Effect of testosterone supplementation with and without a dual 5α-reductase inhibitor on fat-free mass in men with suppressed testosterone production: a randomized controlled trial.
Level 2 - randomized trial
Individual randomized controlled trial in humans
PubMed 22396515 · doi:10.1001/jama.2012.227
What was done
Healthy men aged 18 to 50 years with suppressed endogenous testosterone were randomized into eight treatment groups receiving graded doses of testosterone enanthate (50, 125, 300, or 600 mg/week) combined with either daily dutasteride (2.5 mg/day, a dual 5α-reductase inhibitor) or placebo for 20 weeks. The primary outcome was change in fat-free mass. Secondary outcomes included changes in fat mass, muscle strength, sexual function, prostate volume, sebum production, hematocrit, and lipid levels.
What was found
A total of 139 men were randomized and 102 completed the 20-week protocol. Mean gains in fat-free mass in the dutasteride versus placebo groups across weekly testosterone doses were: at 50 mg/wk, 0.6 kg (95% CI, -0.1 to 1.2) vs 0.8 kg (95% CI, -0.1 to 1.7); at 125 mg/wk, 2.6 kg (95% CI, 0.9 to 4.3) vs 3.5 kg (95% CI, 2.1 to 4.8); at 300 mg/wk, 5.8 kg (95% CI, 4.8 to 6.9) vs 5.7 kg (95% CI, 4.8 to 6.5); and at 600 mg/wk, 7.1 kg (95% CI, 6.0 to 8.2) vs 8.1 kg (95% CI, 6.7 to 9.5). The dose-adjusted difference in fat-free mass between dutasteride and placebo was not significant (P = .18). Changes in fat mass, muscle strength, sexual function, prostate volume, sebum production, hematocrit, and lipid levels did not differ between groups.
Why it matters
This trial shows that conversion of testosterone to 5α-dihydrotestosterone is not required for testosterone to exert its anabolic effects on muscle mass and strength, or its effects on erythropoiesis in men.
Limits
Attrition was substantial, with 26.6% (37/139) of randomized participants failing to complete the 20-week study, resulting in small sample sizes across the eight separate subgroups. The study was conducted strictly in healthy men aged 18 to 50 under experimental suppression of endogenous testosterone, which may limit generalizability to older men or populations with baseline hypogonadism. Specific numeric values for secondary endpoints were not reported in the abstract.
Cited by
- supports Graded dose-response studies using dutasteride alongside testosterone showed that suppressing DHT had no effect on strength or muscular hypertrophy.