Adherence to Initial PDE5 Inhibitor Treatment: Randomized OpenLabel Study Comparing Tadalafil Once a Day,Tadalafil on Demand,and Sildenafil on Demand in Patients with Erectile Dysfunction

IntroductionPhosphodiesterase type 5 (PDE5) inhibitor treatment for erectile dysfunction (ED) is frequently discontinued; adherence may vary depending on the initial regimen.AimTo 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.MethodsIn this multicenter, openlabel study, men (≥18 years) with ED, naïve to PDE5 inhibitors, were randomized (1:1:1) to tadalafil 5 mg OaD, tadalafil 10 mg PRN, or sildenafil 50 mg PRN. An 8week randomized treatment (RT) period (dose adjustment possible) was succeeded by 16 weeks of pragmatic treatment (switches between PDE5 inhibitors allowed).Main Outcome MeasuresTreatment adherence was measured as time to discontinuation of RT (any cause), estimated by Kaplan–Meier productlimit method. Treatmentgroup differences were estimated as hazard ratio (HR; Cox proportional hazards).ResultsSeven 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 betweengroup differences were found in International Index of Erectile FunctionErectile 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.ConclusionsED 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.     

Efficacy and Safety of MED2005, a Topical Glyceryl Trinitrate Formulation,in the Treatment of Erectile Dysfunction: A Randomized Crossover Study

Background

Current treatments for erectile dysfunction (ED) have some limitations.

Efficacy and Safety of Oral Mirodenafil in the Treatment of Erectile Dysfunction in Diabetic Men in Korea: A Multicenter,Randomized, Double-Blind,Placebo-Controlled Clinical Trial

IntroductionMirodenafil is a newly developed selective phosphodiesterase type 5 (PDE5) inhibitor for the treatment of erectile dysfunction (ED).AimTo evaluate the efficacy, safety and tolerability of mirodenafil in the treatment of ED in Korean men with diabetes.MethodsA multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study was conducted with 112 subjects who were randomized to either placebo or mirodenafil 100 mg on demand for 12 weeks.Main Outcome MeasuresPrimary efficacy variable was the erectile function (EF) domain scores of the International Index of Erectile Dysfunction (IIEF) questionnaire. Secondary efficacy variables included change in the scores of IIEF question 3 and 4 (IIEF Q3 and Q4) from baseline, change in all domain scores in the IIEF from baseline, Sexual Encounter Profile questions 2 and 3 (SEP2 and SEP3), the Global Assessment Question (GAQ) and the Life Satisfaction Checklist (LSC).ResultsAfter 12 weeks of treatment, mirodenafil group showed significantly greater change in the IIEF-EF domain score from baseline compared with the placebo group (9.3 vs. 1.4, P < 0.0001). The changes from baseline in the mirodenafil group in IIEF Q3 (1.7 vs. 0.4, P < 0.0001) and Q4 (1.7 vs. 0.3, P < 0.0001) were higher compared with the placebo group. Differences between the mirodenafil and placebo groups were significant in the SEP2 (82.0% vs. 55.2%, P = 0.0003), SEP3 (68.9% vs. 22.3%, P < 0.0001). Difference in GAQ “YES” responses was also significant (76.9% vs. 19.1%, P < 0.0001). Normal EF domain scores (≥26) at study end were achieved by 32.7% and 9.4% in the mirodeniafl and placebo groups, respectively (P = 0.0031). As for the LSC scores, the mirodenafil group showed significantly greater improvements in sexual life and partner relationship than the placebo group. Most treatment-associated AEs were mild that resolved spontaneously.ConclusionsMirodenafil is an effective and well-tolerated agent for the treatment of diabetic patients with ED in Korea. Park HJ, Choi HK, Ahn TY, Park JK, Chung WS, Lee SW, Kim SW, Hyun JS, and Park NC. Efficacy and safety of oral mirodenafil in the treatment of erectile dysfunction in diabetic men in Korea: A multicenter, randomized, double-blind, placebo-controlled clinical trial.     

The Effect of Combination Treatment With Low-Intensity Shockwave Therapy and Tadalafil on Mild and Mild-To-Moderate Erectile Dysfunction: A Double-Blind,Randomized, Placebo-Controlled Clinical Trial

BackgroundCombination of different first-line treatments for erectile dysfunction (ED) has emerged as a promising therapeutic approach.AimTo conduct the first double-blind, randomized, placebo-controlled clinical trial to evaluate the efficacy and safety of combination therapy with low-intensity shockwave therapy (LiST) and tadalafil vs LiST and placebo in patients with mild or mild-to-moderate vasculogenic ED.MethodsFifty sexually active patients fulfilling the eligibility criteria were randomly assigned to 6 sessions of LiST twice weekly for 3 weeks and tadalafil (n = 25) or placebo (n = 25) once daily for 4 weeks. Patients were evaluated at 1, 3, and 6 months after completion of the treatment protocol.OutcomesThe primary outcome was the mean change from baseline in the International Index of Erectile Function-Erectile Function (IIEF-EF) domain between the 2 groups at 3 months after treatment. Erectile function was also assessed at 1 and 6 months. The number of patients attaining a minimal clinically important difference (MCID) in the IIEF-EF, as well as the safety of combination therapy were evaluated.ResultsAdjusting for the baseline values, IIEF-EF improved by 0.8 points more (95% confidence interval [CI] = ?0.2 to 1.9, P = .12) at 1 month, 1 point more (95% CI = 0.1–1.9, P = .02) at 3 months and 1.7 points more (95% CI = 0.8–2.7, P < .001) at 6 months in patients treated with combination therapy compared to monotherapy. The number of patients attaining a MCID in the IIEF-EF between the 2 groups improved significantly only at the 3-month evaluation. No adverse events were reported during the whole study period.Clinical ImplicationsCombination of LiST twice weekly for 3 weeks and tadalafil 5 mg once daily for 4 weeks may further ameliorate mild or mild-to-moderate vasculogenic ED compared to LiST monotherapy.Strengths & LimitationsWe conducted the first randomized trial exploring the role of LiST and tadalafil in the management of ED. Conversely, our study lacks external validity due to its single-center design.ConclusionThe addition of daily low-dose tadalafil during application of LiST may further improve erectile function compared to application of LiST as a standalone treatment in patients with mild or mild-to-moderate vasculogenic ED. Still, further high-quality studies are warranted to corroborate our findings.Mykoniatis I, Pyrgidis N, Zilotis F, et al. The Effect of Combination Treatment With Low-Intensity Shockwave Therapy and Tadalafil on Mild and Mild-To-Moderate Erectile Dysfunction: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial. J Sex Med 2022;19:106–115.     

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.     

Efficacy and Safety of Tadalafil for Erectile Dysfunction in Patients with Multiple Sclerosis

IntroductionData are sparse concerning the effects of phosphodiesterase type 5 (PDE5) inhibitors for erectile dysfunction (ED) in subjects with multiple sclerosis (MS).AimTo evaluate the efficacy and safety of tadalafil use in subjects with ED because of MS.MethodsNinety-six MS patients with ED after a 4-week treatment-free period were given tadalafil 10 mg. All patients were re-evaluated after 4 weeks. Those with a score lower than 26 on the International Index of Erectile Function (IIEF-15) and with less than 75% of total successful sexual attempts assessed by the Sexual Encounter Profile Questions 2 and 3 (SEP2-3) had their dosage of tadalafil increased to 20 mg, whereas responding subjects continued with 10 mg. Subsequently, all patients had a final follow-up visit after 8 weeks.Main Outcome MeasuresSEP2-3, IIEF-15 questionnaire. The Life Satisfaction Checklist (LSC) questionnaire composed of eight questions was used prior to starting tadalafil and at the end of the 12-week treatment.ResultsNinety-two subjects completed the study. Seventy-two responded, 30 of whom used 10 mg. Two subjects discontinued the therapy because of moderate side effects: one suffered from headache and one from tachycardia. Responding patients reached a significant statistical improvement in all follow-ups compared with baseline on the erectile domain and overall sexual satisfaction scores of the IIEF-15 using the Wilcoxon test P < 0.01. Furthermore, they showed statistical improvement through the Wilcoxon test P < 0.01 on the sexual life, family life, and partner relationship questions of the LSC compared with baseline.ConclusionTadalafil is an effective and safe treatment for males with MS suffering from ED. Further studies are needed on MS patients to evaluate the efficacy and safety of long-term use, and to detect predictable parameters for the success of PDE5 inhibitors. Lombardi G, Macchiarella A, and Del Popolo G. Efficacy and safety of tadalafil for erectile dysfunction in patients with multiple sclerosis.     

Daily Oral l-Arginine Plus Tadalafil in Diabetic Patients with Erectile Dysfunction: A Double-Blinded,Randomized, Controlled Clinical Trial

IntroductionErectile dysfunction is a common condition among diabetic men. Many treatments are now available with variable responses.AimThis study aimed to evaluate the effect of daily oral l-arginine plus tadalafil in diabetic patients with mild to moderate erectile dysfunction.MethodsA double-blinded, randomized, controlled clinical trial was conducted with 108 diabetic male patients. Each patient was assessed by medical and sexual histories, International Index of Erectile Function 5-item questionnaires, pharmaco-penile duplex ultrasonography, and serum testosterone level.Main Outcome MeasureImprovement in International Index of Erectile Function 5-item, serum testosterone level and pharmaco-penile duplex ultrasonography.ResultsErectile functions were significantly improved in all patients after treatment as compared with baseline and placebo (P < .001). Patients who received both drugs showed significant improvement compared to those treated with single drugs, as assessed by International Index of Erectile Function scores and total testosterone (P < .001). Pharmaco-penile ultrasound duplex results showed non-significant differences among patients treated with both drugs and those with each drug alone.ConclusionDaily use of l-arginine with tadalafil significantly increased the International Index of Erectile Function scores and total testosterone levels as compared to each drug alone in diabetic patients with erectile dysfunction. No differences were found based on pharmaco-penile duplex findings.El Taieb M, Hegazy E, Ibrahim A. Daily Oral l-Arginine Plus Tadalafil in Diabetic Patients with Erectile Dysfunction: A Double-Blinded, Randomized, Controlled Clinical Trial. J Sex Med 2019; 19:1390–1397.     

The Efficacy of Combination Treatment with Injectable Testosterone Undecanoate and Daily Tadalafil for Erectile Dysfunction with Testosterone Deficiency Syndrome

IntroductionBoth testosterone therapy and chronic treatment with phosphodiesterase type 5 inhibitors (PDE5Is) have positive effects on the histology of penile corpora and erectile function. However, few clinical studies have evaluated the efficacy of combination therapy with both testosterone replacement and chronic PDE5Is.AimThis study was designed to evaluate the efficacy and safety of combination treatment with long‐acting injectable testosterone undecanoate (TU) and a once‐daily tadalafil 5 mg for erectile dysfunction with testosterone deficiency syndrome.MethodsSixty patients were consecutively enrolled and followed for 36 weeks. Thirty patients were randomly assigned to group I and received 1,000 mg of parenteral TU on day 1, followed by additional injections at weeks 6 and 18 with on‐demand tadalafil 10–20 mg during the 30 weeks of treatment. The remaining 30 patients received the same dose and schedule of TU as group I, and were prescribed once‐daily tadalafil 5 mg during 30 weeks.Main Outcome MeasuresSerological tests were performed, and the International Index of Erectile Function (IIEF), Aging Males' Symptoms (AMS) questionnaires, and Global Assessment Question (GAQ) were administered to the patients.ResultsTotal IIEF and AMS scores were significantly improved during the 30 weeks of treatment in both groups. When IIEF scores were compared between the two groups, group II showed better symptom scores than group I at weeks 6 and 30. A similar pattern was observed when comparing AMS scores between the groups. At week 36, changes in IIEF and AMS scores that indicated worsened symptoms compared with week 30 were observed in both groups; group II showed better symptom scores than group I. On the GAQ, the ratio of patients reporting improvement in erectile function was significantly higher in group II than group I.ConclusionsThe combination of long‐acting injectable TU and once‐daily tadalafil 5 mg produced a significant improvement in erectile function. Moreover, the improvement in erectile function was well maintained, even after the cessation of treatment. Park MG, Yeo JK, Cho D‐Y, Kim JW, Kim JW, Oh MM, Kim JJ, and Moon DG. The efficacy of combination treatment with injectable testosterone undecanoate and daily tadalafil for erectile dysfunction with testosterone deficiency syndrome. J Sex Med 2015;12:966–974.     

Evaluation of Patient Expectations and Treatment Satisfaction after 1-Year Tadalafil Therapy for Erectile Dysfunction: The DETECT Study

IntroductionErectile dysfunction (ED) is a self-reported condition and satisfaction with sexual performance is individual, subjective, and multi-factorial. Treatment success depends on several outcomes. Tadalafil is a long-acting, selective inhibitor of phosphodiesterase 5 that has been shown to be effective at treating men with ED.AimTo investigate patient's ED treatment expectations at baseline; patient satisfaction with tadalafil treatment after 12 months; factors associated with satisfaction; and effect of early tadalafil treatment satisfaction on tadalafil continuation at 12 months.MethodsThe Determinants of Continued Use of Tadalafil study is a 12-month, prospective, pan-European, noninterventional, observational study, which enrolled 1,900 patients with ED wishing to initiate or change their treatment to tadalafil. Assessments were made on predefined treatment outcomes in a routine clinical setting.Main Outcome MeasuresInternational Index of Erectile Function-erectile function domain scores (at baseline, 1, 6, and 12 month visit), ED Inventory of Treatment Satisfaction (EDITS) scores (after 1, 6, and 12 months), and patient expectation questionnaire (at baseline visit) were analyzed for these patients.ResultsData were available from 1,567 patients (82%) after 12 months, with similar baseline characteristics as the initial cohort. Treatment expectations identified as important included: erection hardness and ability to maintain erection through intercourse completion (>92% of patients); confidence, partner satisfaction, and naturalness (>84% of patients); rapid effect and long duration of treatment (>75% of patients). Continued tadalafil use from 1,319 (84%) patients at 12 months were reported. Total EDITS scores for those continuing treatment was 85.9 (95% CI: 85.1–86.7). Increased satisfaction was associated with higher effectiveness, number of sexual attempts, partner support, good relationships, and good drug tolerance. Treatment satisfaction at 1 month was best predictive of treatment continuation at 12 months.ConclusionsEighty-four percent of patients reported continued use of tadalafil after 12 months. High satisfaction after first month of treatment was the best predictor of treatment continuation. Perimenis P, Roumeguere T, Heidler H, Roos E, Belger M, and Schmitt H. Evaluation of patient expectations and treatment satisfaction after one year tadalafil therapy for erectile dysfunction: The DETECT study.     

Self-Esteem,Confidence, and Relationships in Brazilian Men with Erectile Dysfunction Receiving Sildenafil Citrate: A Randomized,Parallel-Group,Double-Blind,Placebo-Controlled Study in Brazil

IntroductionPsychosocial manifestations of erectile dysfunction (ED) differ across cultures. Understanding the treatment response to ED medications within cultural groups can aid in resource allocation and in developing treatment strategies.AimEvaluate the effect of sildenafil treatment on self-esteem, confidence, and sexual relationship satisfaction in Brazilian men with ED.Main Outcome MeasureThe Self-Esteem and Relationship (SEAR) questionnaire, a validated, 14-question instrument developed to specifically address self-esteem and relationship issues within the context of ED.MethodsMen aged 18 years or older with a clinical diagnosis of ED (≤21 on the Sexual Health Inventory for Men) and in a stable relationship with a partner during the study were eligible. The primary end point was a change from baseline in the self-esteem subscale of the SEAR questionnaire. Thirteen Brazilian sites participated in a randomized, double-blind, placebo-controlled trial of sildenafil treatment for ED. Patients were randomized to receive either 50 mg of sildenafil (adjustable to 25 mg or 100 mg based on patient response) or matching placebo approximately 1 hour before anticipated sexual activity but not more than once a day.ResultsAt the end of double-blind treatment, 63 and 66 patients in the placebo and sildenafil groups, respectively, from 13 Brazilian sites were assessed for efficacy. Brazilian patients receiving sildenafil had significantly greater improvements in their scores on the SEAR self-esteem subscale (42.9 [95% confidence interval 35.7–50.0]) compared with placebo (21.1 [95% confidence interval 13.7–28.6]; P < 0.0001). Effect sizes ranged from 0.91 to 1.25 for individual SEAR components.ConclusionsThe psychosocial parameters in Brazilian men with ED assessed by the SEAR questionnaire showed significant improvements in self-esteem, confidence, and relationships after treatment with sildenafil. Glina S, Damião R, Abdo C, Afif-Abdo J, Tseng L-J, and Stecher V. Self-esteem, confidence, and relationships in Brazilian men with erectile dysfunction receiving sildenafil citrate: A randomized, parallel-group, double-blind, placebo-controlled study in Brazil.     

Long-term,Multicenter Study of the Safety and Efficacy of Topical Alprostadil Cream in Male Patients with Erectile Dysfunction

IntroductionAlprostadil is approved for treatment of male erectile dysfunction (ED) by injection or urethral insertion. Topical delivery of alprostadil offers an improved alternative.AimTo evaluate the long-term safety and efficacy of topical alprostadil cream.MethodsThis was a multicenter, open-label, long-term study in 1,161 patients (998 double-blind rollover; 163 naïve) with ED. For the first 4 weeks, patients could administer eight doses of 200 mcg alprostadil to the penis meatus before intercourse (up to 2 per/week). Patients then self-selected to administer 300 or 100 mcg doses if hypo-responsive or hyper-responsive, respectively, or 200 mcg if no change, for up to 9 months (2 doses/week).Main Outcome MeasuresSafety evaluated patient/partner adverse events (AEs), changes in vital signs, clinical laboratory tests, physical examinations, and electrocardiograms. Efficacy assessed International Index of Erectile Function, Sexual Encounter Profile, Patient Self Assessment of Erection, and Global Assessment Questionnaire.ResultsApproximately 12% of patients discontinued due to hypo-/hyper-responsiveness, 16% withdrew consent for a variety of reasons, and less than 5% discontinued because of AEs. The majority of patients (73%) selected 300 mcg alprostadil as the final dose. The most common AEs involved application site burning or erythema (12.2%), meatal or glans pain (4.4%), and prolonged or painful erection (1.3%). Only 5 (0.4%) patients reported a prolonged erection of ≥4 hours (priapism). Vaginal burning or itching (2.1%) was reported most frequently by partners. The majority of patients (74%) demonstrated an overall improvement in erectile function on most end-points, especially after adjusting dose strength to their individual responsiveness.ConclusionsTopical alprostadil cream was considered effective and safe by most patients and their partners, with most AEs limited to the application site. Dose adjustment to 300 mcg alprostadil facilitated the greatest improvement in erectile function in the majority of patients. A separate report will integrate patient data from the open-label extension and prior double-blind studies. Rooney M, Pfister W, Mahoney M, Nelson M, Yeager J, and Steidle C. Long-term, multicenter study of the safety and efficacy of topical alprostadil cream in male patients with erectile dysfunction. J Sex Med 2009;6:520–534.     

Efficacy and Safety of Medium and Long-Term Tadalafil Use in Spinal Cord Patients with Erectile Dysfunction

IntroductionThe efficacy of phosphodiesterase type 5 inhibitors for a broad spectrum of erectile dysfunction (ED) is largely reported in literature. Data are lacking concerning medium and long-term effects and safety of these treatments.AimThe aim of this study was to evaluate the efficacy and safety of medium and long-term use of tadalafil in subjects with ED because of spinal cord injury (SCI).MethodsPhase 1: From March 2003 to March 2007, 103 SCI patients with ED, mean age 39 years, were given 10 mg of tadalafil after a 4-week treatment-free period. For patients with a score lower than 26 in the erectile domain of the International Index of Erectile Function (IIEF15) and with total unsuccessful sexual attempts of more than 25% according to the Sexual Encounter Profile questions 2 and 3 (SEP2–3), the dosage of tadalafil was increased to 20 mg.Phase 2: Only responding patients entered phase 2 where the subjects were evaluated in office visits every 6 months using the IIEF15 questionnaire and a diary reporting the day and time the drug was taken. All final visits were concluded by May 2008.Main Outcome MeasuresThe improvement of ED was measured using the IIEF15 and the SEP2–3 questions.ResultsTwenty-nine patients were excluded from phase 2: Twenty-seven did not respond to the drug and two left the study because of mild drawbacks. During the 6-month follow-up, nine left the study. Sixty-five individuals continued treatment with median follow-up of 33.6 months, 31 of whom took 10 mg and 34 who used 20 mg. Each group maintained up until the final visit a significant statistical improvement in erectile function, sexual satisfaction, overall satisfaction and percentages of “yes” responses to the SEP2–3 compared with baseline using the Wilcoxon test (P < 0.05).ConclusionTadalafil represents an effective and safe long-term option for SCI patients with ED. Lombardi G, Macchiarella A, Cecconi F, and Popolo GD. Efficacy and safety of medium and long-term tadalafil use in spinal cord patients with erectile dysfunction. J Sex Med 2009;6:535–543.     

Efficacy of Once-Daily Administration of Udenafil for 24 Weeks on Erectile Dysfunction: Results from a Randomized Multicenter Placebo-Controlled Clinical Trial

IntroductionThe method of administration of oral phosphodiesterase-5 inhibitors has been expanded to once-daily repeated administration with lower initial dosage than on-demand administration.AimThe aim of this study was to evaluate the efficacy and safety of once-daily udenafil as a treatment for erectile dysfunction (ED) for intermediate-term period.MethodsThis multicenter, randomized, double-blind clinical trial included 346 ED patients (placebo, udenafil 50 mg, udenafil 75 mg). Subjects were treated with each medication once daily for 24 weeks.Main Outcome MeasuresSubjects were asked to complete the International Index of Erectile Function (IIEF)-erectile function (EF) domain at baseline, 12 weeks, and 24 weeks and the development of adverse drug reactions (ADRs) was inspected.ResultsBoth dosages of udenafil induced a significant increase in IIEF-EF compared with placebo at both 12 and 24 weeks. When patients were divided according to the severity of baseline EF score, significant improvement was observed only with udenafil 75 mg regardless of the degree of ED. At 24 weeks, the proportions of patients who reported a return to normal EF (IIEF-EF over 26) were 39.1% for udenafil 50 mg and 47.0% for udenafil 75 mg. In terms of safety, ADRs were observed in 6.1%, 12.9%, and 17.9% for placebo, udenafil 50 mg, and 75 mg, respectively. Although a statistically higher rate of ADRs was observed in the udenafil 75 mg group (P = 0.024), the majority were mild and recovered without treatment.ConclusionsOnce-daily administration of udenafil 50 mg and 75 mg for 24 weeks resulted in improvement of EF. In particular, udenafil 75 mg improves EF regardless of the baseline degree of ED. Moon KH, Ko YH, Kim SW, Moon DG, Kim JJ, Park NC, Lee SW, Paick J-S, Ahn TY, Chung WS, Min KS, Park JK, Yang DY, and Park K. Efficacy of once-daily administration of udenafil for 24 weeks on erectile dysfunction: Results from a randomized multicenter placebo-controlled clinical trial. J Sex Med 2015;12:1194–1201.     

Efficacy of Udenafil for the Treatment of Erectile Dysfunction up to 12 Hours after Dosing: A Randomized Placebo-Controlled Trial

IntroductionUdenafil is a newly developed selective phosphodiesterase type 5 inhibitor for the treatment of men with erectile dysfunction (ED).AimTo evaluate the efficacy of udenafil in treating ED for up to 12 hours after dosing.MethodsThis was a randomized, double-blind, placebo-controlled, parallel-group, fixed dose design, multicenter study. Following a 4-week nondrug baseline period, 104 men with ED of broad etiology and severity were randomized to one of two treatment groups: udenafil 100 mg or placebo. Participants were requested to attempt sexual intercourse at 12 hours after udenafil or placebo dosing during a 4-week treatment period.Main Outcome MeasuresThe primary efficacy variable was the response of patients to question 3 of the Sexual Encounter Profile (SEP Q3). The secondary efficacy measures were the response of patients to question 2 of the Sexual Encounter Profile (SEP Q2). Additional secondary efficacy measures included changes from baseline in the erectile function (EF) domain scores of the International Index of Erectile Function (IIEF) questionnaire.ResultsOf the 104 patients, 103 (50 in the udenafil group, 53 in the placebo group) completed the study. Udenafil significantly enhanced the rate of maintenance of erection (SEP Q3; placebo, 28.3% vs. udenafil, 54.7%; P < 0.0001). Significant change from baseline in the IIEF-EF domain was observed in the udenafil group (placebo, –0.58 ± 0.67; udenafil, 4.40 ± 0.84; P < 0.0001). For SEP Q2, there was no difference from baseline and no difference between the two groups. The overall adverse events rate was 11.3%. Most adverse events were mild or moderate in severity, and no serious adverse events were reported during the study and the follow-up period.ConclusionsUdenafil at 100 mg was effective for relieving ED for up to 12 hours after dosing. This duration of effectiveness could allow for flexibility and spontaneity in the sexual lives of patients. Park HJ, Park JK, Park K, Min K, and Park NC. Efficacy of udenafil for the treatment of erectile dysfunction up to 12 hours after dosing: A randomized placebo-controlled trial.     

Effects of Chronic Vardenafil Treatment Persist after End of Treatment in Rats with Acute Arteriogenic Erectile Dysfunction

IntroductionIn our previous study, chronic vardenafil treatment improved erectile function soon after the end of the treatment in rats with acute arteriogenic erectile dysfunction (ED).AimThe aim of this study is to evaluate whether the effects of chronic vardenafil treatment persist after the end of treatment using rats with acute arteriogenic ED.MethodsRats were randomly divided into three groups: (i) control; (ii) ligation; and (iii) vardenafil + no treatment. Rats in the ligation and vardenafil + no treatment groups underwent ligature of the bilateral internal iliac arteries to induce acute arteriogenic ED and were subsequently treated with vehicle or vardenafil (4.0 mg/kg/day), respectively, for 3 weeks. Subsequently, all rats were kept for a further 2 weeks with no treatment. Rats in the control group underwent sham surgery.Main Outcome MeasuresErectile function was assessed by changes in intracavernous pressure (ICP). Smooth muscle (SM)/collagen ratios in corpus cavernosum were analyzed by Masson trichrome staining. Transforming growth factor‐β₁ (TGF‐β₁) mRNA and protein levels in corpus cavernosum (CC) were, respectively, evaluated by real‐time polymerase chain reaction (PCR) analysis and Western blotting analysis.ResultsICP/mean arterial pressure (MAP) in the ligation group remained significantly lower than that in control group (P < 0.01). Despite no treatment for 2 weeks, ICP/MAP in the var + no treatment group remained significantly higher than that in ligation group (P < 0.05). SM/collagen ratio in the ligation group remained significantly lower when compared with the control group (P < 0.01). The ratio in the var + no treatment group remained significantly higher when compared with the ligation group at 2 weeks after the end of treatment (P < 0.05). TGF‐β₁ mRNA and protein levels did not differ among the groups.ConclusionsThe effects of chronic vardenafil treatment on erectile function and penile structure persist, even after the end of treatment, in acute arteriogenic ED rats. Hotta Y, Ohno R, Kataoka T, Mikumo M, Takahata Y, Ohno M, Maeda Y, and Kimura K. Effects of chronic vardenafil treatment persist after end of treatment in rats with acute arteriogenic erectile dysfunction. J Sex Med 2012;9:1799–1805.     

Physical Activity and PDE5 Inhibitors in the Treatment of Erectile Dysfunction: Results of a Randomized Controlled Study

IntroductionPhysical activity (PhA) has proven to be a protective factor for normal erectile function in numerous epidemiological studies.AimThe aim of this study was to establish if PhA could have a therapeutic role in the treatment of erectile dysfunction (ED).MethodsThis was a randomized, open-label study. A total of 60 patients complaining of ED were studied. Patients were assessed at baseline and after 3 months of study treatment. At baseline, patients were randomized to receive phosphodiesterase type 5 inhibitor (PDE5i) alone (group A) or PDE5i plus regular (≥3 hours/week), aerobic, non-agonistic PhA (group B).Main Outcome MeasuresAll subjects completed the International Index of Erectile Function (IIEF-15) questionnaire and performed total testosterone (TT).ResultsMean PhA was 3.4 hours/week in group B vs. 0.43 in group A; mean energy expenditure in group B was 1,868 kcal/ week or 22.8 metabolic equivalent (MET)/week. IIEF restoration of ED occurred in 77.8% (intervention group) vs. 39.3% (control) (P < 0.004). The IIEF-15 score resulted in statistical improvement in intervention group in all the domains but one (orgasm): erectile function 24.7 vs. 26.8 (P = 0.003); confidence (Q15) 3.53 vs. 4.07 (P = 0.006); sexual desire 6.46 vs. 7.18 (P = 0.028); intercourse satisfaction 9.85 vs. 11.25 (P = 0.001); total satisfaction 7.17 vs. 8.07 (P = 0.009); total score 56.2 vs. 61.07 (P = 0.007). TT was statistically similar in the two groups; separate analysis in each group showed statistical increase in group B 4.24 vs. 4.55 (P = 0.012). At multivariate logistic regression analysis, PhA was the only independent variable for normal erection (P = 0.010) (95% confidence interval [CI] 0.036–0.643), higher sexual satisfaction (P = 0.022) (95% CI 0.084–0.821) and normal total IIEF-15 score (P = 0.023) (95% CI 0.85–0.837).ConclusionIn this randomized controlled pilot study, PDE5i plus PhA was more effective than PDE5i alone in the treatment of ED. Maio G, Saraeb S, and Marchiori A. Physical activity and PDE5 inhibitors in the treatment of erectile dysfunction: Results of a randomized controlled study.     

The Real-Life Safety and Efficacy of Vardenafil (REALISE) Study: Results in Men from Europe and Overseas with Erectile Dysfunction and Cardiovascular or Metabolic Conditions

IntroductionThe Real-Life Safety and Efficacy of vardenafil study is an international, open-label, prospective, noncomparative, noninterventional study in men with erectile dysfunction (ED).AimTo determine the safety and efficacy of vardenafil in a large international pool of men with ED (aged ≥18 years) and associated underlying conditions (N = 73,946), in a real-life setting.MethodsPatients attended an initial physician visit and one to two follow-up visits. Data were acquired by physician interviews and patient diaries and recorded in case report forms (CRFs). Data were pooled from 47 countries in Europe, Asia-Pacific, Latin America, and the rest of the world (excluding the United States and Japan for methodological reasons). Results were stratified by baseline ED severity, body mass index (BMI), and the presence of hypertension, diabetes, lipid metabolism disorder, or cardiovascular disease (CVD).Main Outcome MeasuresCRFs and patient questionnaires containing questions on overall improvement of erection, satisfaction with efficacy, and desire to continue vardenafil use.ResultsMany participants had hypertension (32.0%), diabetes (22.1%), lipid metabolism disorder (14.6%), or CVD (42.2%). High percentages of patients reported improvements in erectile function, irrespective of baseline ED severity (mild, 97.0%; moderate, 96.2%; severe, 85.5%), BMI (<25, 94.1%; ≥25 and <30, 94.6%; ≥30, 92.9%), or the presence of hypertension (93.6%), diabetes (92.6%), lipid metabolism disorder (94.7%), or CVD (93.3%). Over 90% of patients, including those with underlying conditions, reported being “satisfied” or “very satisfied” with vardenafil efficacy, and stated their intention to continue vardenafil use after the end of the study period. The incidence of adverse events was low, and 97.0% of patients were either “satisfied” or “very satisfied” with vardenafil tolerability.ConclusionsThese data from a worldwide population of men with ED and associated underlying conditions show that vardenafil is effective and well-tolerated for the treatment of ED in a real-life setting, supporting its use as a first-line ED therapy. van Ahlen H, Zumbé J, Stauch K, and Hanisch JU. The Real-Life Safety and Efficacy of vardenafil (REALISE) study: Results in men from Europe and overseas with erectile dysfunction and cardiovascular or metabolic conditions.     

ORIGINAL RESEARCH—PSYCHOLOGY: Integrated Sildenafil and Cognitive-Behavior Sex Therapy for Psychogenic Erectile Dysfunction: A Pilot Study

IntroductionMen with psychogenic erectile dysfunction (ED) present a challenge to physicians. Treatment with pharmacological agents alone does not address the complexities of the causative or resulting psychological issues.AimTo evaluate the effectiveness of an integrative treatment protocol (ITP) with sildenafil and cognitive-behavior sex therapy (CBST) compared with sildenafil alone for men with psychogenic ED.Main Outcome MeasuresChange from baseline on the International Index of Erectile Function (IIEF) in the domains of erectile function and sexual satisfaction to demonstrate improved sexual functioning and confidence.MethodsMen with psychogenic ED and female partners were randomized to receive either sildenafil alone or an ITP with sildenafil and CBST for the first 4 weeks. In the last 4 weeks, couples in the sildenafil group added CBST sessions to their regimen; patients in the ITP group continued the combined therapy. The IIEF questionnaire was used to compare erectile function and overall satisfaction serially at pretreatment, 4, and 8 weeks. Couples who met the success criteria in both domains after the first 4 weeks received no further treatment.ResultsFifty-three couples constituted the study population. After the first 4 weeks of sildenafil and ITP, 48% of men met criteria for success on erectile function and 65.5% for satisfaction compared to men on sildenafil alone with 29% and 37.5% success rates, respectively. After the last 4 weeks, integration of CBST with sildenafil resulted in a 58% success rate for erectile function which was comparable to the 66% rate for the initial drug/ITP group; satisfaction rates for men were 45% and 75%, respectively.ConclusionsCBST was shown to have a positive influence when used throughout the entire 8 weeks of the ITP or added to the sildenafil in the last 4 weeks. Although patients in both treatment regimens had significant improvements in the IIEF domain scores confirming efficacy of sildenafil, those in the CBST and drug regimen achieved higher rates of clinical success within the first 4 weeks of therapy. Banner LL, and Anderson RU. Integrated sildenafil and cognitive-behavior sex therapy for psychogenic erectile dysfunction: A pilot study.     

Efficacy and Safety of a Fixed-Dose Combination Therapy of Tamsulosin and Tadalafil for Patients With Lower Urinary Tract Symptoms and Erectile Dysfunction: Results of a Randomized,Double-Blinded,Active-Controlled Trial

BackgroundPhosphodiesterase type 5 inhibitors and α-adrenergic blocking agents (α-blockers) are widely used for the treatment of erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH).AimsTo assess the efficacy and safety of fixed-dose combinations (FDCs) of tamsulosin and tadalafil compared with tadalafil monotherapy in patients with comorbid BPH-associated LUTS and ED.MethodsA randomized, double-blinded, active-controlled trial was conducted of 510 men with BPH-associated LUTS and ED. Patients were treated with FDCs of tamsulosin 0.4 mg plus tadalafil 5 mg (FDC 0.4/5 mg), tamsulosin 0.2 mg plus tadalafil 5 mg (FDC 0.2/5 mg), or tadalafil 5 mg for a 12-week treatment period. For a subsequent 12-week extension period, the patients were administered FDC 0.4/5 mg.OutcomesThe primary outcomes were changes from baseline in total International Prostate Symptom Score (IPSS) and International Index of Erectile Function erectile function domain (IIEF-EF) score at week 12 to prove superiority and non-inferiority of FDCs compared with tadalafil 5 mg. The safety assessments were adverse reactions, laboratory test results, and vital signs at week 24.ResultsThe mean changes in total IPSS and IIEF-EF scores were −9.46 and 9.17 for FDC 0.4/5 mg and −8.14 and 9.49 for tadalafil 5 mg, respectively, which indicated superiority in LUTS improvement (P = .0320) and non-inferiority in ED treatment with FDC 0.4/5 mg compared with tadalafil 5 mg. However, the results from FDC 0.2/5 mg failed to demonstrate superiority in LUTS improvement. No clinically significant adverse events regarding the investigational products were observed during the 24-week period.Clinical ImplicationsThe FDC 0.4/5 mg is the first combined formulation of an α-blocker and a phosphodiesterase type 5 inhibitor that offers benefits in patient compliance and as add-on therapy in patients with comorbid BPH-associated LUTS and ED.Strengths and LimitationsThe study clearly demonstrated the advantage of FDC 0.4/5 mg. The main advantage of FDC 0.4/5 mg was the enhanced efficacy on BPH-associated LUTS comorbidity with ED, the lower incidence of side effects, and the simplification and convenience of therapy, which led to better overall patient compliance. However, the lack of a tamsulosin monotherapy control group was a limitation of this study.ConclusionThe FDC 0.4/5 mg therapy was safe, well tolerated, and efficacious, indicating that combination therapy could provide clinical benefits for patients with BPH-associated LUTS complaints and ameliorate the comorbidity of ED.Kim SW, Park NC, Lee SW, et al. Efficacy and Safety of a Fixed-Dose Combination Therapy of Tamsulosin and Tadalafil for Patients With Lower Urinary Tract Symptoms and Erectile Dysfunction: Results of a Randomized, Double-Blinded, Active-Controlled Trial. J Sex Med 2017;14:1018–1027.