Sildenafil improved sexual function in erectile dysfunction
ACP J Club. 1998 Nov-Dec; 129:70. doi:10.7326/ACPJC-1998-129-3-070
Goldstein I, Lue TF, Padma-Nathan H, et al., for the Sildenafil Study Group. Oral sildenafil in the treatment of erectile dysfunction. N Engl J Med. 1998 May 14;338:1397-404.
In men with erectile dysfunction, is sildenafil (Viagra, Pfizer, New York, New York) effective in improving erectile function?
2 randomized, double-blind, placebo-controlled trials with 24-week follow-up for the dose-response study and 12-week follow-up for the dose-escalation study.
37 centers in the United States.
861 men (mean age 58 y) who had erectile dysfunction lasting ≥ 6 months and were in a stable relationship with a female partner for ≥ 6 months. Exclusion criteria were penile anatomical defects, another sexual disorder, spinal cord injury, major psychiatric disorder, poorly controlled diabetes mellitus, peptic ulcer disease, history of alcohol or substance abuse, major systemic abnormalities, recent stroke or myocardial infarction, or receipt of nitrate therapy. 87% of men completed the dose-response study, and 93% completed the dose-escalation study.
In the dose-response study, men were allocated to placebo (n = 216) or to 25, 50, or 100 mg of sildenafil (n = 316). In the dose-escalation study, men were allocated to placebo (n = 166) or to 50 mg of sildenafil (n = 163); the dose could be doubled or reduced by 50% at each follow-up visit.
Main outcome measures
Mean response scores to questions on achieving penetration and maintaining erection (questions 3 and 4 of the International Index of Erectile Function [IIEF]); response scores on IIEF domains for erectile function, orgasmic function, sexual desire, intercourse satisfaction,and overall satisfaction; and response to a global efficacy question: Did the treatment improve your erections?
Analysis was by intention to treat. In the dose-response study, the percentage increases from baseline in response scores for achieving penetration were 60%, 84%, and 100% for 25, 50, and 100 mg of sildenafil, respectively, compared with 5% for placebo (P < 0.001). The increases in scores for maintaining erection were 121%, 133%, and 130% for 25, 50, and 100 mg of sildenafil, respectively, compared with 24% for placebo (P < 0.001). In the dose-escalation study, the percentage increases from baseline for achieving penetration and maintaining an erection were 95% and 140%, respectively, with sildenafil; the increases were 10% and 13%, respectively, with placebo (P < 0.001). Mean scores for the erectile function domain increased with increasing doses of sildenafil in the dose-response study (P < 0.001) and were higher than those for placebo in the dose-escalation study (P < 0.001). In response to the global efficacy question, 56%, 77%, and 84% of patients who received 25, 50, and 100 mg of sildenafil, respectively, compared with 25% of placebo recipients reported improved erections (P < 0.001) in the dose-response study; 74% of sildenafil recipients and 19% of placebo recipients reported improved erections (P < 0.001) in the dose-escalation study. Adverse effects associated with sildenafil were mild and included headache, flushing, dyspepsia, and transient visual disturbances.
In men with erectile dysfunction, sildenafil improved erectile function, increased the rate of successful attempts at sexual intercourse, and was well tolerated.
Source of funding: Pfizer.
For correspondence: Dr. I. Goldstein, Department of Urology, Boston University Medical Center, 720 Harrison Avenue, P (606), Boston, MA 02118, USA. FAX 617-638-8487.
The 2 trials by Goldstein and colleagues show an impressive effect of sildenafil on patients' self-assessments of the quality of their erections. Contributing to these efficacy estimates was a minimal placebo response, even among men with psychogenic dysfunction.
Sildenafil seemed to have a similar effect in men with organic, psychogenic, or mixed causes of dysfunction, but standardized evaluation was not applied and the categories were heterogenous. Further study is needed to determine whether all men in selected patient groups who are currently being considered for treatment can expect similar benefits.
Erectile dysfunction may be a symptom of atherosclerosis as well as a marker for coronary artery disease. The combination of sildenafil and organic nitrates may provoke serious hypotension. It is fairly easy not to prescribe sildenafil to men who have previously had nitrates prescribed, but the real problem is the reverse. If a man has taken sildenafil and develops chest pain (perhaps because of unaccustomed sexual activity), he may reflexively be given nitrates by emergency personnel who normally do not delay nitrate administration to take a careful medication history. Alternatively, the history may be obtained and potentially lifesaving nitrates may be withheld. In these studies, only about 10% of men had known ischemic heart disease but many more undoubtedly had latent disease. No serious adverse events were reported, but the trials were of relatively short duration.
Sildenafil is an effective agent that can help many men with erectile dysfunction. More time is needed to see how often accidental administration of nitrates or withholding of nitrates in the face of acute ischemia causes serious problems in men taking sildenafil.
Michael J. Barry, MD
Massachusetts General HospitalBoston, Massachusetts, USA