Original ResearchPharmacotherapyEfficacy and Safety of Sildenafil by Age in Men With Erectile Dysfunction
Introduction
Erectile dysfunction (ED), defined as the inability to achieve or maintain an erection sufficient for satisfactory sexual performance,1 is a common and age-associated condition. Based on studies published in the past decade,2, 3, 4, 5, 6, 7, 8, 9, 10 the overall prevalence of ED has been estimated at 18%2 to 47%3 in the United States and 6%10 to 49%9 in international studies, with prevalence rates dependent on the age of men in the sample assessed and the method used to identify ED. Based on data from the U.S. National Health and Nutrition Examination Survey, the prevalence of ED increases from 8.2% in men 40 to 49 years old to 77.5% in those at least 75 years old.2 In addition to age, factors identified as significantly associated with ED include diabetes, obesity, smoking, cardiovascular disease, stroke, hypertension, and lower urinary tract symptoms.2, 4, 8, 11, 12, 13, 14 In men 40 to 70 years old with ED, the risk of cardiovascular disease mortality is increased 43% vs men without ED.15
Sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, was the first in-class oral medication approved by the U.S. Food and Drug Administration in 1998 for the treatment of ED based on its efficacy and safety profiles in randomized clinical trials.16 Other oral PDE5 inhibitors, including tadalafil, vardenafil, and avanafil, also have been approved for the treatment of ED.
The 15-item International Index of Erectile Function (IIEF) was developed and validated as a patient-reported outcome measurement for assessing ED in clinical trials and treatment response in men with ED.17 The six-item IIEF erectile function domain is widely accepted by regulatory agencies as a primary end point in clinical trials of ED therapies worldwide. The IIEF erectile function domain is a validated diagnostic tool that is useful for classifying ED severity and for assessing treatment response.18 More recently, estimates of minimal clinically important differences (MCIDs) in the treatment-related change in the IIEF erectile function domain score have provided additional information on treatment response for clinicians managing men with ED.19
Sildenafil has been extensively evaluated in 74 double-blinded, placebo-controlled, clinical trials, with a database of efficacy and safety data from more than 16,000 men with ED. However, published data on the treatment response to sildenafil in men with ED according to patient age are limited,20, 21, 22, 23 especially in men at least 75 years old.
Section snippets
Aims
To assess the efficacy and safety of sildenafil according to age subgroups (<65, 65–74, and ≥75 years) in men with ED using pooled data from 48 randomized, double-blinded, placebo-controlled, parallel-group, flexible-dose sildenafil trials.
Methods
Data for 74 double-blinded, placebo-controlled sildenafil clinical trials were entered in a Pfizer clinical data repository. The main determinant of study inclusion in the present analysis was study design. Overall, 48 of the 74 trials had a similar study design (ie, double-blinded, placebo-controlled, parallel-group, flexible-dose design) and were considered for the present analysis. Forty-two of these 48 studies collected IIEF data and were used for efficacy outcomes reported in this
Main Outcome Measures
The main outcome measurements for treatment efficacy were patient-reported quantitative scores for IIEF Q3, Q4, erectile function domain, orgasmic function domain, sexual desire domain, intercourse satisfaction domain, and overall satisfaction domain, and the qualitative yes-or-no response to the GAQ.
Patients
In the 48 randomized, double-blinded, placebo-controlled, parallel-group, flexible-dose sildenafil trials included in the analysis, 5,237 men received placebo and 6,127 received sildenafil. The baseline demographic and clinical characteristics of the patients according to treatment and age are presented in Table 1. The mean age of the overall population was 55 years (SD = 11 years) in each treatment group, with a mean ED duration of 4.4 years. In the overall population, the prevalence rates of
Discussion
The present post hoc analysis of pooled data from 48 flexible-dose clinical trials provides valuable information on the efficacy and safety of sildenafil in men with ED according to age subgroups (ie, <65, 65–74, and ≥75 years). In each of these age subgroups, the IIEF erectile function domain score was statistically significantly improved from baseline in patients treated with sildenafil vs those receiving placebo. In 2011, Rosen et al19 published estimates of the MCIDs for the erectile
Conclusions
Sildenafil is an effective and well-tolerated treatment for ED regardless of patient age. For men at least 75 years old, sildenafil treatment is associated with statistically significant and clinically meaningful improvements in erectile function. Sexual function and sexual satisfaction can continue with aging for most sildenafil-treated men with ED.
Statement of Authorship
Category 1 Conception and Design Irwin Goldstein; Li-Jung Tseng; Vera Stecher; Jed C. Kaminetsky
Acquisition of Data
Li-Jung Tseng; Dana Creanga
Analysis and Interpretation of Data
Irwin Goldstein; Li-Jung Tseng; Dana Creanga; Vera Stecher; Jed C. Kaminetsky
- (a)
Drafting the Article
Irwin Goldstein; Li-Jung Tseng; Vera Stecher; Jed C. Kaminetsky
- (b)
Revising It for Intellectual Content
Irwin Goldstein; Li-Jung Tseng; Vera Stecher; Jed C. Kaminetsky
- (a)
Final Approval of the Completed Article
Irwin Goldstein; Li-Jung Tseng; Dana
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2022, Sexual Medicine ReviewsCitation Excerpt :Besides, these drugs have been acknowledged for improving other disorders such as; pulmonary arterial hypertension, benign prostatic hyperplasia in addition to diverse therapeutic implications in different systems such as; cardiovascular, pulmonary, cutaneous, gastrointestinal, urogenital, cellular, musculoskeletal, and neurologic disorders.13–18 Generally, these drugs are usually well-tolerated, but minor adverse events may take place include; headache, flushing, nasal congestion, dyspepsia, visual disturbance, or back pain.19 However, these drugs have become used in subjects not suffering from ED for recreational use to enhance their sexual performance.
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2019, Journal of Sexual MedicineCitation Excerpt :Clinically speaking, those findings suggest that a large proportion of older men are apparently reconciled to lower levels of sexual activity. Interestingly, in a large study pooling data of 11,364 patients from 48 randomized placebo-controlled trials investigating the efficacy of sildenafil, Goldstein et al15 showed that, although the treatment was effective across all age groups, the effect size in terms of IIEF improvement from baseline decreased across increasing ages. In our study, we observed that improvement in terms of sexual satisfaction for each IIEF-EF increase eventually decreased as a function of age, with older men with mild ED potentially not even perceiving any difference in terms of sexual satisfaction for further improvement in their EF.
Conflict of Interest: Dr Goldstein is on the advisory board of and receives honorarium from Pfizer and receives research support from Endo. Dr Tseng and Dr Stecher are employees of Pfizer. Dr Creanga is a paid contractor to Pfizer in the development of this article. Dr Kaminetsky consults and speaks for and receives honorarium and research support for erectile dysfunction from Endo and Lipocine.
Funding: This study was sponsored by Pfizer Inc. Editorial and medical writing assistance was provided by Patricia B. Leinen, PhD, of Complete Healthcare Communications, Inc, and funded by Pfizer Inc.