5-ARI with T supplementation does not affect muscle mass, strength

Men receiving testosterone supplementation who also receive the 5-alpha-reductase inhibitor dutasteride (Avodart) do not experience a significant difference in changes in muscle mass, muscle strength, or sexual function compared with men who do not receive dutasteride, according to a recent study.

First author Shalender Bhasin, MD, of the Boston University School of Medicine and Boston Medical Center, and colleagues conducted a study to determine whether the effect of testosterone on muscle mass, strength, and sexual function are outcomes lessened when its conversion to dihydrotestosterone (DHT) is blocked by dutasteride. The randomized, controlled trial of healthy men, ages 18 to 50 years, compared placebo plus testosterone enanthate with dutasteride plus testosterone enanthate from May 2005 through June 2010.

A total of 139 men were randomized; 102 completed the 20-week intervention. Eight treatment groups received 50, 125, 300, or 600 mg/week of testosterone enanthate for 20 weeks plus placebo (four groups) or dutasteride, 2.5 mg/day (four groups).

The changes in fat-free mass were related to testosterone dose and changes in testosterone concentrations in the placebo and dutasteride groups but did not differ between groups, the authors reported in JAMA (2012; 307:931-9). There was no significant interaction between testosterone dose and randomization to dutasteride or placebo. Thus, the effects of testosterone on muscle mass did not differ between the dutasteride and placebo groups, who had very different DHT levels.

The average fat-free mass gained by the dutasteride groups was 0.6 kg when receiving 50 mg/week of testosterone enanthate, 2.6 kg for 125 mg/week, 5.8 kg for 300 mg/week, and 7.1 kg for 600 mg/week. The average fat-free mass gained by the placebo groups was 0.8 kg when receiving 50 mg/week of testosterone enanthate, 3.5 kg for 125 mg/week, 5.7 kg for 300 mg/week, and 8.1 kg for 600 mg/week.

"The finding that 5α-reduction of testosterone to DHT is not obligatory for mediating its effects on outcomes that were studied in this trial has implications for therapeutic applications of androgens and 5α-reductase inhibitors," Dr. Bhasin and co-authors wrote. "These findings bode well for the safety of 5α-reductase inhibitors with respect to their effects on muscle. Our data also predict that efficacy of 5α-reductase inhibitors may be limited in men with normal or high testosterone concentrations; therefore, measurement of testosterone levels might be useful in identifying men less likely to respond to 5α-reductase inhibitors."

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