Resistance exercise and supraphysiologic androgen therapy in eugonadal menwith HIV-related weight loss - A randomized controlled trial

Context Repletion of lean body mass (LBM) that patients lose in human immun odeficiency virus (HIV) infection has proved difficult. in healthy, HIV-ser onegative men, synergy between progressive resistance exercise (PRE) and ve ry high-dose testosterone therapy has been reported for gains in LBM and mu scle strength. Objective To determine whether a moderately supraphysiologic androgen regim en, including an anabolic steroid, would improve LBM and strength gains of PRE in HIV-infected men with prior weight loss and whether protease inhibit or antiretroviral therapy prevents lean tissue anabolism. Design Double-blind, randomized, placebo-controlled trial; post hoc analysi s for effect of HIV-protease inhibitor therapy conducted from January to Oc tober 1997. Setting Referral center in San Francisco, Calif. Patients Volunteer sample of 24 eugonadal men with HIV-associated weightles s (mean, 9% body weight loss), recruited from an AIDS clinic and by referra l and by advertisement. Intervention For 8 weeks, all subjects received supervised PRE with physiol ogic intramuscular testosterone replacement (100 mg/wk) to suppress endogen ous testosterone production. Randomization was between an anabolic steroid, oxandrolone, 20 mg/d, and placebo. Main Outcome Measures Lean body mass, nitrogen balance (10-day metabolic wa rd measurements), body weight, muscle strength, and androgen status. Results Twenty-two subjects completed the study (11 per group). Both groups showed significant nitrogen retention and increases in LBM, weight, and st rength. The mean (SD) gains were significantly greater in the oxandrolone g roup than in the placebo group (5.6 [2.1] vs 3.8 [1.8] g of nitrogen per da y [P = .05]; 6.9[1.7] vs 3.8 [2.9] kg of LBM [P = .005]; greater strength g ains for various upper and lower body muscle groups by maximum weight lifte d CP = .02-.05] and dynamometry [P = .01 -.05]). The mean (SD) high-density lipoprotein cholesterol level declined 0.25 (0.14) mmol/L (9.8 [5.4] mg/dL ) significantly in the oxandrolone group (P < .001 compared with placebo). Results were similar whether or not patients were taking protease inhibitor s. One subject in the oxandrolone group discontinued the study because of e levated liver function test results. Conclusions A moderately supraphysiologic androgen regimen that included an anabolic steroid, oxandrolone, substantially increased the lean tissue acc rual and strength gains from PRE, compared with physiologic testosterone re placement alone, in eugonadal men with HIV-associated weight loss. Protease inhibitors did not prevent lean tissue anabolism.