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 (V̇O2peak), in healthy older men with low testosterone have not been evaluated. Objective To determine the effects of testosterone supplementation on V̇O2peak during incremental cycle ergometry. Design A double-blind, randomized, placebo-controlled, parallel-group trial (Testosterone’s 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 V̇O2peak. Results Mean (±SD) baseline V̇O2peak was 24.2 ± 5.2 and 23.6 ± 5.6 mL/kg/min for testosterone and placebo, respectively. V̇O2peak 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, −1.39 to 0.38 mL/kg/min; P = 0.035); the difference in change in V̇O2peak 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 V̇O2peak in testosterone-treated men. Conclusion The mean 3-year change in V̇O2peak was significantly smaller in men treated with testosterone than in men receiving placebo and was associated with increases in hemoglobin. The difference in V̇O2peak change between groups may indicate attenuation of its expected age-related decline; the clinical meaningfulness of the modest treatment effect remains to be determined.