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Background Clinical study and practice data have shown sildenafil improves sexual function in men with erectile dysfunction (ED). However, some men treated with placebo in double-blind, placebo-controlled sildenafil studies also report improved erectile function as measured by International Index of Erectile Function (IIEF)–Erectile Function Domain (EFD) scores. Aim This analysis estimated the relationship between post-baseline IIEF-EFD scores and demographic variables, including co-morbidities, in men with ED receiving placebo in flexible-dose sildenafil studies. Methods Placebo-treated participants in the intent-to-treat population of 42 double-blind, placebo-controlled, flexible-dose, sildenafil studies were included. A participant was classified as a placebo responder if the IIEF-EFD score was ≥26 at the last visit. Outcomes Variables assessed were age ( Results A total of 4,360 men were included; 13.5% were responders. Odds estimates indicated the largest likelihood of placebo response occurred in men who were black (odds = 20.2, P < .0001), were younger than 45 years (odds = 7.3, P < .0001), had mild ED (baseline IIEF-EFD ≥17; odds >100, P < .0001), and did not have diabetes (odds = 4.5, P < .0001). The likelihood of a placebo response decreased as ED duration increased (odds = 0.74, P < .0001). The frequency of common adverse events was similar between placebo responders and non-responders. Clinical Translation These findings contribute to the improved understanding of predictors of placebo response in sildenafil clinical studies. Elucidation of these factors may contribute to the development of further interventions and treatment strategies and best practices for clinical trials. Strengths and conclusions Strengths of this analysis include the large and diverse population and the duration of follow-up. Limitations include those associated with retrospective analyses and the inability to ascertain to what extent other demographic factors might have contributed to the placebo responses or how these placebo responses might be related to the natural course of ED. Conclusions Certain demographics, co-morbidities, and condition characteristics predicted the odds of a placebo response in sildenafil clinical studies of ED. Underlying reasons behind a placebo response warrant further evaluation.

Background Patient-reported outcomes, such as the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) index, are essential for successful evaluation and treatment of patients with erectile dysfunction. Aim To enrich interpretation of the EDITS index score and to complement the existing 0 to 100 scoring. Methods This supplemental analysis evaluated EDITS questionnaire data (11 items; index score range = 0–100; higher scores indicate more treatment satisfaction) after completion of an 8-week double-blinded trial of 279 men 18 to 65 years old with erectile dysfunction randomized to sildenafil 100 mg, sildenafil 50 mg, or placebo. Response options for each EDITS item were grouped into “success” (the 2 most satisfied or favorable responses) and “no success” (the remaining 3 responses). The binary response (success or no success) for each item was expressed as a function of overall EDITS score in a simple logistic regression model with all treatments combined. Outcomes Odds ratios and success probabilities (using Wald χ2 tests) were calculated for specified point differences and total EDITS index scores, respectively. Results EDITS index score increases corresponded with significant increases in odds of success in different EDITS aspects (P < .0001 for all comparisons). For instance, a 10-point EDITS index score difference was associated with odds ratios of 11.3, 42.0, 17.7, and 6.8 for overall treatment satisfaction, treatment meeting expectations, satisfaction with treatment quickness, and satisfaction with how long treatment lasts, respectively. For a given EDITS index score, likelihood of success was determined for different aspects of treatment satisfaction. For example, a mean EDITS index score of 78 (sildenafil 100 mg; SD = 18) corresponded to 96%, 88%, 94%, and 88% chances of success for the 4 EDITS items referenced earlier, respectively. Corresponding probabilities for a mean EDITS index score of 50 (placebo; SD = 18) were 3%, less than 0.1%, 1%, and 4%, respectively. Clinical Implications Interpretation of the EDITS index score can be augmented using key aspects of treatment satisfaction as reported by the patient. Strengths and Limitations This analysis used a well-established anchor-based approach to interpret EDITS index scores. The methodology used and corresponding results are appropriate for clinical practice and clinical trial settings. Limitations include data evaluation only for the Patient EDITS and not the complementary Partner EDITS and use of data from a clinical trial enrolling a well-defined patient population only in stable relationships. Conclusion These results enable a meaningful interpretation of EDITS index scores, facilitating decision making by stakeholders for better-informed health care choices.

Spinal cord injury (SCI) is estimated to affect approximately 276,000 individuals in the United States. Since 2010, the mean age of individuals at the time of the SCI has been 42 years, with nearly 80% of cases involving men. This means that individuals with SCI generally are young men who typically place a great deal of importance on normal sexual and reproductive function.To assess the effect of sildenafil treatment on erectile function and the frequency of ejaculation in men with SCI.This study was a post hoc analysis of pooled data from two randomized, double-blinded, placebo-controlled, flexible-dose, crossover sildenafil trials conducted in Europe, Australia, and Turkey. Two hundred forty-eight men at least 18 years old with traumatic SCI of at least 6 months' duration, with erectile dysfunction solely attributed to SCI, and in a stable heterosexual relationship were treated sequentially with sildenafil and placebo. Exclusion criteria included taking nitrate therapy, severe cardiac failure, and recent stroke or myocardial infarction. The starting sildenafil dose was 50 mg, taken approximately 1 hour before sexual activity, with subsequent dose adjustment to 100 or 25 mg based on efficacy and safety during treatment. There was a 2-week washout between 6-week treatments.Change from baseline in International Index of Erectile Function question 3 (frequency of penetration), question 4 (maintaining erection after penetration), question 9 (frequency of ejaculation), and erectile function domain scores; intercourse success; and treatment preference.All International Index of Erectile Function outcomes, including achieving and maintaining erections and ejaculation frequency, were statistically significantly greater with sildenafil vs placebo, including the subgroup with complete SCI (P.01 for all comparisons). The percentage of successful intercourse attempts with sildenafil (53% vs 12%) and preference for sildenafil (96% vs 4%) vs placebo were significant (P.001), including the subgroup with complete SCI. The most common all-cause adverse events with sildenafil were headache (16.1%) and urinary tract infection (11.6%).Sildenafil significantly improves erections, intercourse success, and ejaculation frequency vs placebo, including in men with complete SCI. Sildenafil is an effective and well-tolerated treatment for sexual dysfunction in men with SCI. The increase in frequency of ejaculation could allow the possibility of having children without medical intervention in this patient population. Ohl DA, Carlsson M, Stecher VJ, Rippon GA. Efficacy and Safety of Sildenafil in Men With Sexual Dysfunction and Spinal Cord Injury. Sex Med Rev 2017;5:521-528.

SummaryAims With self-reporting of erectile dysfunction (ED) in population-based surveys, men with ED may not represent men who are bothered sufficiently to seek an ED diagnosis and treatment. We used real-world observational data to assess: 1) the prevalence of ED diagnosis or treatment by age subgroups; and 2) the relationship of age with ED diagnosis or treatment after controlling for ED-related comorbidities in the USA. Methods This cross-sectional study used de-identified claims data (MarketScan® databases; primary analysis). Sensitivity analysis was conducted using electronic health records (Humedica® database). Inclusion criteria were men aged ≥18 years with a 360-day continuous enrollment before the index date. We assessed the prevalence of ED diagnosis or phosphodiesterase type 5 inhibitor (PDE5I) prescription by age and the risk for ED diagnosis or treatment by age after controlling for comorbidities (hypertension, other cardiovascular disease, diabetes mellitus, depression and benign prostatic hyperplasia). Results Of 19,833,939 men meeting inclusion criteria in the primary analysis, only 1 108 842 (5.6%) had an ED diagnosis or PDE5I prescription (mean [SD] age: 55.2 [11.2] years). Prevalence of ED diagnosis or treatment increased from age 18–29 years (0.4%) to 60–69 years (11.5%), then decreased in the seventh (11.0%), eighth (4.6%), and ninth (0.9%) decades. Men with ED diagnosis or treatment had a higher prevalence of any comorbidity (63.1% vs 29.3% for men without ED) and of each comorbid condition. In multivariate analyses, age was an independent risk factor for ED diagnosis or treatment. Sensitivity analysis provided consistent results. Conclusions In a real-world setting in the USA, the prevalence of ED diagnosis or PDE5I treatment is generally low, increases with age, decreases in very old men, and is associated with increased prevalence of comorbidities. Age is an independent risk factor for ED diagnosis or treatment after controlling for comorbidities.

Introduction This report describes a post hoc analysis of data from a randomized, double-blinded, placebo-controlled, flexible-dose, sildenafil trial in men with erectile dysfunction. Aims To simplify interpretation of erectile function (EF) domain scores of the International Index of Erectile Function (IIEF). Methods Men at least 18 years old with erectile dysfunction were randomized to receive sildenafil or placebo for 12 weeks. Men taking nitrates or nitric oxide donors were excluded. Responses for each IIEF EF domain question (questions 1–5 and 15) were combined into two broad categories (“success” for responses of the two most favorable categories of a question and “no success” for other responses). Each question was expressed in a logistic regression model (sildenafil and placebo groups combined) as a function of overall EF domain score. Main Outcome Measures IIEF EF domain score and items. Results A four-point increase in the IIEF EF domain score was associated with an odds ratio of success of 6.1 for getting an erection, 29.2 for having a firm erection, 10.0 for able to penetrate,12.8 for maintaining erection, 4.0 for maintaining erection to completion, and 3.7 for erection confidence. An EF domain score of 22 was associated with a probability of success of 81% for getting an erection, 86% for having a firm erection, 89% for able to penetrate, 67% for maintaining an erection, 70% for maintaining an erection to completion, and 32% for erection confidence. For an EF domain score of 16, the corresponding probabilities of success were 22%, 4%, 20%, 4%, 22%, and 6%, respectively. Conclusion These results provide stakeholders with a simplified and meaningful interpretation of IIEF EF domain scores based on six key aspects of EF.

AIMS To evaluate the relationship of comorbidities (cardiovascular disease [CVD], diabetes mellitus [DM] and depression) with erectile dysfunction (ED) and age using real-world claims data from 48 million men in the United States. METHODS This was a cross-sectional, non-interventional study in men aged ≥18 years using data from the Truven Health MarketScan® and Medicare Supplemental Research Databases from January 2010 to December 2015, with an observational period of January 2011 to December 2014 to allow for 12 months pre- and post-index. Comorbidity rate was compared between ED and non-ED groups by age using the χ2 (bivariate) test. Comorbidity relationship to ED after controlling for categorical variables was assessed using logistic regression analysis. RESULTS In all, 48 004 379 men were in the database. Of the 9 839 578 who met the inclusion criteria, 573 313 (6%) were ED patients and 9 266 265 (94%) were non-ED patients. ED diagnosis increased decade to decade from 18-29 years to 50-59 years but decreased from 60-69 years to ≥90 years. ED patients had a higher prevalence of CVD, DM and depression than non-ED patients in all periods (P

The objective of this study was to describe confirmatory factor analysis (CFA) and multidimensional scaling (MDS) on the International Index of Erectile Function (IIEF) to confirm the structure and to enrich understanding of the IIEF, thereby heightening appreciation of the factors and responses underlying sexual functioning for men with erectile dysfunction. Baseline, end of double-blind, and end of open-label data sets were derived from all data from 2 previously published sildenafil trials. For the CFA model, an acceptable fit of the data was shown for each data set, as indicated by a Bentler comparative fit index > 0.9, statistically significant path coefficients (t values > 1.96), and (except for IIEF item 6 at baseline) statistically significant standardized path coefficients ≥0.4. For MDS modeling, the distance matrix created for each data set, based on polychoric correlations, interpreted relationships between the IIEF items in 2-dimensional space across the “sexual intercourse interference” dimension (horizontal axis) and the “sexual satisfaction” dimension (vertical axis). The 5-factor structure of the IIEF was confirmed by CFA and enriched with visual interpretation by MDS.

John P Mulhall,1 Dana L Creanga,2 Vera J Stecher31Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 2Consultant to Pfizer Inc., New York, NY, USA; 3Medical Affairs, Primary Care Business Unit, Pfizer Inc., New York, NY, USAPurpose: To determine, in men with erectile dysfunction (ED), the extent of improvement in erection hardness and in the rate of successful sexual intercourse (SSI) during the final intercourse attempt using sildenafil 50 mg compared with the subsequent initial attempt after a dose increase to 100 mg.Patients and methods: This post hoc analysis used data from two randomized, double-blind, placebo-controlled studies of flexible-dose sildenafil for the treatment of men with ED, who were given sildenafil 50 mg or matching placebo, to be taken as needed before sexual intercourse. After 2 weeks, those with no tolerability concerns were titrated up to 100 mg, forming the subgroup of this analysis. The main outcome measures were event log data, including an Erection Hardness Score (EHS) and a question on SSI (“Did your erection last long enough for you to have successful sexual intercourse?”), for each attempt at sexual intercourse, analyzed by study and treatment group (sildenafil or placebo). Statistical comparisons were conducted by using the Fisher's exact test.Results: In both studies, the sildenafil group had a larger proportion of EHS4 (completely hard and fully rigid) erections (P < 0.001) and SSI (P < 0.005) compared with the placebo group, both before and after the dose increase. Between the final 50 mg sildenafil dose and the initial 100 mg sildenafil dose, the outcomes improved and significantly so in the larger study.Conclusion: The improved efficacy with sildenafil 100 mg versus 50 mg, which occurs rapidly, suggests that patients should be encouraged to use 100 mg if they are unable to achieve completely hard and fully rigid erections or SSI with the 50 mg dose.Keywords: erectile function, successful sexual intercourse, erection hardness score, dose response

To apportion the direct effect and the indirect effect (through erections) that sildenafil (vs placebo) has on individual satisfaction and couple satisfaction over time, longitudinal mediation modeling was applied to outcomes on the Sexual Experience Questionnaire. The model included data from weeks 4 and 10 (double-blind phase) and week 16 (open-label phase) of a controlled study. Data from 167 patients with erectile dysfunction (ED) were available for analysis. Estimation of statistical significance was based on bootstrap simulations, which allowed inferences at and between time points. Percentages (and corresponding 95% confidence intervals) for direct and indirect effects of treatment were calculated using the model. For the individual satisfaction and couple satisfaction domains, direct treatment effects were negligible (not statistically significant) whereas indirect treatment effects via the erection domain represented >90% of the treatment effects (statistically significant). Week 4 vs week 10 percentages of direct and indirect effects were not statistically different, indicating that the mediation effects are longitudinally invariant. As there was no placebo arm in the open-label phase, mediation effects at week 16 were not estimable. In conclusion, erection has a crucial role as a mediator in restoring individual satisfaction and couple satisfaction in men with ED treated with sildenafil.

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-a 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 medica- tions 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 appro- priately 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. ScrantonRE,GoldsteinI,andStecherVJ.Erectiledysfunctiondiagnosisandtreatmentasameanstoimprove medication adherence and optimize comorbidity management. J Sex Med 2013;10:551-561.

To evaluate treatment response in men with erectile dysfunction (ED) and concomitant comorbidities.Data were pooled from 42 placebo-controlled, flexible-dose sildenafil trials. In most trials, the sildenafil dose was 50 mg, taken ~1 hour before sexual activity but not more than once daily, with adjustment to 100 or 25 mg as needed. The overall population (N=9413) was stratified by age (45, 46-64, ≥65 years). Treatment response was defined as a minimal clinically important difference (MCID) from baseline in the International Index of Erectile Function-Erectile Function (IIEF-EF) domain score of2,5 and7 for men with mild, moderate and severe ED at baseline, respectively, or an IIEF-EF domain score ≥26 (no ED) at end-point.In the overall population, treatment response using the IIEF-EF MCID definition was significantly greater (P.0001) with sildenafil vs placebo in men with no comorbidity (77% vs 33%), cardiovascular disease/hypertension only (71% vs 27%), diabetes only (63% vs 24%) or depression only (78% vs 29%). Using an IIEF-EF score ≥26, treatment response was significantly greater (P.0001) with sildenafil vs placebo in men with no comorbidity (49% vs 17%), cardiovascular disease/hypertension only (48% vs 12%), diabetes only (40% vs 12%) or depression only (60% vs 17%). With each definition, the treatment response for each age and comorbidity was significantly greater (P≤.0065) with sildenafil vs placebo.The treatment response was significantly greater with sildenafil vs placebo in men with ED and each comorbidity regardless of age.

Individual domains of multi-domain, patient-reported outcome instruments are typically analyzed independently, without considering inherent interdependency. The authors assessed correlations across time (longitudinal) and across domains of a multi-domain instrument, simultaneously, in a single, unified, and cohesive integrated model. International Index of Erectile Function (IIEF) data from a trial of sildenafil in erectile dysfunction were used. For the multi-domain longitudinal modeling, covariance of response was constructed using (1) the Kronecker product of an unstructured covariance matrix to model across domains, with an unstructured covariance matrix to model across time, and (2) a completely general, unstructured covariance matrix. Treatment effects for all IIEF domain scores calculated using individual or multi-domain modeling were similar, reflecting the robust application of the integrated model to these data. In conclusion, modeling correlations simultaneously across domains and across time more rigorously address the natural interrelationship between domains and can provide a more accurate representation of treatment effects.

Introduction Patient-reported outcomes are a valuable tool used to gauge treatment satisfaction in different conditions, including erectile dysfunction (ED). Aim To use person-item maps to quantify barriers to improvement of treatment satisfaction in men with ED. Methods Men 18 to 65 years old with documented ED received sildenafil 50 mg, sildenafil 100 mg, or placebo for 8 weeks in a double-blinded manner. Post hoc analyses were conducted on Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) data (11 items rating treatment satisfaction; each item score range = 0–4). Main Outcome Measures Person-item maps were developed based on Rasch models. To quantify barriers to improvement of treatment satisfaction, responses to the 11 items of the EDITS questionnaire were dichotomized to indicate improvement (responses of 3 or 4 were combined to a score of 1) vs no change or worsening (responses of 0, 1, or 2 were combined to a score of 0). Results Analyses were conducted using data from 278 men who completed the EDITS questionnaire at the end of double-blinded treatment. The person-item map indicated that EDITS item 4 (ease of use of treatment) was the easiest barrier to overcome, whereas the most difficult barrier to improvement of treatment satisfaction was EDITS item 2 (degree to which treatment met expectations). Most men in the sildenafil 100-mg group endorsed most EDITS items, consistent with substantial improvement. The sildenafil 50-mg group was similar, but with smaller frequencies for endorsing improvement of the more difficult EDITS items. In contrast, men receiving placebo endorsed mainly the easiest EDITS items, with only a small number of men endorsing the difficult items. Conclusion A person-item map is a useful means for quantifying barriers to improvement of treatment satisfaction represented by EDITS items in patients with ED.

Phosphodiesterase-5 inhibitors (PDE5Is) improve erectile function by enhancing nitric oxide availability in the penis and its supplying vasculature, resulting in vasodilation and increased blood flow. PDE5Is might benefit cardiovascular diseases because phosphodiesterase-5 is also located elsewhere in the body, including the pulmonary and systemic vasculature and in hypertrophied myocardium. PDE5Is are approved for pulmonary arterial hypertension, given that they improved several hemodynamic and clinical parameters in large randomized trials. Initial evidence suggests that PDE5Is benefit patients with congestive heart failure and secondary pulmonary hypertension. PDE5Is seem to improve hemodynamic and clinical parameters in patients with high-altitude pulmonary edema (HAPE) and high-altitude pulmonary hypertension. In climbers with prior episodes of HAPE, PDE5Is prevented HAPE in 2 small randomized trials. In small randomized trials of PDE5Is, patients with Raynaud's phenomenon demonstrated improved blood flow, fewer symptoms and frequency of attacks, and resolution of digital ulcers. In addition to enhancing vasodilation, PDE5Is seem to protect the myocardium through complex pathways that involve nitric oxide, cyclic guanosine monophosphate, protein kinase G, extracellular-signal-regulated kinase, B-cell lymphoma protein-2, and Rho kinase inhibition. In animal models of acute myocardial infarction, PDE5Is consistently reduced infarct size indicating cardioprotection and PDE5Is also promote reverse remodeling and reduce myocardial apoptosis, fibrosis, and hypertrophy. PDE5Is might also benefit patients with treatment-resistant hypertension, preeclampsia, or peripheral arterial disease. This review presents the pathophysiology and trial data with regard to the use of PDE5Is for cardiac diseases.

Rationale Research on relationships often does not refer to a single person but rather to two persons. Nonetheless, such data has been often analysed by examining individuals in isolation, which falls short of capturing their truly interpersonal and non-independent nature. Aims and objectives This paper highlights and illustrates some analytic tools for such dyadic data that are essential for theories about dyadic relationships to be tested adequately. Methods The methodology is applied to clinical trial data from male patients treated for their erectile dysfunction and data from their partners with respect to treatment satisfaction. Multi-level modelling was used to analyse the data. Results The approaches outlined allow researchers to assess both individual effects and companion effects (e.g. of baseline intercourse satisfaction on subsequent treatment satisfaction), role of participant (e.g. patient or partner) or treatment condition (e.g. test or placebo) on outcome (e.g. treatment satisfaction), and differences on individual and companion effects when couples differ on important variables (e.g. differences on the individual and companion effects of baseline intercourse satisfaction on treatment satisfaction when couples differ with respect to treatment condition). Conclusion Researchers are encouraged to consider implementing dyadic data analysis in their own work.

The prescribing information for sildenafil citrate (VIAGRA, Pfizer, New York, NY, USA) recommends flexible dosing (50 mg initially, adjusted to 100 or 25 mg based on effectiveness and tolerability) in most men with erectile dysfunction (ED). In many men, however, 100 mg may be the most appropriate initial dose because it would reduce the need for titration and could prevent discouragement and treatment abandonment should 50 mg be insufficient. Results of two previously published double-blind, placebo-controlled sildenafil trials of similar design except for a fixed-dose vs flexible-dose regimen were analyzed. Relative to the flexible-dose, approximately one-third more men were satisfied with an initial and fixed dose of 100 mg. In addition, tolerability was similar, and improvements from baseline in outcomes on validated, ED-specific, patient-reported questionnaires were either similar (erectile function and the percentage of completely hard and fully rigid erections) or greater (emotional well-being and the overall sexual experience). The similarity in outcomes is not surprising given that almost 90% of the men in the flexible-dose trial titrated to 100 mg after 2 weeks. These data suggest prescription of an initial dose of 100 mg for men with ED, except in those for whom it is inappropriate.

Aim To determine what constitutes a clinically important difference (CID) on the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), an 11-item validated questionnaire assessing treatment satisfaction used in clinical trials for patients with erectile dysfunction (ED). Methods Erectile Dysfunction Inventory of Treatment Satisfaction data were evaluated from a double-blind, fixed-dose trial of 279 men aged 18-65 years with ED who were treated with sildenafil 50 or 100 mg or placebo. The primary anchor measure was the erectile function (EF) domain of the International Index of Erectile Function (IIEF), which has a 4-point minimal CID. The CID on the EDITS index score was determined using a regression analysis comparing EDITS and IIEF EF scores at the end of the 8-week treatment. A similar analysis was performed for EDITS and the Erection Hardness Score (EHS) instrument, a single-item questionnaire measuring hardness, which was used as a secondary anchor measure. Results Erectile Dysfunction Inventory of Treatment Satisfaction and IIEF EF domain scores were highly correlated (Pearson correlation coefficient = 0.75). EDITS total scores across treatments at week 8 averaged (mean ± standard deviation [SD]) 67.5 ± 21.6 (range, 0-100; higher scores indicate greater treatment satisfaction); IIEF EF domain scores averaged 22.2 ± 6.9 (range, 1-30; higher scores indicate higher erectile functioning). The calculated CID for EDITS scores was 9.5 (95% CI, 8.5-10.4; 0.44 SD units), corresponding to a medium effect size. EDITS and EHS instrument scores also correlated highly (Pearson correlation coefficient = 0.64). Placebo-adjusted EDITS mean scores were more than twice the CID, at 23 (95% CI, 17-28) and 28 (95% CI, 23-33) for the 50- and 100-mg doses, respectively. Conclusion Approximately 10 points on the EDITS index score is considered a CID. Serving as a benchmark, this finding aids interpretation of the clinical relevance of a difference in mean EDITS index scores between treatments for patients with ED.

Counterfeit drugs are inherently dangerous and a growing problem; counterfeiters are becoming increasingly sophisticated. Growth of the counterfeit medication market is attributable in part to phosphodiesterase type 5 inhibitor (PDE5i) medications for erectile dysfunction (ED). Millions of counterfeit PDE5is are seized yearly and account for the bulk of all counterfeit pharmaceutical product seizures. It has been estimated that up to 2.5 million men in Europe are exposed to illicit sildenafil, suggesting that there may be as many illegal as legal users of sildenafil. Analysis of the contents of counterfeit PDE5is shows inconsistent doses of active pharmaceutical ingredients (from 0% to > 200% of labelled dose), contaminants (including talcum powder, commercial paint and printer ink) and alternative ingredients that are potentially hazardous. In one analysis, only 10.1% of samples were within 10% of the labelled tablet strength. Estimates place the proportion of counterfeit medications sold over the Internet from 44% to 90%. Of men who purchase prescription-only medication for ED without a prescription, 67% do so using the Internet. Counterfeit PDE5is pose direct and indirect risks to health, including circumvention of the healthcare system. More than 30% of men reported no healthcare interaction when purchasing ED medications. Because > 65% actually had ED, these men missed an opportunity for evaluation of comorbidities (e.g. diabetes and hypertension). Globally, increased obstacles for counterfeiters are necessary to combat pharmaceutical counterfeiting, including fines and penalties. The worldwide nature of the counterfeit problem requires proper coordination between countries to ensure adequate enforcement. Locally, physicians who treat ED need to inform patients of the dangers of ordering PDE5is via the Internet.

Introduction Sildenafil citrate 50 mg is the recommended starting dose for men with erectile dysfunction (ED); however, most men are later titrated to sildenafil 100 mg for improved efficacy. Aim Assess the tolerability and efficacy of sildenafil initiated at the 100-mg dose in men with ED. Methods Men with ED (score Main outcome measures Efficacy, tolerability, treatment satisfaction, and other end points were measured at baseline and/or the end of the double-blind and open-label phases and compared between placebo and sildenafil initiated at doses of 50 and 100 mg. Results Improvements in DBPC patient-reported outcomes from baseline were statistically significant for both sildenafil 50 and 100 mg compared with placebo. At the end of DBPC treatment, 56% of men on the 100-mg dose felt no anxiety about the next intercourse attempt compared with 39% in the 50-mg group (odds ratio 2.03; P = 0.0197). Changes in functional scores from baseline were not statistically significant with the 100-mg dose compared with the 50-mg dose in the DBPC. Measures of treatment satisfaction and sexual experience significantly favored the 100-mg dose compared with the 50-mg dose in the DBPC. There was no increase in adverse events with the higher dose. Conclusions Sildenafil at 50 mg or 100 mg significantly improved erection quality, treatment satisfaction, anxiety levels, and the sexual experience compared with placebo during DBPC. Sildenafil 100 mg improved the sexual experience and treatment satisfaction, and reduced feelings of anxiety compared with the 50-mg dose.

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

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

The Sexual Experience Questionnaire (SEX-Q) enables quick and easy assessment of functional, emotional, and satisfaction-related aspects of the sexual experience in men with erectile dysfunction (ED).To assess correlations between improvement on the SEX-Q and outcomes on other validated questionnaires. METHODS. Men with ED (scoreor =25 on the Erectile Function domain of the International Index of Erectile Function [IIEF]) who had used less than or equal to six doses of any phosphodiesterase 5 inhibitor (none within 6 months) were randomized to 10 weeks of double-blind, placebo-controlled (DBPC) flexible-dose sildenafil citrate (50 or 100 mg, as needed), followed by 6 weeks of open-label (OL) sildenafil.SEX-Q, IIEF, Quality of Erection Questionnaire (QEQ), Self-Esteem and Relationship (SEAR) Questionnaire, Erection Hardness Score (EHS), successful intercourse attempts (SIAs), Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), and global efficacy questions (GEQs).Compared with the placebo group (N = 105), the sildenafil group (N = 104) at DBPC end of treatment (EOT) had significantly more improvement (P0.05) on all SEX-Q, IIEF (except the Sexual Desire domain), QEQ, and SEAR outcomes, more frequent SIAs and EHS 3 (hard enough for penetration but not completely hard) or EHS 4 (completely hard) erections (odds ratio [OR], 2.52 and 3.46, respectively), EHS 4 erections four times as often (OR, 6.41), more men satisfied with treatment (EDITS; OR, 2.6), approximately twice as many men with improved erections (GEQ1; OR, 5.8) and ability to have sexual intercourse (GEQ2; OR, 5.4), and GEQ3 scores that indicated better sex (P0.0001). SEX-Q score improvements correlated positively with all other outcomes. At OL EOT, most outcomes were60% (and approximately half wereor =80%) of the maximum positive result.SEX-Q change scores correlate with several other functional, emotional, and satisfaction-related outcomes in men treated with sildenafil for ED, allowing a simple and focused evaluation of the sexual experience.

Erectile dysfunction (ED) negatively impacts self-esteem and relationship satisfaction. The Self-Esteem and Relationship (SEAR) questionnaire is a validated, ED-specific, patient-reported instrument that specifically addresses self-esteem and relationship issues within the context of ED. Effective ED treatment with sildenafil in a double-blind, placebo-controlled clinical trial conducted in Brazil, Mexico, Australia and Japan showed pooled cross-cultural improvements in self-esteem, confidence and relationship satisfaction. This report focuses on the results from the subgroup of men from nine Mexican centers who participated in the multinational study. A total of 95 men agedor=18 years with clinically diagnosed ED and currently in a stable relationship were randomized to placebo (n=47) or sildenafil (n=48). The SEAR results for Mexican men showed that sildenafil treatment led to significant improvements in self-esteem, confidence and relationship satisfaction. These data support an earlier study showing that Latin American men taking sildenafil have similar safety and efficacy profiles compared to non-Latin counterparts.

To estimate the minimal clinically meaningful improvement (MCMI) on the Self-Esteem And Relationship (SEAR) questionnaire. Using combined data from the 2 pivotal SEAR trials of men treated with sildenafil for erectile dysfunction (ED), MCMIs were estimated as the lower limit of the 2-sided 95% confidence intervals of SEAR mean change scores (from baseline to end of study) for 2 anchor groups: (1) men who improved 1 ED severity category on the Erectile Function domain of the International Index of Erectile Function, and (2) men who improved 5–60% (inclusive) on these erectile function scores. Both anchors gave comparable results. A 10-point MCMI was proposed because the estimates of 95% lower bounds centered on around 10 points for most SEAR components (Sexual Relationship, Confidence, Self-Esteem, Overall Score). An exception was the Overall Relationship whose 95% lower bounds were too low to recommend them as an MCMI. Two anchor-based approaches suggest that a change of about 10 points represents an MCMI on most components of the SEAR questionnaire.

Introduction There are no psychometrically validated assessment tools designed to solely and specifically evaluate satisfaction with the quality of erections. Aim To develop and psychometrically analyze the Quality of Erection Questionnaire (QEQ), a new patient-reported measure developed to evaluate men’s satisfaction with the quality of their erections. Methods The questionnaire was developed through in-depth qualitative interviews of men with erectile dysfunction (ED) in the United States and Australia. An exploratory methodology study was conducted on 65 men with ED. Subsequently, the psychometric properties were confirmed in a larger dataset of 558 men with ED from two combined clinical trials. Main Outcome Measures Identification of potential redundancy or outliers in items (Pearson inter-item correlations); exploratory factor analysis (unrotated and varimax rotated); internal consistency (Cronbach’s alpha); convergent validity (Pearson correlation coefficients between the QEQ total score and domain scores of the International Index of Erectile Function); known-groups validity (ability of the QEQ scores to differentiate between ED severity groups); test–retest reliability (Pearson correlation coefficient). Results The QEQ demonstrated excellent convergent and known-groups validity. Additional analysis demonstrated high internal consistency (Cronbach’s alpha, 0.92). Item analysis demonstrated a unidimensional structure and suggested that satisfaction with hardness may be the key driver for satisfaction with overall quality of erections ( r = 0.8). The smaller exploratory study demonstrated good test–retest reliability ( r = 0.82). Conclusions The QEQ is a six-item, patient-reported measure with a unidimensional structure, which produces a total score that may be transformed to a 0–100 scale. Psychometric analysis confirmed reliability and validity of the QEQ, which solely and specifically evaluates satisfaction of men with the quality of their erections. The QEQ is a potentially useful measure for monitoring and evaluating treatment in those who are bothered by, or concerned about, their erectile function. Porst H, Gilbert C, Collins S, Huang X, Symonds T, Stecher V, and Hvidsten K. Development and validation of the Quality of Erection Questionnaire.

Introduction The validated Quality of Erection Questionnaire (QEQ) is a six-question, patient-reported outcome measure for comprehensively evaluating satisfaction with the quality of erections in terms of hardness, onset, and duration, which can be used to develop and monitor individualized treatment goals. Aims To further validate the QEQ by determining responsiveness/sensitivity to change in erectile function, erection hardness grade, and psychosocial outcomes in men treated with sildenafil for erectile dysfunction (ED). Methods This open-label, noncomparative, multicenter trial of sildenafil (50 or 100 mg as needed for 10 weeks) enrolled men with ED who were in a stable, sexual relationship for at least 6 months. Previous phosphodiesterase type 5 inhibitor use must have been no more than 6 doses ever and no doses more recently than the previous 4 weeks. Main Outcome Measures The baseline to week 10 change in the QEQ total score and its correlations with the end-of-treatment Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) score and with changes in: (i) International Index of Erectile Function (IIEF) domain scores; (ii) Self-Esteem And Relationship (SEAR) questionnaire component scores; and (iii) the frequency of erections graded hard enough for penetration (grade 3) or completely hard (grade 4) on the event log Erectile Hardness Grading Scale. Results The mean ± standard deviation transformed QEQ total score tripled from 22.0 ± 21.1 to 69.9 ± 35.9 ( P r = 0.71) and with changes in IIEF domain scores ( r = 0.29–0.86), SEAR component scores ( r = 0.37–0.78), and the percentage of occasions that grade 3 or 4 erections were achieved ( r = 0.66). Conclusions The brief, easy-to-administer QEQ is responsive to the benefits of sildenafil treatment of men for ED and has convergent validity with measures of clinical and psychosocial outcomes. Lowy M, Collins S, Bloch M, Gillman M, Lording D, Sutherland P, Wang H, and Stecher V. Quality of Erection Questionnaire correlates: Change in erection quality with erectile function, hardness, and psychosocial measures in men treated with sildenafil for erectile dysfunction. J Sex Med 2007;4:83–92.

Introduction Sildenafil, an oral phosphodiesterase type 5 inhibitor, has been extensively investigated for the treatment of erectile dysfunction in randomized controlled trials. Aim To assess the efficacy and safety of sildenafil vs placebo according to age subgroups ( Methods Most trials had a 12-week treatment duration. The starting sildenafil dose was 50 mg, taken 1 hour before sexual activity, with subsequent adjustment to 100 or 25 mg based on efficacy and safety. Men taking nitrate therapy or nitric oxide donors and men with severe cardiac failure, unstable angina, or recent stroke or myocardial infarction were excluded. Efficacy analyses included all subjects with baseline and at least one postrandomization evaluation. Safety analyses included subjects who received study medication. Main Outcome Measures The International Index of Erectile Function and a global assessment question (“Did the treatment improve your erections?”). Results Mean International Index of Erectile Function scores for question 3 (frequency of penetration), question 4 (maintenance of erections after penetration), and the erectile function domain were statistically significantly improved with sildenafil vs placebo for each age subgroup; orgasmic function, intercourse satisfaction, sexual desire, and overall satisfaction domain scores also were statistically significantly improved with sildenafil vs placebo. The percentage of men reporting improved erections on the global assessment question was statistically significantly higher with sildenafil vs placebo for all age subgroups; the percentage with sildenafil tended to decrease with increasing age ( Conclusion Sildenafil is an effective and well-tolerated treatment for erectile dysfunction regardless of patient age, including men at least 75 years old.

The quality of life consequences of erectile dysfunction (ED) include depression, anxiety, and loss of self-esteem. The Self-Esteem And Relationship (SEAR) questionnaire is a validated, patient-administered, psychometric instrument specific to ED.To determine correlations between erectile function (EF), intercourse success, and emotional well-being measured with the SEAR questionnaire in men treated with sildenafil citrate for ED and stratified by age (50 years, 50-65 years, and65 years).This was an open-label, flexible-dose trial of sildenafil (25, 50 and 100 mg) administered for 10 weeks to 382 men with ED (mean +/- SD age, 55 +/- 13 years; mean ED duration, 4 years), which was conducted at 62 centers in the United States.Analysis (by intent-to-treat, n = 368) of the change from baseline to the week-10 endpoint in the SEAR questionnaire Self-Esteem subscale, the intercourse success rate (percent of occasions at which an erection that lasted long enough for successful intercourse was achieved), and their correlation.For the overall population, there was mean +/- SD improvement (p0.0001, paired t-tests) in the Self-Esteem subscale (56 +/- 25 to 79 +/- 22) and intercourse success rate (21 +/- 30% to 70 +/- 36%), which showed positive correlation (p0.0001). Secondary outcomes (i.e., EF domain of the International Index of Erectile Function; event log frequency of erection hard enough for sexual intercourse and of ejaculation/orgasm) also improved (p0.0001) and correlated positively with the SEAR Self-Esteem subscale and Sexual Relationship domain (p0.05 for all correlations). All 10 correlations were positive (p0.05) in men aged 50 to 65 years, eight were positive in men aged65 years, and six were positive in men aged50 years. The most common treatment-related adverse events were mild-to-moderate headache (12% of patients), vasodilatation (7%), and rhinitis (4%).Men treated with sildenafil for ED demonstrated improved erectile function and an increased intercourse success rate, which correlated positively with improvement in SEAR measures of self-esteem and sexual relationship.

Objective: To evaluate the efficacy of short-term treatment with sildenafil citrate in men with serotonin reuptake inhibitor (SRI)-associated erectile dysfunction (ED). Method: Men (aged ≥ 18 years) with major depressive disorder (MDD; DSM-IV criteria) in remission and taking SRIs who experienced SRI-associated ED were enrolled in this multicenter, 6-week, randomized, flexible-dose, double-blind, placebo-controlled trial. The primary study measures were questions 3 (Q3: frequency of penetration) and 4 (Q4: frequency of maintained erections after penetration) of the International Index of Erectile Function (IIEF) questionnaire. Secondary study measures were all other questions and domains of the IIEF, the Erectile Dysfunction Index of Treatment Satisfaction (EDITS), a global efficacy questionnaire (GEQ), and a patient-maintained event log of sexual activity. Results: Patients receiving sildenafil (N =71) versus placebo (N = 71) reported significantly higher mean ± SE scores on Q3 (3.9 ± 0.2 vs. 3.1 ± 0.2, p =.003) and Q4 (3.7 ± 0.2 vs. 2.8 ± 0.2, p

Objectives Research is lacking on the correlation between treatment satisfaction and confidence, self-esteem, and relationships for men receiving treatment for erectile dysfunction (ED). We sought to correlate scores between the validated Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) index and the validated Self-Esteem And Relationship (SEAR) questionnaire following treatment with sildenafil citrate (VIAGRA). Methods This study was based on an open-label, flexible-dose trial of 93 sildenafil-naive patients with ED. Pearson correlation coefficients between EDITS index and SEAR questionnaire scores, each of which can range from 0 to 100 (most favorable), were calculated at end of treatment (EOT). An analysis of covariance model was applied to associate changes from baseline to EOT in SEAR scores with EDITS score at EOT, controlling for baseline SEAR score. Results Significant and sizable Pearson's correlations between SEAR and EDITS scores ( P ≤ 0.0001; range: 0.49–0.84) were observed. A 10-point higher EDITS scores at EOT corresponded to a significant and tangible average improvement in SEAR scores from baseline to EOT ( P ≤ 0.0001; range: 6.6–8.7). Average SEAR scores at EOT were markedly different between patients with greater treatment satisfaction at EOT (EDITS score ≥ median EDITS score of 88.6; n = 50) and those with lesser treatment satisfaction at EOT (EDITS score Conclusions The data add to the validity of the SEAR questionnaire, suggest a tangible relationship between treatment satisfaction and psychosocial benefit among men with ED treated with sildenafil, and highlight the importance of assessing the psychosocial impact of ED in men undergoing treatment.

Objectives To determine the treatment responsiveness of the disease-specific Self-Esteem And Relationship (SEAR) questionnaire in erectile dysfunction. Methods The SEAR questionnaire was administered at baseline and at the end of the study in 93 patients with erectile dysfunction enrolled in a 10-week, open-label, flexible-dose (50-mg sildenafil, adjustable to 25 mg or 100 mg) trial. Changes from the baseline score were analyzed using the paired t test. The correlation between the changes from baseline on the SEAR questionnaire and the Erectile Function domain of the International Index of Erectile Function was examined. Results Significant and meaningful differences ( P = 0.0001) from baseline were observed in the two primary domains (Sexual Relationship and Confidence) and the two Confidence domain subscales (Self-Esteem and Overall Relationship). The magnitude of the change was quite high for most aspects (Sexual Relationship, effect size [ES] = 1.6; Confidence, ES=1.0; Self-Esteem, ES=1.1) and moderate for one (Overall Relationship, ES=0.6). Changes in Erectile Function domain score correlated moderately with changes in the SEAR domain and subscale scores (Sexual Relationship, r = 0.69; Confidence, r = 0.48; Self-Esteem, r = 0.47; and Overall Relationship, r = 0.35; P ≤0.001). Conclusions The SEAR questionnaire is responsive to effective treatment of erectile dysfunction. These data suggest that the SEAR questionnaire is a valid instrument for detecting psychosocial gains from beneficial intervention.

SummaryAims The aim of this study was to assess erection quality with sildenafil vs placebo and adverse events (AEs) according to age (≤45, 46-55 and ≥56 years) in 997 men with erectile dysfunction (ED) using pooled data from four randomized, double-blind, placebo-controlled, flexible-dose trials. Methods The trials included 6- to 10-week treatment periods. The starting sildenafil dose was 50 mg, taken ~1 hour before sexual activity but not more than once daily, with subsequent adjustment to 100 or 25 mg based on efficacy and safety. Exclusion criteria included blood pressure 170/110 mmHg, taking nitrate therapy or nitric oxide donors, severe cardiac failure/unstable angina or recent stroke or myocardial infarction. Changes from baseline in Quality of Erection Questionnaire (QEQ), International Index of Erectile Function (IIEF) and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) scores were analysed. Results Improvements in QEQ scores with sildenafil vs placebo were significant (P

Introduction Sildenafil has been evaluated in >16 000 men with erectile dysfunction (ED) in double-blind, placebo-controlled trials. Aim To assess efficacy and safety of sildenafil in ED by ethnicity (white, black Asian) and age (≤45, 46-60, ≥61 years). Methods Data were pooled from 38 double-blind, placebo-controlled, flexible-dose trials. Most had starting sildenafil doses of 50 mg once daily, ~1 hour before sexual activity, with adjustment to 100 or 25 mg as needed. Main Outcome Measures Change from baseline in International Index of Erectile Function erectile function (IIEF-EF) domain score assessed with analysis of covariance and a Global Assessment Question (GAQ; “Did the treatment improve your erections?”) at endpoint assessed with logistic regression analysis. Results 4120 and 3714 men received sildenafil and placebo, respectively (2740 and 2671 White; 407 and 385 Black; 973 and 658 Asian). For sildenafil vs. placebo groups, overall treatment differences for IIEF-EF domain and GAQ were significant for each ethnic and age group (P

To assess the efficacy and safety of Viagra (sildenafil citrate) in male outpatients with erectile dysfunction and patient and partner satisfaction with treatment using the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS).A total of 247 patients with erectile dysfunction of broad-spectrum etiology were treated in a randomized, double-blind, parallel-group, multicenter study conducted at outpatient clinics. Patients receiving oral sildenafil (25, 50, and 100 mg) were compared with patients receiving placebo during a 12-week period. The principal efficacy measures were responses to question 3 (ability to achieve an erection) and question 4 (ability to maintain an erection) on the International Index of Erectile Function and three global efficacy questions. Patient and partner satisfaction with treatment were assessed, for the first time, using the EDITS questionnaire.Efficacy scores for the International Index of Erectile Function questions and the global efficacy questions were significantly higher for patients receiving sildenafil than for those receiving placebo (P0.001). Both patients and partners receiving sildenafil also had significantly higher EDITS scores than those receiving placebo (P0.001). Adverse events were chiefly mild or moderate. Two patients receiving sildenafil and none receiving placebo discontinued treatment because of adverse events.Sildenafil was an effective, well-tolerated treatment for erectile dysfunction in an outpatient setting. Partner evaluations corroborated patient assessments. The results from the EDITS questionnaire indicated that after 12 weeks of receiving sildenafil both patients and partners reported higher levels of treatment satisfaction relative to placebo.

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. Campbell N, Clark JP, Stecher VJ, Thomas JW, Callanan AC, Donnelly BF, Goldstein I, and Kaminetsky JC. Adulteration of purported herbal and natural sexual performance enhancement dietary supplements with synthetic phosphodiesterase type 5 inhibitors.

We have previously described the inhibition of human immunodeficiency virus serotype 1 (HIV-1) using the antimalarial hydroxychloroquine (HCQ), a weak base that inhibits the posttranslational modification of glycoprotein 120 (gp 120) in T cells and monocytes. The mechanism of inhibition of gp 120 production was presumed to be the ability of HCQ to increase endosomal pH and therefore alter enzymes required for gp120 production. To further clarify this action, we have determined the effect of HCQ and its enantiomers on endosomal pH. Pretreatment of cells with HCQ and the levo- and dextro-enantiomers at concentrations demonstrated to suppress anti-HIV-1 activity increased endosomal pH to levels similar to increases seen with chloroquine and ammonium chloride, two other weak bases, and decreased gp 120 production. The dextro- and levo-enantiomers suppressed HIV-1 replication to a similar extent and were no more toxic than racemic HCQ. We next compared the anti-HIV-1 effect of HCQ with zidovudine (ZDV) in both newly and chronically HIV-1-infected T-cell and monocytic cell lines (63 and 63HIV). HCQ suppressed HIV-1 replication in a dose-dependent manner in both recently and chronically infected T-cell and monocytic cell lines. In contrast, ZDV pretreatment had potent anti-HIV-1 activity in the newly infected T and monocytic cells but not in chronically infected cells. An additive effect of HCQ with ZDV was observed in the newly infected T and monocytic cells but not in the chronically infected cells. Although the anti-HIV-1 effect of HCQ was less than that of ZDV, HCQ may still be potentially useful either as an alternative HIV-1 treatment or in combination with other anti-HIV-1 agents, especially in patients who have rheumatic manifestations of HIV-1 infection.

Hydroxychloroquine (HCQ), an antimalarial agent used to treat patients with autoimmune diseases, has been shown to suppress human immunodeficiency virus type 1 (HIV-1) replication in vitro in T cells and monocytes by inhibiting posttranscriptional modification of the virus. These in vitro observations have been expanded into an in vivo study of HCQ as a potential anti-HIV-1 agent in HIV-1-infected patients. A randomized, double-blind, placebo-controlled clinical trial was conducted in 40 asymptomatic HIV-1-infected patients who had CD4+ counts between 200 and 500 cells/mm3. Patients were randomly assigned to receive either HCQ 800 mg/d or placebo for 8 weeks. Virologic and immunologic parameters, including HIV-1 ribonucleic acid (RNA) via use of polymerase chain reaction, viral culture, antigen and mitogen responses, and proinflammatory cytokine levels were measured at the beginning and end of the study. The amount of recoverable HIV-1 RNA in plasma declined significantly in the HCQ group over the 8-week period (P = 0.022), while it increased in the placebo group. The percentage of CD4+ T cells remained stable in the HCQ-treated group (18.1 +/- 9.2% before treatment vs 18.6 +/- 10.5% after treatment) and fell significantly in the placebo group (21 +/- 7% before treatment vs 19.3 +/- 6.3% after treatment; P = 0.032). However, this was not reflected as a change in absolute CD4+ counts for either group (HCQ, 262.8 +/- 166 cells/mm3 vs 251 +/- 163 cells/mm3; placebo, 312 +/- 121 cells/mm3 vs 321 +/- 124 cells/mm3). Mitogen- and antigen-specific responses remained constant in the HCQ group while T cell proliferative responses to Candida decreased in the placebo group (4.8 +/- 3.6 x 10(3) SI [stimulation index] vs 3.0 +/- 3.0 x 10(3) SI; P = 0.032). Lastly, serum interleukin 6 levels declined in the HCQ group (14.3 +/- 13.5 U/mL vs 12.0 +/- 16.7 U/mL; P = 0.023) but not in the placebo group (11.3 +/- 8.8 U/mL vs 7.0 +/- 11.7 U/mL); this was coincident with a decrease in serum immunoglobulin (Ig)G (2563 +/- 1352 mg/mL vs 2307 +/- 1372 mg/dL; P = 0.032), compared with the placebo group (2733 +/- 1473 mg/dL vs 2709 +/- 1501 mg/dL). No other parameters, including serum p24 and beta-2 microglobulin levels, were altered by HCQ therapy. HCQ thus may be useful in the treatment of patients with HIV-1 infection.

available at http://jurology.com/ Editorial Comment: Men with comorbid erectile dysfunction (ED) and premature ejaculation (PE) may be given a phosphodiesterase type 5 (PDE5) inhibitor as first-line treatment. This study eval- uated the efficacy and safety of 30mg and 60mg dapoxetine on demand as add-on therapy in men with PE and ED who were being treated with PDE5 inhibitors for the ED. Of 495 subjects randomized 429 completed the study. Arithmetic mean average intravaginal ejaculatory latency time significantly increased with dapoxetine vs placebo at end point. The incidence of treatment emergent adverse events (TEAEs) was 20.0% and 29.6% in placebo and dapoxetine treated subjects, respectively (p¼0.0135). TEAEs led to discontinuation in 1.6% of subjects in both groups. The most frequent TEAEs were known adverse drug reactions of dapoxetine treatment, including nausea (9.2% of patients), headache (4.4%), diarrhea (3.6%), dizziness (2.4%) and postural dizziness (2.4%). In men with PE and comorbid ED on a stable regimen of PDE5 inhibitors dapoxetine provided meaningful treatment benefit and was generally well tolerated. Dapoxitene is not approved for use in the United States. It is unclear if the same level of efficacy would be seen with selective serotonin reuptake inhibitors or similar off-label use agents to treat premature ejaculation. Abstract available at http://jurology.com/ Editorial Comment: The data from this pooled analysis of 5 studies demonstrate that during the first 2 weeks of treatment 100 mg sildenafil is more likely to achieve a greater improvement in erectile function than the 50 mg dose. This finding suggests that the patient should be moved to the 100 mg dose of sildenafil early in treatment if 50 mg does not produce the desired improvement in erectile function. Abstract available at http://jurology.com/ Editorial Comment: These data highlight the benefits of restoration of male erectile function for the patient and his partner. In this report penile prosthesis implantation was successful and produced a high level of patient satisfaction for the implanted male and partner. Importantly there were no statistically significant differences according to level of education or implant characteristics. Thus, when considering penile prosthesis surgery, many positive downstream sexual satisfaction benefits can be discussed with the patient that may help in the decision process.

Introduction Counterfeit medication is a growing problem. This study assessed the requirement for prescription, cost, origin, and content of medications sold via the Internet and purporting to be the phosphodiesterase type 5 inhibitor Viagra (sildenafil citrate). Methods Pfizer monitored top search results for the query “buy Viagra” on the two leading Internet search engines in March 2011. Orders were placed from 22 unique Web sites claiming to sell Viagra manufactured by Pfizer. Tablets received were assessed for chemical composition. Results No Web site examined required a prescription for purchase or a health screening survey; 90% offered illegal “generic Viagra.” Cost per tablet ranged from $3.28–$33.00. Shipment origins of purchases were Hong Kong (N = 11), the United States (N = 6), and the United Kingdom (N = 2) as well as Canada, China, and India (N = 1 each). Notably, the four Internet pharmacies claiming to be Canadian did not ship medication from a Canadian address. Of 22 sample tablets examined, 17 (77%) were counterfeit, 4 (18%) were authentic, and 1 (5%) was an illegal generic. Counterfeit tablets were analyzed for sildenafil citrate, the active pharmaceutical ingredient (API) of Viagra, and contents varied between 30% and 50% of the label claim. Counterfeits lacked product information leaflets, including appropriate safety warnings, and genuine Viagra formulations. Conclusion Internet sites claiming to sell authentic Viagra shipped counterfeit medication 77% of the time; counterfeits usually came from non‐U.S. addresses and had 30% to 50% of the labeled API claim. Caution is warranted when purchasing Viagra via the Internet. Campbell N, Clark JP, Stecher VJ, and Goldstein I. Internet‐ordered Viagra (sildenafil citrate) is rarely genuine. J Sex Med 2012;9:2943–2951.

The effects of phosphodiesterase type 5 inhibitors on vasodilation mediated via nitric oxide-cyclic guanosine monophosphate are well described. Less is known about other mechanisms through which phosphodiesterase type 5 inhibitors benefit endothelial function, including normalization of serum biomarkers, increased levels of endothelial progenitor cells, ischemia-reperfusion protection mechanisms, and other actions specific to patients with diabetes. These various mechanisms are reviewed. Their impact on several cardiovascular diseases, including erectile dysfunction, pulmonary hypertension, heart failure, high-altitude pulmonary edema, Raynaud's phenomenon, coronary artery disease, diabetes, and atherosclerosis, is presented.

At the present time, inhibitors of phosphodiesterase type 5 (PDE5) have Food and Drug Administration approval only for the treatment of erectile dysfunction and pulmonary artery hypertension, for which their mechanism of action is vasodilation and augmentation of blood flow by impeding PDE5-mediated breakdown of cyclic guanosine monophosphate. However, these agents are also being investigated in a wide range of other potential medical and surgical applications for which current treatment options are limited and in which their mechanism of action may be the same as or different from their effects in the two approved indications. Even if only some of these potential applications prove useful, the effect on clinical practice could be far reaching.This literature review summarizes potential noncardiovascular uses of PDE5 inhibitors, with emphasis on clinical research. Topics include a variety of male genitourinary disorders other than erectile dysfunction: cutaneous ulcerations, tissue protection, neurological conditions, diabetes, cancer, transplant and reconstructive surgery, female sexual dysfunction and disorders of pregnancy.The exceptionally wide range of research taking place with PDE5 inhibitors holds promise not only for improved therapeutic options but also for an improved understanding of the basic biological mechanisms that underlie scientific medicine.