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Background: Combination of different first-line treatments for erectile dysfunction (ED) has emerged as a promising therapeutic approach., Aim: To 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., Methods: Fifty 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., Outcomes: The 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., Results: Adjusting 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 Implications: Combination 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 & Limitations: We 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., Conclusion: The 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., (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: High-sensitivity C-reactive protein (hs-CRP), a marker of inflammation, is known to be elevated in patients with erectile dysfunction (ED). However, its role in predicting therapeutic response to phosphodiesterase-5 inhibitors is incompletely understood., Aim: The aim of this study was to understand the relationship among hs-CRP, mechanism of ED, and therapeutic response of ED to tadalafil, a phosphodiesterase-5 inhibitor., Methods: A total of 282 men (mean age 36.6 ± 12.0 years) with ED were included. All subjects underwent detailed evaluation, including estimation of a 6-item abbreviated version of the International Index of Erectile Function (IIEF-6) score, penile Doppler studies, and measurement of hs-CRP. IIEF-6 scoring and hs-CRP measurement were repeated after 6 weeks of tadalafil therapy (10 mg/day). The patients were categorized into vasculogenic and nonvasculogenic ED groups based on penile Doppler findings., Main Outcome Measure: The main outcome measure was the therapeutic response to tadalafil, in relation to the mechanism of ED and hs-CRP levels., Results: Vasculogenic ED was much less common (23.8% of the subjects) than non-vasculogenic ED. Subjects with vasculogenic ED were older, had higher prevalence of cardiovascular risk factors, had more severe (mean IIEF-6 score 9.2 ± 4.6 vs 14.8 ± 4.7; P < .001) and longer duration ED, and responded less favorably to therapy (response rate 10.4% vs 75.0%; P < .001). Those showing improvement with tadalafil had lower hs-CRP at baseline (median 1.5 mg/L [interquartile range 0.9-2.3] vs 2.0 mg/L [interquartile range 1.1-3.1; P = .034]) and had proportionately greater reduction in its level. However, on multivariate analysis, only shorter duration of ED (P = .008), non-vasculogenic origin (P = .025), and higher IIEF-6 score at baseline (P = .013) were independent predictors of response to treatment., Clinical Implications: Serum hs-CRP is elevated in patients who are less likely to respond to vasodilator therapy but does not have an independent predictive value for this purpose., Strengths & Limitations: This is the largest study to evaluate the relationship among the mechanism of ED, serum hs-CRP level, and therapeutic response of ED to tadalafil. All patients underwent a penile Doppler study to characterize the type of ED. The limitations were nonrandomized nature of the study and nearly 22% dropout rate., Conclusion: Serum hs-CRP level is higher in vasculogenic ED compared with non-vasculogenic ED, and is associated with poorer response to tadalafil therapy. However, this association is not independent of underlying risk factors and mechanism of ED. Jamaluddin, Bansal M, Srivastava GK, et al. Role of Serum High-Sensitivity C-Reactive Protein as a Predictor of Therapeutic Response to Tadalafil in Patients With Erectile Dysfunction: A Prospective Observational Study. J Sex Med 2019;16:1912-1921., (Copyright © 2019 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Both 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., Aim: This 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., Methods: Sixty 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 Measures: Serological 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., Results: Total 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., Conclusions: The 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., (© 2015 International Society for Sexual Medicine.)

Introduction: Tadalafil (TAD) 5 mg coadministered with finasteride (FIN) 5 mg significantly improves lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH) and prostatic enlargement. However, its effects on erectile/sexual function have yet to be fully described., Aim: Assess the effects of TAD/FIN coadministration (compared with placebo [PBO]/FIN) on erectile and sexual function in sexually active men with LUTS and prostatic enlargement secondary to BPH with or without baseline comorbid erectile dysfunction (ED)., Methods: A randomized, double-blind, PBO-controlled study of 695 men (610 sexually active; 450 with baseline ED; 404 sexually active with baseline ED) conducted at 70 sites in 13 countries. TAD 5 mg or PBO once daily coadministered with FIN 5 mg once daily for 26 weeks., Main Outcome Measures: International Index of Erectile Function (IIEF) domain and single-item scores; proportions of patients who demonstrated minimal clinically important differences (MCIDs) in IIEF-Erectile Function domain scores (IIEF-EF; MCID defined as ≥4-point improvement); and sexual dysfunction adverse events (AEs)., Results: Compared with PBO/FIN, TAD/FIN resulted in improvements for all IIEF domain and single-item scores assessed among patients with baseline ED (P ≤ 0.002 for all measures) and among patients without baseline ED (P ≤ 0.041 for all measures). Compared with PBO/FIN, significantly larger percentages of sexually active men with baseline ED treated with TAD/FIN achieved an IIEF-EF MCID after 4, 12, and 26 weeks of therapy (P < 0.001 for odds ratio comparisons between TAD/FIN and PBO/FIN at all 3 three postbaseline timepoints). The incidence of sexual AEs was low: five TAD/FIN patients and seven PBO/FIN patients reported sexual AEs, including ED, decreased/lost libido, and ejaculation disorders., Conclusions: TAD/FIN coadministration for the treatment of men with LUTS and prostatic enlargement secondary to BPH concurrently leads to statistically significant improvements in erectile/sexual function and is well-tolerated, regardless of the presence/absence of ED at treatment initiation., (© 2014 International Society for Sexual Medicine.)

Introduction: The United Kingdom is unusual in that a significant proportion of patients with erectile dysfunction (ED) have their treatment fully reimbursed by the National Health Service (NHS). This may have consequences for the choice of treatment and for compliance with treatment., Aims: The aim of this study was to evaluate the use and cost implications of phosphodiesterase type 5 inhibitor in an NHS setting., Methods: Basic demographics and data on ED management for patients treated from January 2000 to April 2011 were obtained from a prospectively accrued database. We reviewed drug usage and costs as well as switching between drugs. Patients were given the choice of all available therapies and were followed up annually., Main Outcome Measures: Switching, compliance, and costs of treating ED under the "severe distress" criteria in the NHS were reviewed for this study., Results: Two thousand one hundred fifty-nine patients qualified for reimbursed therapy. Two hundred twenty-six patients were excluded from further analysis owing to missing data. Patients were followed up on an annual basis. The mean patient age was 60.2 years (min 23, max 90), and the mean follow-up was 50.8 months (min 1, max 127). Six hundred ninety-six were started on sildenafil, 990 on tadalafil, 163 on vardenafil, and 84 on intracavernosal alprostadil. Eighteen percent of patients initially started on the scheme and stopped medication unilaterally. Of the patients, 12.3% changed their medication during follow-up. The cost of drugs increased year by year from £257,100 in 2007 to £352,519 in 2011., Conclusions: Our real-life observational study shows that in our institution, dropout of therapy is unusual. We hypothesize that this reflects, in part, the reimbursement issue. We also found that switching between drugs was unusual, although there are several possible explanations for that. Although this is a successful system for the patients, the hospital, which bears the costs of medication, is finding this an increasing economic drain., (© 2014 International Society for Sexual Medicine.)

Introduction: Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and erectile dysfunction are common disorders of advancing age., Aim: To evaluate the efficacy and safety of tamsulosin and tadalafil in patients with LUTS due to BPH., Methods: In this prospective randomized study, 133 men complaining of LUTS due to BPH were included. Forty-five patients received tamsulosin 0.4 mg/day alone (Group A), 44 patients received tadalafil 10 mg/day (Group B), and combination therapy (tamsulosin and tadalafil both) was instituted in 44 patients (Group C). After a 2-week medication free run-in period, they were evaluated for International Prostatic Symptom Score (IPSS), International Index of Erectile Function score (IIEF5), quality of life (IPSS QoL), maximum urinary flow rate (Qmax), post-void residual urine (PVR) volume, and safety parameters before and at 3 months of treatment., Main Outcome Measures: There were primary (IPSS, IPSS QoL index, Qmax, and PVR) and secondary (erectile function [EF] domain scores from IIEF5) efficacy end points. Safety assessment included laboratory tests and patient's reporting of adverse event., Results: A significant improvement in IPSS score was observed in all the 3 groups A, B, and C (-50.90%, P < 0.05; -33.50%, P < 0.05; and -53.90%, P < 0.05, respectively). IIEF5 score increased significantly in these three groups (+39.28%, P < 0.05; +45.96%, P < 0.05; and +60.23%, P < 0.05, respectively). A significant increase in Qmax and decrease in PVR were also observed (33.99%, P < 0.05; 29.78%, P < 0.05; and 37.04%, P < 0.05) and (-60.90%, P < 0.05; -49.45%, P < 0.05; and -62.97%, P < 0.05, respectively). The QoL scores improved significantly (-73.35%, P < 0.05; -70.26%, P < 0.05; and -79.65%, P < 0.05, respectively). Side effects were dyspepsia, heartburn, headache, flushing, myalgia, and backache. Adverse effect dropout was 3.7%. No participant experienced any severe or serious adverse events., Conclusions: In patients with LUTS due to BPH, tamsulosin and tadalafil alone or in combination cause a significant improvement in patients with LUTS. Their EF also improves with these medications. The improvement is better with combination therapy compared with single agent alone., (© 2013 International Society for Sexual Medicine.)

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

Introduction: Erectile dysfunction (ED) and lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) are common in aging males and frequently occur together. Tadalafil has demonstrated efficacy in treating both conditions., Aim: The study aims to evaluate the efficacy and safety of tadalafil 5 mg once daily vs. placebo over 12 weeks in treating both LUTS/BPH and ED in sexually active men. We also assessed relationships of baseline disease severity and prostate specific antigen (PSA) to outcomes., Methods: Data were pooled from four multinational, randomized studies of men ≥45 years with LUTS/BPH, with analyses restricted to sexually active men with ED. Randomization (baseline) followed a 4-week placebo run-in; changes from baseline were assessed vs. placebo using analysis of covariance., Main Outcome Measures: International Prostate Symptom Score (IPSS), IPSS subscores, Quality-of-Life Index (IPSS-QoL), BPH Impact Index (BII), and International Index of Erectile Function-Erectile Function (IIEF-EF) Domain score were used in this study., Results: Tadalafil (N = 505) significantly improved total IPSS vs. placebo (N = 521); mean changes from baseline were -6.0 and -3.6, respectively (P < 0.001). Improvements in IIEF-EF Domain score (tadalafil, 6.4; placebo, 1.4) were also significant vs. placebo, as were the IPSS storage and voiding subscores, IPSS-QoL, and BII (all P < 0.001). No significant impact of baseline ED severity or PSA category on IPSS response was observed (interaction P values, 0.463 and 0.149, respectively). Similarly, improvement in IIEF-EF Domain score was not significantly impacted by baseline LUTS/BPH severity or PSA category (interaction P values, 0.926 and 0.230, respectively). Improvements in IPSS and IIEF-EF Domain score during treatment were weakly correlated (r = -0.229). Treatment-emergent adverse events were consistent with previous reports., Conclusions: Tadalafil was efficacious and well tolerated in treating ED and LUTS/BPH in sexually active men with both conditions. Improvements in both conditions were significant regardless of baseline severity. Improvements in the total IPSS and the IIEF-EF Domain score were weakly correlated., (© 2013 International Society for Sexual Medicine.)

Introduction: Many products labeled "herbal" or "all natural" (herbal/natural) that claim to enhance sexual performance and imply use for the treatment of erectile dysfunction (ED) are marketed as over-the-counter (OTC) dietary supplements. However, adulteration with undeclared phosphodiesterase type 5 (PDE5) inhibitors appears widespread., Aim: To assess the availability, cost, origin, categorical content, and adulteration with PDE5 inhibitors of purported herbal/natural OTC dietary supplements claiming to naturally enhance sexual performance., Methods: Pfizer Global Security coordinated sample collection (all from convenience stores and filling stations in two U.S. metropolitan areas except for seven from U.S. Customs seizures) and liquid chromatography/mass spectrometry examination., Main Outcome Measure: Adulteration with synthetic PDE5 inhibitors., Results: Ninety-one samples labeled as 58 distinct products and priced from $2.99 to $17.99 were evaluated. Origin/manufacture was claimed as United States (n = 62), apparently Asian (n = 15), and not clearly identified (n = 14). Although no sample claimed to include synthetic substances, 74 (81%) contained PDE5-inhibitor pharmaceutical ingredients, including tadalafil and/or sildenafil (n = 40, of which 18 contained >110% of the highest approved drug product strength) or PDE5-inhibitor analogs (n = 34). Pronounced heterogeneity of contents between samples within individual products indicated minimal quality control during manufacture. Labeling was inadequate (e.g., lacking lot number and/or expiry date) for 17 products (23 samples) and inconsistent between samples within a given product (e.g., in manufacturer, lot number, and/or expiry date) for seven of 17 products having multiple samples. Only 14 samples warned against concomitant nitrate use., Conclusions: Ethical pharmaceutical companies are concerned for an unsuspecting public when their products are counterfeited, mislabeled, and illegally offered for sale in an unsafe manner. Because of the dangers of adulteration with synthetic PDE5 inhibitors, absent safety warnings, and lack of quality or consistent manufacture, men with ED unknowingly risk their health by using OTC herbal/natural products that claim to enhance sexual performance., (© 2013 International Society for Sexual Medicine.)

INTRODUCTION.: Phosphodiesterase type 5 inhibitors PDE5Is are less effective in diabetic men with erectile dysfunction (ED); however, the effect of combination therapy with folic acid and PDE5Is in these patients has not been investigated. AIM.: To evaluate the efficacy and safety of combination therapy with folic acid and tadalafil for the management of ED in men with type 2 diabetes mellitus. METHODS.: Eighty-three patients with type 2 diabetes mellitus and ED were included in this randomized double-blind clinical trial. They were randomly divided into two groups. Group A was treated with tadalafil 10 mg every other day plus folic acid 5 mg daily and group B received tadalafil 10 mg every other day plus placebo daily for 3 months. The mean International Index of Erectile Function (IIEF) scores before and after treatment in each groups were recorded. Men with diagnosis of psychological ED, spinal cord injury, or who used folic acid in the past 3 months and patients with any contradiction for use of PDE5Is were excluded. MAIN OUTCOMES MEASURES.: The cross tabulation and independent t-test were used to evaluate the difference between baseline characteristic of the patients in the two groups. Wilcoxon signed-ranks test and Mann-Whitney U-test were used to evaluate the IIEF score and also its changes before and after treatment in the two groups. RESULTS.: The mean IIEF scores before and after treatment were 11.65 ± 2.67 and 16.80 ± 4.03 in group A (P < 0.001) and 12.70 ± 2.31 and 14.37 ± 2.17 in group B (P < 0.001), respectively. The difference of mean IIEF score after treatment between the two groups was significant (16.80 ± 4.03 vs. 14.37 ± 2.17 in groups A and B, respectively) (P = 0.002). Also, the mean IIEF score was significantly increased in group A as compared with group B (5.14 ± 3.84 vs. 1.68 ± 0.99 in groups A and B, respectively) (P < 0.001). Both folic acid and tadalafil were well tolerated by all the patients. CONCLUSION.: Sexual function in diabetic patients with ED treated with the combination of tadalafil and folic acid improved significantly as compared with the placebo group. The use of folic acid and tadalafil is safe., (© 2013 International Society for Sexual Medicine.)

Introduction: Tadalafil, a long-acting phosphodiesterase type 5 inhibitor, is approved for treating signs and symptoms of benign prostatic hyperplasia (BPH) and erectile dysfunction (ED); tamsulosin, an alpha-blocker, is approved for treating signs and symptoms of BPH., Aim: To determine the effects of tadalafil or tamsulosin on sexual function, including ejaculation and orgasm, satisfaction, and erectile function, in sexually active men with ED and lower urinary tract symptoms suggestive of BPH (LUTS/BPH)., Methods: A randomized, double-blind, placebo-controlled study of tadalafil 5 mg once daily for 12 weeks in men with LUTS/BPH; tamsulosin 0.4 mg once daily was an active control., Main Outcome Measures: The International Index of Erectile Function (IIEF) questionnaire was administered at baseline and 4, 8, and 12 weeks. Analysis of orgasm and ejaculation was post hoc based on the IIEF-Orgasmic Function (OF) domain (IIEF-Q9 [ejaculatory frequency] and Q10 [orgasmic frequency]). Other measures included IIEF-Intercourse Satisfaction (IS), Overall Satisfaction (OS), and Erectile Function (EF) domains. Changes from baseline to 12 weeks (or last observation) vs. placebo were analyzed using analysis of covariance. Higher IIEF scores indicate better functioning., Results: Of 511 study participants, 310 (60.7%) had ED and were sexually active. The IIEF-OF increased significantly through 12 weeks with tadalafil vs. placebo (P = 0.048), as did IIEF-Q9 (P = 0.045) but not IIEF-Q10 (P = 0.100). Compared with placebo, IIEF-OF, Q9, and Q10 decreased significantly with tamsulosin (all P < 0.05). The IIEF-IS and OS increased significantly at end point with tadalafil (both P < 0.001); for tamsulosin, change was not significant for IS, while OS decreased significantly (P = 0.009). The IIEF-EF domain increased significantly vs. placebo with tadalafil (P < 0.001) but not tamsulosin (P = 0.699)., Conclusions: Tadalafil 5 mg once daily significantly improved ejaculation and orgasm, intercourse and overall satisfaction, and erectile function. Men receiving tamsulosin 0.4 mg once daily experienced a decrease in both ejaculatory/orgasmic frequency and overall satisfaction vs. placebo, with no significant effect on erectile function., (© 2013 International Society for Sexual Medicine.)

Introduction: Tadalafil is efficacious and well tolerated for erectile dysfunction (ED), but effects in men with "complete ED" are unclear., Aim: To investigate effects of once-daily tadalafil in men with no successful intercourse attempts at baseline., Methods: Through a post hoc, pooled-data analysis of four randomized, double-blind trials on the effects of tadalafil 2.5 or 5 mg (vs. placebo) in men with ED, we evaluated efficacy and safety in subjects with 0 "yes" responses to Sexual Encounter Profile question 3 (SEP3) during an initial 4-week treatment-free run-in period., Main Outcome Measures: Changes from baseline in the SEP diary and the International Index of Erectile Function-erectile function (IIEF-EF) domain were subjected to analysis of covariance models., Results: Five hundred ninety-five subjects with no successful attempts at baseline were included in the analysis. The mean (± standard deviation) age was 58.2 ± 10.7 years; and most subjects had ED for ≥ 1 year (95.0%). ED was severe in 61.5% and moderate in 26.4%. Approximately 45% had diabetes mellitus or hypertension. After 12 weeks, the mean per-patient SEP3 percentage increased from 0% to 32.4% with tadalafil 2.5 mg and to 46.4% with tadalafil 5 mg (each P < 0.001 vs. placebo). Corresponding data for successful penetration (SEP2) were increases from 21.1% to 48.2% with tadalafil 2.5 mg and from 24.4% to 66.2% with 5 mg (each P < 0.001 vs. placebo). Mean IIEF-EF increased from 9.7 to 15.7 with tadalafil 2.5 mg and from 10.7 to 19.2 with 5 mg (each P < 0.001 vs. placebo). Tadalafil also significantly improved the intercourse-satisfaction and overall-satisfaction domains (vs. placebo). Both doses of tadalafil were generally well tolerated, with adverse event rates similar to placebo., Conclusions: The posttreatment intercourse success rate was 32% and 46% for tadalafil 2.5 mg and 5 mg, respectively, in men with no successful intercourse attempts at baseline., (© 2012 International Society for Sexual Medicine.)

Introduction: Optimal pharmacologic management of diseases comorbid with erectile dysfunction (ED), such as cardiovascular disease, depression, diabetes, dyslipidemia, hypertension, and benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS), is dependent upon long-term treatment compliance and may be complicated by poor adherence to medication use. ED may contribute to poor adherence to medication use because poor quality erectile function may be an unwanted adverse effect of antihypertensives, antidepressants, and 5-α reductase inhibitors for treatment of BPH/LUTS. Diminished erectile spontaneity, rigidity, and/or sustaining capability also negatively affects mood, self-esteem, and confidence, which compromise motivation to be compliant with medications that treat diseases comorbid with ED., Aim: Literature review was performed to explore the role of ED diagnosis and effective treatment in enhancing overall management of selected ED comorbidities, highlighting the role of medication adherence., Methods: Several PubMed searches were performed., Results: Diagnosis and successful treatment of concomitant ED may promote improved adherence and management of comorbid diseases. Concomitant ED management may improve treatment outcome, decrease healthcare costs, and possibly prevent or even improve deterioration in medical conditions comorbid with ED. Because ED is a silent marker and predictor of comorbidities, especially cardiovascular disease, earlier diagnosis of ED may provide an opportunity to prevent future cardiovascular events. In men presenting with complaints of ED, screening for, monitoring, and appropriately treating diseases that are comorbid with ED is essential. Screening for and appropriately treating ED is important for enhanced life quality and improved motivation in men with existing ED comorbidities or risk factors., Conclusions: Appropriate management of ED and its risk factors may have beneficial effects on diseases that are comorbid with ED, and vice versa, most likely via shared pathophysiological pathways. Clinicians may need to consider men's health overall, of which sexual health is a central component, in order to provide optimal disease management., (© 2012 International Society for Sexual Medicine.)

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

Introduction: Utility of phosphodiesterase inhibitors (PDEi's) for the treatment of erectile dysfunction (ED) has been the focus of experimental and clinical studies. However, public preferences, attitudes, and experiences with PDEi's are rarely addressed from a population/epidemiology viewpoint. The Global Online Sexuality Survey (GOSS) is a worldwide epidemiologic study of sexuality and sexual disorders, first launched in the Middle East in 2010, followed by the United States in 2011., Aim: To describe the utilization rates, trends, and attitudes toward PDEi's in the United States in the year 2011., Methods: GOSS was randomly deployed to English-speaking male Web surfers in the United States via paid advertising on Facebook®, comprising 146 questions., Main Outcome Measures: Utilization rates and preferences for PDEi's by brand., Results: Six hundred three subjects participated; mean age 53.43 years ± 13.9. Twenty-three point seven percent used PDEi's on more consistent basis, 37.5% of those with ED vs. 15.6% of those without ED (recreational users). Unrealistic safety concerns including habituation were pronounced. Seventy-nine point six percent of utilization was on prescription basis. PDEi's were purchased through pharmacies (5.3% without prescription) and in 16.5% over the Internet (68% without prescription). Nine point six percent nonprescription users suffered coronary heart disease. Prescription use was inclined toward sildenafil, generally, and particularly in severe cases, and shifted toward tadalafil in moderate ED and for recreational use, followed by vardenafil. Nonprescription utilization trends were similar, except in recreational use where sildenafil came first., Conclusion: In the United States unrealistic safety concerns over PDEi's utility exist and should be addressed. Preference for particular PDEi's over the others is primarily dictated by health-care providers, despite lack of guidelines that govern physician choice. Online and over-the-counter sales of PDEi's are common, and can expose a subset of users to health risks. Recreational use of PDEi's is common, and could be driven by undiagnosed premature ejaculation., (© 2012 International Society for Sexual Medicine.)

Introduction: Erectile dysfunction (ED) is the most frequently treated male sexual dysfunction worldwide. ED is a chronic condition that exerts a negative impact on male self-esteem and nearly all life domains including interpersonal, family, and business relationships., Aim: The aim of this study is to provide an updated overview on currently used and available conservative treatment options for ED with a special focus on their efficacy, tolerability, safety, merits, and limitations including the role of combination therapies for monotherapy failures., Methods: The methods used were PubMed and MEDLINE searches using the following keywords: ED, phosphodiesterase type 5 (PDE5) inhibitors, oral drug therapy, intracavernosal injection therapy, transurethral therapy, topical therapy, and vacuum-erection therapy/constriction devices. Additionally, expert opinions by the authors of this article are included., Results: Level 1 evidence exists that changes in sedentary lifestyle with weight loss and optimal treatment of concomitant diseases/risk factors (e.g., diabetes, hypertension, and dyslipidemia) can either improve ED or add to the efficacy of ED-specific therapies, e.g., PDE5 inhibitors. Level 1 evidence also exists that treatment of hypogonadism with total testosterone < 300 ng/dL (10.4 nmol/L) can either improve ED or add to the efficacy of PDE5 inhibitors. There is level 1 evidence regarding the efficacy and safety of the following monotherapies in a spectrum-wide range of ED populations: PDE5 inhibitors, intracavernosal injection therapy with prostaglandin E1 (PGE1, synonymous alprostadil) or vasoactive intestinal peptide (VIP)/phentolamine, and transurethral PGE1 therapy. There is level 2 evidence regarding the efficacy and safety of the following ED treatments: vacuum-erection therapy in a wide range of ED populations, oral L-arginine (3-5 g), topical PGE1 in special ED populations, intracavernosal injection therapy with papaverine/phentolamine (bimix), or papaverine/phentolamine/PGE1 (trimix) combination mixtures. There is level 3 evidence regarding the efficacy and safety of oral yohimbine in nonorganic ED. There is level 3 evidence that combination therapies of PDE5 inhibitors + either transurethral or intracavernosal injection therapy generate better efficacy rates than either monotherapy alone. There is level 4 evidence showing enhanced efficacy with the combination of vacuum-erection therapy + either PDE5 inhibitor or transurethral PGE1 or intracavernosal injection therapy. There is level 5 evidence (expert opinion) that combination therapy of PDE5 inhibitors + L-arginine or daily dosing of tadalafil + short-acting PDE5 inhibitors pro re nata may rescue PDE5 inhibitor monotherapy failures. There is level 5 evidence (expert opinion) that adding either PDE5 inhibitors or transurethral PGE1 may improve outcome of penile prosthetic surgery regarding soft (cold) glans syndrome. There is level 5 evidence (expert opinion) that the combination of PDE5 inhibitors and dapoxetine is effective and safe in patients suffering from both ED and premature ejaculation., (© 2013 International Society for Sexual Medicine.)

Introduction: Phosphodiesterase 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., Aim: To 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., Methods: Review 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 Measures: A low incidence of some PDE-related adverse events may be reflected by the high selectivity of avanafil against non-PDE5 isozymes., Results: Avanafil 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., Conclusions: Data 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., (© 2012 International Society for Sexual Medicine.)

Introduction: There is a high prevalence of erectile dysfunction (ED) in men with epilepsy; however, few studies have been conducted concerning the treatment of ED in this neurological group., Aim: The main purpose of this review is to highlight the influence of phosphodiesterase type 5 inhibitor (PDEI-5) for ED on seizure susceptibility., Methods: All available online articles with information pertaining to PDEI-5 and seizure susceptibility were included in this review., Main Outcome Measures: The main outcome assessed demonstrated the intriguing role of PDEI-5 and its metabolites on seizure susceptibility., Results: Case reports in men without epilepsy described seizure occurrence and electrophysiological changes following sildenafil, tadalafil, or vardenafil treatment. Consistent with these findings, preclinical studies suggested a proconvulsant effect of PDEI-5 on models of seizure induction., Conclusions: Evidence suggests an influence of PDEI-5 on seizure susceptibility in humans. In addition, preclinical studies have demonstrated the role of nitric oxide metabolites in the facilitation of paroxysmal phenomenon. Although there are many causes of seizures, medical professionals should be aware of the possible influence of PDEI-5 on seizure susceptibility. Further investigation by physicians and scientists is required to improve our understanding of this important topic., (© 2012 International Society for Sexual Medicine.)

Aim: To compare Sexual Self-Confidence and other treatment outcomes following 8 weeks of treatment with tadalafil 5 mg once a day (OaD) vs. tadalafil 20 mg or sildenafil 100 mg as needed (pro re nata [PRN]) in patients with erectile dysfunction (ED)., Methods: A randomized, open-label, crossover study in men ≥18 years of age with history of ED and satisfactory response to current oral phosphodiesterase 5 (PDE5) inhibitor PRN. Data were analyzed with a mixed effects model for crossover design., Main Outcome Measures: The primary outcome measure was the Sexual Self-Confidence domain of the Psychological and Interpersonal Relationship Scales (PAIRS) between tadalafil OaD and sildenafil PRN. SECONDARY OUTCOMES INCLUDED: Time Concerns and Spontaneity domains of PAIRS, and the Self-Esteem and Relationship (SEAR) scale., Results: Men naive to tadalafil OaD were enrolled (N = 378), with 61-69% prior PDE5 inhibitor use. There were improvements in all PAIRS domains from baseline when comparing tadalafil OaD and PRN with sildenafil PRN (P < 0.001). The Sexual Self-Confidence domain improved from baseline and was 0.50 ± 0.78 following tadalafil OaD, 0.5 ± 0.72 for tadalafil PRN, and 0.39 ± 0.67 for sildenafil PRN. The difference in least-squares mean was 0.12 ± 0.04 (confidence interval [CI] = 0.04, 0.19; P = 0.001) between tadalafil OaD and sildenafil PRN and 0.01 ± 0.04 (CI = -0.06, 0.08; P = 0.872) between tadalafil OaD and tadalafil PRN. The Time Concerns domain score was lower with tadalafil OaD than tadalafil PRN (P < 0.001). There were no differences in SEAR scores between treatments., Conclusions: Tadalafil OaD and tadalafil PRN compared with sildenafil PRN demonstrated greater improvements in Sexual Self-Confidence, Time Concerns, and Spontaneity. There was no significant difference in Sexual Self-Confidence between tadalafil OaD and tadalafil PRN. Changes in SEAR, the erectile function domain of the International Index of Erectile Function, and the Erectile Dysfunction Inventory of Treatment Satisfaction scores from baseline to end point were similar., (© 2012 International Society for Sexual Medicine.)

Introduction: Erectile dysfunction (ED) is reported in a high percentage of patients with central neurological disorders (CND)., Aim:   An up-to-date review on oral phosphodiesterase 5 inhibitors (PDE5): sildenafil, tadalafil, and vardenafil for individuals with CND and ED., Main Outcome Measures: Various questionnaires on ED, such as the International Index of Erectile Function composed of 15 questions., Methods: Internationally published clinical studies evaluating the efficacy and safety of PDE5 on subjects with CND and ED were selected., Results: Overall, 28 articles on PDE5 used to treat patients with CND and ED were included. With each of the three PDE5 compared to placebo or erectile baseline, literature reported significant statistical improvement (P < 0.01; P < 0.05) only in patients with spinal cord injury (SCI). PDE5 efficacy was documented for SCI patients up to 10 years. The most frequent predicable factor for PDE5 success was the presence of upper motoneuron lesion. Each of the three clinical sildenafil studies documented statistically significant improvement on erectile function in Parkinson's patients (P < 0.01; P < 0.05). Two studies reported discordant results about sildenafil's effectiveness on multiple sclerosis (MS) patients; one on tadalafil showed significant statistical efficacy on erection versus baseline (P < 0.01; P < 0.05). The only spina bifida article determined that sildenafil remarkably improved erectile function. Overall, drawbacks were mostly slight-moderate, except in subjects with multiple system atrophy where sildenafil caused severe hypotension., Conclusions: PDE5 represent first line ED therapy only for SCI patients, though treatment results through meta-analysis were not possible. Encouraging results are reported for Parkinson's and MS patients. PDE5 use for other CND patients is limited for various reasons, such as ED and concomitant libido impairment caused by depression and/or sexual endocrinology dysfunctions, and because PDE5 may cause a worsening of neurological illness. Medical centers staffed by health professionals able to counsel patients on the possible use of PDE5 are needed., (© 2012 International Society for Sexual Medicine.)

Background: Currently, there is no ideal agent to prevent adhesion formation. We have shown that sildenafil, a phosphodiesterase-5 (PDE-5) inhibitor, reduces post-operative adhesion formation by vasodilatation and increases fibrinolytic activity. Here, we evaluated whether tadalafil, a long-acting PDE-5 inhibitor, decreases post-operative adhesion reformation in rats., Materials and Methods: Standardized lesions were created in Wistar albino rats by cauterization of uterine horns and abrasion of adjacent peritonium. The extent and severity of adhesions were scored on the 14th post-operative day and adhesiolysis was performed at the second laparotomy. Animals were then assigned randomly into two groups. The study group (n = 11) received 10 mg/kg oral tadalafil by gavage 60 min before the second laparotomy and daily for 14 days afterwards. Controls (n = 11) received the same volume of tap water for 14 days by gavage. Animals were killed 15 days after adhesiolysis and adhesions were scored blind during the third laparotomy. RESULTS Basal adhesion scores at the time of the second laparotomy were comparable in the study and control groups. Scores for the extent of adhesion reformation in the study and control groups did not differ [median 1 (range 0-3) versus median 2 (range 1-3); P: 0.81] but tadalafil reduced the respective severity scores [median 0.5 (range 0-1) versus median 1 (range 0.5-1); P: 0.02] and total scores [median 2 (range 0-4) versus median 2.5 (range 1.5-4); P: 0.042]., Conclusions: Oral administration of tadalafil during the perioperative period reduces intra-abdominal adhesion reformation in rats.

Introduction: Several methods have been so far proposed to compare the effectiveness of the three available phosphodiesterase type 5 inhibitors (PDE5Is)., Methods: Two urologists (E.C. and G.B.B.), together with the Controversy's Editor (E.A.J.), with expertise in the area of medical treatment of erectile dysfunction (ED) present the various perspectives on the evaluation of PDE5Is in ED. The use of the most popular psychometric tool, the International Index of Erectile Function, is presented by an expert psychologist (L.R.D.)., Main Outcome Measures: Expert opinion supported by the critical review of the currently available literature., Results: Trials have demonstrated that the PDE5Is are excellent drugs with a great specificity of action and an almost perfect tolerance profile. Some instruments for comparison of clinical efficacy have to be considered subjective (psychometry, patient's preference, changes in quality of general, or sexual life). Some others are more objective (hardness, hormonal levels, and local circulation). An evidence-based comparison of the three PDE5Is should in the future be rooted in both subjective and objective methods. This will be of paramount importance in the drug trial design of new, forthcoming PDE5Is., Conclusions: Comparison between PDE5Is using both subjective and objective parameters will permit to individuate, on the basis of the evidence, the subset of couples where one drug, or one dose, or dose regimen, is to be considered of first choice., (© 2012 International Society for Sexual Medicine.)

Introduction: Erectile dysfunction (ED) and lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH-LUTS) commonly coexist in aging men. Tadalafil, a phosphodiesterase type 5 inhibitor approved for treating ED, is currently being evaluated for treating BPH-LUTS., Aims: This multinational Phase 3 study assessed effects of tadalafil 2.5 or 5 mg once daily on ED and BPH-LUTS in men with both conditions during 12 weeks of double-blinded therapy., Methods: Men were ≥ 45 years old, sexually active, and experiencing ED for ≥ 3 months and BPH-LUTS for >6 months. Randomization (baseline) followed a 4-week placebo lead-in; changes from baseline were assessed via analysis of covariance and compared to placebo. A gatekeeping procedure controlled for multiple comparisons of co-primary and key secondary measures at end point (last post-baseline observation)., Main Outcome Measures: The co-primary measures were the International Index of Erectile Function-erectile function (IIEF-EF) domain and International Prostate Symptom Score (IPSS) score; key secondary measures were the Sexual Encounter Profile Question 3 (SEP Q3) and BPH Impact Index (BII). Treatment-emergent adverse events, serious adverse events, orthostatic vital signs, clinical laboratory and uroflowmetry parameters, and postvoid residual volume were assessed., Results: Tadalafil 2.5 mg (N = 198) and 5 mg (N = 208) significantly improved IIEF-EF domain scores (both P < 0.001) vs. placebo (N = 200) at end point. For IPSS, improvements were significant with tadalafil 5 mg (P < 0.001), but not 2.5 mg, for observations from 2 weeks through end point (least-squares mean ± standard error change from baseline at end point, placebo -3.8 ± 0.5, tadalafil 2.5 mg -4.6 ± 0.4, and 5 mg -6.1 ± 0.4). Tadalafil 5 mg significantly improved SEP Q3 and BII (P < 0.001). Overall, tadalafil was well tolerated with no clinically adverse changes in orthostatic vital signs or uroflowmetry parameters., Conclusions: Tadalafil 5 mg significantly improved both ED and BPH-related outcomes through 12 weeks and was well tolerated., (© 2011 International Society for Sexual Medicine.)

Introduction: Despite adoption of the successful vaginal insertion (Q2) and intercourse (Q3) items of the sexual encounter profile (SEP) as end points in clinical trials, there are no objective data on what constitute minimal clinically important differences (MCIDs) in these items., Aim: The objective was to estimate the MCID for SEP Q2 and Q3., Methods: Using data from 17 randomized, controlled trials of the phosphodiesterase type 5 inhibitor tadalafil, we estimated MCIDs for the SEP using anchor-based approaches. The 17 studies included 3,345 patients treated for 12 weeks. The anchor for the MCID is the minimal improvement measure calculated using change from baseline to 12 weeks on the following question: "Over the past 4 weeks, when you attempted sexual intercourse how often was it satisfactory for you?" MCIDs were developed using analysis of variance- and receiver operating characteristic (ROC)-based methods in a subset of studies (N = 11) by comparing patients with and without minimal improvement (N = 863). MCIDs were validated in the remaining six studies (N = 377)., Main Outcome Measures: The main outcome measures of this study are SEP Q2 and Q3., Results: Using the ROC-based approach, the MCID for SEP Q2 was 21.4%, with estimated sensitivity of 0.55 and specificity of 0.73; the MCID for SEP Q3 was 23.0%, with estimated sensitivity of 0.72 and specificity of 0.78. MCIDs for SEP Q2/Q3 varied significantly (P < 0.001) according to baseline erectile dysfunction (ED) severity. MCIDs distinguished between patients in the validation sample classified as no change or minimally improved in each ED etiology, ED duration, and age group, but less well across geographic regions., Conclusions: The contextualization of treatment-related changes into clinically relevant terms is essential to understanding treatment efficacy, interpreting results across studies, and for effective patient management. Overall, there was a better balance between sensitivity and specificity of the MCIDs using the ROC-based approach for the SEP intercourse success item than for the vaginal insertion item., (© 2011 International Society for Sexual Medicine.)

Introduction: To ensure public safety all Food and Drug Administration (FDA)-approved medications undergo postapproval safety analysis. Phosphodiesterase type-5 inhibitors (PDE5-i) are generally regarded as safe and effective., Aim: We performed a nonindustry-sponsored analysis of FDA reports for sildenafil, tadalafil, and vardenafil to evaluate the reported cardiovascular and mortality events over the past 10 years., Methods: Summarized reports of adverse events (AEs) for each PDE5-i were requested from the Center for Drug Evaluation and Research within the FDA. These data are available under the Freedom of Information Act and document industry and nonindustry reports of AEs entered into the computerized system maintained by the Office of Surveillance and Epidemiology., Main Outcome Measure: The data were analyzed for the number of AE reports, number of objective cardiovascular events, and reported deaths., Results: Overall, 14,818 AEs were reported for sildenafil. There were 1,824 (12.3%) reported deaths, and reports of cardiovascular AEs numbered 2,406 (16.2%). Tadalafil was associated with 5,548 AEs and 236 deaths were reported. Vardenafil was associated with 6,085 AEs and 121 reports of deaths. The percentage of reported severe cardiovascular disorders has stabilized at 10% to 15% of all AE reports for sildenafil and tadalafil and 5% to 10% for vardenafil. Only 10% of AE reports sent to the FDA for PDE5-i were from pharmaceutical manufacturers., Conclusion: Reports of deaths associated with PDE5-i remain around 5% of total reported events. Despite inherent limitations from evaluating FDA reports of AEs, it is important that these reports be reviewed outside pharmaceutical industry support in order to provide due diligence and transparency. Lowe G and Costabile RA. 10-year analysis of adverse event reports to the Food and Drug Administration for phosphodiesterase type-5 inhibitors. J Sex Med 2012;9:265-270., (© 2011 International Society for Sexual Medicine.)

Introduction: Erectile dysfunction (ED) is a very common multidimensional disorder affecting men worldwide. Physical illness, reaction to life stresses, or an unhappy couple relationship influence clinical outcome. Phosphodiesterase type 5 (PDE5) inhibitors are recognized as efficacious and well tolerated, and are the first-line treatment for ED. Sildenafil, tadalafil, and vardenafil are the most widely used and studied PDE5 inhibitors. Data acquired during a routine diagnostic workup for ED should be taken into account when choosing the best PDE5 inhibitor for the individual patient, creating an individualized treatment plan, and going beyond "experience-based" subjective opinion and unfounded ideas and prejudice regarding currently available drugs., Aim: As the process of matching a given patient's profile to any selected PDE5 inhibitor often relies more on physician's personal convictions than on solid evidence, the aim of this review is to identify the main clinical, demographic, and relational factors influencing the choice of the PDE5 inhibitor to be used for the treatment of ED., Methods: A systematic literature search and current treatment guidelines were evaluated in a systematic manner., Main Outcome Measures: The main clinical, cultural, and demographical factors to be considered for the treatment of ED have been identified., Results: Main factors influencing the choice of the treatment for ED have been described. A short list of items that may help in choosing the right PDE5 inhibitor for the treatment of different patients in daily clinical practice has been prepared., Conclusions: The simple algorithms prepared should be a useful tool to be used in daily practice, which may help in choosing the right treatment for each subject affected by ED., (© 2011 International Society for Sexual Medicine.)

Introduction: The majority of subjects included in previous tadalafil once-a-day clinical trials were non-naïve to previous phosphodiesterase 5 (PDE5) inhibitors on demand. A study on PDE5 inhibitor naïve subjects was therefore warranted., Aim: To evaluate the efficacy and safety of once-a-day tadalafil in PDE5 inhibitor-naïve men with erectile dysfunction (ED)., Main Outcomes Measures: Primary efficacy end points were changes from baseline to end point in the International Index of Erectile Function (IIEF) Erectile Function (EF) domain score and the per-subject proportion of "yes" responses to sexual encounter profile (SEP) question 2 (SEP2) and question 3 (SEP3)., Methods: PDE5 inhibitor-naïve men with ED (N=217) were randomized in a 1:2 ratio to receive placebo or tadalafil 5 mg once a day for 12 weeks. Enrollment began in January 2009 and the last subject completed in January 2010., Results: At end point, least square mean change from baseline IIEF-EF domain score (7.3 vs. 3.4), SEP2 (23.8% vs. 12.2%) and SEP3 (39.5% vs. 21.5%), was significantly larger for tadalafil vs. placebo (all P<0.001). The most common adverse events (AEs) in tadalafil-treated subjects were back pain, nasopharyngitis, dyspepsia, headache, and myalgia. Four subjects (2.7%) in the tadalafil group and one subject (1.4%) in the placebo group discontinued because of AEs., Conclusions: In PDE5 inhibitor-naïve men, tadalafil once a day significantly improved EF compared with placebo. Safety results were consistent with previous tadalafil once-a-day clinical trials., (© 2011 International Society for Sexual Medicine.)

Introduction: Effective oral medication for use in men with Peyronie's disease (PD) has been an area of interest of the medical community and lay public for decades. Isolated septal scars (ISS) without evidence of penile deformity is a relatively new clinical entity, and at present, there is paucity in the published literature regarding its treatment. Current research into the use of phosphodiesterase type 5 (PDE5) inhibitors in regulating penile erectile response has revealed an alternative role for PDE5 inhibitors in decreasing oxidative stress-associated inflammatory change as seen in PD., Aim: To examine the presence of ISS and assess the efficacy of PDE5 inhibitor use in septal scar remodeling., Methods: Retrospective review of prospective database on all men who underwent penile Doppler ultrasound between December 2007 and December 2009., Main Outcome Measures: Of the 65 men with ultrasonographic-confirmed ISS, 35 men received tadalafil 2.5 mg daily over a 6-month period. The clinical outcomes between the two groups were compared using International Index of Erectile Function (IIEF)-5 score and 6 months penile Doppler ultrasound follow up., Results: The mean age for the tadalafil group was 43.2 (20-65) years, similar to the control group at 44.2 (34-72) years. The length of time from onset to presentation was 22 (6 to 40) months. The majority of ultrasonographic-proven ISS was not clinically palpable and complaint of decreased penile rigidity (66%) was the predominant feature. Treatment with low-dose daily tadalafil did not result in any significant side effects (such as headache and flushing) or discontinuation. The tadalafil group reported higher IIEF-5 score (pretreatment 11/25 to post-treatment 18/25) (P < 0.01) and resolution of septal scar were recorded in 24 patients (69%) compared to three patients (10%) in the control group., Conclusion: Low-dose daily tadalafil is a safe and effective treatment option in septal scar remodeling., (© 2011 International Society for Sexual Medicine.)

Introduction: Diabetic neuropathy (DN) is one of the key pathogenetic factors for diabetic erectile dysfunction (DED)., Aim: The aim of this study was to compare the effect of the first intake of tadalafil and vardenafil in men with DN and DED., Methods: In this comparative prospective randomized study were included 49 phosphodiesterase type 5 (PDE5) inhibitor-naïve men (80% type 2 diabetes). DN was assessed by a modified Neuropathy Disability Score (NDS ≥ 3). Each patient received two pills containing 20 mg of either tadalafil (N = 24) or vardenafil (N = 25). They had to be taken after discharge from the hospital at a time interval of at least 3 and 1 day, respectively, and 1 to 6 hours before the intended sexual activity., Main Outcome Measures: The treatment efficacy was evaluated by the changes in the erectile domain of International Index of Erectile Function (IIEF), Sexual Encounter Profile Question 2 (SEP2) and 3 (SEP3), and the Global Assessment Question (GAQ)., Results: For all patients, IIEF increased from 12.6 ± 6.8 to 19.6 ± 9.0 (P < 0.001) points after treatment. The number of men with positive answers on SEP2 increased from 27 (55.1%) to 38 (77.6%), on SEP3 from 7 (14.3%) to 30 (61.2%). Thirty-one (63.3%) evaluated the effect of the drugs as beneficial (GAQ). No significant efficacy difference between tadalafil and vardenafil was observed. The initial indicators for DED, as well as the treatment efficacy, correlated highly significant with NDS. Both PDE5 inhibitors were well tolerated. Before entering the study, 28% of men have seen a physician, but only 57.1% of them have started treatment., Conclusions: In this study design, tadalafil and vardenafil are equally effective with the first intake in patients with diabetes and DN. Baseline indicators of erectile dysfunction and the ones verifying the effect of the treatment show significant correlation with the DN indicator-NDS. Tadalafil and vardenafil are well tolerated with no serious side effects., (© 2010 International Society for Sexual Medicine.)

Introduction: Research has demonstrated that erectile dysfunction (ED) is a couple's problem, and that treatment for this condition is likely to impact on the man and his partner., Aim: The current study utilized a qualitative approach to evaluate the impact of treatment for ED on the female partner's perception of changes in the relationship., Main Outcome Measures: Analyses of the transcripts from the interviews., Methods: In total, 96 men were treated for ED using tadalafil and then sildenafil (or vice versa) each for 3 months. Their female partners were interviewed 3 months after the commencement of treatment., Results: The findings demonstrated an overall positive effect of the treatment. Female partners perceived improvements in emotional closeness, and communication, and reported that their relationship was more loving, less stressful, and more stable., Conclusions: This study demonstrates the positive effects of treatment for ED on the female partner; in particular, on her perception of the quality of her relationship., (© 2010 International Society for Sexual Medicine.)

Objective: To evaluate the efficacy of tadalafil as add-on therapy in secondary RP resistant to vasodilators., Methods: Patients with scleroderma and MCTD having four or more RP attacks per week despite being on vasodilators were randomized to receive either placebo or tadalafil (20 mg) on alternate days as add-on therapy to their current vasodilators for 6 weeks. After a 7-day washout, patients were crossed over to the other arm. Primary endpoints were improvement in the daily frequency and duration of RP episodes and RP condition score (RCS). Secondary outcome measures were healing of existing and appearance of new digital ulcers (DUs) and improvement in scleroderma-specific HAQ (SHAQ), quality of life (QoL), flow-mediated dilatation (FMD), patient and physician global assessment., Results: Twenty-four of 25 recruited patients completed the study. All the patients were receiving calcium channel blockers and in addition 18 were receiving other vasodilators. During tadalafil therapy significant improvement in mean daily frequency, mean daily duration of RP and mean daily RCS were observed as compared with baseline and placebo. All the 24 digital lesions healed during tadalafil therapy as compared with 3/13 during the placebo treatment (P<0.0001). One new DU was reported during tadalafil therapy vs 13 during placebo therapy (P=0.0005). QoL, SHAQ, FMD, patient and physician global assessment significantly improved while on tadalafil. No serious adverse event was observed., Conclusion: Tadalafil as add-on therapy improves symptoms of RP, heals and prevents new DUs and improves QoL in patients with resistant secondary RP., Trial Registration: Clinicaltrials.gov, http://clinicaltrials.gov/, identifier: NCT00626665.

Introduction: Research has focused on improvement of erectile function during treatment with phosphodiesterase type 5 (PDE5) inhibitors, but less is known about what occurs after treatment cessation., Aim: The aim of this retrospective analysis was to examine durability of response, defined as sustainability of erectogenic benefits following treatment cessation, in men with erectile dysfunction (ED) following long-term treatment with daily tadalafil., Methods: The subjects (N=160) had participated in a 12-week double-blind trial followed by a one-year, open-label extension of tadalafil 5mg once daily. The extension was followed by a 4-week, treatment-free follow-up period. A total of 158 subjects completed International Index of Erectile Function-Erectile Function (IIEF-EF) domain score and were included in this analysis., Main Outcome Measures: The primary measures for this analysis were changes in ED severity category as captured by the IIEF-EF domain score., Results: At the end of the 1-year open-label treatment period, a majority (86.1%, n=136) of subjects had either improved by at least one ED severity category (e.g., Severe to Moderate) (n=128), or maintained Normal erectile function (EF domain score ≥26) (n=8), compared to baseline. Following the 4-week, treatment-free period, 63 of those subjects (46.3% of the 136 subjects) had continued improvement of at least one ED severity category (n=61) or maintained scores in the Normal category (n=2) compared with baseline. Subjects who showed a sustained benefit of treatment were considered to have demonstrated a "durable response." Seventy-three subjects (53.7%) did not have a durable response following treatment cessation. A few patient characteristics were associated with durability of response., Conclusions: Of those men who demonstrated improved erectile function while taking tadalafil 5mg once daily for 1 year, 46.3% continued to show improvement compared with baseline following a 4-week treatment free period. Durability of response should be a focus of future research., (© 2010 International Society for Sexual Medicine.)

Benign prostatic hyperplasia (BPH) is characterized by tissue overgrowth and stromal reorganization primarily due to cellular proliferation and fibroblast-to-myofibroblast trans-differentiation. To evaluate the potential of phosphodiesterase type 5 (PDE5) inhibitors like tadalafil for prevention and treatment of BPH, we analyzed the role of the nitric oxide/cyclic GMP (cGMP)/PDE5 pathway for cellular proliferation and TGFbeta1-induced fibroblast-to-myofibroblast trans-differentiation in primary prostate stromal cells. Inhibition by tadalafil of PDE5, which is mainly expressed in the stromal compartment of the prostate, reduced proliferation of primary prostate stromal cells and to a lesser extent of primary prostate basal epithelial cells. Attenuated proliferation due to elevated intracellular cGMP levels was confirmed by inhibition of the cGMP-dependent protein kinase G by its inhibitor KT2358. Moreover, tadalafil strongly attenuated TGFbeta1-induced fibroblast-to-myofibroblast trans-differentiation. The inhibitory effect on trans-differentiation was also observed after small interfering RNA-mediated PDE5 knockdown. As confirmed by the MAPK kinase 1 inhibitor PD98059, this effect was mediated via MAPK kinase 1 signaling. We conclude that BPH patients might benefit from adjuvant therapies with PDE5 inhibitors that inhibit stromal enlargement due to cell proliferation, as well as TGFbeta1-induced trans-differentiation processes.

Introduction: Data are sparse concerning the effects of phosphodiesterase type 5 (PDE5) inhibitors for erectile dysfunction (ED) in subjects with multiple sclerosis (MS)., Aim: To evaluate the efficacy and safety of tadalafil use in subjects with ED because of MS., Methods: Ninety-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 Measures: SEP2-3, 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., Results: Ninety-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., Conclusion: Tadalafil 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.

Introduction: Phosphodiesterase type 5 inhibitors (PDE5), such as sildenafil, tadalafil, and vardenafil, have revolutionized the treatment of erectile dysfunction. Few successes, in contrast, have been reported for the use of these agents in treatment of sexual arousal problems in women., Aim: To review research examining efficacy of PDE5 in women, critique the methods and models employed, and integrate the findings within a broader, gender-specific understanding of female sexual response., Methods: A conceptual and methodological review of all published studies examining PDE5 efficacy in female samples., Main Outcome Measures: Study methods, populations, outcome measures, study results., Results: A total of 16 studies were reviewed. Studies using self-reported measures of sexual functioning showed mixed results whereas studies examining physiological effects of PDE5 on genital vasocongestion consistently report significant effects on genital sexual response., Conclusions: The lack of efficacy of PDE5 treatment in women is likely attributable to gender differences in the concordance between physiological and psychological components of sexual response. Discordance between genital and subjective measures of sexual response in women may be augmented by PDE5 effects on genital vasocongestion in some populations, rendering successful treatment unlikely via pharmacological treatment alone.

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 > or =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 > or =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 > or =26 at endpoint (adjusted OR = 41.0; 95% CI = 33.6-50.2; P < 0.0001). Satisfaction emerged as a strong correlate of a > or =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.

Introduction: Erectile dysfunction (ED) is distressing and can affect a couple's relationship., Aim: To investigate partner awareness of ED, relationship problems, and the effects of tadalafil treatment over 12 months., Methods: The Determinants of Continued Use of Tadalafil study is a prospective 12-month European observational study in patients with ED initiating or changing treatment to on-demand tadalafil. A total of 1,900 patients were enrolled in eight countries. Assessments were made on predefined treatment outcomes in a routine clinical setting., Main Outcome Measures: At baseline, 1, 6, and 12 months, patients were asked about relationship problems (unspecified), partner awareness and support of consultation, and partner sexual problems. Data were analyzed for patients continuing tadalafil at 12 months., Results: At baseline, 96% of patients had a partner, 80% of partners supported an ED consult, and 73% were aware of the consultation. Relationship problems were reported by 17% of patients at baseline. At 12 months, 84% of patients were still taking tadalafil. Of these, 19% reported relationship problems at baseline. After 12 months of treatment with tadalafil, 4% of patients still reported perceived problems. Factors associated with no relationship problems at 12 months were: at baseline, no previous ED treatment, partner in poor health; and at 12 months a lower ED severity. If the partner was felt to have a sexual problem at 12 months, relationship improvement was less likely. Further, 3% of patients developed relationship problems during treatment. Factors associated with developing a relationship problem were: a history of pelvic surgery at baseline, a different partner at 12 months than at baseline, and a partner with a sexual problem at 12 months., Conclusions: Improvement of ED with tadalafil was associated with reduced relationship problems, suggesting that problems were associated with ED and resolved with treatment.

Introduction: Previous research has demonstrated that sildenafil citrate users alter dosing-sexual attempt behavior when switched to tadalafil. The impact of geography and culture on sexual behavior with phosphodiesterase type 5 (PDE5) inhibitor treatment has not been fully investigated., Aim: To describe and compare the changes in dosing-sexual attempt behavior with sildenafil citrate vs. tadalafil treatment across four distinct geographies: Asia, Australia/New Zealand (ANZ), Central Eastern Europe/Middle East (CEE/ME), and Latin America (LA)., Methods: Data from a single-arm, open-label clinical trial conducted in 21 countries from November 2002 to May 2004 were used in this analysis. Men with erectile dysfunction and a history of > or =6-week prior sildenafil citrate use continued sildenafil citrate treatment for 4 weeks then switched to tadalafil for 8 weeks. Dosing instructions were provided., Main Outcomes Measures: Timing of dose and sexual intercourse was assessed through patient diaries for the final 4 weeks of each treatment period., Results: A total of 2,760 men were enrolled: Asia 15.8%; ANZ 29.4%; CEE/ME 19.7%; LA 35.1%. The median time from dosing to intercourse was significantly increased during tadalafil treatment across all geographical regions; however, the magnitude of increase differed significantly by geography (P < 0.0001). The Asian cohort demonstrated the shortest duration between dosing and sexual intercourse attempts (irrespective of drug), and altered sexual behavior the least upon switching to tadalafil. The ANZ cohort demonstrated the longest duration between dosing and sexual intercourse attempts (irrespective of drug), and altered sexual behavior the most upon switching to tadalafil., Conclusion: Men with a history of established sildenafil citrate use alter their dose-attempt behavior when treated with tadalafil irrespective of geography. However, the extent to which sexual behavior alters is not uniform across geographical regions, suggesting that dosing instructions and duration of drug effectiveness, in combination with personal and cultural preferences, may determine sexual behavior with PDE5 inhibitor use.

Introduction: The three effective, commercially available drugs for the treatment of erectile dysfunction-sildenafil, vardenafil, and tadalafil-inhibit the same substrate, the erectolytic enzyme phosphodiesterase type 5 (PDE5). Although there are pharmacological differences between these three compounds, few comparative studies have been conducted to date., Aim: The aim of this study was to determine the efficacy of sildenafil, tadalafil, and vardenafil in a randomly assigned 8-week fixed regimen., Methods: This was a spontaneous, open-label, randomized, multicenter, crossover study where the patients were randomized to receive sildenafil 50 mg, sildenafil 100 mg, tadalafil 20 mg, or vardenafil 20 mg., Main Outcome Measures: The primary outcome included the posttreatment analysis of erectile function domains of the abridged International Index of Erectile Function (IIEF5+1). The secondary objectives included the analysis of peak-systolic velocities (PSVs), end-diastolic velocities (EDVs), and resistive index (RI), and the estimate of the percentage of men with normal penile hemodynamic parameters after each treatment., Results: In all groups of patients taking sildenafil 50 mg, sildenafil 100 mg, tadalafil 20 mg, and vardenafil 20 mg at a frequency reflecting the common treatment regimens in real life, there was a statistically significant baseline-to-end point improvement in subjective perception of erectile function measured by IIEF5+1. When the four groups were compared, the treatments were not different in modifying IIEF5+1 and penile flow parameters. However, the within-group analysis showed that PSV improved in the sildenafil 50 mg group and that PSV together with RI significantly ameliorated in patients receiving 100 mg of sildenafil. Regression analysis confirmed an independent effect of sildenafil on hemodynamic efficacy parameters., Conclusions: An overall equivalence was demonstrated in the subjective perception of treatment benefits for all the PDE5i tested. However, sildenafil, in a dose-dependent manner, was the unique PDE5i able to ameliorate some of the penile flow parameters within the 8-week treatment period. These findings should be interpreted conservatively because of the observational nature of the study.

Introduction: Highly selective inhibitors of phosphodiesterase type 5 (PDE5I) have been commercially available for over a decade. Our knowledge of these drugs continues to expand., Aims: To review recent (since 2007) developments on the utilization of PDE5I in clinical practice. The focus of this manuscript is on the use of PDE5I for sexual concerns. Also reviewed are recent reports of rare but potentially serious toxicity., Methods: Pubmed search utilizing the search terms "phosphodiesterase type 5 inhibitor," "PDE5 inhibitor,""sildenafil," "vardenafil," and "tadalafil." Articles were screened for their relevance to the clinical practice of sexual medicine and/or PDE5I toxicity. Publications on routine dose PDE5I for penile rehabilitation, lower urinary tract symptoms, and stuttering priapism are summarized in a separate manuscript in this series., Main Outcome Measures: Peer-reviewed publications since the last major update on PDE5I published in the medical literature., Results: Recent investigations have suggested a number of interventions to potentially improve patient compliance with PDE5I therapy. Additionally, the approval in the past year of tadalafil as a daily medication signifies a potential paradigm shift in our concept of this disorder. Daily dosing may be useful in some men; however, the other available PDE5I continue to show excellent efficacy in the management of erectile dysfunction (ED). In addition to direct effects on ED, several recent reports highlight the use of PDE5I for improvement of premature ejaculation, sexual relationship status, and sexual function in women. There have also been several recent reports of rare but serious toxicity, particularly ototoxicity, associated with PDE5I use., Conclusions: Recent studies have suggested new ways to optimize utilization of PDE5I not only for the management of ED but also for other sexual concerns in both men and women. Rare but serious toxicities have been reported with PDE5I and, therefore, judicious counseling is indicated before prescribing these medications.

Introduction: Several phosphodiesterase type 5 (PDE5) inhibitors are commercially available for the treatment of erectile dysfunction (ED). Development of the first once-daily alternative dosing regimen with a PDE5 inhibitor was motivated by the behavioral complexities associated with sexual intimacy., Aim: To provide an alternative dosing option for certain men who may benefit from the removal of the temporal linkage between administration of an ED therapy and sexual intimacy or for men and their partners who anticipate at least twice-weekly sexual activity., Methods: Pharmacokinetic predictions of tadalafil plasma concentrations were generated based upon empirical data following 20-mg, single-dose administration coupled with tadalafil usage patterns from as-needed clinical trials. To support the pharmacokinetic simulations and pharmacodynamic assumptions, clinical trials were conducted to demonstrate the efficacy and safety of once-daily, low-dose tadalafil 2.5 and 5 mg., Main Outcome Measures: Simulated tadalafil plasma concentrations and comparison with safety and efficacy measures from clinical trials., Results: Based upon pharmacodynamic and pharmacokinetic data, once-daily doses of tadalafil 5 mg were predicted to provide therapeutic concentrations that would be maintained throughout the 24-hour dosing interval. Additionally, for a subgroup of men who anticipate at least twice-weekly sexual activity and are currently taking tadalafil 20 mg, a reduction in daily tadalafil exposure was predicted. To support the hypothesis that low-dose, once-daily tadalafil may be a safe and effective treatment alternative, clinical trials were conducted to demonstrate the safety and efficacy of once-daily tadalafil 2.5 and 5 mg. These results were similar to those of historical as-needed studies evaluating tadalafil 10 and 20 mg., Conclusions: Consistent with pharmacokinetic predictions, data from clinical trials indicate that once-daily use of low-dose tadalafil is a safe and effective treatment for men with ED.

Introduction: In recent years, the availability of effective oral pharmacological treatment for erectile dysfunction (ED) has revolutionized its management; however, it is still unclear how everyday clinical practice has changed in response to this evolving scenario., Aim: The aim of this study is to describe general practitioners' (GPs) beliefs and attitudes toward the management of ED., Methods: Each GP was asked to recruit consecutive men aged >or=18 years and sexually active, with already known erectile problems or with newly diagnosed ED., Main Outcomes Measures: A written questionnaire was used to investigate GPs' sociodemographic characteristics and their beliefs toward the management of ED., Results: Overall, 127 GPs (53.4%) returned the questionnaire and 124 enrolled patients for the study. Only 9.5% of the GPs reported routinely inquiring about ED of patients >40 years of age, whereas 45.7% did it only when the patient raised the problem. GPs' gender and age were associated with their beliefs about ED treatment and referral to specialist care. Overall, 932 patients were enrolled, of whom 38% had newly diagnosed ED. The problem came to light for initiative of patient in 80% of cases, and 84.8% of men were prescribed a treatment. Patients who on their own initiative discussed of their condition had an almost 3-fold increased probability to be treated than those whose GP began the discussion about ED (odds ratio [OR] = 2.6, confidence interval [CI] 95% 1.5-4.5). Patients followed by female physicians were significantly more likely to be referred to a specialist than those followed by male physicians (OR = 3.3, CI 95% 1.4-5.0)., Conclusions: The management of ED has become an integral component of clinical practice in primary care. Nevertheless, barriers in addressing sexual issues still persist. Appropriate training is needed for a proactive approach to ED screening and management in men over 40s.

Introduction: The 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., Aim: The 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)., Methods: Phase 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 Measures: The improvement of ED was measured using the IIEF15 and the SEP2-3 questions., Results: Twenty-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)., Conclusion: Tadalafil represents an effective and safe long-term option for SCI patients with ED.

Introduction: Alpha1-blockers (AB) are the first-line monotherapy for lower urinary tract symptoms (LUTS). Phosphodiesterase type 5 (PDE5) inhibitors are the first-line treatment for erectile dysfunction (ED). Numerous studies have supposed a significant association between ED and LUTS, but a causal relationship cannot be established., Aim: The aim was to evaluate the efficacy of a combined therapy with an AB (alfuzosin) and PDE5 inhibitors (tadalafil) in patients with LUTS and ED., Methods: This was a randomized, open-label, three-arm study. A total of 66 men complaining of ED and LUTS were included in the study. Patients were assessed at baseline and after 12 weeks of study treatment, and then underwent randomized allocation to either alfuzosin 10 mg once a day (22 patients) or tadalafil 20 mg on alternative days (21 patients), or a combination of both (23 patients)., Main Outcome Measures: All participants completed the erectile function domain of the International Index of Erectile Function (IIEF-EF) and the International Prostatic Symptom Score (IPSS). Other efficacy variables included maximum urinary flow rate (Qmax) and medium urinary flow rate (Qave)., Results: IIEF-EF tended to improve with alfuzosin alone (+15%), while it was clearly improved with tadalafil alone (+36.3%). The greatest improvement was experienced with the combination therapy (+37.6%). Improvement in Qmax was observed in all groups, but patients receiving combination therapy had greater improvement (29.6%) than patients receiving either only alfuzosin (21.7%) or only tadalafil (9.5%). IPSS was significantly improved in alfuzosin group (27.2%), was more marked with the combination therapy (41.6%), and a small increase, although not significant, was also observed with tadalafil (8.4%)., Conclusions: Combined therapy improved ED and LUTS as demonstrated by the significant improvement in uroflowmetry measures and in IPSS and IIEF-EF scores. A significant improvement was also observed in quality of life assessments. The beneficial effects of tadalafil on LUTS similar to the benefits of alfuzosin on ED, although present, were smaller.

Introduction: Erectile 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., Aim: To 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., Methods: The 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 Measures: International 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., Results: Data 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., Conclusions: Eighty-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.