). The mean difference in IIEF-EF scores between the aerobic exercise and nonexercising control groups was estimated by a random-effects meta-analysis. Meta-regression was used to evaluate the association of moderator variables on meta-analysis results. OUTCOMES: The IIEF-EF score is reported on a 6-30 scale, with higher values indicating better erectile function. RESULTS: Among 11 randomized controlled trials included in the analysis, aerobic exercise resulted in statistically significant improvements in IIEF-EF scores as compared with controls, with a mean difference of 2.8 points (95% CI, 1.7-3.9; P < .001) and moderate heterogeneity among studies (I2 = 53%). The effect of aerobic exercise on erectile function was greater in men with lower baseline IIEF-EF scores, with improvements of 2.3, 3.3, and 4.9 points for mild, moderate, and severe erectile dysfunction, respectively (P = .02). The meta-analysis results were not influenced by publication bias or individual study effects. CLINICAL IMPLICATIONS: Health care providers should consider recommending regular aerobic exercise as a low-risk nonpharmacologic therapy for men experiencing erectile difficulties. STRENGTHS AND LIMITATIONS: The primary strength of this review was the generation of level 1 evidence on a topic of general interest regarding sexual health in men. However, the included studies evaluated diverse groups, which may complicate data interpretation for specific segments of the population. CONCLUSION: Regular aerobic exercise can improve the erectile function of men, particularly those with lower baseline IIEF-EF scores.

Effects of long-term testosterone treatment on cardiovascular outcomes in men with hypogonadism: Rationale and design of the TRAVERSE study.

BACKGROUND: Testosterone exerts some effects on the cardiovascular system that could be considered beneficial; some other effects may potentially increase the risk of cardiovascular (CV) events. Neither the long-term efficacy nor safety of testosterone treatment has been studied in an adequately-powered randomized trial. METHODS: The Testosterone Replacement therapy for Assessment of long-term Vascular Events and efficacy ResponSE in hypogonadal men (TRAVERSE) study is a randomized, double-blind, placebo-controlled, parallel group, non-inferiority, multicenter study. Eligible participants are men, 45 to 80 years, with serum testosterone concentration <300 ng/dL and hypogonadal symptoms, who have evidence pre-existing CV disease or increased risk of CV disease. Approximately 6,000 subjects will be randomized to either 1.62% transdermal testosterone gel or a matching placebo gel daily for an anticipated duration of up to 5 years. The primary outcome is CV safety defined by the major adverse CV event composite of nonfatal myocardial infarction, nonfatal stroke, or death due to CV causes. The trial will continue until at least 256 adjudicated major adverse CV event endpoints have occurred to assess whether the 95% (2-sided) upper confidence limit for a hazard ratio of 1.5 can be ruled out. Secondary endpoints include prostate safety defined as the incidence of adjudicated high grade prostate cancer and efficacy in domains of sexual function, bone fractures, depression, anemia, and diabetes. RESULTS: As of July 1, 2021, 5,076 subjects had been randomized. CONCLUSIONS: The TRAVERSE study will determine the CV safety and long-term efficacy of testosterone treatment in middle-aged and older men with hypogonadism with or at increased risk of CV disease.

The Low Submuscular Reservoir Placement With Transfascial Fixation for Inflatable Penile Prostheses.

BACKGROUND: Several techniques have been described for placement of inflatable penile prostheses (IPP) reservoirs, with variable satisfaction. Standard placement in the Space of Retzius can present with several complications and may be technically difficult in patients with a violated space. Concerns with ectopic reservoir placement have included reservoir herniation and lack of reservoir concealability. AIM: To present a novel technique to achieve reservoir concealment with decreased postoperative complications as an alternative to standard approaches of ectopic reservoir placement. METHODS: We describe our novel low submuscular reservoir (LSM) placement with transfascial fixation (TFF) for inflatable penile prostheses. OUTCOMES: Patient satisfaction with reservoir concealment, complication rate or need for additional surgeries. RESULTS: A total of 31 cases successfully underwent our technique. The low submuscular placement with TFF of the IPP reservoir offers an optimal approach for reservoir placement with a high degree of patient satisfaction with significant ease of placement compared to alternative methods. CLINICAL IMPLICATIONS: Penile prosthetic surgeons should be familiar with several techniques for concealment of reservoir as an option to improve patient satisfaction. STRENGTHS AND LIMITATIONS: Given the small sample size of patients who have undergone this novel technique, current literature regarding the topic is limited. CONCLUSION: Low submuscular reservoir placement with transfascial fixation for IPPs is a technically feasible approach that can be employed to achieve patient satisfaction and decrease the risk of reservoir herniation. Khoei A, Racik N, Bansal U, et al. The Low Submuscular Reservoir Placement With Transfascial Fixation for Inflatable Penile Prostheses. J Sex Med 2022;19:1309-1312.

The role of testosterone replacement therapy and statin use, and their combination, in prostate cancer.

PURPOSE: Previous studies have reported conflicting results in the associations of testosterone replacement therapy (TTh) and statins use with prostate cancer (PCa). However, the combination of these treatments with PCa stage and grade at diagnosis and prostate cancer-specific mortality (PCSM) and by race/ethnicity remains unclear. METHODS: We identified non-Hispanic White (NHW, N = 58,576), non-Hispanic Black (NHB, n = 9,703) and Hispanic (n = 4,898) men diagnosed with PCa in SEER-Medicare data 2007-2011. Pre-diagnostic prescription of TTh and statins was ascertained for this analysis. Multivariable-adjusted logistic and Cox proportional hazards models were used to evaluate the association of TTh and statins use with PCa stage and grade and PCSM. RESULTS: 22.5% used statins alone, 1.2% used TTh alone, and 0.8% used both. TTh and statins were independently, inversely associated with PCa advanced stage and high grade. TTh plus statins was associated with 44% lower odds of advanced stage PCa (OR 0.56, 95% CI 0.35-0.91). As expected, similar inverse associations were present in NHWs as the overall cohort is mostly comprised NHW men. In Hispanic men, statin use with or without TTh was inversely associated with aggressive PCa. CONCLUSIONS: Pre-diagnostic use of TTh or statins, independent or in combination, was inversely associated with aggressive PCa, including in NHW and Hispanics men, but was not with PCSM. The findings for use of statins with aggressive PCa are consistent with cohort studies. Future prospective studies are needed to explore the independent inverse association of TTh and the combined inverse association of TTh plus statins on fatal PCa.

Testosterone's Role in COVID-19.

COVID-19 consistently displays a higher mortality in males. This sex-specific difference in outcomes is seen not only in the current COVID-19 pandemic, but also in prior viral epidemics and pandemics. Sex hormones, such as testosterone, play a clear role in modulating the immune response, providing a clue that may illuminate the underpinnings of these outcomes. Developing a deeper understanding of these epidemiological findings permits a more effective response to the disease. This article summarizes the sex-specific COVID-19 outcomes, the role of androgens in generating these outcomes, and the potential role of modifying testosterone levels as a form of treatment of COVID-19. Auerbach JM, Khera M. Testosterone's Role in COVID-19. J Sex Med 2021;18:843-848.

Differential Gene Expression in Post-Finasteride Syndrome Patients.

BACKGROUND: An organic etiology underpinning post-finasteride syndrome, a constellation of persistent sexual, neuropsychiatric, and somatic symptoms reported by men exposed to 5-alpha-reductase inhibitors (5ARIs), is debated. Persistent changes in neurosteroid levels or androgen receptor expression have been implicated. AIM: To determine whether differences in gene expression, especially in relevant biologic pathways, exist between patients reporting post-finasteride syndrome symptoms and healthy controls. METHODS: This was a single center, prospective case-control study taking place between March 2013 and September 2018. Men 18 years and older being evaluated for sexual dysfunction (study) or circumcision (control) were eligible for inclusion. Twenty-six men with a history of 5ARI use reporting symptoms consistent with post-finasteride syndrome were included in the patient group. Twenty-six men consented to inclusion in the control group. OUTCOMES: The primary outcome measure is gene expression data for genes affecting neurosteroid levels and androgen receptor activity from penile skin cells. RESULTS: Gene expression of cells from penile skin samples from twenty-six men of median age 38 years (IQR, 33-42) in the study group was compared with that from twenty-six men of median age 41 years (IQR, 35-62) in the control group (P = .13), with 1,446 genes significantly over-expressed and 2,318 genes significantly under-expressed in study patients. Androgen receptor expression was significantly higher in study patients compared to controls (9.961 vs 9.494, adjusted P value = .01). Serum levels of androgen receptor activity markers 5α-androstanediol (0.950 ng/mL [0.749-1.587] vs 0.949 [0.817-1.337], P = .34) or 3α-androstanedione (3.1 ng/mL [1.925-5.475] vs 6.7 [3.375-11.4], P = .31) revealed no significant differences. No significant differences were found between the number of trinucleotide repeats (21.5 [20-23.75], 22 [19-25], P = .94). CLINICAL IMPLICATIONS: In this study we present evidence of gene expression correlating with observed biologic differences in patients with post-finasteride syndrome; providers who prescribe 5ARIs should be aware and advise their patients accordingly. STRENGTHS & LIMITATIONS: Strengths of this study include the evaluation of multiple proposed etiologies for post-finasteride syndrome. The study is also strengthened by the fact that not all data matched the initial hypotheses, qualifying the argument for the existence of PFS. Limitations include potential selection bias arising from more severe phenotypes seeking care; lack of gene expression data prior to 5ARI exposure; lack of non-penile tissue samples supposedly involved; and a lack of mechanistic data to imply causality. CONCLUSION: This study is the first to consider and demonstrate gene expression differences in patients with PFS as a potential etiology of sexual dysfunction. Howell S, Song W, Pastuszak A, et al. Differential Gene Expression in Post-Finasteride Syndrome Patients. J Sex Med 2021;18:1479-1490.

Testosterone Therapy and Cardiovascular Risk: A Critical Analysis of Studies Reporting Increased Risk.

BACKGROUND: Treatment of "adult-onset hypogonadism" (AOH) with exogenous testosterone therapy (TTh) to raise serum testosterone (T) levels may influence cardiovascular (CV) risk factors in patients with AOH, whereas low endogenous T levels are associated with an increased CV risk and mortality. AIM: To critically evaluate studies reporting increased CV risk associated with TTh and to provide an overview of the risks and benefits of restoring T levels through exogenous TTh. METHODS: A review of publications focusing on the association between TTh and increased CV risk was conducted, and the study methodologies and conclusions of each were critically evaluated. Further, recent clinical and epidemiological studies associating AOH or TTh with a change in CV risk, and pertinent hematologic and vascular effects noted in animal studies and in vitro, as well as in clinical practice were also reviewed. OUTCOMES: A review of the literature shows that untreated testosterone deficiency and/or low T is associated with an increase in CV risk and adverse outcomes, with numerous studies and meta-analyses to support a positive association between exogenous TTh and an improvement in CV risk factors in men with AOH. RESULTS: Numerous studies in the literature demonstrate the positive benefits of using TTh; however, since 2013, some publications have suggested a link to increased CV risk associated with TTh. A number of these studies retrospectively analyzed insurance claims databases using diagnosis codes, procedures codes, and prescription information. Many reviews published since have pointed out the methodological flaws and debatable conclusions of these studies. CLINICAL IMPLICATIONS: A careful assessment of the patient's current health status and CV risk factors should be weighed against the benefits and possible risks resulting from TTh, and consideration should be given to deferring treatment pending resolution or stabilization of CV disease or risk factors. STRENGTHS & LIMITATIONS: In this review, we provide an in-depth analysis of studies reporting increased CV risk with TTh. Many of the studies were not well-designed, randomized, double-blind, prospective clinical trials but rather post hoc analyses of cohort data. These studies may reflect bias in how treatment and nontreatment decisions are made or reflect conclusions based on widely cited methodological flaws. CONCLUSION: Appropriate patient selection supported by low pre-treatment T levels and monitoring T levels during treatment with the goal of achieving and maintaining physiologic levels all contribute to the safe and effective use of TTh in men with AOH. Khera M, Miner M, Jaffe J, et al. Testosterone Therapy and Cardiovascular Risk: A Critical Analysis of Studies Reporting Increased Risk. J Sex med 2021;18:83-98.

Ectopic low submuscular pressure regulating balloon placement with transfascial fixation for artificial urinary sphincter.

INTRODUCTION: To present our novel low submuscular (LSM) pressure regulating balloon (PRB) placement for artificial urinary sphincter (AUS) technique as an alternative to standard approaches with patient-reported satisfaction outcomes. MATERIAL AND METHODS: A retrospective review was conducted on patients who underwent an AUS implantation using the LSM PRB placement with transfascial fixation technique from July 2019 to August 2020. Preoperative characteristics were collected. Patients then conducted a postoperative phone interview using an adapted questionnaire to assess satisfaction of device and PRB concealment. RESULTS: During the study period, nine patients had undergone AUS placement using the LSM technique by a single surgeon at our private institution. Eight of the nine patients had undergone a radical prostatectomy while the ninth patient developed stress urinary incontinence after radiation treatment for prostate cancer. All patients were 'very satisfied' with PRB placement and concealment with no patients endorsing PRB complications. The majority of patients (78%) were satisfied with the device. One patient was able to palpate the PRB while another patient endorsed mild soreness around the PRB. No surgical revisions were required and there were no surgical complications such as bowel obstruction, herniations, bladder erosions, or vascular injuries. CONCLUSION: LSM placement of AUS PRB with transfascial fixation offers an improved technique for balloon placement with decreased risk for complications. This can be performed as a safe, alternative approach to current standard techniques with a high degree of patient satisfaction.

Controversies with testosterone therapy.

INTRODUCTION: Over the past decade, there have been concerns with safety of testosterone therapy (TTh) in hypogonadal men. Several concerns have centered on the use of TTh and its potential link to cardiovascular (CV) events, prostate cancer, and benign prostatic hyperplasia (BPH). There has also been controversy in determining which patients are appropriate candidates for TTh and if lifestyle modification has any role in improving serum testosterone values in hypogonadal men. MATERIALS AND METHODS: A literature review of all articles assessing testosterone and the use of TTh and the association with CV events, prostate cancer, BPH and lifestyle modification was conducted. RESULTS: Majority of patients treated with TTh today are treated off-label. Low serum testosterone levels have been associated with increased CV events. Currently, there is inconclusive evidence to support that TTh increases the risk of CV events. There is an absence of evidence linking TTh to the development of prostate cancer or worsening of BPH symptoms. Finally, lifestyle modification, such as decreasing weight and improving sleep, can improve serum testosterone levels in hypogonadal men. CONCLUSIONS: Clinicians prescribing testosterone should be aware of the current controversies associated with TTh. The current literature does not suggest that there is a significant risk with TTh and prostate cancer, worsening of BPH symptoms or CV events. However, more studies, including randomized placebo-controlled trials, are needed. Finally, patients should be counseled appropriately regarding the indications for TTh and the benefits of lifestyle modification prior to initiating TTh.

Association of the extent of therapy with prostate cancer in those receiving testosterone therapy in a US commercial insurance claims database.

BACKGROUND: Conflicting evidence remains in the association of testosterone therapy (TTh) with prostate cancer (PCa). This inconsistency maybe due, in part, to the small sample sizes from previous studies and an incomplete assessment of comorbidities, particularly diabetes. OBJECTIVE: We investigated the association of PCa with TTh (injection or gel) and different TTh doses and determined whether this association varies by the presence of diabetes at baseline in a large, nationally representative, commercially insured cohort. DESIGN: We conducted a retrospective cohort study of 189 491 men aged 40-60 years old in the IBM MarketScan® Commercial Database, which included 1424 PCa cases diagnosed from 2011 to 2014. TTh was defined using CPT codes from inpatient and outpatient, and NDC codes from pharmacy claims. Multivariable adjusted Cox proportional hazards models were used to compute hazard ratios for patients with incident PCa. RESULTS: We found a 33% reduced association of PCa after comparing the highest category (>12) of TTh injections with the lowest (1-2 injections) category (HR = 0.67, 95% CI: 0.54-0.82). Similar statistical significant inverse association for PCa was observed for men who received TTh topical gels (>330 vs 1- to 60-days supply). Among nondiabetics, we found significant inverse association between TTh (injection and gel) and PCa, but a weak interaction between TTh injections and diabetes (P = .05). CONCLUSION: Overall, increased use of TTh is inversely associated with PCa and this remained significant only among nondiabetics. These findings warrant further investigation in large randomized placebo-controlled trials to infer any health benefit by TTh.

Caffeine intake is not associated with serum testosterone levels in adult men: cross-sectional findings from the NHANES 1999-2004 and 2011-2012.

OBJECTIVE: The association of caffeine intake with testosterone remains unclear. We evaluated the association of caffeine intake with serum testosterone among American men and determined whether this association varied by race/ethnicity and measurements of adiposity. METHODS: Data were analyzed for 2581 men (≥20 years old) who participated in the cycles of the NHANES 1999-2004 and 2011-2012, a cross-sectional study. Testosterone (ng/mL) was measured by immunoassay among men who participated in the morning examination session. We analyzed 24-h dietary recall data to estimate caffeine intake (mg/day). Multivariable weighted linear regression models were conducted. RESULTS: We identified no linear relationship between caffeine intake and testosterone levels in the total population, but there was a non-linear association (pnonlinearity < .01). Similarly, stratified analysis showed nonlinear associations among Mexican-American and Non-Hispanic White men (pnonlinearity ≤ .03 both) and only among men with waist circumference <102 cm and body mass index <25 kg/m2 (pnonlinearity < .01, both). CONCLUSION: No linear association was identified between levels of caffeine intake and testosterone in US men, but we observed a non-linear association, including among racial/ethnic groups and measurements of adiposity in this cross-sectional study. These associations are warranted to be investigated in larger prospective studies.

Erectile Dysfunction: AUA Guideline.

PURPOSE: The purpose of this guideline is to provide a clinical strategy for the diagnosis and treatment of erectile dysfunction. MATERIALS AND METHODS: A systematic review of the literature using the Pubmed, Embase, and Cochrane databases (search dates 1/1/1965 to 7/29/17) was conducted to identify peer-reviewed publications relevant to the diagnosis and treatment of erectile dysfunction. Evidence-based statements were based on body of evidence strength Grade A, B, or C and were designated as Strong, Moderate, and Conditional Recommendations with additional statements presented in the form of Clinical Principles or Expert Opinions. RESULTS: The American Urological Association has developed an evidence-based guideline on the management of erectile dysfunction. This document is designed to be used in conjunction with the associated treatment algorithm. CONCLUSIONS: Using the shared decision-making process as a cornerstone for care, all patients should be informed of all treatment modalities that are not contraindicated, regardless of invasiveness or irreversibility, as potential first-line treatments. For each treatment, the clinician should ensure that the man and his partner have a full understanding of the benefits and risk/burdens associated with that choice.

The state of testosterone therapy since the FDA's 2015 labelling changes: Indications and cardiovascular risk.

OBJECTIVE: A label change in testosterone (T) products in March 2015 followed a highly publicized FDA advisory committee meeting in September 2014. Changes included a warning of possible increased cardiovascular (CV) risks and restriction of indicated populations to younger men with a limited set of known aetiologies of testosterone deficiency (TD). These changes greatly impacted clinical practice and public perception of T therapy (TTh). Our aim was to review these changes in the light of subsequently published studies. DESIGN: We identified 23 studies through June 2017, including 12 clinical trials and 11 observational studies. The Testosterone Trials included 790 men aged 65 years and older with TD without known aetiology, assigned to 1-year T gel or placebo. RESULTS: Demonstrated benefits of T included sexual activity and desire, physical activity and mood. There were 9 major adverse CV events (MACE) in the T arm and 16 in the placebo arm. No study reported increased MACE with TTh. A 3-year RCT showed no difference in carotid atherosclerosis. Several large observational studies reported reduced CV events with TTh, including one showing progressively reduced CV and mortality risk with greater duration of TTh. Men whose serum T normalized with TTh had reduced risk of MI and death compared with men whose T levels failed to normalize. CONCLUSION: We conclude that existing evidence fails to support increased CV risk with TTh; on the contrary, there is evidence suggestive of real-world CV benefits. Finally, existing evidence provides benefits of TTh in older men without known aetiology for T deficiency.

Topical Testosterone Therapy Adherence and Outcomes Among Men With Primary or Secondary Hypogonadism.

BACKGROUND: Men with primary or secondary hypogonadism (HG) prescribed testosterone therapy (TTh) who terminate treatment early might not obtain the benefit of symptom relief. AIM: To estimate adherence to topical TTh and to compare baseline characteristics and follow-up outcomes between adherent and non-adherent patients in a population of commercially insured US men with primary or secondary HG. METHODS: A retrospective cohort of adult men with primary or secondary HG and initiating topical TTh from 2007 through 2014, with continuous coverage during 12-month baseline and follow-up periods, was identified from a large US health plan. Clinical conditions were assessed using International Classification of Diseases, 9th Revision, Clinical Modification codes. Adherence to initial topical TTh was defined as proportion of days covered of at least 80%. Characteristics and outcomes were compared across adherent and non-adherent patients. OUTCOMES: Adherence to topical TTh, occurrence of HG-related clinical outcomes, and total health care costs. RESULTS: We identified 3,184 topical TTh initiators (mean age = 49 years), of whom 17% (n = 538) were adherent at 12 months. Factors positively associated with adherence included prescribing by specialists, a lower prevalence of certain comorbidities at baseline, residence in the Northeast, and an earlier start year of the topical TTh prescription. Adherence to topical TTh was associated with lower odds of having HG-associated clinical conditions (composite measure) over 12-month follow-up. In the subset of patients with available laboratory results, adherent patients had greater increases in testosterone levels compared with non-adherent patients. Increased pharmacy costs for adherent patients were partly offset by decreases in medical costs. CLINICAL IMPLICATIONS: Adherence to topical testosterone is low but associated with positive outcomes, demonstrating the need for future efforts to focus on improving adherence in this population. STRENGTHS AND LIMITATIONS: Strengths of this study include the large number of analyzed patients and the routine care (rather than interventional trial) setting, which maximizes generalizability within the source population. Limitations are primarily a result of reliance on medical claims data, which lack clinical context and are subject to potential coding errors. Certain factors of potential importance for adherence, such as patient and provider preferences, were not available in the dataset. The study analyzed commercially insured US patients and our ability to generalize these results to the entire US population or other countries might be limited. CONCLUSION: Study findings provide further evidence for suboptimal topical TTh adherence among men treated for primary or secondary HG. Adherence is associated with greater improvement in total testosterone laboratory values and might be associated with a lower likelihood of having certain HG-related conditions. Grabner M, Hepp Z, Raval A, et al. Topical Testosterone Therapy Adherence and Outcomes Among Men With Primary or Secondary Hypogonadism. J Sex Med 2018;15:148-158.

Penile Prosthesis Implantation in Patients With Peyronie's Disease: Results of the PROPPER Study Demonstrates a Decrease in Patient-Reported Depression.

BACKGROUND: Although there is a strong correlation between erectile dysfunction and Peyronie's disease (PD), there are limited data on the efficacy and satisfaction of inflatable penile prosthesis (IPP) placement in this population. AIM: To assess the efficacy and overall satisfaction of IPP placement in men with erectile dysfunction and concomitant PD using the Prospective Registry of Outcomes with Penile Prosthesis for Erectile Restoration (PROPPER). METHODS: Data from the PROPPER study were examined to determine patient baseline characteristics and primary and secondary etiologies before IPP treatment and included type and size of implant received, presence of corporal fibrosis, and operative time. Men completed 5 validated questionnaires at baseline and annually out to 5 years. OUTCOMES: IPP placement was performed in 250 patients with PD with comparable surgical times and outcomes as in patients without PD. RESULTS: 1,180 men underwent IPP insertion at 11 sites; of these, 250 (21.2%) were diagnosed with PD. This is an ongoing study; 1- and 2-year data are available for 177 (70.8%) and 130 (52.0%) patients, respectively. Intraoperatively, 51.2% patients with PD had corporal fibrosis, with an average operative time of 52.8 minutes. At baseline, 19.3% of men (36 of 187) with PD reported being depressed, with a decrease to 10.5% (6 of 57; P = .02) and 10.9% (5 of 46; P = .07) at 1- and 2-year follow-ups, respectively. More than 80% of patients with PD were satisfied or very satisfied at 1- and 2-year follow-ups. In addition, more than 88% of patients with PD were using their device at the 1- and 2-year follow-up visits. CLINICAL IMPLICATIONS: Patients with concomitant PD and erectile dysfunction can safely and effectively have an IPP placed with similar outcomes as patients without PD. STRENGTHS AND LIMITATIONS: The 1st limitation was that all participating prosthetic urologists were high-volume implanters and these results might not be representative of those of general urologists. A 2nd limitation was that none of the patients were randomized. A 3rd limitation was that although most study points were mandatory, some of the data collection, including depression data, was optional, with not all sites participating. A 4th limitation was that depression data were self-reported. CONCLUSION: IPP can be inserted in patients with PD with acceptable patient satisfaction and usage and depressive symptoms appear to lessen in patients with PD after IPP placement. Khera M, Bella A, Karpman E, et al. Penile Prosthesis Implantation in Patients With Peyronie's Disease: Results of the PROPPER Study Demonstrates a Decrease in Patient-Reported Depression. J Sex Med 2018;15:786-788.

The Role of Testosterone Therapy in the Setting of Prostate Cancer.

PURPOSE OF REVIEW: The role of testosterone in the development of prostate cancer and the safety of testosterone therapy (TTh) after prostate cancer treatment, or in the setting of active surveillance, remains controversial. There are many concerns about using TTh in men, particularly those with a history of prostate cancer, ranging from a possible increased risk of cardiovascular disease to cancer progression or recurrence. With many prostate cancer patients living longer, and hypogonadism having significant morbidity, much care must go into the decision to treat. Here, we review the literature investigating the effects of testosterone on the prostate as well as the efficacy and safety of exogenous testosterone in men with a history of prostate cancer. RECENT FINDINGS: The improvement in quality of life with TTh is well studied and understood, while the argument for significantly increased risk of cancer or other adverse effects is much less robust. Neither increased rates of prostate cancer, cancer recurrence, or cardiovascular risk have been well established. In men with high-risk prostate cancer, evidence in the setting of TTh is very limited, and TTh should be used with caution. The fears of TTh causing or worsening prostate cancer do not appear to be well supported by available data. Though more studies are needed to definitively determine the safety of TTh in men with prostate cancer, consideration should be given to treatment of hypogonadal men with a history of CaP.

Testosterone inhibits the growth of prostate cancer xenografts in nude mice.

BACKGROUND: Traditional beliefs of androgen's stimulating effects on the growth of prostate cancer (PCa) have been challenged in recent years. Our previous in vitro study indicated that physiological normal levels of androgens inhibited the proliferation of PCa cells. In this in vivo study, the ability of testosterone (T) to inhibit PCa growth was assessed by testing the tumor incidence rate and tumor growth rate of PCa xenografts on nude mice. METHODS: Different serum testosterone levels were manipulated in male nude/nude athymic mice by orchiectomy or inserting different dosages of T pellets subcutaneously. PCa cells were injected subcutaneously to nude mice and tumor incidence rate and tumor growth rate of PCa xenografts were tested. RESULTS: The data demonstrated that low levels of serum T resulted in the highest PCa incidence rate (50%). This PCa incidence rate in mice with low T levels was significantly higher than that in mice treated with higher doses of T (24%, P < 0.01) and mice that underwent orchiectomy (8%, P < 0.001). Mice that had low serum T levels had the shortest tumor volume doubling time (112 h). This doubling time was significantly shorter than that in the high dose 5 mg T arm (158 h, P < 0.001) and in the orchiectomy arm (468 h, P < 0.001). CONCLUSION: These results indicated that low T levels are optimal for PCa cell growth. Castrate T levels, as seen after orchiectomy, are not sufficient to support PCa cell growth. Higher levels of serum T inhibited PCa cell growth.