Long-Term Testosterone Supplementation in Older Men Attenuates Age-Related Decline in Aerobic Capacity

J Clin Endocrinol Metab. 2018 Aug 1;103(8):2861-2869. doi: 10.1210/jc.2017-01902.


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.

Trial registration: ClinicalTrials.gov NCT00240981.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / blood
  • Aging / drug effects
  • Aging / metabolism*
  • Atherosclerosis / complications
  • Atherosclerosis / pathology*
  • Atherosclerosis / physiopathology
  • Body Composition / drug effects
  • Body Composition / physiology
  • Disease Progression
  • Double-Blind Method
  • Hormone Replacement Therapy
  • Humans
  • Hypogonadism / complications
  • Hypogonadism / drug therapy*
  • Hypogonadism / metabolism
  • Hypogonadism / physiopathology
  • Lung / drug effects*
  • Lung / physiology
  • Lung Volume Measurements
  • Male
  • Middle Aged
  • Muscle, Skeletal / drug effects
  • Oxygen Consumption / drug effects*
  • Placebos
  • Testosterone / therapeutic use*
  • Time Factors


  • Placebos
  • Testosterone

Associated data

  • ClinicalTrials.gov/NCT00240981