Long-term testosterone supplementation in older men attenuates age-related decline in aerobic capacity

Context: Testosterone increases skeletal muscle mass and strength, but long-term effects of testosterone supplementation on aerobic capacity, or peak oxygen uptake (V.O2peak), in healthy older men with low testosterone have not been evaluated. Objective: To determine the effects of testosterone supplementation on V.O2peak during incremental cycle ergometry. Design: A double-blind, randomized, placebo-controlled, parallel-group trial (Testosterones Effects on Atherosclerosis Progression in Aging Men). Setting: Exercise physiology laboratory. Participants: Healthy men aged ≥ 60 years with total testosterone levels of 100 to 400 ng/dL (3.5 to 13.9 nmol/L) or free testosterone levels <50 pg/mL (174 pmol/L). Interventions: Randomization to 1% transdermal testosterone gel adjusted to achieve serum levels of 500 to 950 ng/dL or placebo applied daily for 3 years. Main Outcome Measures: Change in V.O ₂ peak. Results: Mean (6SD) baseline V.O ₂ peak was 24.2 ± 5.2 and 23.6 ± 5.6 mL/kg/min for testosterone and placebo, respectively. V.O ₂ peak did not change in men treated with testosterone but fell significantly in men receiving placebo (average 3-year decrease, 0.88 mL/kg/min; 95% CI, 21.39 to 0.38 mL/kg/min; P = 0.035); the difference in change in V.O ₂ peak between groups was significant (average 3-year difference, 0.91 mL/kg/min; 95% CI, 0.010 to 0.122 mL/kg/min; P = 0.008). The 1-g/dL mean increase in hemoglobin (P < 0.001) was significantly associated with changes in V.O ₂ peak in testosterone-treated men. Conclusion: The mean 3-year change in V.O ₂ peak was significantly smaller in men treated with testosterone than in men receiving placebo and was associated with increases in hemoglobin. The difference in V.O ₂ peak change between groups may indicate attenuation of its expected agerelated decline; the clinical meaningfulness of the modest treatment effect remains to be determined.