ORIGINAL RESEARCH—ED PHARMACOTHERAPYUnderstanding the Effects of Sildenafil Treatment on Erection Maintenance and Erection Hardness
Introduction
Erectile dysfunction (ED) is defined as “. . . the inability to attain and/or maintain penile erection sufficient for satisfactory sexual performance.”[1] Erection maintenance depends in part on the integrity of the veno-occlusive mechanism, and erection hardness depends in part on the cavernosal artery perfusion pressure. Therefore, in men with ED, the effect of treatment on erection maintenance should be closely related to the effect of treatment on erection hardness.
In the treatment of ED, erection hardness is a well-established clinical outcome 2, 3. The Erection Hardness Score (EHS) is a validated single-item patient-reported outcome (PRO) for assessing erection hardness (Table 1) [4]. It became and remains an integral part of the clinical trials program for sildenafil citrate (VIAGRA®, Pfizer Inc., New York, NY, USA). The degree of penile rigidity assessed with the EHS can be mapped to other PROs such as the International Index of Erectile Function (IIEF), the Quality of Erection Questionnaire, the Sexual Experience Questionnaire, and the Self-Esteem and Relationship Questionnaire [5]. However, the extent to which ED treatment affects erection maintenance directly vs. indirectly (via erection hardness), when both maintenance and hardness are determined by patient questionnaire data, has not been established. Thus, the main objective of this report is to explore, by means of statistical modeling, the interrelationships among effective treatment of ED (as the factor), erection hardness (as the mediator), and erection maintenance (as the outcome) in men with ED, to guide treatment goals toward optimizing erection maintenance and achieving successful sexual intercourse.
Section snippets
Dataset
The dataset, which was described previously [6], was derived from a multinational (Republic of Korea, Russian Federation, Spain, and Sweden), parallel-group, randomized (1:1:1), double-blind placebo-controlled (DBPC) trial of fixed-dose sildenafil (100 or 50 mg, 8 weeks) with open-label (OL) extension of flexible-dose sildenafil (50 and 100 mg, 4 weeks). Medication was taken as needed for sexual activity but not more than once daily. Institutional review board approval was obtained from all study
Results
The 288 men randomized to sildenafil 50 mg (N = 94), sildenafil 100 mg (N = 99), or placebo (N = 95) were similar in age (mean, 51 years; range, 20–65 years) and ethnicity (approximately two-thirds white and one-third Asian).
Discussion
Using IIEF items 4 or 5 as a proxy for erection maintenance, we estimated that roughly half of the total effect of sildenafil treatment on erection maintenance was direct and the other half was mediated via erection hardness, which shows that erection hardness plays a substantial and crucial role in improving erection maintenance. Mapping showed a strong, positive, linear relationship of the EHS with IIEF items 4 and 5, which allowed us to approximate the path from hardness to maintenance as
Category 1
- (a)
Conception and Design
Hubert I.M. Claes; Irwin Goldstein; Stanley E. Althof; Michael M. Berner; Joseph C. Cappelleri; Andrew G. Bushmakin; Tara Symonds; Gabriel Schnetzler
- (b)
Acquisition of Data
Joseph C. Cappelleri; Andrew G. Bushmakin; Tara Symonds; Gabriel Schnetzler
- (c)
Analysis and Interpretation of Data
Joseph C. Cappelleri; Andrew G. Bushmakin; Tara Symonds; Gabriel Schnetzler
Category 2
- (a)
Drafting the Article
Hubert I.M. Claes; Irwin Goldstein; Stanley E. Althof; Michael M. Berner; Joseph C. Cappelleri; Andrew G.
Acknowledgments
This study was sponsored by Pfizer Inc. Editorial support was provided by Deborah M. Compoli-Richards, BSPHA, RPh, of Complete Healthcare Communications, Inc., and was funded by Pfizer, Inc. ClinicalTrials.gov Identifier: NCT00245258.
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2014, Journal of Sexual MedicineCitation Excerpt :It has been formally validated in patients reporting all causes of ED and treated by phosphodiesterase type 5 inhibitors (PDE5), demonstrating satisfying psychometric properties and a good treatment responsiveness [17]. However, despite the apparent valuable properties provided by single‐items scales, concern has been raised with respect to the less comprehensive evaluation of ED severity in its various facets when compared with multidimensional tools such as the IIEF [9-18]. Second, because establishing the reliability and validity of a measurement instrument is of paramount importance, robustness of these psychometric properties should be confirmed when used in diversified contexts as well, so as to ensure the appropriateness and actual usefulness of a tool to clinical decision making in the field.
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2010, Journal of Sexual MedicineCitation Excerpt :Mean scores on all domains of the IIEF, on the QEQ, and on analog scales assessing erection firmness, ability to maintain erections, reliability of erection, and general sexual performance were >80% of the maximum possible; responses to event log questions on hardness sufficient for penetration, duration long enough for successful intercourse, and ejaculation/orgasm were positive on >80% of occasions; 77% of men had IIEF-EF scores indicating no ED; approximately 90% of men reported improved erections and improved ability to have sexual intercourse on the GEQs; and erections were completely hard and fully rigid on 60% of occasions. Achieving completely hard and fully rigid erections is an important clinical target in men with ED [31–33]. Sildenafil was well tolerated.
Interrelationship of Sildenafil Treatment Effects on the Physiological and Psychosocial Aspects of Erectile Dysfunction of Mixed or Organic Etiology
2010, Journal of Sexual MedicineCitation Excerpt :The impact of sildenafil on erectile function and erection hardness, and the resulting improvement in confidence, sexual relationship satisfaction, and the level of anxiety about the next intercourse attempt, were assessed in men with ED in a double-blind placebo-controlled (DBPC) trial of sildenafil at a fixed dose of 50 mg or 100 mg [4]. The effect of sildenafil on erection maintenance, indirectly (mediated through erection hardness) and directly, was previously estimated [5]. In follow up to the previous modeling of the relationships between the physiological aspects of the treatment of ED (i.e., hardness and maintenance), the main objective of the current report is to test the historical psychosocial paradigm of ED, which focuses on performance anxiety, 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.
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