Interrelationship of Sildenafil Treatment Effects on the Physiological and Psychosocial Aspects of Erectile Dysfunction of Mixed or Organic Etiology

Abstract

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.

Avanafil for the Treatment of Erectile Dysfunction: A Multicenter, Randomized, Double-Blind Study in Men With Diabetes Mellitus

“…Adverse events, such as priapism, visual disturbances, and hemodynamic change, which have been reported in studies of other PDE5 inhibitors, are thought to be related to the lack of stringent PDE5 specificity; although all of these agents are specific for the PDE5 isoenzyme, unintentional cross-reactivity may occur with other PDE isoenzymes, including inhibition of PDE6 and PDE11, which may lead to AEs. 20,[30][31][32][33][34] In this study, none of these types of events was reported, and there was only 1 report of blurred vision, supporting the high PDE5 specificity of avanafil.…”

Interpretation of patient-reported outcomes

“…These advanced, more complicated types of mediation models have also been used to more deeply understand PROs. 61,62 Other applications of mediation models with PROs can be found elsewhere. 63 Missing data are common for PRO data, especially when they are assessed over time, and are a separate issue from interpretation of PRO scores.…”

Effects of repeated dosing with Udenafil (Zydena) on cognition, somatization and erection in patients with erectile dysfunction: a pilot study

“…Hence, the results might have been influenced by several hidden clinical factors such as amelioration of anxiety or performance anxiety over the study period. 30 Based on an IIEF-5 cutoff score of 7 points, patients were divided into two groups, which were the responder and non-responder groups. There was a significant difference in the change in cognitive function between the two groups.…”