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Background: To explore the impact of patient-characteristics and relevant comorbidities on treatment continuation rates, effectiveness, and satisfaction in patients with erectile dysfunction (ED) who started or switched to tadalafil 5 mg once daily (TAD-OaD) at baseline.Methods: In the EDATE observational study, phosphodiesterase-type-5 (PDE5)-inhibitor pretreated or naïve ED patients who started or switched to TAD-OaD were prospectively followed for 6 months. Time to discontinuation of TAD-OaD was estimated using the Kaplan-Meier product-limit method at Months 2, 4, and 6 in subgroups stratified by age (18 - 65 years and >65 years), PDE5-inhibitor pretreatment, ED-severity (mild, moderate, severe), and presence or absence of relevant comorbidities (BPH, diabetes, CVD, hypertension, dyslipidemia). LSmean change from baseline in International Index of Erectile Function (IIEF) and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) scores and associated 95 % CIs were assessed using a mixed-model for repeated measures. Visit, ED etiology, and subgroups were included as fixed-effects.Results: Overall, 778 patients received prescriptions for initiating or switching to TAD-OaD at baseline. At Month 2, >90 % of patients remained on TAD-OaD, except those aged >65 years (86.7 %) and patients with severe ED (89.0 %). More than 80 % of patients in all subgroups, except those aged >65 years (75.0 %), continued TAD-OaD at Month 6. There was a significant LSmean negative effect on IIEF- EF domain-score improvement for BPH (LSmean effect [95 % CI]: -2.77 [-4.98, -0.55], p = 0.014), previous PDE5-inhibitor treatment (-2.13 [-3.33,-0.94], p < 0.001), and mild vs moderate ED (-2.00 [-3.54,-0.46], p = 0.011); the latter possibly linked with a bigger treatment-effect in those with more severe ED at baseline. The LSmean effect on change in IIEF-EF was significantly positive for diabetes (2.28 [0.64,3.92], p = 0.007), most likely because those with diabetes had more severe ED at baseline. For all other parameters, no statistically significant LSmean effects in IIEF-EF changes were observed. No comorbidity or baseline-characteristic except age (18 - 65 years vs >65 years: 11.25 [2.96,19.54], p = 0.008) affected changes in EDITS.Conclusions: Under routine clinical conditions, treatment continuation rate or satisfaction does not seem to be significantly affected by the presence of comorbidities in men who choose ED-treatment with TAD-OaD. The magnitude of treatment effectiveness was affected by certain baseline characteristics and comorbid conditions.Trial Registration: The study (H6D-EW-LVIU) is registered in the German VfA Registry of Non-Interventional Studies (Verband Forschender Arzneimittelhersteller) since 06 December 2011; available at: http://www.vfa.de/de/arzneimittel-forschung/datenbanken-zu-arzneimitteln/nisdb/nis-details/_741 . [ABSTRACT FROM AUTHOR]

Abstract: Context: Androgen modulation of erectile function (EF) is widely accepted. However, the use of testosterone replacement therapy (TRT) in men with erectile dysfunction (ED) has generated an unprecedented debate. Objective: To summarize the relevant data on the incidence, diagnosis, and management of ED coexisting with hypogonadism and to develop a pathophysiology-based treatment algorithm. Evidence acquisition: We reviewed the relevant medical literature, with a particular emphasis on original molecular studies, prospective observational data, and randomized controlled trials performed in the past 20 yr. Evidence synthesis: Testosterone modulates nearly every component involved in EF, from pelvic ganglions to smooth muscle and the endothelial cells of the corpora cavernosa. It also regulates the timing of the erectile process as a function of sexual desire, coordinating penile erection with sex. Epidemiologic studies confirm the significant overlap of hypogonadism and ED; however, most guidelines do not consider the differential diagnosis of hypogonadism or the relevance of subclinical disease. Various clinical tools can help the physician to assess and restore androgen levels in men with ED. Special attention is given to fertility-sparing treatments, due to the increasing number of older men desiring fatherhood. The simultaneous use of phosphodiesterase type 5 inhibitors (PDE5-Is) and TRT has recently been questioned. Originally proposed as a salvage therapy for nonresponders to PDE5-Is, this approach has been inappropriately transformed into a combination therapy. Clinical data are consistent when reinterpreted in the proper framework, whereas molecular evidence remains controversial. Conclusions: A body of molecular and clinical evidence supports the use of TRT in hypogonadal patients with ED, although the benefit–risk ratio is uncertain in advanced age. Critical appraisal of this evidence enabled the development of a pathophysiology-oriented algorithm designed to avoid inappropriate treatments and support whether to start with TRT, PDE5-I only, or both. Apparently divergent findings are reconciled when TRT is correctly indicated. An improved diagnosis and individualized management is desirable in light of the many available options. [Copyright &y& Elsevier]

Introduction Phosphodiesterase type 5 ( PDE-5) inhibitor treatment for erectile dysfunction ( ED) is frequently discontinued; adherence may vary depending on the initial regimen. Aim To evaluate the effects of initiating treatment with tadalafil once a day ( OaD), tadalafil on demand (pro re nata [ PRN]), or sildenafil PRN on treatment adherence. Methods In this multicenter, open-label study, men (≥18 years) with ED, naïve to PDE-5 inhibitors, were randomized (1:1:1) to tadalafil 5 mg OaD, tadalafil 10 mg PRN, or sildenafil 50 mg PRN. An 8-week randomized treatment ( RT) period (dose adjustment possible) was succeeded by 16 weeks of pragmatic treatment (switches between PDE-5 inhibitors allowed). Main Outcome Measures Treatment adherence was measured as time to discontinuation of RT (any cause), estimated by Kaplan- Meier product-limit method. Treatment-group differences were estimated as hazard ratio ( HR; Cox proportional hazards). Results Seven hundred seventy patients (mean age 53 years) were randomized to tadalafil OaD (N = 257), tadalafil PRN (N = 252), and sildenafil PRN (N = 261). Kaplan- Meier estimates for patients discontinuing RT were 52.2, 42.0, and 66.7%, respectively. Median time to discontinuation of RT was significantly longer for tadalafil OaD and PRN (130 and >168 days) compared with sildenafil (67 days) ( HR [97.5% confidence interval]: 0.66 [0.51, 0.85] and 0.49 [0.37, 0.65]; P < 0.001). Reasons for discontinuation with significant differences between groups ( P < 0.05) included 'lack of efficacy (duration of erection)' (sildenafil 9.2% vs. tadalafil OaD 4.3%, PRN 2.8%), 'time constraints due to short window of action' (sildenafil 4.2% vs. tadalafil OaD 0%, PRN 0.4%), and 'feel medication controls my sexual life' (sildenafil 2.7% vs. tadalafil OaD 0%). No between-group differences were found in International Index of Erectile Function- Erectile Function domain change from baseline to end of RT (least squares mean: 9.4-10.0, P = 0.359) or discontinuations due to adverse events (1.2-1.6%). The most common adverse event (≥4%) was headache. Conclusions ED patients assigned to tadalafil OaD or PRN adhered significantly longer to initial treatment than patients assigned to sildenafil PRN. Improvement of erectile function and safety profiles were similar in all three treatment groups. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction. Although the characteristics of premature ejaculation (PE) are established, the exact aetiology is largely unknown. Genetic, neurobiological, pharmacological, psychological, urological and endocrine factors have all been proposed. In addition PE and erectile dysfunction are often co-morbid. Aim. This article provides an overview of the proposed biological and psychological aetiologies of PE. Methods. Review of the literature. Main Outcome Measures. Current data on the pathophysiology of PE. Results. This review shows that most of the proposed biological and psychological aetiologies of PE are not evidence-based and/or that attempts to confirm them have given conflicting results. There are good data to support roles for genetic and psychological factors, either causal, or secondary to PE for the latter, in lifelong PE. Conversely, more evidence-based data support the responsibility of opioid substance withdrawal, prostatic inflammation or hyperthyroidism in some cases of acquired PE, in addition to a probable role of psychological factors. Conclusions. The determinants of PE are certainly complex and multifactorial, while each partner's reaction to the frustration caused by the sexual dysfunction may exacerbate or perpetuate it. It is important to understand, as far as possible, the aetiology in the individual patient to ensure appropriate assessment and treatment. It should be noted that identification of an aetiological factor does not necessarily mean the cause of the PE has been completely explained, and the patient may require a combination of treatment approaches. Buvat J. Pathophysiology of premature ejaculation. J Sex Med 2011;8(suppl 4):316-327. [ABSTRACT FROM AUTHOR]

Addition of testosterone (T) may improve the action of phosphodiesterase type 5 inhibitors (PDE5-Is) in patients with erectile dysfunction not responding to PDE5-Is with low or low-normal T levels. To confirm this add-on effect of T in men optimally treated with PDE5-Is and to specify the baseline T levels at which such an effect becomes significant. A multicenter, multinational, double-blind, placebo-controlled study of 173 men, 45-80 years, nonresponders to treatment with different PDE5-Is, with baseline total T levels ≤4 ng/mL or bioavailable T ≤ 1 ng/mL. Men were first treated with tadalafil 10 mg once a day (OAD) for 4 weeks; if not successful, they were randomized in a double-blind, placebo-controlled design to receive placebo or a 1% hydroalcoholic T gel (50 mg/5 g gel), to be increased to 10 mg T if results were clinically unsatisfactory. Mean change from baseline in the Erectile Function Domain Score of the International Index of Erectile Function and rate of successful intercourses (Sexual Encounter Profile 3 question). Erectile function progressively improved over a period of at least 12 weeks in both the placebo and T treatment groups. In the overall population with a mean baseline T level of 3.37 ± 1.48 ng/mL, no additional effect of T administration to men optimally treated with PDE5-Is was encountered. The differences between the T and placebo groups were significant for both criteria only in the men with baseline T ≤3 ng/mL. The maximal beneficial effects of OAD dosing with 10 mg tadalafil may occur only after as many as 12 weeks. Furthermore, addition of T to this PDE5-I regimen is beneficial, but only in hypogonadal men with baseline T levels ≤3 ng/mL. [ABSTRACT FROM AUTHOR]

Introduction. Sexual satisfaction is an important treatment objective for men with erectile dysfunction (ED). Aims. To evaluate potential associations between International Index of Erectile Function (IIEF) satisfaction at study endpoint and a range of baseline, on-treatment, and endpoint variables. Methods. An exploratory analysis was conducted involving 3,935 subjects with ED randomized to on-demand tadalafil (N = 2,824) or placebo (N = 1,111) in randomized, controlled trials across 28 countries. Patients achieving scores ≥16 on IIEF questions 7, 8, 13, and 14 at study endpoint were operationally defined as satisfied (vs. <16, not satisfied). Multivariate logistic regression and other analyses were conducted to ascertain correlates and potential predictors of improvements in the IIEF-erectile function domain (IIEF-EF). Main Outcome Measures. Satisfaction on the IIEF at study endpoint, on-treatment improvements in IIEF-EF, and endpoint sexual frequency. Results. Patients who were satisfied with sexual function were on average younger and had less severe ED, a shorter history of the condition, and no history of vascular disorders, hypertension, or diabetes mellitus/insulin use at baseline ( P < 0.01 vs. not satisfied for each). Satisfied patients were also more likely to experience a ≥4-point increase on the IIEF-EF domain on treatment (adjusted odds ratio [OR] = 22.4; 95% CI = 17.6–28.5; P < 0.0001) or IIEF-EF ≥26 at endpoint (adjusted OR = 41.0; 95% CI = 33.6–50.2; P < 0.0001). Satisfaction emerged as a strong correlate of a ≥4-point increase in the IIEF-EF on treatment; however, as a correlate of endpoint sexual frequency, baseline sexual frequency was stronger than endpoint satisfaction. Conclusions. Satisfaction is associated with certain baseline, on-treatment, and endpoint variables in ED patients. Further studies are needed to confirm these preliminary findings and explore their meaning for female partners. Althof SE, Buvat J, Gutkin SW, Belger M, Stothard DR, and Fugl-Meyer AR. Sexual satisfaction in men with erectile dysfunction: Correlates and potential predictors. J Sex Med 2010;7:203–215. [ABSTRACT FROM AUTHOR]

The article analyzes the paper "Is Intracavernous Injection of Papaverine a Reliable Screening Test for Vascular Impotence?" by J. Buvat, M. Herbaut-Buvat, J. L. Dehaene, and A. Lemaire. It notes that the authors regarded the nocturnal penile tumescence test as the only investigation that is able to discriminate psychogenic from organic erectile dysfunction (ED). One cited lesson from the study is that pharmacological erection can stratify patients into groups with varying degrees of vascular disease which help guide therapy.

OBJECTIVE To evaluate the efficacy, tolerability, and treatment satisfaction after initiating treatment with sildenafil 50 mg and later titrating to 100 mg, compared with continuing treatment with sildenafil 50 mg, in men with erectile dysfunction (ED). PATIENTS AND METHODS A multicentre, parallel-group trial was conducted in two 4-week periods. In period 1, patients received 50-mg doses of sildenafil single-blinded for 4 weeks. In period 2, patients were randomized to double-blind, placebo-controlled treatment with sildenafil 50 mg or sildenafil 100 mg for 4 weeks. All patients were aged ≥18 years with a documented clinical diagnosis of ED (score of ≤25 on the International Index of Erectile Function, IIEF, Erectile Function, EF, domain), and met the prescribing criteria for sildenafil 50 mg and 100 mg. RESULTS Of 492 enrolled patients (mean age 53 years,sd 11), 476 (97%) completed period 1 and 473 (96%) completed period 2. Patients receiving sildenafil 50 mg in period 1 had an increase in the mean (sd) baseline EF domain score from 12.8 (5.2) to 22.5 (6.6) ( P < 0.001), and improved scores on the Quality of Erection Questionnaire (QEQ) and Sexual Experience Questionnaire (SEX-Q). The IIEF EF domain scores were similar in the two groups at baseline and randomization. Patients titrated to the 100-mg dose (237 men) showed a significantly greater improvement than those who continued on the 50-mg dose (240; P < 0.001). There was a significant increase in QEQ and SEX-Q scores in patients titrated to sildenafil 100 mg compared with patients continuing at sildenafil 50 mg. At either sildenafil dose, headache, flushing and hot flushes were the most common adverse events. Neither the frequency nor the severity of adverse events increased with titration to sildenafil 100 mg. CONCLUSIONS After initial treatment with sildenafil 50 mg, patients titrated to 100 mg showed further increases in efficacy and satisfaction with no increase in the number or severity of adverse events than in those remaining on the starting dose. [ABSTRACT FROM AUTHOR]

To review the role and significance of hypogonadism, defined as a low testosterone (T) level, in erectile dysfunction (ED). Review of literature. Serum T is below 3 ng/ml in 12% of ED patients, including 4% before and 15% after the age of 50. Replacement studies in men with severe hypogonadism demonstrate that sexual desire and arousal, as well as the frequency of sexual activity and spontaneous erections are clearly T-dependant. Psychic erections are partly T-dependant. The effects of T upon sexual function are dose-dependant up to a threshold level that is consistent within an individual, but markedly variable between individuals, ranging from 2 to 4.5 ng/ml. More evidence is required to confirm a significant impact of T on the intrapenile vascular mechanisms of erections in men as it is the case in animals. No convincing association of T with ED has been found in epidemiological studies. As concerns clinical experience, although a meta-analysis of the randomized controlled trials established that T therapy consistently restores erectile function in young hypogonadal patients with T below 3.46 ng/ml, the effects of this treatment have been mostly disappointing when used alone in older patients consulting for ED who are subsequently diagnosed to have hypogonadism following routine T measurement. These poor results may probably be explained by the high prevalence of co-morbidities, and by the fact that ED itself may induce hypogonadism. Combination therapy with T and PDE5 inhibitor (PDE5I) may be effective in the hypogonadal ED patients when T therapy alone fails. However, more evidence is required to confirm the hypothesis that a minimum level of T is required for a complete effect of PDE5I in certain men, since a PDE5I was able to restore complete erections in severely hypogonadal men. Though a low T level is not always the only cause of ED in hypogonadal ED patients, there are important benefits in screening for hypogonadism in ED. A low T level justifies a 3 month trial of T therapy, before combining a PDE5I if T therapy alone fails [ABSTRACT FROM AUTHOR]

Introduction. The efficacy of phosphodiesterase-5 inhibitors in the treatment of erectile dysfunction may depend on patient characteristics. Aim. To determine whether patient characteristics influence the efficacy of two tadalafil dosage regimens and to identify prognostic factors predictive of tadalafil efficacy. Methods. This was a multicenter, open-label study in which men with erectile dysfunction were randomized to tadalafil 20 mg either on demand or three times per week for a period of 5–6 weeks. After a 1-week washout period, patients were crossed over to the alternate regimen for another 5–6 weeks. Main Outcome Measures. Score of the Erectile Function (EF) domain of the International Index of Erectile Function Questionnaire (IIEF) and percentage of positive responses to questions 3 and 5 of the Sexual Encounter Profile (SEP) diary. Results. A total of 4,262 patients were randomized. A normal EF domain score (≥26) at the end of on-demand and three-times-per-week treatment was reported by 60.2% and 62.3% of patients, respectively. The percentage of patients who achieved a normal EF domain score and the percentages reporting positive responses to SEP3 and SEP5 depended on the severity of erectile dysfunction and the presence of certain comorbidities, irrespective of the tadalafil dosage regimen. On regression analysis, the two best predictors of tadalafil efficacy were the baseline score of the IIEF-EF domain and the baseline percentage of “Yes” responses to SEP2. Conclusions. On-demand and three-times-per-week dosage regimens of tadalafil 20 mg were equally efficacious in men with erectile dysfunction. Among the possible prognostic factors tested in this study, baseline disease severity scores were the strongest predictors of efficacy endpoint scores. Costa P, Buvat J, Holmes S, Weitckus S, Petto H, Hamidi K, and Varanese L. Predictors of tadalafil efficacy in men with erectile dysfunction: The SURE study comparing two dosing regimens. J Sex Med 2006;3:1050–1058. [ABSTRACT FROM AUTHOR]

Aim. The aim of this article is to evaluate the efficacy and safety of 20-mg tadalafil taken on demand or three times per week and its effect on the sexual activity of patients with diabetes mellitus and erectile dysfunction (ED). Methods. The scheduled use vs. on-demand regimen evaluation (SURE) was a randomized, crossover, open-label study with 4,262 patients in 14 European countries. The efficacy measures for the 762 patients with diabetes and ED included changes from baseline in the erectile function (EF) domain of the International Index of Erectile Function (IIEF), and the proportion of “yes” responses to patient Sexual Encounter Profile (SEP) questions 2 (SEP2) and 3 (SEP3). The treatment satisfaction was measured with responses to SEP question 4 (SEP4) and SEP question 5 (SEP5), and sexual attempts data were collected. Patient preference for either regimen was determined by the treatment preference question (TPQ). Results. At end point on both regimens, the mean IIEF EF domain score was 22, and >40% of the patients had a normal EF domain score (≥26). The proportion of “yes” responses was ≥73% for SEP2 (penetration), ≥58% for SEP3 (successful intercourse), >46% for SEP4 (hardness of erection), and ≥45% for SEP5 (overall satisfaction). Efficacy was maintained up to 36 hours post-dosing. More than 70% of sexual attempts while on the three-times-per-week regimen and approximately 50% of the attempts on the on-demand treatment occurred >4 hours post-dosing. Tadalafil was well tolerated, with dyspepsia and headache as the most frequent adverse events reported. Treatment preference was 57.2% for on demand and 42.8% for three times per week. Conclusions. Tadalafil, when taken on demand or three times per week, is efficacious and safe in men with diabetes and ED. Buvat J, van Ahlen H, Schmitt H, Chan M, Kuepfer C, and Varanese L. Efficacy and safety of two dosing regimens of tadalafil and patterns of sexual activity in men with diabetes mellitus and erectile dysfunction: Scheduled use vs. on-demand regimen evaluation (SURE) study in 14 European countries. J Sex Med 2006;3:512–520. [ABSTRACT FROM AUTHOR]

Introduction Sexual dysfunction is common in patients after radical prostatectomy (RP) for prostate cancer. Aim To provide the International Consultation for Sexual Medicine (ICSM) 2015 recommendations concerning prevention and management strategies for post-RP erectile function impairment in terms of preoperative patient characteristics and intraoperative factors that could influence erectile function recovery. Methods A literature search was performed using Google and PubMed databases for English-language original and review articles published up to August 2016. Main Outcome Measures Levels of evidence (LEs) and grades of recommendations (GRs) based on a thorough analysis of the literature and committee consensus. Results Nine recommendations are provided by the ICSM 2015 committee on sexual rehabilitation after RP. Recommendation 1 states that clinicians should discuss the occurrence of postsurgical erectile dysfunction (temporary or permanent) with every candidate for RP (expert opinion, clinical principle). Recommendation 2 states that validated instruments for assessing erectile function recovery such as the International Index of Erectile Function and Expanded Prostate Cancer Index Composite questionnaires are available to monitor EF recovery after RP (LE = 1, GR = A). Recommendation 3 states there is insufficient evidence that a specific surgical technique (open vs laparoscopic vs robot-assisted radical prostatectomy) promotes better results in postoperative EF recovery (LE = 2, GR = C). Recommendation 4 states that recognized predictors of EF recovery include but are not limited to younger age, preoperative EF, and bilateral nerve-sparing surgery (LE = 2, GR = B). Recommendation 5 states that patients should be informed about key elements of the pathophysiology of postoperative erectile dysfunction, such as nerve injury and cavernous venous leak (expert opinion, clinical principle). Conclusions This article discusses Recommendations 1 to 5 of the ICSM 2015 committee on sexual rehabilitation after RP. Salonia A, Adaikan G, Buvat J, et al. Sexual Rehabilitation After Treatment for Prostate Cancer—Part 1: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015). J Sex Med 2017;14:285–296. [ABSTRACT FROM AUTHOR]

Introduction Sexual dysfunction is common in patients after radical prostatectomy (RP) for prostate cancer. Aim To provide the International Consultation for Sexual Medicine (ICSM) 2015 recommendations concerning management strategies for post-RP erectile function impairment and to analyze post-RP sexual dysfunction other than erectile dysfunction. Methods A literature search was performed using Google and PubMed database for English-language original and review articles published up to August 2016. Main Outcome Measures Levels of evidence (LEs) and grades of recommendations (GRs) are provided based on a thorough analysis of the literature and committee consensus. Results Nine recommendations are provided by the ICSM 2015 committee on sexual rehabilitation after RP. Recommendation 6 states that the recovery of postoperative erectile function can take several years (LE = 2, GR = C). Recommendation 7 states there are conflicting data as to whether penile rehabilitation with phosphodiesterase type 5 inhibitors improves recovery of spontaneous erections (LE = 1, GR = A). Recommendation 8 states that the data are inadequate to support any specific regimen as optimal for penile rehabilitation (LE = 3, GR = C). Recommendation 9 states that men undergoing RP (any technique) are at risk of sexual changes other than erectile dysfunction, including decreased libido, changes in orgasm, anejaculation, Peyronie-like disease, and changes in penile size (LE = 2, GR = B). Conclusion This article discusses Recommendations 6 to 9 of the ICSM 2015 committee on sexual rehabilitation after RP. Salonia A, Adaikan G, Buvat J, et al. Sexual Rehabilitation After Treatment For Prostate Cancer–Part 2: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015). J Sex Med 2017;14:297–315. [ABSTRACT FROM AUTHOR]

Introduction. The International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP), and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) assess efficacy of phosphodiesterase type 5 (PDE5) inhibitor treatment of erectile dysfunction (ED). Aims. To determine the degree that multiplicity of satisfaction questions in ED treatment evaluation instruments are congruent, to better understand the concept of sexual “satisfaction,” and to identify factors that correlate with improvement. Methods. Questionnaire data from 4,174 placebo- or tadalafil-treated patients with ED were analyzed. Principal component analysis (PCA) was performed on IIEF and SEP satisfaction questions. Spearman correlation coefficients were determined. Data from 431 of the 4,174 patients who completed EDITS questionnaires were analyzed. Logistic regression was used to investigate improvement of each IIEF satisfaction question. Results. PCA rotated on three factors explained 91% of total variance and separated IIEF Q6 (intercourse frequency) from a SEP and a remaining IIEF factor. All correlations between and among questions were close (ρ = 0.62–0.98; P < 0.0001), except for those with IIEF Q6 (ρ = 0.28–0.34; P < 0.0001). In a sub-sample, PCA of five IIEF, two SEP, and three EDITS questions identified four factors that explained 90% of all variance: EDITS questions, IIEF questions except Q6, SEP questions, and IIEF Q6. Greater improvement in IIEF-EF domain score was consistently and positively associated with satisfaction measures ( P < 0.0001). Conclusions. Factor analysis detected close relationships among satisfaction questions in IIEF, SEP, and EDITS instruments, each of which, apart from IIEF Q6 (intercourse frequency), appeared to be an independent measure of satisfaction. Cultural differences may explain different satisfaction correlations with baseline ED severity in different regions. Clinicians may make use of the correlation between intercourse frequency (Q6) and satisfaction when prescribing a PDE5 inhibitor for ED, by explaining that the inhibitor should enable more frequent intercourse. Fugl-Meyer A, Althof S, Buvat J, Paget M-A, Sotomayor M, and Stothard D. Aspects of sexual satisfaction in men with erectile dysfunction: A factor analytic and logistic regression approach. J Sex Med 2009;6:232–242. [ABSTRACT FROM AUTHOR]

Summary of Committee. Results of this study have been presented in part at the American Urological Association Meeting, May 2002, Orlando, FL (Donatucci C, Eardley I, McVary KT, Thibonnier J, and the Vardenafil Study Group. Vardenafil improves erectile function of aetiology or baseline severity in men with erectile dysfunction. J Urol 2002;167:178). Conflict of Interest. Dr. Segerson and Mr Homering are employees of Bayer. Background. Vardenafil (Levitra®) is a potent and selective phosphodiesterase 5 (PDE5) inhibitor used in the management of erectile dysfunction (ED). This retrospective subgroup analysis assessed the effectiveness of vardenafil treatment in men with ED of different baseline severity and disease classification. Methods. Data from two pivotal, randomized, double-blind, placebo-controlled clinical trials enrolling men from the general ED population who received placebo or vardenafil 5 mg, 10 mg, or 20 mg during a 12-week treatment period were retrospectively analysed, stratifying by psychogenic, organic, and mixed ED disease classification as determined by the investigator. Efficacy endpoints included the International Index of Erectile Function (IIEF)-Erectile Function (EF) domain score, per-patient diary response rates to questions on penile insertion [Sexual Encounter Profile (SEP-2)] and maintenance of erection (SEP-3) and rates of positive response to the Global Assessment Question (GAQ). Results. Data from 1,385 men who received at least one dose of study medication and had pre- and post-baseline measures of efficacy available (intent-to-treat population) are presented. At baseline 37–41% of patients had severe ED, 30–34% moderate, 22% mild-to-moderate and 6–8% mild ED. At baseline, 46–51% of patients were considered to have an organic cause for ED, 13–16% psychogenic ED, and 36–38% mixed classification of ED. For all classifications and for mild-to-moderate to severe ED, men treated with 10 or 20 mg of vardenafil showed statistically and clinically significant improvements ( P < 0.001) in IIEF-EF scores, diary response rates to the SEP-2 and SEP-3 questions, and GAQ as compared with those given placebo. The greatest improvements relative to placebo were noted in patients with more severe ED. The most common treatment-emergent adverse events were headache, flushing, rhinitis, dyspepsia, and were dose-related, mostly mild to moderate in intensity and consistent with the class. Conclusions. Vardenafil improves EF in men with ED irrespective of investigator-determined classification and baseline ED severity. [ABSTRACT FROM AUTHOR]

Conflict of Interest. Supported by Bayer Corporation, Bayer AG, GlaxoSmithKline. Francesco Montorsi, MD—Disclosures: Consultant/Advisor, Investigator, and Lecturer for Bayer Corporation, GlaxoSmithKline, Pfizer, Lilly Icos and American Medical Systems. Harin Padma-Nathan, MD—Disclosures: Consultant/Advisor, Investigator, and Lecturer for Bayer Corporation, GlaxoSmithKline, Pfizer, and Lilly Icos. Jaques Buvat, MD—Disclosures: Consultant/Advisor, Investigator, and Lecturer for Bayer Corporation, Pfizer, and Lilly Icos. Hartwig Schwaibold, MD—Disclosures: Consultant/Advisor, Investigator, and Lecturer for Bayer Corporation, GlaxoSmithKline, Pfizer, and Lilly Icos. Manfred Beneke, PhD—Disclosures: Employee, Bayer Vital GmbH. Tiemo Joerg Bandel, MD—Disclosures: Employee, Bayer HealthCare AG. Ernst Ulbrich, MD—Disclosures: Employee, Bayer Vital GmbH. Hartmut Porst, MD—Disclosures: Consultant/Advisor, Investigator, and Lecturer for Bayer AG, GlaxoSmithKline, Pfizer, and Lilly Icos. Introduction. Vardenafil, a potent and selective oral PDE5 inhibitor, is efficacious and generally well-tolerated in men with erectile dysfunction (ED). Of considerable interest to patients and physicians is an understanding of the time required after dosing to attain penile erection sufficient for successful sexual intercourse. Aim. To determine the earliest time to onset of action of vardenafil 10 and 20 mg leading to successful intercourse compared to placebo in men with ED. Methods. A prospective, randomized, double-blind, parallel-group, at-home study of 732 men with ED (mean age 55.5 years) was conducted at 64 sites in North America and Europe. Following a 4-week run-in period, patients were randomized to either vardenafil 10 (N = 237) or 20 mg (N = 248) or placebo (N = 247) to be taken on demand over 4 weeks. Using a stopwatch, patients recorded the elapsed time from dosing to attainment of an erection perceived to be adequate for penetration that led to intercourse completion. Earliest time of onset was defined as the fastest time among the first four doses for each patient. Time points from 25 to 5 minutes were tested for significance (alpha = 0.025) using a backward stepping procedure. Results. Mean baseline erectile function domain score (13.4) indicated moderate ED. Within 25 minutes after dosing, 50%/53% of men on vardenafil 10/20 mg had at least one erection in the first four doses perceived to be sufficient for penetration with subsequent intercourse completion compared to 26% on placebo ( P < 0.0001). A statistically superior response to vardenafil vs. placebo was observed in these responders at all times ≥ 10 and ≥ 11 minutes ( P < 0.025) in the 10 and 20 mg groups, respectively. In a retrospective analysis using time intervals of ≤ 15, ≤ 20, ≤ 25 and ≤ 30 minutes between dosing and erection adequate for penetration, 75–77% of these intercourse attempts were successful (SEP3 positive) by patients receiving vardenafil 10/20 mg, compared to 45–47% of attempts by those who received placebo. Vardenafil 10/20 mg was generally well-tolerated with headache (7%/12% vs. 1%) and flushing (6%/9% vs. < 1%) reported more frequently than with placebo. No patient discontinued vardenafil therapy due to adverse events. Conclusion. In this large, at-home study, the onset of action of vardenafil with subsequent intercourse completion was recognized as early as 10 minutes after dosing. [ABSTRACT FROM AUTHOR]

Background: In fixed-dose studies, vardenafil 5, 10, and 20 mg improves erectile function in men with erectile dysfunction (ED). Here, the efficacy and tolerability of vardenafil when used in a flexible-dose regimen was assessed.Methods: In this multicenter trial, 323 patients randomly received vardenafil 10 mg or placebo. After 4 weeks, patients could switch to 5 or 20 mg (or corresponding placebo), or remain on 10 mg for an additional 4 weeks; dose-switching was optional for the last 4 weeks. Efficacy variables included the IIEF-EF domain score, GAQ, and percentage of positive responses to SEP2/SEP3 questions.Results: The IIEF-EF domain score significantly improved from a baseline of moderate ED (12.6–13.1) to mild ED in men on vardenafil (21.0–24.2) compared with placebo (13.7–15.6) at weeks 4, 8, 12, and last observation carried forward (LOCF) (p<0.005 vs. placebo). A significantly greater proportion of men receiving vardenafil at weeks 4, 8, 12, and LOCF reported improved erections (80–86% vs. 21–36% for placebo, p<0.005). Successful SEP2 rates increased after vardenafil, reaching 84% at weeks 8 and 12 vs. 49–53% receiving placebo (p<0.005 vs. placebo). Vardenafil improved successful SEP3 rates ranging from 58% to 74% compared to 22–34% for placebo. The most common adverse events, flushing and headache, were generally mild and transient.Conclusion: In this flexible dose study, vardenafil was well-tolerated, and produced clinically relevant improvements in erectile function in men with ED. [Copyright &y& Elsevier]

Introduction Treatment of erectile dysfunction is based on pharmacotherapy for most patients. Aim To review the current data on pharmacotherapy for erectile dysfunction based on efficacy, psychosocial outcomes, and safety outcomes. Methods A review of the literature was undertaken by the committee members. All related articles were critically analyzed and discussed. Main Outcome Measures Levels of evidence (LEs) and grades of recommendations (GRs) are provided based on a thorough analysis of the literature and committee consensus. Results Ten recommendations are provided. (i) Phosphodiesterase type 5 (PDE5) inhibitors are effective, safe, and well-tolerated therapies for the treatment of men with erectile dysfunction (LE = 1, GR = A). (ii) There are no significant differences in efficacy, safety, and tolerability among PDE5 inhibitors (LE = 1, GR = A). (iii) PDE5 inhibitors are first-line therapy for most men with erectile dysfunction who do not have a specific contraindication to their use (LE = 3, GR = C). (iv) Intracavernosal injection therapy with alprostadil is an effective and well-tolerated treatment for men with erectile dysfunction (LE = 1, GR = A). (v) Intracavernosal injection therapy with alprostadil should be offered to patients as second-line therapy for erectile dysfunction (LE = 3, GR = C). (vi) Intraurethral and topical alprostadil are effective and well-tolerated treatments for men with erectile dysfunction (LE = 1, GR = A). (vii) Intraurethral and topical alprostadil should be considered second-line therapy for erectile dysfunction if available (LE = 3, GR = C). (viii) Dose titration of PDE5 inhibitors to the maximum tolerated dose is strongly recommended because it increases efficacy and satisfaction from treatment (LE = 2, GR = A). (ix) Treatment selection and follow-up should address the psychosocial profile and the needs and expectations of a patient for his sexual life. Shared decision making with the patient (and his partner) is strongly recommended (LE = 2, GR = A). (x) Counterfeit medicines are potentially dangerous. It is strongly recommended that physicians educate their patients to avoid taking any medication from unauthorized sources (LE = 2, GR = A). The first seven recommendations are the same as those from the Third International Consultation for Sexual Medicine and the last three are new recommendations. Conclusion PDE5 inhibitors remain a first-line treatment option because of their excellent efficacy and safety profile. This class of drugs is continually developed with new molecules and new formulations. Intracavernosal injections continue to be an established treatment modality, and intraurethral and topical alprostadil provide an alternative, less invasive treatment option. [ABSTRACT FROM AUTHOR]

Abstract: An association between erectile dysfunction and cardiovascular disease has long been recognized, and studies suggest that erectile dysfunction is an independent marker of cardiovascular disease risk. Therefore, assessment and management of erectile dysfunction may help identify and reduce the risk of future cardiovascular events, particularly in younger men. The initial erectile dysfunction evaluation should distinguish between predominantly vasculogenic erectile dysfunction and erectile dysfunction of other etiologies. For men believed to have predominantly vasculogenic erectile dysfunction, we recommend that initial cardiovascular risk stratification be based on the Framingham Risk Score. Management of men with erectile dysfunction who are at low risk for cardiovascular disease should focus on risk-factor control; men at high risk, including those with cardiovascular symptoms, should be referred to a cardiologist. Intermediate-risk men should undergo noninvasive evaluation for subclinical atherosclerosis. A growing body of evidence supports the use of emerging prognostic markers to further understand cardiovascular risk in men with erectile dysfunction, but few markers have been prospectively evaluated in this population. In conclusion, we support cardiovascular risk stratification and risk-factor management in all men with vasculogenic erectile dysfunction. [Copyright &y& Elsevier]

ABSTRACT Introduction. Erectile dysfunction (ED) impacts on both members of the couple. Female partners of men with ED are more likely to report reduced sexual quality of life than women whose partners do not have ED. Aim. To assess vardenafil efficacy in men with ED and determine the effects of treatment on their female partner's sexual quality of life. Methods. Study participants comprised men aged 18-64 years with ED and their female partners. Eligible men had ED of ≥6 months' duration and a female partner who was motivated to support their ED treatment. Eligible women had a total Female Sexual Function Index score >23.55, indicating absence of significant sexual dysfunction. Following a 4-week screening period, men were randomized to treatment with vardenafil 10 mg or placebo, which could be titrated to 20 or 5 mg after 4 weeks. Main Outcomes Measures. Primary efficacy variables were question 3 of the Sexual Encounter Profile questionnaire (SEP3) and the quality-of-life domain of the modified Sexual Life Quality Questionnaire (mSLQQ-QOL). Results. The intent-to-treat population included 343 couples, with 168 and 175 men receiving vardenafil or placebo, respectively. Vardenafil treatment significantly improved both erection maintenance and the female partners' sexual quality of life. Least squares (LS) mean SEP3 overall success rates after 12 weeks of treatment were 9.5 (baseline) vs. 67.2 (week 12) and 12.4 (baseline) vs. 24.2 (week 12) in the vardenafil and placebo groups, respectively ( P < 0.0001). In female partners, LS mean mSLQQ-QOL scores were 28.8 (baseline) vs. 68.2 (last observation carried forward [LOCF]) in the vardenafil group and 24.6 (baseline) vs. 40.5 (LOCF) in the placebo group ( P < 0.0001). Conclusions. Vardenafil treatment of men with ED improved both their erectile function and the sexual quality of life of their female partners. Martín-Morales A, Graziottin A, Bou Jaoudé G, Debruyne F, Buvat J, Beneke M, and Neuser D. Improvement in sexual quality of life of the female partner following vardenafil treatment of men with erectile dysfunction: A randomized, double-blind, placebo-controlled study. J Sex Med 2011;8:2831-2840. [ABSTRACT FROM AUTHOR]

Introduction. The validated Quality of Erection Questionnaire (QEQ) evaluates satisfaction with erection quality. Aim. To collate QEQ data, including correlations between QEQ outcomes and outcomes assessing emotional well-being, treatment satisfaction, and erection hardness after sildenafil citrate treatment. Methods. In four trials, men older than 18 years and with erectile dysfunction, a stable sexual partner, and no recent phosphodiesterase type 5 inhibitor use were randomized to double-blind flexible-dose sildenafil or placebo (1:1 ratio) for 6 or 10 weeks (two trials), fixed-dose 50 mg, 100 mg, and placebo (1:1:1 ratio) for 8 weeks (one trial), and 50 mg and 100 mg (1:1 ratio) for 4 weeks after 4 weeks of single-blind sildenafil 50 mg. Exclusion criteria included recent significant cardiovascular disease, use of nitrates, nitric oxide donors, cytochrome P450 3A4 inhibitors, or other erectile dysfunction treatment, and sildenafil hypersensitivity or previous severe or serious treatment-related adverse event. Main Outcomes Measures. Scores on the QEQ, QEQ Question 5 (satisfaction with erection hardness), the Self-Esteem and Relationship Questionnaire, and the Erectile Dysfunction Inventory of Treatment Satisfaction; the percentage of occasions with Erection Hardness Score 3 (EHS 3, hard enough for penetration but not completely hard) and/or EHS 4 (completely hard and fully rigid); and Pearson correlation coefficients. Results. 1,296 men (18–80 years) were randomized. Except for the percentage of occasions with EHS 3, all outcomes improved in men treated with sildenafil and correlated positively with the change in QEQ scores in all trials. Conclusions. Satisfaction with the quality of erections, which is easily monitored with the QEQ, correlated positively with measures of emotional well-being and treatment satisfaction and with the change in percentage of erections that were completely hard and fully rigid, but not with the change in percentage of erections that were hard enough for penetration but not completely hard. Kaminetsky JC, Depko AJ, Ströberg P, Buvat J, Tseng L-J, and Stecher VJ. In men with erectile dysfunction, satisfaction with quality of erections correlates with erection hardness, treatment satisfaction, and emotional well-being. J Sex Med 2009;6:800–808. [ABSTRACT FROM AUTHOR]

Vardenafil is a potent and selective phosphodiesterase 5 (PDE5) inhibitor developed for the treatment of erectile dysfunction (ED). Fixed-dose and flexible-dose studies have previously established the efficacy and tolerability of vardenafil.To assess, besides the usual measures of efficacy, the quality of erection, satisfaction with the sexual experience, symptoms of depression, and overall confidence.This 12-week double-blind, placebo-controlled flexible-dose study assessed patients from the general ED population. Patients underwent a 4-week treatment-free period before randomization to vardenafil or matching placebo. Initial dosage was vardenafil 10 mg for 4 weeks. At 4 weeks, patients could switch to 5 or 20 mg (or corresponding placebo), or remain on 10 mg for an additional 4 weeks; dose switching was also optional for the last 4 weeks. This paper describes per-patient success in satisfaction with hardness of erection, satisfaction with overall sexual experience, effect on overall self-confidence, and an assessment of symptoms of depression using the Center for Epidemiologic Studies Depression Scale.Mean per-patient satisfaction rates with erection hardness increased after vardenafil treatment to 43%, 59%, and 63% at weeks 4, 8, and 12, respectively, compared to placebo with 10%, 21%, and 23% (allP < 0.005 vs. placebo). Vardenafil also improved mean per-patient overall satisfaction 50–65% over the 4–12 week study period compared with 17–28% for placebo (P < 0.005). Symptoms of depression were statistically significantly reduced compared to placebo (P = 0.02); the effect was observed particularly in patients who were depressed at baseline (P = 0.01). Significantly more patients in the vardenafil treatment group reported improved self-confidence than those who received placebo (P < 0.005).A flexible-dose regimen of vardenafil improved satisfaction rates, symptoms of depression, and self-confidence, providing patients with an effective ED therapy that contributes to overall improvements in sexual function and confidence. [ABSTRACT FROM AUTHOR]

: ObjectivesTo assess whether vardenafil would improve erectile function irrespective of etiology, baseline severity, or patient age. The consistency of the response over time was also evaluated.: MethodsA multicenter, randomized, double-blind, placebo-controlled at-home study of vardenafil treatment (5, 10, and 20 mg) was performed. This secondary analysis compared the mean International Index of Erectile Function (IIEF) erectile function domain scores of various subgroups at 12 weeks of treatment. These populations included organic, psychogenic, or mixed etiologies; mild, moderate, or severe baseline severity; and four age groups (younger than 45, 45 to 55, 56 to 65, and older than 65 years). In addition, all IIEF domains were compared at sequential 4-week periods, before and during treatment.: ResultsIn the 580 men of the intent-to-treat population, the mean erectile function domain scores were statistically greater than placebo, irrespective of etiology, baseline severity, or age. This was seen at all dosages. Compared with placebo, vardenafil statistically improved the IIEF domain scores of erectile function, orgasmic function, intercourse satisfaction, and overall satisfaction after 4 weeks of treatment, and these improvements were maintained for 12 weeks. The rates of the most common adverse events (headache, flushing, and dyspepsia) were either constant or declined over time; they were generally mild to moderate and transient in nature.: ConclusionsVardenafil improved erectile function regardless of the general etiology, baseline severity of erectile dysfunction, or patient age. Improvements in erectile function and other key IIEF domains were consistently seen throughout the study. [Copyright &y& Elsevier]