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Background: Tadalafil is a long-acting phosphodiesterase-5 inhibitor (PDE-5i) indicated for erectile dysfunction (ED)., Hypothesis: Our hypothesis was that tadalafil will reduce the risk of major adverse cardiovascular events (MACE: composite of cardiovascular death, myocardial infarction, coronary revascularization, unstable angina, heart failure, stroke) and all-cause death in men with ED., Methods: A retrospective observational cohort study was conducted in a large US commercial insurance claims database in men with a diagnosis of ED without prior MACE within 1 year. The exposed group (n = 8156) had ≥1 claim for tadalafil; the unexposed group (n = 21 012) had no claims for any PDE-5i., Results: Primary outcome was MACE; secondary outcome was all-cause death. Groups were matched for cardiovascular risk factors, including preventive therapy. Over a mean follow-up of 37 months for the exposed group and 29 months for the unexposed group, adjusted rates of MACE were 19% lower in men exposed to tadalafil versus those unexposed to any PDE-5i (hazard ratio [HR] = 0.81; 95% confidence intervals [CI] = 0.70-0.94; p = .007). Tadalafil exposure was associated with lower adjusted rates of coronary revascularization (HR = 0.69; 95% CI = 0.52-0.90; p = .006); unstable angina (HR = 0.55; 95% CI = 0.37-0.81; p = .003); and cardiovascular-related mortality (HR = 0.45; CI = 0.22-0.93; p = .032). Overall mortality rate was 44% lower in men exposed to tadalafil (HR = 0.56; CI = 0.43-0.74; p < .001). Men in the highest quartile of tadalafil exposure had the lowest rates of MACE (HR: 0.40; 95% CI: 0.28-0.58; p < .001) compared to lowest exposure quartile., Conclusion: In men with ED, exposure to tadalafil was associated with significant and clinically meaningful lower rates of MACE and overall mortality., (© 2024 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Background: In 1999, 1 year after the approval of the first oral phosphodiesterase type 5 (PDE5) inhibitor for the treatment of erectile dysfunction (ED), the first Princeton Consensus Conference was held to address the clinical management of men with ED who also had cardiovascular disease. These issues were readdressed in the second and third conferences. In the 13 years since the last Princeton Consensus Conference, the experience with PDE5 inhibitors is more robust, and recent new data have emerged regarding not only safety and drug-drug interactions, but also a potential cardioprotective effect of these drugs., Aim: In March 2023, an interdisciplinary group of scientists and practitioners met for the fourth Princeton Consensus Guidelines at the Huntington Medical Research Institutes in Pasadena, California, to readdress the cardiovascular workup of men presenting with ED as well as the approach to treatment of ED in men with known cardiovascular disease., Method: A series of lectures from experts in the field followed by Delphi-type discussions were developed to reach consensus., Outcomes: Consensus was reached regarding a number of issues related to erectile dysfunction and the interaction with cardiovascular health and phosphodiesterase-5 inhibitors., Results: An algorithm based on recent recommendations of the American College of Cardiology and American Heart Association, including the use of computed tomography coronary artery calcium scoring, was integrated into the evaluation of men presenting with ED. Additionally, the issue of nitrate use was further considered in an algorithm regarding the treatment of ED patients with coronary artery disease. Other topics included the psychological effect of ED and the benefits of treating it; the mechanism of action of the PDE5 inhibitors; drug-drug interactions; optimizing use of a PDE5 inhibitors; rare adverse events; potential cardiovascular benefits observed in recent retrospective studies; adulteration of dietary supplements with PDE5 inhibitors; the pros and cons of over-the-counter PDE5 inhibitors; non-PDE5 inhibitor therapy for ED including restorative therapies such as stem cells, platelet-rich plasma, and shock therapy; other non-PDE5 inhibitor therapies, including injection therapy and penile prostheses; the issue of safety and effectiveness of PDE5 inhibitors in women; and recommendations for future studies in the field of sexual dysfunction and PDE5 inhibitor use were discussed., Clinical Implications: Algorithms and tables were developed to help guide the clinician in dealing with the interaction of ED and cardiovascular risk and disease., Strengths and Limitations: Strengths include the expertise of the participants and consensus recommendations. Limitations included that participants were from the United States only for this particular meeting., Conclusion: The issue of the intersection between cardiovascular health and sexual health remains an important topic with new studies suggesting the cardiovascular safety of PDE5 inhibitors., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine.)

Background: Treatment with phosphodiesterase type 5 inhibitors (PDE-5is) is effective in treating erectile dysfunction (ED)., Aim: The objective of this study was to determine the effect of PDE-5is on the incidence of major adverse cardiovascular (CV) events (MACE; composite outcome of CV death, hospitalization for myocardial infarction, coronary revascularization, stroke, heart failure, and unstable angina pectoris) and overall mortality., Methods: A retrospective observational cohort study was conducted in a large US claims database in men with ≥1 diagnosis of ED without prior MACE within 1 year, from January 1, 2006, to October 31, 2020. The exposed group had ≥1 claim for PDE-5i and the unexposed group had no claims for PDE-5i, and the groups were matched up to 1:4 on baseline risk variables., Outcome: The primary outcome was MACE and the secondary outcomes were overall mortality and individual components of MACE, determined by multivariable Cox proportional hazard modeling., Results: Matched plus multivariable analyses showed that MACE was lower by 13% in men exposed (n = 23 816) to PDE-5is (hazard ratio [HR] 0.87; 95% CI 0.79-0.95; P = .001) vs nonexposure (n = 48 682) over mean follow-up periods of 37 and 29 months, respectively, with lower incidence of coronary revascularization (HR 0.85; 95% CI 0.73-0.98; P = .029), heart failure (HR 0.83; 95% CI 0.72-0.97; P = .016), unstable angina (HR 0.78; 95% CI 0.64-0.96; P = .021), and CV death (HR 0.61; 95% CI 0.41-0.90; P = .014) with PDE-5i exposure. Phosphodiesterase type 5 inhibitor-exposed men had a 25% lower incidence of overall mortality (HR 0.75; 95% CI 0.65-0.87; P < .001). Men without coronary artery disease (CAD) but with CV risk factors at baseline showed a similar pattern. In the main study cohort, men in the highest quartile of PDE-5i exposure had the lowest incidence of MACE (HR 0.45; 95% CI 0.37-0.54; P < .001) and overall mortality (HR 0.51; 95% CI 0.37-0.71; P < .001) vs the lowest exposure quartile. In a subgroup with baseline type 2 diabetes (n = 6503), PDE-5i exposure was associated with a lower MACE risk (HR 0.79; 95% CI 0.64-0.97; P = .022)., Clinical Implications: PDE-5is may have cardioprotective effects., Strengths and Limitations: Strengths are the large numbers of participants and consistency of the data; limitations include the retrospective nature of the study and unknown confounders., Conclusions: In a large population of US men with ED, PDE-5i exposure was associated with lower incidence of MACE, CV death, and overall mortality risk compared to non-exposure. Risk reduction correlated with PDE-5i exposure level., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine.)

Aims: Five-α reductase inhibitor (5ARI) therapy has been associated with sexual dysfunction in some patients. This study assessed the impact of a fixed-dose combination of the 5ARI dutasteride 0.5 mg and the α 1 -adrenoceptor antagonist tamsulosin 0.4 mg (DUT-TAM FDC) on Men's Sexual Health Questionnaire (MSHQ) domain scores in patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH)., Methods: This was a post hoc analysis of a double-blind, randomised, placebo-controlled, parallel-group, multicentre study in sexually active patients, aged ≥50 years, with a confirmed clinical diagnosis of BPH. Sexual activity, sexual desire, and bother domain scores of the MSHQ were assessed at baseline and at Months 1, 3, 6, 9, and 12. Correlation between MSHQ sexual activity/desire scores and ejaculation, erection, and satisfaction domains at baseline was also evaluated., Results: In the intent-to-treat population (N = 489), 243 and 246 patients were randomised to DUT-TAM FDC and placebo groups, respectively. Compared with placebo, DUT-TAM FDC therapy resulted in statistically significant reductions (worsening) from baseline in adjusted mean MSHQ sexual activity and bother domain scores at Months 1, 3, 6, 9, and 12 (all P < 0.05) and in adjusted mean MSHQ sexual desire domain scores at Months 6, 9, and 12 (all P < 0.05). Significant moderate correlations in the expected direction were observed at baseline between the sexual activity/desire domains and the ejaculation, erection, and satisfaction domains (P < 0.0001)., Conclusions: These findings help clarify the degree and impact of libido changes in sexually active men treated with DUT-TAM FDC and may support clinical decision-making., (© 2018 The Authors. International Journal of Clinical Practice Published by John Wiley & Sons Ltd.)

Introduction: The serendipitous discovery of sildenafil (Viagra [sildenafil citrate]) as a treatment for erectile dysfunction (ED) is one of the most fascinating drug development stories of our time. When sildenafil was approved by the U.S. Food and Drug Administration in 1998, it revolutionized the treatment protocol for men with ED, once considered a psychological issue or an inevitable part of aging., Aim: To review the discovery of sildenafil and its role in changing the field of sexual medicine in the context of the epidemiology and history of treatment for ED., Methods: For this narrative review, a literature search was conducted to identify essential articles and was supplemented by author observations from a historical perspective., Main Outcome Measure: A broad overview of ED and its past, current, and future treatments., Results: ED is a prevalent condition for which medical treatment had been limited to genitally localized interventions, including surgery, vacuum pumps, injectable therapies, and intraurethral suppositories. The discovery of sildenafil provided a safe, oral pharmacotherapy for the treatment of ED, sparking greater understanding of the science behind ED and its role in men's overall health., Conclusion: The approval of sildenafil initiated a global conversation about ED that had profound implications for patients, methods of clinical practice, and academic sexual medicine. These changes will catalyze continued advances in ED treatment. Goldstein I, Burnett AL, Rosen RC, et al. The serendipitous story of sildenafil: an unexpected oral therapy for erectile dysfunction. Sex Med Rev 2019;7:115-128., (Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To prospectively assess the impact of the fixed-dose combination (FDC) of the 5α-reductase inhibitor (5ARI), dutasteride 0.5 mg and the α 1 -adrenoceptor antagonist, tamsulosin 0.4 mg (DUT-TAM FDC) therapy on sexual function domain scores in sexually active men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH), using the Men's Sexual Health Questionnaire (MSHQ)., Patients and Methods: This European and Australian double-blind, placebo-controlled, parallel-group study was conducted at 51 centres., Inclusion Criteria: age ≥50 years, International Prostate Symptom Score ≥12, prostate volume ≥30 cc, prostate-specific antigen 1.5-10 ng/mL. Patients were randomised 1:1 to DUT-TAM FDC therapy or placebo for 12 months. The change from baseline to Month 12 on the total MSHQ (primary endpoint) and MSHQ erection, ejaculation and satisfaction domains (secondary outcome) was assessed, using a mixed model repeated measures analysis. Safety was evaluated., Results: The intention-to-treat population included 489 patients (243 DUT-TAM FDC therapy; 246 placebo). A significant decrease (worsening) was observed with DUT-TAM FDC therapy versus placebo on the total MSHQ score (-8.7 vs -0.7; standard error [se]: 0.81, 0.78; P < 0.001), and the ejaculation (-7.5 vs -0.6; se: 0.56, 0.55; P < 0.001) and satisfaction (-0.6 vs +0.3; se: 0.3, 0.29, P = 0.047) domains, but not the erection domain (-1.0 vs -0.5; se: 0.19, 0.19, P = 0.091)., Conclusion: This is the first domain-specific quantitative evaluation of DUT-TAM FDC therapy on sexual function in men with LUTS secondary to BPH. The observed changes in the MSHQ with DUT-TAM FDC therapy were mainly driven by changes in the ejaculation domain. These findings will help give context to erectile and ejaculatory dysfunction AEs reported spontaneously in earlier 5ARI studies., (© 2017 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: Erectile dysfunction (ED) after treatment for prostate cancer with radiotherapy (RT) is well known, and pooled estimates of ED after RT will provide more accurate patient education., Aim: To systematically evaluate the natural history of ED in men with previous erectile function after prostate RT and to determine clinical factors associated with ED., Methods: We performed a review of the PubMed and Medline, Embase, Cochrane Library, and Web of Science databases in April 2016 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Identified reports included a measurement of ED before and after prostate RT. Two hundred seventy-eight abstracts were screened and 105 publications met the criteria for inclusion. Only men with known erectile function before RT were included in the analysis., Outcome: ED after RT of the prostate., Results: In total, 17,057 men underwent brachytherapy (65%), 8,166 men underwent external-beam RT (31%), and 1,046 men underwent both (4%). Seven common instruments were used to measure ED, including 23 different cutoffs for ED. The Sexual Health Inventory for Men (SHIM) was used in 31 studies (30%). Pooled estimates of SHIM-confirmed ED (score <10-17) suggested the prevalence of ED after RT is 34% of men (95% CI = 0.29-0.39) at 1 year and 57% (95% CI = 0.53-0.61) at 5.5 years. Compared with brachytherapy, studies of the two types of radiation increased the proportion of new-onset ED found by 12.3% of studies (95% CI = 2.3-22.4). For every 10% who were lost to follow-up, the proportion of ED reported increased by 2.3% (95% CI = 0.03-4.7)., Clinical Implications: ED is common regardless of RT modality and increases during each year of follow-up. Using the SHIM, ED is found in approximately 50% patients at 5 years., Strengths and Limitations: The strengths of this systematic review include strict inclusion criteria of studies that measured baseline erectile function, no evidence for large effect size bias, and a large number of studies, which allow for modeling techniques. However, all data included in this analysis were observational, which leaves the possibility that residual confounding factors increase the rates of ED., Conclusion: Definitions and measurements of ED after RT vary considerably in published series and could account for variability in the prevalence of reported ED. Loss to follow-up in studies could bias the results to overestimate ED. Gaither TW, Awad MA, Osterberg EC, et al. The Natural History of Erectile Dysfunction After Prostatic Radiotherapy: A Systematic Review and Meta-Analysis. J Sex Med 2017;14:1071-1078., (Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To analyse the proportion of men taking tadalafil 5 mg once daily who experience a combined improvement in symptoms of both erectile dysfunction (ED) and lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH)., Materials and Methods: The data from men aged ≥45 years randomized to tadalafil 5 mg once daily or placebo enrolled in one of four randomized, placebo-controlled LUTS/BPH clinical trials were analysed (N = 927). A novel classification of 'combined responders' to ED and LUTS/BPH treatment was defined, based on published criteria for men who showed improvement in both International Index of Erectile Function - Erectile Function domain (IIEF-EF) score and total International Prostate Symptom Score (IPSS). Descriptive analyses assessed the covariate distribution by responder status. Unadjusted and adjusted logistic regressions provided odds ratios with 95% confidence intervals comparing combined responders with all others (partial and non-responders)., Results: Among men randomized to tadalafil 5 mg, 40.5% were combined responders (n = 189). Among placebo randomized men, 18.3% were combined responders (n = 84). Combined responders, in the total population, had the highest baseline IPSS and lowest baseline IIEF-EF scores, corresponding to the highest level of dysfunction. The majority of men were aged ≤65 years, white, non-obese, non-smokers, and regular alcohol consumers. Only treatment, baseline IPSS, baseline IIEF-EF, obesity and psychoactive medication use were significantly associated with responder status (P ≤ 0.05). Tadalafil-treated men had 2.8 times significantly increased adjusted odds of being combined responders vs non-responders (P < 0.001). For each unit decrease in baseline IIEF-EF or alcoholic drink consumption per week there was a 4% significant increase in the adjusted odds of being a combined responder to tadalafil therapy., Conclusions: This novel measure of combined response is useful in differentiating patients with clinically relevant symptom improvement for both ED and LUTS/BPH after treatment with tadalafil 5 mg once daily vs placebo. This combined responder measure may be useful in future assessment of treatment benefits across patient groups after various types of treatment intervention (e.g. surgical vs pharmacotherapy vs non-pharmacological intervention)., (© 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.)

Epidemiologic studies of sexual function problems in men have focused on the individual male and related sociodemographic characteristics, individual risk factors and lifestyle concomitants, or medical comorbidities. Insufficient attention has been given to the role of sexual and relationship satisfaction and, more particularly, to the perspective of the couple as causes or correlates of sexual problems in men or women. Previously, we reported results of the first large, multi-national study of sexual satisfaction and relationship happiness in 1,009 midlife and older couples in five countries (Brazil, Germany, Japan, Spain, U.S.). For the present study, we examined, within each problem, the association of four major sexual problems in men (loss of sexual desire, erectile problems, premature ejaculation, delayed/absent orgasm) and multiple problems, with male and female partners' assessments of physical intimacy, sexual satisfaction, and relationship happiness, as well as associations with well-known health and psychosocial correlates of sexual problems in men. Sexual problem rates of men in our survey were generally similar to rates observed in past surveys in the general population, and similar risk factors (age, relationship duration, overall health) were associated with lack of desire, anorgasmia, or erection difficulties in our sample. As in previous surveys, there were few correlates of premature ejaculation. As predicted, men with one or more sexual problems reported decreased relationship happiness as well as decreased sexual satisfaction compared to men without sexual problems. Moreover, female partners of men with sexual problems had reduced relationship happiness and sexual satisfaction, although these latter outcomes were less affected in the women than the men. The association of men's sexual problems with men's and women's satisfaction and relationship happiness were modest, as these couples in long-term, committed relationships were notable for their relatively high levels of physical affection and relationship happiness.

Objective: To establish a descriptive profile of men with coexistent erectile dysfunction (ED) and/or benign prostatic hyperplasia (BPH), ED only or BPH only compared to those with neither condition and to identify the determinants of coexisting disease., Materials and Methods: Self-report and/or medication use measures defining ED and BPH were assessed in men aged ≥40 years (N = 2142) between 2001 and 2004 using the National Health and Nutrition Examination Surveys. Descriptive analyses examined the ED and/or BPH covariate distribution. Logistic regressions calculated odds ratios (ORs, 95% confidence interval) comparing men with ED and/or BPH, BPH only, or ED only to men with neither condition., Results: Of 393 men with BPH, 57.8% had coexistent ED, confirming the moderately strong co-occurrence of the conditions (P <.0001). Coexisting ED and/or BPH occurred in 10.6% of participants, whereas 24.4% and 7.7% reported ED and BPH. After age 60, the odds of reporting ED, BPH, or ED/BPH vs neither almost tripled per decade of increasing age, corresponding to prevalence increases. The unadjusted odds of ED and/or BPH vs no disease increased 1.3 times per prostate-specific antigen unit (ng/mL) increase and 1.1 times per C-reactive protein unit (mg/dL) increase. Other predisposing factors for ED and/or BPH included higher body mass index (OR = 2.5), increased antidiabetic (OR = 2.9) or proton pump inhibitor use (OR = 2.3), increased healthcare visits (≥4; OR = 3.5), and more frequent urinary voiding difficulties (OR = 9.7)., Conclusion: Co-occurring ED and/or BPH is evident in ~10% of men ≥40 years old and is associated with significant clinical correlates. Clinicians need to pay greater attention to this clinically important syndrome in aging men., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Treatment satisfaction of men receiving phosphodiesterase 5 inhibitors (PDE5) for erectile dysfunction (ED) and their partners is essential to successful long-term therapy., Aim: This study aims to assess treatment satisfaction, in men with a partial response to on-demand (PRN) PDE5 and their female partners, following tadalafil 5 mg once daily or placebo., Methods: The study was randomized, double-blind, parallel, and placebo-controlled in men primarily with mild to moderate ED. Treatment satisfaction was assessed following a 4-week maximum dose PRN lead-in, 4-week nondrug washout, and treatment through 12 weeks. Men were ≥18 years old with ED for ≥3 months and International Index of Erectile Function Erectile Function score of ≥17 and <26 at screening and <26 following PRN lead-in., Main Outcome Measures: Treatment satisfaction was assessed using the Treatment Satisfaction Scale (TSS) for patients and partners. TSS domain scores range from 0 to 100, with higher values indicating greater satisfaction. Statistical comparisons were made using analysis of covariance., Results: Treatment satisfaction was significantly greater with tadalafil once daily vs. placebo across all TSS domains for both patients and their partners (all P < 0.001). For patients, mean scores for the TSS domains Confidence to Complete Sexual Activity and Satisfaction with Orgasm ranged from 53.7 to 57.8 after the PRN lead-in and 26.7 to 31.9 following the nondrug washout. Following randomized treatment, scores for tadalafil and placebo were 55.4 and 32.6, respectively, for Confidence to Complete Sexual Activity and 57.5 and 37.9, respectively, for Satisfaction with Orgasm. Results were comparable for other TSS domains and between men and their partners., Conclusions: Treatment satisfaction was comparable for tadalafil 5 mg once daily and PRN PDE5 for both patients and female partners, suggesting that tadalafil once daily is a viable therapy option for men with ED who had a partial response to PRN PDE5 therapy., (© 2015 International Society for Sexual Medicine.)

Erectile dysfunction negatively affects men and women in relationships; however, the subjective experience of erectile dysfunction and phosphodiesterase-type 5 inhibitor therapy remains poorly understood. The authors therefore characterized participants' subjective understanding of erectile dysfunction and phosphodiesterase-type 5 inhibitor therapy using individual interviews with affected heterosexual men (n = 58) and women (n = 65). Responses were characterized by 6 psychosocial domains: explanation of the experience, emotional responses, socially expected responses, value of sex, communication with the partner, and treatment expectations. The findings may aid clinicians in relating to men with erectile dysfunction and thus potentially improve effectiveness of therapy.

Introduction: Erectile dysfunction (ED) is associated with cardiovascular disease (CVD); however, the association between change in ED status over time and future underlying CVD risk is unclear., Aim: The aim of this study was to investigate the association between change in ED status and Framingham CVD risk, as well change in Framingham risk., Methods: We studied 965 men free of CVD in the Boston Area Community Health (BACH) Survey, a longitudinal cohort study with three assessments. ED was assessed with the five-item International Index of Erectile Function at BACH I (2002-2005) and BACH II (2007-2010) and classified as no ED/transient ED/persistent ED. CVD risk was assessed with 10-year Framingham CVD risk algorithm at BACH I and BACH III (2010-2012). Linear regression models controlled for baseline age, socio-demographic and lifestyle factors, as well as baseline Framingham risk. Models were also stratified by age (≥/< 50 years)., Main Outcome Measures: Framingham CVD risk and change in Framingham CVD risk were the main outcome measures., Results: Transient and persistent ED was significantly associated with increased Framingham risk and change in risk over time in univariate and age-adjusted models. In younger men, persistent ED was associated with a Framingham risk that was 1.58 percentage points higher (95% confidence interval [CI]: 0.11, 3.06) and in older men, a Framingham risk that was 2.54 percentage points higher (95% CI: -1.5, 6.59), compared with those without ED. Change in Framingham risk over time was also associated with transient and persistent ED in men <50 years, but not in older men., Conclusions: Data suggest that even after taking into account other CVD risk factors, transient and persistent ED is associated with Framingham CVD risk and a greater increase in Framingham risk over time, particularly in younger men. Findings further support clinical assessment of CVD risk in men presenting with ED, especially those under 50 years., (© 2014 International Society for Sexual Medicine.)

Introduction: Despite widespread use of the International Index of Erectile Function (IIEF) in erectile dysfunction (ED) research, there are no published criteria for classifying ED treatment responders in clinical trials or patient management settings. A new classification for treatment response in men with ED has been developed and validated in a large clinical trial database., Aim: The study aims to test discriminant and convergent validity of the responder classification and examine the role of covariates., Method: Treatment assignment was used to test discriminant validity. The diary-based Sexual Encounter Profile (SEP) question ("Did your erection last long enough for you to have successful intercourse?") and Global Assessment Question (GAQ) ("Has the treatment you have been taking over the past study interval improved your erections?") were used to evaluate convergent validity. Chi-square and Cochran-Armitage trend tests were used to examine outcome associations. Logistic regression was used to further assess the relationship of outcomes controlling for covariates., Main Outcome Measure: The classification measure was developed and validated in a database from 17 clinical trials in 3,252 men with ED randomized to placebo or tadalafil. The treatment responder is defined as complete (erectile function [EF] ≥ 26); partial (EF < 26; met minimal clinically important difference [MCID] criteria); or nonresponder following treatment (EF < 26; did not meet MCID)., Results: The new responder definition performed consistently well in all prespecified tests of validity. Eighty-nine percent of subjects classified as complete responders were in the treatment group, and the responder definition was associated with changes on the SEP and GAQ measures, respectively (SEP odds ratio [OR] = 14, 95% confidence intervals [CI] 11-17; GAQ OR = 50, 95% CI 39-88; complete vs. nonresponders)., Conclusions: We developed and validated a novel method of defining an ED treatment responder based on multiple IIEF criteria and using other measures (SEP, GAQ) for validation. The results have implications for understanding results of clinical trials in ED, and in monitoring response to treatment in the clinic., (© 2013 International Society for Sexual Medicine.)

Background: Many individuals with obesity are motivated to lose weight to improve weight-related co-morbidities or psychosocial functioning, including sexual functioning. Few studies have documented rates of sexual dysfunction in persons with obesity. This study investigated sexual functioning, sex hormones, and relevant psychosocial constructs in individuals with obesity who sought surgical and nonsurgical weight loss., Methods: One hundred forty-one bariatric surgery patients (median BMI [25th percentile, 75th percentile] 44.6 [41.4, 50.1]) and 109 individuals (BMI = 40.0 [38.0, 44.0]) who sought nonsurgical weight loss participated. Sexual functioning was assessed by the Female Sexual Function Index (FSFI) and the International Index of Erectile Function (IIEF). Hormones were assessed by blood assay. Quality of life, body image, depressive symptoms, and marital adjustment were assessed by validated questionnaires., Results: Fifty-one percent of women presenting for bariatric surgery reported a sexual dysfunction; 36% of men presenting for bariatric surgery reported erectile dysfunction (ED). This is in contrast to 41% of women who sought nonsurgical weight loss and reported a sexual dysfunction and 20% of men who sought nonsurgical weight loss and reported ED. These differences were not statistically significant. Sexual dysfunction was strongly associated with psychosocial distress in women; these relationships were less strong and less consistent among men. Sexual dysfunction was unrelated to sex hormones, except for sex hormone binding globulin (SHGB) in women., Conclusion: Women and men who present for bariatric surgery, compared with individuals who sought nonsurgical weight loss, were not significantly more likely to experience a sexual dysfunction. There were few differences in reproductive hormones and psychosocial constructs between candidates for bariatric surgery and individuals interested in nonsurgical weight loss., (Copyright © 2013 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: We established erectile dysfunction as an often neglected but valuable marker of cardiovascular risk, particularly in younger men and men with diabetes. We also reviewed evidence that lifestyle change, combined with informed prescribing of pharmacotherapies used to mitigate cardiovascular risk, can improve overall vascular health and sexual functioning in men with erectile dysfunction., Materials and Methods: We performed a PubMed® search for articles and guidelines pertinent to relationships between erectile dysfunction and cardiovascular disease, cardiovascular and all cause mortality, and pharmacotherapies for dyslipidemia and hypertension. The clinical guidance presented incorporates the current literature and the expertise of the multispecialty investigator group., Results: Numerous cardiovascular risk assessment tools exist but risk stratification remains challenging, particularly in patients at low or intermediate short-term risk. Erectile dysfunction has a predictive value for cardiovascular events that is comparable to or better than that of traditional risk factors. Interventional studies support lifestyle changes as a means of improving overall vascular health as well as sexual functioning. Statins, diuretics, β-blockers and renin-angiotensin system modifiers may positively or negatively affect erectile function. Furthermore, the phosphodiesterase type 5 inhibitors used to treat erectile dysfunction may have systemic vascular benefits., Conclusions: Erectile dysfunction treatment should be considered secondary to decreasing cardiovascular risk. However, informed prescribing may prevent worsening sexual function in men receiving pharmacotherapy for dyslipidemia and hypertension. As the first point of medical contact for men with erectile dysfunction symptoms, the primary care physician or urologist has a unique opportunity to identify those who require early intervention to prevent cardiovascular disease., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Reliability of successful outcomes in men with erectile dysfunction (ED) on phosphodiesterase type 5 inhibitors is an important aspect of patient management., Aims: We examined reliability of successful outcomes in a large integrated dataset of randomized tadalafil trials., Main Outcome Measures: Success rates, time to success, subsequent success after first success, and probability of success were analyzed based on Sexual Encounter Profile questions 2 and 3., Methods: Data from 3,254 ED patients treated with tadalafil 10 mg (N = 510), 20 mg (N = 1,772), or placebo (N = 972) were pooled from 17 placebo-controlled studies., Results: Tadalafil patients had significantly higher first-attempt success rates vs. placebo. This effect was consistent across most subgroups; however, patients with severe ED experienced a greater response to tadalafil than patients with mild-moderate ED. Approximately 80% of patients achieved successful penile insertion within two attempts with either tadalafil dose and successful intercourse within eight attempts for tadalafil 10 mg and four attempts for tadalafil 20 mg. However, approximately 70% of tadalafil-treated patients achieved successful intercourse even by the second attempt. Subsequent success rates were higher for patients with first-attempt success (81.5% for 10 mg and 86.1% for 20 mg vs. 66.2% for placebo, P < 0.001) vs. patients with later initial success (53.2% for 10 mg and 56.4% for 20 mg vs. 39.9% for placebo, P < 0.001). Among patients treated with tadalafil, intercourse success rates at early attempts were similar to rates at later attempts (i.e., attempts 5 and 10 vs. 25), although insertion success rates were significantly lower earlier in treatment., Conclusions: The findings affirm the reliability of successful outcomes with tadalafil treatment and that first-attempt success is a critical factor affecting subsequent outcomes. The results further show that even among men who did not succeed on first attempt, a substantial proportion will have successful outcomes if treatment is maintained., (© 2012 International Society for Sexual Medicine.)

Background: Erectile dysfunction and low testosterone levels frequently occur together., Objective: To determine whether addition of testosterone to sildenafil therapy improves erectile response in men with erectile dysfunction and low testosterone levels., Design: Randomized, double-blind, parallel, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00512707), Setting: Outpatient academic research center., Participants: Men aged 40 to 70 years with scores of 25 or less for the erectile function domain (EFD) of the International Index of Erectile Function, total testosterone levels less than 11.45 nmol/L (<330 ng/dL), or free testosterone levels less than 173.35 pmol/L (<50 pg/mL)., Intervention: Sildenafil dose was optimized, and 140 participants were then randomly assigned to 14 weeks of daily transdermal gel that contained 10-g testosterone for 70 participants and placebo for the remaining 70 participants. All participants were included in the primary analysis, although 10 in the testosterone group and 12 in the placebo group did not complete the study., Results: At baseline, the 2 groups had similar EFD scores. Administration of sildenafil alone was associated with a substantial increase in EFD score (mean, 7.7 [95% CI, 6.5 to 8.8]), but change in EFD score after randomization did not differ between the groups (difference, 2.2 [CI, -0.8 to 5.1]; P = 0.150). The findings were similar for other domains of sexual function in younger men, more obese men, and men with lower baseline testosterone levels or an inadequate response to sildenafil alone. Frequency of adverse events was similar for testosterone and placebo groups., Limitation: Whether testosterone could improve erectile function without sildenafil was not studied., Conclusion: Sildenafil plus testosterone was not superior to sildenafil plus placebo in improving erectile function in men with erectile dysfunction and low testosterone levels., Primary Funding Source: National Institute of Child Health and Human Development.

Background: Although the initial robot-assisted radical prostatectomy (RARP) series showed 12-mo potency rates ranging from 70% to 80%, the few available comparative studies did not permit any definitive conclusion about the superiority of this technique when compared with retropubic radical prostatectomy (RRP) and laparoscopic radical prostatectomy (LRP)., Objectives: The aims of this systematic review were (1) to evaluate the current prevalence and the potential risk factors of erectile dysfunction after RARP, (2) to identify surgical techniques able to improve the rate of potency recovery after RARP, and (3) to perform a cumulative analysis of all available studies comparing RARP versus RRP or LRP., Evidence Acquisition: A literature search was performed in August 2011 using the Medline, Embase, and Web of Science databases. Only comparative studies or clinical series including >100 cases reporting potency recovery outcomes were included in this review. Cumulative analysis was conducted using Review Manager v.4.2 software designed for composing Cochrane Reviews (Cochrane Collaboration, Oxford, UK)., Evidence Synthesis: We analyzed 15 case series, 6 studies comparing different techniques in the context of RARP, 6 studies comparing RARP with RRP, and 4 studies comparing RARP with LRP. The 12- and 24-mo potency rates ranged from 54% to 90% and from 63% to 94%, respectively. Age, baseline potency status, comorbidities index, and extension of the nerve-sparing procedure represent the most relevant preoperative and intraoperative predictors of potency recovery after RARP. Available data seem to support the use of cautery-free dissection or the use of pinpointed low-energy cauterization. Cumulative analyses showed better 12-mo potency rates after RARP in comparison with RRP (odds ratio [OR]: 2.84; 95% confidence interval [CI]: 1.46-5.43; p=0.002). Only a nonstatistically significant trend in favor of RARP was reported after comparison with LRP (OR: 1.89; p=0.21)., Conclusions: The incidence of potency recovery after RARP is influenced by numerous factors. Data coming from the present systematic review support the use of a cautery-free technique. This update of previous systematic reviews of the literature showed, for the first time, a significant advantage in favor of RARP in comparison with RRP in terms of 12-mo potency rates., (Copyright © 2012. Published by Elsevier B.V.)

Introduction: Erectile dysfunction (ED) is thought to affect some 150 million men worldwide, but many men with ED symptoms do not seek treatment. Existing surveys suggest that men with severe ED and who report support from their partners are more likely to receive treatment than were others. Less is known, however, concerning the influence of sociomedical factors such as income and body composition on receipt of treatment., Aim: The aim of this study was to determine the importance of socioeconomic status, comorbidities, and body composition on receipt of treatment for ED symptoms., Methods: We used data on 638 men enrolled in the Boston Area Community Health (BACH) survey reporting ED symptoms and/or treatment for ED as evidenced by phosphodiesterase type 5 inhibitor (PDE5i) use. Logistic regression was employed to assess the relative strength of association between receipt of treatment and socioeconomic factors, body mass index, and medical factors. A replication of these results was then provided via a parallel model using the 2004 follow-up of the Men's Attitudes to Life Events and Sexuality (MALES)., Main Outcome Measure: In BACH, ED was deemed present if a subject scored 16 points or fewer on the five-item International Index of Erectile Function or reported PDE5i use. In MALES, presence of ED was indicated by use of a validated single question querying ED severity., Results: Controlling for age, body composition and other factors, increased household income, availability of a sexual partner, and provider diagnosis of high blood pressure were positively associated with treatment seeking via the use of PDE5i therapy in BACH. Results on data available in MALES produced similar results for household income and partner availability., Conclusion: These data provide evidence that financial disadvantage may present a barrier to treatment of ED, an increasingly important sentinel marker of the cardiovascular and overall health among aging men., (© 2011 International Society for Sexual Medicine.)

Background: Despite widespread adoption of the six-item erectile function (EF) domain of the International Index of Erectile Function (IIEF) as a clinical trial end point, there are currently no objective data on what constitutes a minimal clinically important difference (MCID) in the EF domain., Objective: Estimate the MCID for the IIEF EF domain., Design, Setting, and Participants: Anchor-based MCIDs were estimated using data from 17 randomized, double-blind, placebo-controlled, parallel-group clinical trials of the phosphodiesterase type 5 inhibitor (PDE5-I) tadalafil for 3345 patients treated for 12 wk., Measurements: The anchor for the MCID is the minimal improvement measure calculated using change from baseline to 12 wk on IIEF question 7: "Over the past 4 weeks, when you attempted sexual intercourse how often was it satisfactory for you?" MCIDs were developed using analysis of variance (ANOVA)- and receiver operating characteristic (ROC)-based methods in a subset of studies (n=11) by comparing patients with and without minimal improvement (n=863). MCIDs were validated in the remaining six studies (n=377)., Results and Limitations: The ROC-based MCID for the EF domain was 4, with estimated sensitivity and specificity of 0.74 and 0.73, respectively. MCIDs varied significantly (p<0.0001) according to baseline ED severity (mild: 2; moderate: 5; severe: 7). MCIDs consistently distinguished between patients in the validation sample classified as no change or minimally improved overall and by geographic region, ED etiology, and age group. MCIDs did not differ by age group, geographic region, or ED etiology. Current analyses were based on 17 clinical trials of tadalafil. Results need to be replicated in studies using other PDE5-Is or in nonpharmacologic intervention studies., Conclusions: The contextualization of treatment-related changes in terms of clinically relevant improvement is essential to understanding treatment efficacy, to interpreting results across studies, and to managing patients effectively. This analysis provides, for the first time, anchor-based estimates of MCIDs in the EF domain score of the IIEF., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: Sexual arousal is a multifaceted process that involves both mental and physical components. No instrument has been developed and validated to assess subjective aspects of male sexual arousal., Aim: To develop and psychometrically validate a self-administered scale for assessing subjective male sexual arousal., Methods: Using recommendations of the Food and Drug Administration (FDA) guidance on patient-reported outcome instruments, important aspects of male sexual arousal were identified via qualitative research (focus groups and interviews) of U.S. men with erectile dysfunction (ED) and healthy controls. After a preliminary questionnaire was developed by a panel of experts, a quantitative study of men with ED and controls was conducted to psychometrically validate the Subjective Sexual Arousal Scale for Men (SSASM)., Main Outcome Measures: To develop a male sexual arousal scale and determine its factor structure, reliability, and construct validity., Results: Five aspects of male sexual arousal were identified from the qualitative focus groups and cognitive interviews. Men's preferred language for describing sexual arousal and preferred response formats were incorporated into the questions. Factor analysis of data from the quantitative study of 304 men aged 21 to 70 years identified five domains with eigenvalues >1: sexual performance (six items), mental satisfaction (five items), sexual assertiveness (three items), partner communication (three items), and partner relationship (three items). The five domains had a high degree of internal consistency (Cronbach's alpha values 0.88-0.94). Test-retest reliability over a 2- to 4-week period was high-moderately high (r values 0.75-0.88) for the five domain scores. Correlations between SSASM domain scores and standardized scale scores for social desirability, general health, life satisfaction, and sexual function demonstrated the construct validity of the scale., Conclusions: Preliminary validation data suggest that the 20-item SSASM scale may be useful as a multidimensional, reliable, self-administered instrument for assessing subjective sexual arousal in men of different ages., (© 2011 International Society for Sexual Medicine.)

Introduction: Using the Massachusetts Male Aging Study (MMAS) data from the years 1987-1995, we previously demonstrated high rates of both progression (33%) and regression (35%) of self-reported severity of erectile dysfunction (ED). These results have not been replicated using more recent data-relevant in light of the introduction of phosphodiesterase type 5 inhibitors (PDE5i) to treat ED-nor compared with those from other populations., Aim: To estimate age-specific progression and regression of ED severity among subjects with at least mild self-reported ED., Methods: We used the two most recent data collection waves from the MMAS (baseline in 1995-1997 and follow-up in 2002-2004, approximately 7 years of follow-up) and data from the Men's Attitudes to Life Events and Sexuality (MALES) study (baseline in 2001 and follow-up in 2004, approximately 3 years of follow-up); 367 MMAS and 617 MALES subjects contributed data. MMAS participants were a population-based sample of men living in Boston, Massachusetts, United States. MALES subjects were obtained from a multinational convenience sample., Main Outcome Measures: ED was measured using the validated single-question self-report of ED severity ("none,""minimal,""moderate," or "complete"). ED progression was defined as worsening of ED over time, whereas regression was defined as a lessening of ED severity. Logistic regression analyses were adjusted for age, body mass index (MMAS only), and use of PDE5i., Results: In MMAS and MALES, 21% (confidence interval [CI]: 17%, 25%) and 25% (22%, 29%) of subjects, respectively, exhibited regression; 51% (45%, 57%) in MMAS and 28% (23%, 33%) in MALES exhibited ED progression. A minority of subjects (14% in MMAS and 28% in MALES) reported use of PDE5i. The proportion of subjects reporting progression increased with age. The higher rate of progression in MMAS may be due in part to the shorter follow-up time (∼3 years) in MALES., Conclusions: Among subjects with some level of self-reported ED, progression and regression are common over a several-year period. Strategies for therapy and intervention for ED should acknowledge this basic evolution with time., (© 2011 International Society for Sexual Medicine.)

Introduction: Although the Sexual Encounter Profile (SEP) and International Index of Erectile Function (IIEF) are frequently used to measure erectile dysfunction (ED) treatment outcomes, stopwatch-assessed duration of erection is a new, objective, and potentially useful endpoint of ED treatment effect., Aims: To assess the validity and reliability of stopwatch-assessed erection duration against responses to SEP items 2 (SEP-2) and 3 (SEP-3) and IIEF scale scores., Methods: Data were taken from a multi-center trial of vardenafil for the treatment of ED. Patients were randomized to vardenafil 10 mg or placebo for 4 weeks. After a 1-week washout period, patients received the alternate therapy for an additional 4 weeks. An electronic diary was used to record information about sexual attempts. The duration of erection was measured using a stopwatch and transcribed into the diary. The SEP was completed following each sexual attempt, and the IIEF was completed at the end of each treatment period., Main Outcome Measures: Mean and median values of erection duration, mean SEP-2 and SEP-3 success rates, and scores for each of the 5 IIEF scales were calculated., Results: At baseline, correlations of median erection duration with the 5 IIEF scale scores ranged from 0.06 to 0.53, while correlations with mean SEP-2 and SEP-3 success rates were 0.66 and 0.49, respectively. Compared with the other measures, mean and median values of erection duration were less sensitive to differences between placebo- and vardenafil-treated patients and less responsive to clinical change associated with treatment crossover. However, mean erection duration exhibited a good level of reliability (intraclass correlation coefficient = 0.72, P < 0.001)., Conclusions: This study provides evidence for the validity and reliability of stopwatch-assessed duration of erection. Our findings suggest that erection duration is suitable for use as a unique endpoint in ED treatment-efficacy trials conducted for phosphodiesterase type 5 inhibitors.

Introduction: Compared to the prevalence of erectile dysfunction (ED), fewer studies have focused on the incidence of ED and even fewer have focused on nonmedical risk factors., Aim: We examined psychosocial, demographic/socioeconomic, medical/behavioral, and sexual function risk factors at T1 (1987-1989) and development of incident ED at T2 (1995-1997)., Methods: Longitudinal population-based epidemiologic study of 814 community-dwelling men participating in the Massachusetts Male Aging Study., Main Outcome Measure: ED was defined according to a validated, discriminant-analytic formula based on questionnaire responses and categorized as moderate/complete ED vs. none/minimal. Multivariate logistic regression models (odds ratios [ORs] and 95% confidence intervals [CI]) were used to estimate the association of risk factors with ED., Results: Among 814 men free of ED at T1, 22% developed moderate/complete ED at T2 (on average, approximately 8.8 years later). In a multivariate model, sexual function variables captured at baseline were inversely associated with ED (e.g., more or similar level of sexual arousal compared to adolescence vs. less, OR = 0.56, 95% CI: 0.34, 0.92; frequency of sexual thoughts at least two to three times weekly vs. less, OR = 0.55, 95% CI: 0.33, 0.92) after adjustment for age, education, and other risk factors., Conclusions: Our results indicate that in the context of other risk factors, sexual desire variables at baseline were associated with incident ED. This in turn suggests that indications of reduced function appear earlier than ED itself, and that there may be a time window for intervention before a loss of erectile function.

Objectives: This study was designed to determine whether erectile dysfunction (ED) predicts cardiovascular disease (CVD) beyond traditional risk factors., Background: Both ED and CVD share pathophysiological mechanisms and often co-occur. It is unknown whether ED improves the prediction of CVD beyond traditional risk factors., Methods: This was a prospective, population-based study of 1,709 men (of 3,258 eligible) age 40 to 70 years. The ED data were measured by self-report. Subjects were followed for CVD for an average follow-up of 11.7 years. The association between ED and CVD was examined using the Cox proportional hazards regression model. The discriminatory capability of ED was examined using C statistics. The reclassification of CVD risk associated with ED was assessed using a method that quantifies net reclassification improvement., Results: Of the prospective population, 1,057 men with complete risk factor data who were free of CVD and diabetes at baseline were included. During follow-up, 261 new cases of CVD occurred. We found ED was associated with CVD incidence controlling for age (hazard ratio [HR]: 1.42, 95% confidence interval [CI]: 1.05 to 1.90), age and traditional CVD risk factors (HR: 1.41, 95% CI: 1.05 to 1.90), as well as age and Framingham risk score (HR: 1.40, 95% CI: 1.04 to 1.88). Despite these significant findings, ED did not significantly improve the prediction of CVD incidence beyond traditional risk factors., Conclusions: Independent of established CVD risk factors, ED is significantly associated with increased CVD incidence. Nonetheless, ED does not improve the prediction of who will and will not develop CVD beyond that offered by traditional risk factors., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Although erectile dysfunction (ED) is considered a well-established risk factor for cardiovascular disease (CVD), few studies have investigated whether other aspects of sexual function might predict CVD independently of ED. In a longitudinal, population-based study of community-dwelling men participating in the Massachusetts Male Aging Study, we examined sexual function variables (including ED) and the subsequent development of CVD. ED was defined according to a validated, discriminant-analytic formula determined from the questionnaire responses and categorized as moderate/complete ED versus none/minimal. CVD included a wide range of major end points and was ascertained through self-report, medical records, and the National Death Index. We calculated the age-adjusted incidence rates according to the person-years of follow-up, and Cox proportional hazards models were used to estimate covariate-adjusted, Framingham risk score-adjusted, and ED-adjusted hazard ratios and 95% confidence intervals for sexual function variables and the subsequent risk of CVD. Of the 1,165 men free of CVD at baseline, the age-adjusted CVD incidence rate for moderate/complete ED and none/minimal ED was 17.9/1,000 person-years and 12.5/1,000 person-years, respectively. In multivariate models adjusted for age, covariates, ED, and the Framingham risk score, a low frequency of sexual activity (once a month or less vs >or=2 times weekly) was associated with increased risk of CVD (hazard ratio 1.45, 95% confidence interval 1.04 to 2.01). In conclusion, our results suggest that a low frequency of sexual activity predicts CVD independently of ED and that screening for sexual activity might be clinically useful., (Copyright 2010 Elsevier Inc. All rights reserved.)

Introduction: Overweight men with diabetes often report erectile dysfunction (ED), but few studies have examined effects of weight loss on this problem., Aim: This study examined 1-year changes in erectile function (EF) in overweight/obese men with type 2 diabetes participating in the Look AHEAD (Action for Health in Diabetes) trial., Methods: Participants in Look AHEAD were randomly assigned to a control condition involving diabetes support and education (DSE) or to intensive lifestyle intervention (ILI) involving group and individual sessions to reduce weight and increase physical activity. Men from five of the clinical sites in Look AHEAD completed the International Index of Erectile Function (IIEF) at baseline (N = 372) and at 1 year (N = 306) (82%)., Main Outcome Measures: Changes in EF as reported on the EF subscale of the IIEF., Results: At 1 year, the ILI group lost a greater percent of initial body weight (9.9% vs. 0.6 %) and had greater improvements in fitness (22.7% vs. 4.6%) than DSE. EF improved more in ILI (17.3 +/- 7.6 at baseline; 18.6 +/- 8.1 at 1 year) than in DSE (18.3 +/- 7.6 at baseline; 18.4 +/- 8.0 at 1 year); P = 0.04 and P = 0.06 after adjusting for baseline differences. Using established norms for none (i.e., normal EF), and three grades (i.e., mild, moderate, and severe) ED, 8% of men in ILI reported a worsening of EF from baseline to 1 year, 70% stayed in the same category, and 22% reported improvements. In contrast, 20% of DSE reported worsening, 57% stayed in the same category, and 23% improved (P = 0.006)., Conclusion: In this sample of older overweight/obese diabetic men, weight loss intervention was mildly helpful in maintaining EF.

Objectives: The objective of this study was to determine the relative contribution of modifiable risk factors (physical activity, smoking, and alcohol consumption) to inter-subject variation in erectile dysfunction (ED)., Methods: The Boston Area Community Health (BACH) Survey used a multistage stratified random sample to recruit 2301 men age 30-79 years from the city of Boston between 2002 and 2005. ED was assessed using the 5-item International Index of Erectile Function (IIEF-5). Multiple linear regression models and R(2) were used to determine the proportion of the variance explained by modifiable risk factors., Results: In unadjusted analyses, lifestyle factors accounted for 12.2% of the inter-subject variability in IIEF-5 scores, comparable to the proportion explained by comorbid conditions (14.7%) and socioeconomic status (9%). Lifestyle factors were also significantly associated with age, comorbid conditions and socioeconomic status (SES). A multivariate model including all covariates associated with ED explained 29% of the variance, with lifestyle factors accounting for 0.9% over and above all other covariates in the model. Analyses repeated in a subgroup of 1215 men without comorbid conditions show lifestyle factors accounting for 2.5% of the variance after accounting for all other variables in the model., Conclusions: Results of the present study demonstrate the contribution of modifiable lifestyle factors to the prevalence of ED. These results suggest a role for behavior modification in the prevention of ED., (Copyright 2009. Published by Elsevier Inc.)

Background & Aims: The recommended therapy for chronic hepatitis C, pegylated interferon and ribavirin for 24 or 48 weeks, has many known adverse side effects. The aim of this study was to evaluate the impact of antiviral therapy on male sexual health., Methods: As part of the Study of Viral Resistance to Antiviral Therapy of Chronic Hepatitis C (Virahep-C), 260 men treated with pegylated interferon alfa-2a and ribavirin completed self-administered questionnaires concerning sexual desire, sexual function, including erectile and ejaculatory function, and sexual satisfaction before, during, and after treatment., Results: Before therapy, 37% of men reported at least some degree of impairment in sexual desire and 44% reported dissatisfaction with their sexual life, while 26% reported impairment in erectile and 22% in ejaculatory function. During therapy, significant declines were observed in all components of sexual health compared with pretreatment. At the end of therapy (24 or 48 weeks), an estimated 38%-48% of men reported that overall sexual function was worse than before treatment. African American patients reported less impairment in sexual desire and satisfaction than Caucasian American patients during therapy. By 24 weeks after treatment, sexual desire and satisfaction improved and were comparable to baseline levels. However, among men who received 48 weeks of therapy, the estimated percentage of men reporting posttreatment erectile or ejaculatory problems remained higher than baseline, although persistent erectile impairment was limited to Caucasian American patients., Conclusions: Sexual impairment is common among men with chronic hepatitis C undergoing therapy with pegylated interferon and ribavirin and should be considered as a potential side effect of antiviral therapy.

Introduction: The Sexual Confidence Scale (SCS) and the Sexual Relationship Scale (SRS) are two new measures designed for use by men and women across sexual dysfunction groups. The SCS assesses how confident an individual feels as a sexual partner, while the SRS assesses feelings that an individual has about their sexual relationship with their partner., Aim: To conduct item reduction and psychometric validation of the SCS and SRS instruments., Methods: To validate the new measures, 104 men with premature ejaculation (PE), 101 men with erectile dysfunction (ED) and 106 women with female sexual arousal disorder (FSAD) took part in the study. One hundred and one males and 53 females without sexual dysfunction also completed the measures., Main Outcome Measures: The internal consistency, convergent, and discriminant validity, test-retest reliability and known-groups validity of the instruments were assessed., Results: The number of items in each scale was reduced following standard item reduction analyses and reference to the conceptual framework. Factor analysis confirmed a one-factor solution for the SCS and a two-factor solution for the SRS. Internal consistency was good, with cronbach's alpha >or=0.7 across the groups for both the SCS and SRS. Excellent test-retest reliability and ability to discriminate between men and women with and without sexual dysfunction were also demonstrated for both scales. Correlations with the Sexual Quality of Life Questionnaire (SQOL) ranged from 0.48 to 0.80 indicating good convergent validity., Conclusions: The SCS and the SRS are reliable and valid instruments in men with PE or ED and in women with FSAD. These modules may be used either as stand-alone measures or, preferably, in conjunction with the SQOL to provide a complete assessment of sexual quality of life.

Introduction: Determinants of erectile dysfunction in diabetic men have not been adequately investigated as potential mediators of change., Aim: To determine the prevalence and correlates of erectile dysfunction (ED) in overweight men with type 2 diabetes in the multicenter, Look AHEAD trial (Action for Health in Diabetes)., Main Outcome Measures: International Index of Erectile Function (IIEF), self-reported use of phosphodiesterase type 5 inhibitors, laboratory measures of adiposity, cardiometabolic parameters, and exercise fitness., Methods: Male participants aged 45-75 in the Look AHEAD trial in a committed relationship were recruited for an ongoing study of sexual function and diabetes. Eligible participants completed the IIEF questionnaire and provided updated information on use of medical treatments for sexual dysfunction. Baseline sexual function results for participants in the male ancillary study are reported here; intervention data and results for female participants are presented elsewhere., Results: A total of 373 eligible male participants completed all sexual function questionnaires, of whom 263 (68.7%) were sexually active at the time of the study. Almost half (49.8%) of the men reported mild or moderate degrees of ED, and 24.8% had complete ED. Among sexually active participants, 42.6% had sought medical help for their problem, and 39.7% reported use of ED medications. ED was significantly associated with age (odds ratio [OR] = 1.05; confidence interval [CI]: 1.01-1.10) baseline HbA(1c) (OR = 1.31; CI: 1.05-1.63), hypertension history (OR = 2.41; CI: 1.34-4.36), and metabolic syndrome (OR = 3.05, CI: 1.31-7.11). Of note, cardiorespiratory fitness was found to be protective of ED in a multivariable analysis (OR = 0.61; P < 0.001)., Conclusions: ED is prevalent in this sample of obese, type 2 diabetic men in the Look AHEAD study. Cardiovascular risk factors were highly associated with ED in this population, and cardiorespiratory fitness was protective in this analysis.

Introduction: Clinical research on erectile dysfunction (ED) has focused primarily on the male and the impact of treatment on their erectile function (EF) and sexual quality of life. However, ED affects the quality of life of both the male and the female partner. The literature examining the impact on the female partner resulting from treating the male's ED is somewhat limited., Aims: To determine the efficacy of tadalafil 5 mg taken once daily compared with placebo on men's EF and sexual quality of life, and to determine the impact of this treatment on the female partner's sexual quality of life., Main Outcome Measures: The co-primary outcome measures for this study were changes from baseline to end point in the EF domain of the International Index of Erectile Function (IIEF), the Sexual Encounter Profile (SEP) question 2 (SEP-2) and question 3 (SEP-3), and the Sexual Quality of Life (SQoL) domain of the Sexual Life Quality Questionnaire (SLQQ) (subject and partner). Methods. Following a 4-week treatment-free run-in phase, 342 subjects and their partners were randomly assigned to either placebo (N = 78) or tadalafil 5 mg (N = 264) for 12 weeks. The subjects' and partners' responses to study measures were collected throughout the study., Results: Compared with placebo, tadalafil-treated subjects showed a significant improvement on efficacy measures (P < 0.001) including changes in the IIEF-EF, SEP-2 and SEP-3. In addition, the sexual quality of life of men and their female partners, as measured by the SQoL domain, was significantly improved with tadalafil 5 mg taken once daily (P < 0.001) compared with placebo., Conclusions: Tadalafil 5 mg once daily significantly improved EF and sexual quality of life for men with ED. In addition, the sexual quality of life of the female partners of the men treated with tadalafil was significantly improved.

Introduction: Studies and reports suggest that both hyperlipidemia and its pharmacologic treatment may lead to an increased risk of erectile dysfunction (ED)., Aims: Our objectives were to examine the association between (i) treated hyperlipidemia and ED; and (ii) untreated hyperlipidemia and ED., Methods: Data from 1,899 men aged 30-79 were used from the Boston Area Community Health Survey of community-dwelling residents of Boston, MA, collected during 2002-2005 using an in-person interview, self-administered questionnaires, and a venous blood draw., Main Outcome Measures: ED was measured using the short form International Index of Erectile Function. A case of treated hyperlipidemia was defined by use of anti-lipemics in the past month, while untreated hyperlipidemia was serum total cholesterol > or =240 milligrams per deciliter with no anti-lipemic use. We estimated associations using odds ratios (ORs) and 95% confidence intervals (CIs) from multivariate logistic regression., Results: Men with treated hyperlipidemia were older, had more comorbidities, and used more medications compared with men with untreated hyperlipidemia or no hyperlipidemia. In multivariate models stratified by age and the presence of diabetes and/or cardiovascular disease (CVD), we saw no association between hyperlipidemia drug treatment and ED, except among younger men (<55) who had diabetes and/or CVD, where a strong association with an imprecise CI was observed (OR = 10.39, 95% CI: 3.25, 33.20). There was no significant positive association between untreated hyperlipidemia and ED in any multivariate model., Conclusion: Lipid-lowering medications may be associated with ED among some men. The well-established benefits of lipid-lowering therapy should always be weighed against potential adverse effects.

Introduction: Few population-based studies have assessed variations in the burden of erectile dysfunction (ED) by race/ethnicity., Aim: To estimate prevalence rates of ED by race/ethnicity and determine the contribution of behavioral risk factors, chronic illnesses, and socioeconomic factors to potential race/ethnic differences in ED., Methods: The Boston Area Community Health (BACH) Survey is a study of urologic symptoms in a racially and ethnically diverse population. BACH used a multistage stratified random sample to recruit 2,301 men aged 30-79 years from the city of Boston. Self-reported race/ethnicity was defined as Black, Hispanic, and White. Socioeconomic status (SES) was defined as a combination of education and household income., Main Outcome Measures: ED assessed using the 5-item International Index of Erectile Function (IIEF-5). IIEF-5 scores were used both as a continuous variable and dichotomized as /=17., Results: Overall prevalence of ED (defined as an IIEF-5 score

Purpose: We evaluated the responsiveness and treatment sensitivity of the Erection Quality Scale, and provided further psychometric validation of this scale., Materials and Methods: An 8-week, placebo controlled, randomized clinical trial investigating the efficacy and safety of vardenafil in patients with erectile dysfunction was performed. The Erection Quality Scale, together with a number of other patient and partner questionnaires, was administered at a screening visit, at baseline, and weeks 4 and 8 of treatment. Erection Quality Scale responsiveness was investigated by evaluating treatment induced changes and modeling using ANCOVA. Internal consistency, convergent and discriminant validity, and minimum important difference of the Erection Quality Scale were also assessed., Results: Efficacy evaluations demonstrated that the Erection Quality Scale was sufficiently responsive to differentiate the treatment benefits of vardenafil compared with placebo. Internal consistency for the Erection Quality Scale total score was similar across visits, with values high enough to suggest reliability of items included in the scale. Discriminant validity of the Erection Quality Scale total score was demonstrated, with a high correlation with the erectile function domain of the International Index of Erectile Function (0.88, p <0.0001) and negligible correlations with clinical measures assumed to be unrelated to erection quality. All Erection Quality Scale total score comparisons substantially exceeded the 5-point minimum important difference estimate., Conclusions: The Erection Quality Scale was responsive and internally consistent, and demonstrated convergent and discriminant validity. Furthermore, this instrument provided a unique contribution to the measurement of erection quality compared to the International Index of Erectile Function. This study provides strong evidence supporting the use of the Erection Quality Scale in clinical trials.

Objective: To assess the influence of vardenafil on treatment satisfaction in men with erectile dysfunction (ED) and their female partners., Patients and Methods: This was a pooled analysis of three randomized, double-blind, placebo-controlled, 12-week studies of flexible-dose vardenafil vs placebo, in men with ED for >/=6 months (n = 788) and their untreated female partners. Measures of efficacy included the Treatment Satisfaction Scale (TSS), International Index of Erectile Function, Erectile Function domain (IIEF-EF), and Sexual Encounter Profile (SEP) questions 2 and 3 (SEP-2, 'Were you able to insert your penis into your partner's vagina?'; and SEP-3, 'Did your erection last long enough for you to have sexual intercourse?'). In addition to the overall analysis, there was a subgroup analysis for potential moderators of response, e.g. whether patients who had undergone previous phosphodiesterase type 5 (PDE-5) treatment., Results: At baseline, least-squares (LS) mean scores for all TSS domains were similar in the vardenafil and placebo groups. After 12 weeks of treatment, vardenafil significantly improved the LS mean score for all domains compared with placebo, among both patients and their female partners (P < 0.0001, 'last'-observation-carried- forward analysis). Absolute between- group differences in LS mean TSS scores (vardenafil - placebo) were: ease of erection (patients 23.4, partners 24.9), erectile function satisfaction (36.7 and 32.9), pleasure from sexual activity (23.0, 23.7), satisfaction with orgasm (27.6, 21.8), confidence to complete sexual activity (28.2, 32.5), and satisfaction with medication (37.4, 35.6). The benefits of vardenafil were greater in men who had undergone previous PDE-5-inhibitor treatment and men aged <45 years, while the overall pattern of benefit was similar in all examined subgroups. There were significant benefits with vardenafil in all other variables (IIEF-EF scores and positive response rates to SEP-2 and SEP-3)., Conclusions: Vardenafil significantly improved treatment satisfaction in men with ED, and in their partners. The results provide further evidence of the validity of the TSS.

Erectile dysfunction (ED) has been linked increasingly to cardiovascular risk factors and comorbidities. Considering the potential risk associated with sexual activity, guidelines were developed (Princeton I) for assessment and management of patients with varying degrees of cardiac risk. These guidelines were recently updated (Princeton II) based on new data concerning the link between ED and cardiovascular disease and the availability of additional phosphodiesterase type 5 inhibitors (vardenafil, tadalafil). Despite the need for careful risk assessment in all cases, sexual activity remains safe for the large majority of patients. However, all patients presenting with complaints of ED should be carefully assessed for the presence of cardiovascular risk factors (eg, obesity, hypertension, hyperlipidemia). Risk-factor modification, including lifestyle interventions (eg, exercise, weight loss) is strongly encouraged. Guidelines are presented for the management of acute coronary syndromes in patients taking phosphodiesterase type 5 inhibitors, including alternatives to the use of nitrates for these patients. Other drug interactions and the cardiovascular safety of testosterone replacement therapy are considered.

As the incidence and prevalence of erectile dysfunction (ED) increase, healthcare providers will require robust, accurate, and efficient tools for appropriately diagnosing and treating patients with ED. Moreover, clinicians will need effective follow-up tools that assess treatment efficacy and satisfaction, to help patients meet their expectations for successful treatment of ED. We provide a summary of some of the most commonly used instruments for the diagnosis and assessment of ED treatment efficacy that will be referred to in this supplement.

Introduction: Although sildenafil citrate (sildenafil) and tadalafil are efficacious and well-tolerated treatments for erectile dysfunction (ED), preference studies have shown that patients may favor one medication over the other., Aim: To determine whether psychosocial outcomes differed when men with ED received tadalafil compared with sildenafil., Main Outcome Measures: Measures included a treatment preference question, Psychological and Interpersonal Relationship Scales (PAIRS), and Drug Attribute Questionnaire., Methods: Randomized, open-label, crossover study. After a 4-week baseline, men with ED (N = 367; mean age = 54 years; naïve to type 5 phosphodiesterase inhibitor therapy) were randomized: tadalafil for 12 weeks then sildenafil for 12 weeks or vice versa (8-week dose optimization/4-week assessment phases). During dose optimization, patients started with 10 mg tadalafil, or 25 or 50 mg sildenafil and could titrate to their optimal dose (10 or 20 mg tadalafil; 25, 50, or 100 mg sildenafil). Medications were taken as needed. Patients completing both 12-week periods chose which medication to continue during an 8-week extension., Results: Of 291 men completing both treatment periods, 71% (N = 206) chose tadalafil and 29% (N = 85) chose sildenafil (P < 0.001) for the 8-week extension. When taking tadalafil compared with sildenafil men had higher mean endpoint scores on PAIRS Sexual Self-Confidence (tadalafil = 2.91 vs. sildenafil = 2.75; P < 0.001) and Spontaneity (tadalafil = 3.32 vs. sildenafil = 3.17; P < 0.001) Domains and a lower mean endpoint score on Time Concerns Domain (tadalafil = 2.2 vs. sildenafil = 2.59; P < 0.001). The two most frequently chosen drug attributes to explain treatment preference were ability to get an erection long after taking the medication and firmness of erections. Tadalafil and sildenafil were well tolerated with 12 (3.3%) patients discontinuing for an adverse event., Conclusions: As measured with PAIRS, men with ED had higher sexual self-confidence and spontaneity and less time concerns related to sexual encounters when treated with tadalafil compared with sildenafil. These psychosocial outcomes may help explain why more men (71%) preferred tadalafil for the treatment of ED in this clinical trial.

Introduction: Erectile dysfunction (ED) is a highly prevalent disorder associated with a significant burden of illness. The prevalence and incidence of ED are strongly age-related, affecting more than half of men >60 years. The first Princeton Consensus Conference (Princeton I) in 1999 developed guidelines for safe management of cardiac patients regarding sexual activity and the treatment of ED., Aim: The second conference (Princeton II) was convened to update the recommendations based on the expanding knowledge base and new treatments available. This article reviews and expands on the Princeton II guidelines to address sexual dysfunction and cardiac risk., Methods: A consensus panel of experts reviewed recent multinational studies in safety and drug interaction data for three phosphodiesterase type 5 (PDE5) inhibitors (sildenafil, tadalafil, vardenafil), with emphasis on the safety of these agents in men with ED and concomitant cardiovascular disease., Results: Erectile dysfunction is an early symptom or harbinger of cardiovascular disease, due to the common risk factors and pathophysiology mediated through endothelial dysfunction. Major comorbidities include diabetes, hypertension, hyperlipidemia and heart disease. Any asymptomatic man who presents with ED that does not have an obvious cause (e.g., trauma) should be screened for vascular disease and have blood glucose, lipids, and blood pressure measurements. Ideally, all patients at risk but asymptomatic for coronary disease should undergo an elective exercise electrocardiogram to facilitate risk stratification. Lifestyle intervention in ED, specifically weight loss and increased physical activity, particularly in patients with ED and concomitant cardiovascular disease, is literature-supported., Conclusions: The recognition of ED as a warning sign of silent vascular disease has led to the concept that a man with ED and no cardiac symptoms is a cardiac (or vascular) patient until proven otherwise. Men with ED and other cardiovascular risk factors (e.g., obesity, sedentary lifestyle) should be counseled in lifestyle modification.

The influence and significance of lifestyle factors in erectile dysfunction (ED) have been demonstrated in cross-sectional and prospective, randomized, controlled trials. Recent epidemiologic studies in several countries have shown that modifiable lifestyle or risk factors, including physical activity in particular, are directly related to the occurrence of ED. In this article, we review several recent observational studies, 2 of which include a longitudinal follow-up component in the study design. The levels of physical activity in both of these studies predicted ED prevalence and incidence. Furthermore, the role of lifestyle changes (weight loss, physical activity) were recently demonstrated to be effective in modifying ED in a prospective, randomized Italian trial in moderately obese, sedentary men. Men without overt diabetes mellitus or cardiovascular disease participated in this landmark study. Other studies have shown that aggressive management of cardiovascular risk factors can increase the effectiveness or outcomes associated with pharmacologic management of ED. Taken together, these studies support the value of risk factor modification and lifestyle change in the clinical management in men with ED and concomitant cardiovascular illness.

Background: Satisfaction with the sexual experience is considered important when evaluating the impact of treatments for erectile dysfunction (ED), yet satisfaction has been infrequently assessed in clinical trials., Objective: To evaluate satisfaction with, and enjoyment of, the sexual experience in men with ED enrolled in 11 placebo-controlled clinical trials of tadalafil., Study Design and Methods: Retrospective pooled analysis of data from 11 randomized, double blind, placebo-controlled clinical trials of tadalafil. Men with mild (N = 838), moderate (N = 558), or severe (N = 703) ED who were randomized to tadalafil 10 mg or 20 mg or placebo taken as needed for 12 weeks were included in this analysis. Efficacy measures included the International Index of Erectile Function (IIEF). Reported herein are the scores on the IIEF overall satisfaction domain and individual IIEF questions (IIEF-Q7, satisfaction with intercourse; and IIEF-Q8, enjoyment of intercourse)., Results: At least moderate satisfaction (IIEF overall satisfaction domain) was reported by 55% and 72% of patients with mild ED taking tadalafil 10 mg and 20 mg, respectively, compared with 33% taking placebo (p < 0.002); 60% and 65% vs. 19% of patients with moderate ED (p < 0.001); and 32% and 49% vs. 9% with severe ED (p < 0.001). Satisfactory intercourse during most attempts or almost always/always (IIEF-Q7) was reported by 59% and 79% of patients with mild ED taking tadalafil 10 mg and 20 mg vs. 32% taking placebo (p < 0.001); 52% and 65% vs. 18% with moderate ED (p < 0.001); and 28% and 49% vs. 5% with severe ED (p < 0.001). Highly or very highly enjoyable intercourse (IIEF-Q8) was reported by 45% and 63% of patients with mild ED taking tadalafil 10 mg and 20 mg vs. 21% taking placebo (p < 0.001); 43% and 56% vs. 16% with moderate ED (p < 0.001); and 19% and 44% vs. 5% with severe ED (p < 0.001)., Conclusions: Compared with placebo, tadalafil 10 mg and 20 mg improved overall satisfaction with the sexual experience, intercourse satisfaction, and intercourse enjoyment in men with mild, moderate, and severe ED.

Erectile dysfunction (ED) is a highly prevalent condition in aging men with significant interpersonal and psychosocial consequences. Large-scale epidemiologic studies have demonstrated a consistent age-related loss of erectile function in men from different geographic and ethnic backgrounds, with approximately half of men over 70 years of age reporting moderate to severe symptoms. ED is associated strongly with specific comor-bidities, such as cardiovascular disease and hypertension, diabetes mellitus, lower urinary tract symptoms, prostate cancer, and depression. Lifestyle factors, including obesity and exercise frequency, also have been implicated in recent studies.

Introduction: There are limited data concerning the sexual function of women whose male partners receive pharmacological treatment for erectile dysfunction (ED)., Aim: One objective of this research was to prospectively compare the efficacy of vardenafil vs. placebo administered to men with ED in improving men's and women partners' sexual function and satisfaction. Another goal was to assess the relationship of erectile function changes in men with ED receiving treatment with sexual function changes in women partners not directly receiving treatment., Methods: A randomized, double-blind, placebo-controlled, multi-institutional comparison of vardenafil vs. placebo was performed in 229 couples (treated man with ED>6 months and untreated woman partner). Co-primary outcomes for which this research was statistically powered were Sexual Encounter Profile (SEP3) (treated man with ED) and Sexual Life Quality Questionnaire (mSLQQ-QOL) (untreated woman partner)., Main Outcome Measures: Erectile function changes in men with ED receiving vardenafil vs. placebo were compared at last observation carried forward (LOCF) in SEP3, International Index of Erectile Function (IIEF-EF) and Erection Quality Scale (EQS). Sexual function at LOCF in women partners was determined by mSLQQ-QOL and Female Sexual Function Index (FSFI)., Results: Compared with placebo at LOCF, vardenafil significantly increased least square (LS) mean scores in: (i) overall per-treated male SEP3 success rate, IIEF-EF, and EQS; and (ii) mSLQQ-QOL, total FSFI and sexual desire, subjective arousal, lubrication, orgasm and satisfaction FSFI domains in untreated women partners. Treatment-related improvement in erectile function as assessed by IIEF-EF and EQS was correlated reliably with improvement in women partners' FSFI total and individual domain scores., Conclusions: Vardenafil is an effective ED treatment in men that also significantly improves sexual function/satisfaction in untreated women partners. Women partners' sexual function improvements relate significantly and consistently to treatment-related improvements in men's erectile function. ED management should emphasize both members of the couple.