Phosphodiesterase Type 5 Inhibitor Treatment for Erectile Dysfunction in Patients with End-Stage Renal Disease Receiving Dialysis or After Renal Transplantation

IntroductionThe phosphodiesterase type 5 (PDE5) inhibitors are generally well tolerated and effective for treating erectile dysfunction (ED), including in patients with significant comorbidity. Because of this benign safety profile, investigators have used PDE5 inhibitors to treat patients with ED and severe renal disease or those who have received renal transplants.AimTo assess safety and efficacy of PDE5 inhibitors in patients receiving dialysis or renal transplants.Main Outcome MeasuresErectile function as assessed by the International Index of Erectile Function (IIEF) and Global Assessment Questions; adverse events (AEs).MethodsWe reviewed published studies of PDE5 inhibitors in patients receiving dialysis or renal transplants.ResultsIn double-blind, placebo-controlled studies in patients receiving dialysis or renal transplants, sildenafil significantly improved erectile function as assessed by the IIEF, and 75–85% of patients reported improved erectile function on Global Assessment Questions; efficacy was more variable in less well-controlled studies. In >260 patients undergoing dialysis who received sildenafil in clinical studies, there were only six reported discontinuations because of AEs (headache [N=3], headache and nausea [N=1], gastrointestinal [N=1], and symptomatic blood pressure decrease [N=1]). In approximately 400 patients with renal transplants who received sildenafil, only three patients discontinued because of AEs. Vardenafil improved IIEF scores of up to 82% of renal transplant recipients in randomized, controlled studies (N=59, total), with no reported discontinuations because of AEs. Limited data also suggest benefit with tadalafil.Conclusions.ED is common in patients undergoing renal dialysis or postrenal transplant and substantially affects patient quality of life. Sildenafil and vardenafil appear to be efficacious and well tolerated in patients receiving renal dialysis or transplant. Lasaponara F, Sedigh O, Pasquale G, Bosio A, Rolle L, Ceruti C, Timpano M, Negro CLA, Paradiso M, Abbona A, Segoloni GP, and Fontana D. Phosphodiesterase type 5 inhibitor treatment for erectile dysfunction in patients with end-stage renal disease receiving dialysis or after renal transplantation. J Sex Med 2013;10:2798–2814.     

Efficacy of Phosphodiesterase Type 5 Inhibitor Treatment in Men with Erectile Dysfunction and Dyslipidemia: A Post Hoc Analysis of the Vardenafil Statin Study

IntroductionDyslipidemia occurs often in subjects with erectile dysfunction (ED), but there is little information about how this condition affects ED treatment responses.AimTo determine whether low-density lipoprotein cholesterol (LDL-C) levels, total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio; or the presence of metabolic syndrome influenced efficacy of vardenafil in men with ED and dyslipidemia.MethodsPost hoc subgroup analysis of a 12-week study of the influence of lipid levels and presence of metabolic syndrome on the efficacy of vardenafil as measured by International Index of Erectile Function-Erectile Function (IIEF-EF) domain score, responses to Sexual Encounter Profile (SEP) SEP2 and SEP3 questions, duration of erection leading to successful intercourse, and erection duration regardless of the answer to SEP3. Lipid values were obtained at study start, after patients had received at least 3 months of therapy with a statin.Main Outcome MeasuresOutcomes in subjects with LDL-C <100, ≥100 to <130, or ≥130 mg/dL [<2.59, ≥2.59 to <3.36, or ≥3.36 mmol/L]; TC/HDL-C ratio <3.5 vs. ≥3.5, and presence or absence of metabolic syndrome.ResultsVardenafil improved all endpoints evaluated compared with placebo in all subgroups, however, nominally significant treatment by subgroup interaction terms did not follow a distinct pattern. Increasing LDL-C (P = 0.033), but not TC/HDL-C ratio or metabolic syndrome, was associated with an increase in treatment response measured by the IIEF-EF domain score. Responses to SEP3 were nominally influenced by LDL-C levels (P = 0.019), but were not significantly influenced by TC/HDL-C ratio, or the metabolic syndrome. Only higher TC/HDL-C ratios (≥3.5) were associated with larger treatment differences in duration of erection leading to successful intercourse (P = 0.028).ConclusionsVardenafil was effective in men with dyslipidemia regardless of LDL-C levels, TC/HDL-C ratio, and/or presence of metabolic syndrome. Despite the known presence of ED and dyslipidemia, other cardiovascular risk factors were apparently not aggressively managed. Miner MM, Barnes A, and Janning S. Efficacy of phosphodiesterase type 5 inhibitor treatment in men with erectile dysfunction and dyslipidemia: A post hoc analysis of the vardenafil statin study.     

Female Assessment of Male Erectile Dysfunction Detection Scale (FAME): Development and Validation

IntroductionAlthough erectile dysfunction (ED) affects both members of the couple, no tools exist for the detection of ED by the female partner.AimThe aim of this study was to develop a scale for the detection of ED, as assessed by the female partner.MethodsDevelopment and validation of the Female Assessment of Male Erectile dysfunction detection scale (FAME) consisted of five stages: (i) two focus group discussions conducted among female partners of ED sufferers; (ii) item construction; (iii) initial content validation to document face validity and reduce number of items; (iv) final selection of items and investigation of concurrent validity and reliability, sensitivity and specificity of the scale in 83 Spanish-speaking couples; and (v) multicenter study conducted in a group of 106 English-speaking couples. Concurrent validity was assessed using Spearman's rho correlation coefficients between FAME and clinical diagnosis, the Sexual Health Inventory for Men (SHIM), and the erectile function domain of the International Index of Erectile Function (IIEF-EF). Reliability was tested using Cronbach's alpha, and sensitivity and specificity was investigated using clinical diagnosis as the gold standard criterion.Main Outcome MeasuresValidity, reliability, specificity, and sensitivity of the FAME scale when correlated with SHIM, IIEF-EF, and clinical diagnosis.ResultsQualitative analysis yielded 44 clues; 21 items demonstrated statistical significance as the best discriminating items using a t-test for independent samples. A final scale of six items was tested for validity, reliability, specificity, and sensitivity. FAME correlated significantly with clinical diagnosis (0.791, P < 0.001), the SHIM (0.788, P < 0.001), and the IIEF-EF (0.777, P < 0.001). Additional support for discriminant validity was obtained with receiver operating characteristics analysis. Cronbach's alpha was 0.941. Sensitivity was 96.1% and specificity 86.0%.ConclusionsAccurate detection of ED in men by the female partner is possible. In this study, FAME demonstrated concurrent validity and very good reliability, as well as excellent sensitivity and specificity. Rubio-Aurioles E, Sand M, Terrein-Roccatti N, Dean J, Longworth J, Eardley I, Brock G, Lee J, Arango de Montis I, and Rampazzo-Bonaldo C. Female assessment of male erectile dysfunction detection scale (FAME): Development and validation. J Sex Med 2009;6:2255–2270.     

Risk of Melanoma With Phosphodiesterase Type 5 Inhibitor Use Among Patients With Erectile Dysfunction,Pulmonary Hypertension,and Lower Urinary Tract Symptoms

Background

Phosphodiesterase type 5 inhibitors (PDE5is), a treatment for erectile dysfunction, pulmonary hypertension (pHTN), and lower urinary tract symptoms (LUTS), have been implicated in melanoma development.

Off-Label Use of Phosphodiesterase Type 5 Inhibitor Erectile Dysfunction Medication to Enhance Sex Among Gay and Bisexual Men in Australia: Results From the FLUX Study

BackgroundGay and bisexual men (GBM) use oral erectile dysfunction medications (EDMs) often with little evidence of medical indication necessitating their use.AimTo investigate the prevalence, contexts, and motivations for oral EDM use and its relation to sexual risk behavior.MethodsA total of 2,250 Australian GBM completed an online survey of licit and illicit drug use and their associated behaviors. Multivariate logistic regression analysis identified factors associated with use of EDMs in the previous 6 months and, for those who had used EDMs, factors associated with use on a weekly basis.OutcomesAny EDM use and at least weekly use in the previous 6 months.ResultsThe median age of the sample was 33.0 years (range = 16–81). Two thirds (67.7%) reported no lifetime history of EDM use. Approximately 1 in 10 participants (11.1%) had last used an EDM more than 6 months previously. In the previous 6 months, 11.5% reported using EDMs less than monthly, 5.3% reported using EDMs approximately monthly, and 4.5% reported using EDMs at least weekly. Of men who had used EDMs in the previous 6 months, common reasons cited for its use were to maintain an erection for longer (73.3%), to make it easier to “get hard” (67.3%), and difficulty in attaining or maintain an erection (53.5%). Use of EDMs in the previous 6 months was associated with illicit drug use and higher rates of sexual risk behavior. Weekly users were more likely to have severe anxiety than less frequent users.Clinical TranslationThe use of EDMs in the context of intensive sex partying, with the associated potential for increased risk of HIV transmission and illicit drug use, indicates a need to consider the use of EDMs among GBM in HIV prevention and minimizing harm.Strengths and LimitationsThis large-scale study of drug use among GBMs includes comprehensive detailed data on their history of use and rationales for use. Our online methodology potentially decreases social desirability bias in reporting illegal or stigmatized behaviors. This volunteer online convenience sample might not be representative of all GBMs in Australia.ConclusionGBMs who used an oral EDM in the previous 6 months often used it for recreational purposes, but many of those who used it on a weekly basis also might have used it for therapeutic reasons. GBMs often use EDMs to enhance their sexual experiences often in the context of intensive sex partying (which can include risky sexual behavior).Hammoud MA, Jin F, Lea T, et al. Off-Label Use of Phosphodiesterase Type 5 Inhibitor Erectile Dysfunction Medication to Enhance Sex Among Gay and Bisexual Men in Australia: Results From the FLUX Study. J Sex Med 2017;14:774–784.     

Efficacy and Safety of Dapoxetine in Men with Premature Ejaculation and Concomitant Erectile Dysfunction Treated with a Phosphodiesterase Type 5 Inhibitor: Randomized,Placebo-Controlled,Phase III Study

IntroductionMen with comorbid erectile dysfunction (ED) and premature ejaculation (PE) may be concomitantly prescribed a phosphodiesterase type 5 (PDE5) inhibitor and dapoxetine.AimEvaluate efficacy and safety of dapoxetine 30 mg and 60 mg on demand (prn) in men with PE and ED who were being treated with PDE5 inhibitors.MethodsThis randomized, double-blind, placebo-controlled, flexible-dose, multicenter study enrolled men ≥18 years who met diagnostic criteria for PE including intravaginal ejaculatory latency time (IELT) of ≤2 minutes in ≥75% of sexual intercourse episodes; were on stable regimen of a PDE5 inhibitor; and had International Index of Erectile Function-erectile function domain score ≥21. Subjects received placebo, dapoxetine 30 mg, or dapoxetine 60 mg prn (1–3 hours before intercourse) for 12 weeks.Main Outcome MeasureStopwatch-measured average IELT, Clinical Global Impression of Change (CGIC) in PE, Premature Ejaculation Profile (PEP), and treatment-emergent adverse events (TEAEs).ResultsOf 495 subjects randomized, 429 completed the study. Arithmetic mean average IELT significantly increased with dapoxetine vs. placebo at end point (5.2 vs. 3.4 minutes) and weeks 4, 8, and 12 (P ≤ 0.002 for all). Men who described their PE at least “better” using the CGIC were significantly greater with dapoxetine vs. placebo at end point (56.5% vs. 35.4%) and weeks 4, 8, and 12 (P ≤ 0.001 for all). Significantly better outcomes were also reported with dapoxetine vs. placebo on PEP measures. Incidence of TEAEs was 20.0% and 29.6% in placebo- and dapoxetine-treated subjects, respectively (P = 0.0135). TEAEs led to discontinuation in 1.6% of subjects in both groups. Most frequent TEAEs were known adverse drug reactions of dapoxetine treatment including nausea (9.2%), headache (4.4%), diarrhea (3.6%), dizziness (2.4%), and dizziness postural (2.4%).ConclusionsIn men with PE and comorbid ED on a stable regimen of PDE5 inhibitor, dapoxetine provided meaningful treatment benefit and was generally well tolerated. McMahon CG, Giuliano F, Dean J, Hellstrom WJG, Bull S, Tesfaye F, Sharma O, Rivas DA, and Aquilina JW. Efficacy and safety of dapoxetine in men with premature ejaculation and concomitant erectile dysfunction treated with a phosphodiesterase type 5 inhibitor: Randomized, placebo-controlled, phase III study. J Sex Med 2013;10:2312–2325.     

Validation of Stopwatch Measurements of Erection Duration against Responses to the Sexual Encounter Profile and International Index of Erectile Function in Patients Treated with a Phosphodiesterase Type 5 Inhibitor

IntroductionAlthough 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.AimsTo 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.MethodsData 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 MeasuresMean 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.ResultsAt 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).ConclusionsThis 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. Shaw JW, Reardon G, Sandor DW, Rosen RC, and Ferguson DM. Validation of stopwatch measurements of erection duration against responses to the Sexual Encounter Profile and International Index of Erectile Function in patients treated with a phosphodiesterase type 5 inhibitor.     

Selectivity of Avanafil,a PDE5 Inhibitor for the Treatment of Erectile Dysfunction: Implications for Clinical Safety and Improved Tolerability

IntroductionPhosphodiesterase type 5 (PDE5) inhibitors are indicated for the treatment of erectile dysfunction (ED); however, they can also inhibit other PDE isozymes, affecting their target tissues (e.g., PDE1: heart; PDE6: retina; and PDE11: skeletal muscle), which in some cases can cause unwanted side effects and therapy discontinuation. Data from in vitro studies showed that avanafil, a PDE5 inhibitor for the treatment of ED, exhibited strong selectivity toward PDE5 and against all other PDE isozymes.AimTo review the inhibitory effects of avanafil for PDE isozymes compared with those of sildenafil, tadalafil, and vardenafil and to discuss these results within the context of clinical trial safety observations.MethodsReview of in vitro selectivity data for avanafil (published primary data from a peer‐reviewed journal and scientific congress abstracts); PubMed search for pertinent publications on PDE5 inhibitor safety data; and review of published articles and abstracts from avanafil phase 1, 2, and 3 clinical trials.Main Outcome MeasuresA low incidence of some PDE‐related adverse events may be reflected by the high selectivity of avanafil against non‐PDE5 isozymes.ResultsAvanafil is highly selective toward PDE5 and against all other PDE isozymes tested. Lower selectivity against PDE1, PDE6, and PDE11 is consistent with results from randomized, placebo‐controlled, phase 3 trials in which musculoskeletal and hemodynamic adverse events were reported in <2% of patients and no color vision‐related abnormalities were reported with avanafil doses up to 200 mg once daily.ConclusionsData suggest that avanafil may confer a safety benefit, in terms of a lower incidence of specific adverse events, by virtue of its high specificity to PDE5 and its overall selectivity against other PDE isozymes. Wang R, Burnett AL, Heller WH, Omori K, Kotera J, Kikkawa K, Yee S, Day WW, DiDonato K, and Peterson CA. Selectivity of avanafil, a PDE5 inhibitor for the treatment of erectile dysfunction: Implications for clinical safety and improved tolerability. J Sex Med 2012;9:2122–2129.     

Comparison of Correlated Comorbidities in Male and Female Sexual Dysfunction: Findings From the Third National Survey of Sexual Attitudes and Lifestyles (Natsal-3)

Background

Many of the same mechanisms involved in the sexual arousal-response system in men exist in women and can be affected by underlying general medical conditions.

Improvement in Quality of Sexual Life in Female Partners of Men with Erectile Dysfunction Treated with Sildenafil Citrate: Findings of the Index of Sexual Life (ISL) in a Couple Study

IntroductionWomen's quality of sexual life is strongly impaired by erectile dysfunction (ED). Women's involvement in ED treatment is important for compliance and long-term efficacy but remains difficult. The Index of Sexual Life (ISL), specific of the quality of sexual life of women with ED partners, is used here to assess the impact of ED treatment on female partners.AimThe study explored in a context close to routine clinical practice the effect of sildenafil citrate (Viagra®; Pfizer, New York, NY, USA) treatment on women's quality of sexual life, in parallel with men's ED evaluations.MethodsThis prospective, open-labeled clinical trial was performed in France in 2006. Sexologists and andrologists recruited 67 volunteer couples for a 14-week sildenafil citrate treatment of male partners, without sex therapy in parallel.Main Outcome MeasuresWomen's quality of sexual life using ISL, and men's ED using International Index of Erectile Function (IIEF) and Self-Esteem And Relationship (SEAR) were assessed at baseline and at the end of the study. Satisfaction for treatment was measured using Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) and EDITS Partner.ResultsThe ISL sexual life satisfaction score was low at baseline (12.3), and increased by 8.3 during the study (P < 0.0001). Women were 79.0% to be responders according to ISL assessment. The other ISL dimensions also improved. The final ISL sexual life satisfaction score was dependant on women's age and final IIEF scores. The observed correlations between the ISL sexual life satisfaction dimension and the IIEF erectile function dimension, and the SEAR confidence dimension confirmed our assumptions. Both partners were highly satisfied with the treatment.ConclusionWomen satisfaction with their sex life was improved by ED treatment (sildenafil citrate). Couple global caring seemed to amplify the well-known effect of ED treatment for men. The ISL could be a useful tool to help women in their partner's treatment and to integrate ED treatment in a couple approach. Chevret-Méasson M, Lavallée E, Troy S, Arnould B, Oudin S, and Cuzin B. Improvement in quality of sexual life in female partners of men with erectile dysfunction treated with sildenafil citrate: Findings of the index of sexual life (ISL) in a couple study. J Sex Med 2009;6:761–769.     

Hypogonadal Men Nonresponders to the PDE5 Inhibitor Tadalafil Benefit from Normalization of Testosterone Levels with a 1% Hydroalcoholic Testosterone Gel in the Treatment of Erectile Dysfunction (TADTEST Study)

IntroductionAddition 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.AimsTo 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.MethodsA 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.Main Outcomes MeasuresMean 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).ResultsErectile 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.ConclusionsThe 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. Buvat J, Montorsi F, Maggi M, Porst H, Kaipia A, Colson MH, Cuzin B, Moncada I, Martin‐Morales A, Yassin A, Meuleman E, Eardley I, Dean JD, and Shabsigh R. Hypogonadal men nonresponders to the PDE5 inhibitor tadalafil benefit from normalization of testosterone levels with a 1% hydroalcoholic testosterone gel in the treatment of erectile dysfunction (TADTEST study).     

Pornography Addiction: An Exploration of the Association Between Use,Perceived Addiction,Erectile Dysfunction,Premature (Early) Ejaculation,and Sexual Satisfaction in Males Aged 18-44 Years

IntroductionThe way men consume pornography changed over the last decade, with increased numbers of men presenting with self-perceived Internet pornography (IP) addiction and related sexual dysfunction. A lack of consensus and formal recognition in the DSM-5 lead to a variety of definitions of IP addiction. Currently, the majority of evidence linking IP addiction and sexual dysfunction was derived from consumers, case studies, and qualitative research. Where empirical measures were used, researchers found mixed outcomes in sexual response. Inconclusive data appeared to relate to the conflation of IP use and self-perceived IP addiction, and normal variations in sexual response with clinical diagnosis of sexual dysfunction. Thus, further empirical clarification is required to assess the impact of both IP use and self-perceived IP addiction, on men's sexual function.AimsThis study has 3 aims: First, to assess if there is an association between IP use alone and erectile dysfunction (ED), premature (early) ejaculation (EE) and sexual satisfaction (SS); Second, to assess whether there is an association between self-perceived IP addiction and ED, EE and SS. Third, to assess whether IP use or self-perceived IP addiction uniquely predicts ED, EE, SS in men.MethodCorrelation and regression analysis was conducted on a cross-sectional sample of 942 heterosexual men aged 18-44 years who participated in an online survey sourced from Reddit IP subgroups.Main Outcome MeasuresCyber-Pornography Use Inventory; International Index Erectile Dysfunction; The Checklist for Early Ejaculation Symptoms; New Sexual Satisfaction Scale; Depression Anxiety Stress Scale-21.ResultsThere was no evidence for an association between IP use with ED, EE, or SS. However, there were small to moderate positive correlations between self-perceived IP addiction and ED, EE and sexual dissatisfaction. Further, self-perceived IP addiction uniquely predicted increased ED, EE and individual sexual dissatisfaction. Contrary to expectations, self-perceived IP addiction did not predict sexual dissatisfaction with one's sexual partner.ConclusionThese results suggest that IP use alone does not predict sexual dysfunction. Rather, self-perception of increased IP addiction was related to negative sexual outcomes. Thus, we concluded that subjective interpretation of ones IP use was a contributor to IP related sexual problems in our sample of males who share IP on social media sites. We recommend that clinicians consider self-perceived IP addiction as a possible contributing factor to sexual dysfunction. Whelan G, Brown J. Pornography Addiction: An Exploration of the Association Between Perceived Addiction, Erectile Dysfunction, Premature (Early) Ejaculation, and Sexual Satisfaction in Males Aged 18-44 Years. J Sex Med 2021;18:1582–1591.