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Introduction Men may choose to bypass the healthcare system to obtain a phosphodiesterase type 5 inhibitor (PDE5i). Aim Evaluate the characteristics and purchasing patterns of men obtaining a PDE5i without prior healthcare professional (HCP) interaction. Main Outcome Measures Prior HCP interaction, defined as having a prescription for any PDE5i, having a PDE5i sample from a physician, or buying the PDE5i in a retail pharmacy; and erectile dysfunction (ED, the Massachusetts Male Aging Study single-item question) were assessed. A multivariate regression analysis determined predictive factors for PDE5i purchase without prior HCP interaction. Methods A Web-based observational study was conducted in the United Kingdom, Germany, and Italy. Results Of the 11,899 participants, 1,252 (10.5% [95% CI, 10.0–11.1%]) reported PDE5i use in the last 6 months. PDE5is were obtained without prior HCP interaction by 403 users (32.3% [95% CI, 29.6–34.8%]); 65.5% of them had ED. Overall prevalence of men using PDE5is without HCP interaction was 3.0% (95% CI, 2.6–3.5%), 4.1% (95% CI, 3.5–4.6%), and 2.8% (95% CI, 2.1–3.5%) for men aged 18–34, 35–50, and >50 years, respectively (P = 0.0045). Predictive factors for obtaining a PDE5i without prior HCP interaction were embarrassment to speak to a physician (P = 0.0009) and the perception that this would be the cheapest way to get the medicine (P = 0.03). Conclusions Based on these findings, it can be estimated that approximately 6 million men in Europe might currently bypass the healthcare system to obtain a PDE5i. In addition to the risks associated with use of PDE5is from uncontrolled sources, because most of these men have ED, they also miss the opportunity for important health information or medical follow-up. HCPs should actively address ED and offer treatment to discourage men from seeking uncontrolled sources of ED medicines.

Introduction Erectile dysfunction (ED) has been associated with several comorbidities and can cause significant loss of quality of life and self-esteem. Aim In men with ED, to use the validated Self-Esteem and Relationship (SEAR) questionnaire to evaluate changes in self-esteem associated with sildenafil treatment of ED and to assess changes dependent on concomitant comorbid conditions. Methods This was a 14-week, international, randomized, parallel-group, double-blind, flexible-dose (25, 50, or 100 mg), placebo-controlled study of sildenafil in men aged ≥18 years with a clinical diagnosis of ED (score ≤ 21 on the Sexual Health Inventory for Men). Main Outcome Measures The primary outcome was the change in the SEAR Self-Esteem subscale score from baseline to the end of treatment. Secondary outcomes were the change in SEAR component scores stratified by ED comorbidity, the change in the International Index of Erectile Function (IIEF) domain scores and in the intercourse success rate, and the response to the global efficacy assessment and to the global satisfaction assessment. Results A total of 841 patients were included in the intent-to-treat efficacy analysis (559 sildenafil, 282 placebo). Patients randomized to sildenafil had significantly greater change scores from baseline to the end of treatment on all components of the SEAR and all domains of the IIEF (P < 0.0001) compared with placebo. This finding was also consistent for all SEAR components when stratified by each ED comorbidity. In the sildenafil group, the improvement in the mean Self-Esteem subscale score correlated with improvements in the mean Erectile Function domain score (r = 0.6338, P < 0.0001). Conclusions The physiologic and emotional benefits of sildenafil in the treatment of ED were confirmed, overall and in men with comorbid hypertension, hyperlipidemia, benign prostatic hypertrophy, and/or depression. Using both the IIEF and the SEAR questionnaires provides a more complete assessment of ED.

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Introduction In a previous paper using mediation modeling, the direct and indirect effects of sildenafil on erection maintenance were demonstrated. Objective In an extension of this previous work, the historical psychosocial paradigm of ED, which focuses on performance anxiety, is tested by using mediation modeling to define the relationship of the physiological aspects (hardness and maintenance) and the associated psychosocial aspects (confidence, sexual relationship satisfaction, and performance anxiety) of ED. Methods Statistical mediation analysis using the following outcomes from a double-blind placebo-controlled trial of fixed-dose sildenafil 100 mg or 50 mg: Erection Hardness Score; the 15-item International Index of Erectile Function (IIEF), including item 4 (frequency of erection maintenance after penetration) and item 5 (difficulty of erection maintenance to intercourse completion); the Self-Esteem And Relationship questionnaire; and the question, “Do you feel anxious about your next attempt at sexual intercourse?” Main Outcome Measures Estimated percentages of direct and indirect effects of sildenafil on psychosocial aspects of ED (95% confidence intervals). Results The model estimated that erection hardness mediated 43.7% (29.3%, 62.4%) of the effect of treatment onto confidence and 45.9% (32.2%, 61.8%) of the effect of treatment onto sexual relationship satisfaction, and that erection maintenance (using IIEF item 4 as a proxy) mediated 23.0% (10.1%, 39.1%) and 22.4% (10.1%, 36.5%), respectively. Similar results were obtained when IIEF item 5 was used as the proxy for measurement of maintenance. Of all possible paths to performance anxiety, only that from treatment via confidence was statistically significant, mediating an estimated 88.6% (55.5%, 146.2%; item 4 model) or 74.9% (47.0%, 121.0%; item 5 model) of the effect of treatment onto anxiety. The direct path to anxiety from treatment was not statistically significant. Conclusions In men treated with sildenafil for ED, performance anxiety might be ameliorated by improved confidence. Improved confidence might be mainly mediated via increased erection hardness.

Death receptors play an important role in controlling cell numbers and immune responses. In contrast to TNF receptors, little is known about non‐apoptosis functions of the Fas receptor (CD95, APO‐1). Here we demonstrate that Fas receptor engagement results in the induction of the IL‐10 gene in monocytes, but not in lymphocytes or dendritic cells. In contrast, TNF‐α stimulated IL‐10 production in dendritic cells but not monocytes. Fas receptor‐mediated transcriptional activation of the IL‐10 gene was followed by the release of large amounts of the cytokine in cell cultures and occurred in the absence of apoptosis induction. Since caspase activation did not occur in monocytes following Fas receptor engagement, it is unlikely that caspases are involved in IL‐10 gene activation. Monocyte‐derived IL‐10 suppressed T cell proliferation induced by anti‐CD3 monoclonal antibody without affecting CD3‐mediated transmembrane signal transduction. In conclusion, we report about a novel pathway initiated via the Fas receptor leading to transcriptional activation of at least one cytokine gene. Fas ligand‐induced IL‐10 production in monocytes might represent an important anti‐inflammatory mechanism in secondary immune responses.

Summary Aim:  To determine the rate of newly detected underlying disease in men receiving their first (index) phosphodiesterase type 5 inhibitor (PDE5i) prescription. Methods:  This non‐interventional, retrospective study used anonymised patient records from UK general practices identified from the THIN database. Records of men aged ≥ 18 years, who received an index PDE5i prescription between January 1999 and June 2008 and with a continuous medical history (≥ 60 months) before the index prescription were included. Primary end‐points were the prevalence of underlying disease prior to the index prescription and to establish the detection rate, defined as cumulative incidence of such a diagnosis in the 3 months following the index prescription. Assessments included comparison with age‐matched controls, comparison with identical time periods immediately before and 1 year after, index prescription, and changes over time during the study period. Descriptive statistics, analysis of proportions and multivariate logistic regression analysis were used. Results:  Among the 24,708 patients receiving a PDE5i, the prevalence of any underlying diagnosis before the index prescription was 70.23%; prevalence of vasculogenic disease was highest (48.20%). The detection rate of any underlying disease was 11.53%, and again highest for vasculogenic disease (4.07%). Compared with an age‐matched control population, the additional detection rate of an unknown underlying disease at PDE5i prescription was 45 for hypertension, 61 for hypercholesterolaemia, 38 for diabetes and 5 for hypogonadism per 10,000 men. Conclusion:  Only a minority of men with erectile dysfunction have a previously undiagnosed important underlying disease that is uncovered at the time of an initial PDE5i prescription by a GP.

Introduction Erectile dysfunction is a treatable condition that affects a large proportion of men. Most men do not seek medical help for their ED because of embarrassment or social stigma that may lead some men to self-treat. Aim To evaluate men’s ability to self-assess their suitability for 50 mg sildenafil use after reviewing patient information materials. Main Outcome Measures Patient rating of patient information materials, self-assessment of suitability for sildenafil use, and clinician assessment of sildenafil suitability. Methods Men in the UK were recruited through newspaper, radio, and internet advertisements. Eligible men reviewed the 50 mg sildenafil patient information materials (packaging materials and patient information leaflet) at the in-person visit and then completed a survey to rate the materials and self-assess their suitability for sildenafil use. A clinician, blinded to the participant’s ED status and self-assessed sildenafil suitability, then conducted a one-on-one interview to assess the participant’s ED status and suitability for sildenafil treatment. The primary analysis was the concordance of self-assessed suitability versus clinician-assessed suitability. Results The initial study phase included 113 generally healthy men, mean age 40.2 ± 13.1 years. The second phase included 70 men with comorbid prostate or cardiac conditions, mean age 60.7 ± 7.8 years. The 183 men rated the patient information materials as easy to understand; few participants reported problems understanding the materials, and many participants learned new information. The concordance rate between clinician-assessed suitability and self-assessed suitability was 73.9% (95% confidence interval [CI]=66.7–81.2%). When accounting for men who would not take sildenafil even though they were suitable or would seek additional information from a healthcare professional prior to using sildenafil, the concordance rate was 90.1% (95% CI=85.8–94.4%). Conclusion The results of this UK study suggest that men are capable of using written sildenafil patient education materials to accurately assess their suitability for treatment with 50 mg sildenafil.