Erectile Function, Erection Hardness and Tolerability in Men Treated With Sildenafil 100 mg vs. 50 mg for Erectile Dysfunction

M. Kirby; D. L. Creanga; V. J. Stecher


Int J Clin Pract. 2013;67(10):1034-1039. 

In This Article

Abstract and Introduction


Aim To compare efficacy and tolerability between 100-mg and 50-mg sildenafil doses in five double-blind, placebo-controlled (DBPC) fixed-dose studies.

Methods Doses were compared for the change (baseline to end of 8–12 weeks of DBPC treatment) in score on the Erectile Function (EF) domain of the International Index of Erectile Function (IIEF; from five fixed-dose studies, > 1500 men); the per-patient estimated percentage of occasions that a specified Erection Hardness Score (EHS; from two of the five fixed-dose studies, > 500 men) was achieved, computed from logistic regression; the odds ratio (OR) of achieving EHS3 (hard enough for penetration, but not completely hard) and EHS4 (fully hard and completely rigid); and the adverse event incidence by treatment (from all five fixed-dose studies).

Results For the 100-mg vs. 50-mg dose, IIEF-EF score improvement was consistently greater across the five studies and was statistically significant when data from two studies with similar design were pooled (10.7 ± 0.64 vs. 8.9 ± 0.83, p = 0.0287); and during the first 2 weeks of treatment, the odds of achieving EHS4 erections were almost doubled in one study (OR = 1.77, p = 0.0398). Sildenafil was generally well tolerated at either dose.

Conclusion Men with erectile dysfunction treated with 100-mg compared with 50-mg sildenafil may be more likely to achieve a greater improvement in erectile function and, within the first 2 weeks, completely hard and fully rigid erections, with little or no greater risk to tolerability.


The effectiveness and safety of sildenafil citrate for treating erectile dysfunction (ED) have been well established in 136 manufacturer-sponsored clinical studies and in other independent studies. In most of the clinical trials, sildenafil was administered on demand as a flexible-dose regimen (starting dose of 50 mg and subsequent adjustment to 25 or 100 mg, depending on tolerability and efficacy).

For most men with ED, 50 mg (the recommended starting dose of sildenafil) is effective and provides a clinically meaningful benefit.[1] However, the 100-mg dose may provide a superior clinical benefit. Evidence of a dose–response between sildenafil 50 and 100 mg was seen in early controlled clinical studies supporting regulatory approval.[1] More recently, a comparison of two double-blind, placebo-controlled (DBPC) studies of similar design, except for a flexible-dose vs. fixed-dose regimen, suggested that an initial dose of 100-mg sildenafil may be a better choice because it would reduce the need for titration and could prevent discouragement and treatment abandonment if 50 mg should be insufficient for optimal efficacy.[2]

The tolerability and safety of sildenafil 50 and 100 mg in men with ED have been established using collated data from 67 DBPC studies (> 14,000 men) conducted by the manufacturer and from the manufacturer's postmarketing safety database (39,277 cases).[3] Sildenafil was well tolerated, overall, in those aged ≥ 65 years and in those aged ≥ 75 years, with no apparent causal link to cardiovascular events and no new safety risks relating to cardiovascular events, priapism, non-arteritic anterior ischaemic optic neuropathy, hearing loss or drug interactions.

The objective of the current analyses was to compare efficacy and tolerability between treatment with 100-mg and 50-mg doses of sildenafil in a subset of five fixed-dose studies (> 1500 men).