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

Abstract

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.

Figure 1.

Changes in mean total testosterone levels at 6, 18, and 36 mo for testosterone and placebo groups. P value derived from t test comparing difference between groups for average changes over time from baseline in total testosterone.

Figure 2.

Mean 3-y changes from baseline for V̇O₂peak [(A) L/min and (B) mL/kg/min] and changes in (C) peak work rate and (D) peak heart rate for testosterone-treated men (solid lines) and men receiving placebo (dashed lines). Data points represent mean values at each time point. Error bars are 95% CIs. P values indicate the overall effect of the testosterone intervention over time.

Figure 3.

(A) Mean 3-y changes from baseline in hemoglobin for testosterone-treated men (solid lines) and men receiving placebo (dashed lines). Data points represent mean values at each measurement period. (B) Scatterplot of relationship between changes in V̇O₂peak and changes in hemoglobin over 3 y. P values extracted from mixed-model regressions.

Figure 4.

(A) Mean 3-y changes from baseline for LBM in testosterone-treated men (solid lines) and men receiving placebo (dashed lines). Data points represent mean values at each measurement period. (B) Scatterplot of relationship between changes in V̇O₂peak and changes in LBM over 3 y. P values extracted from mixed-model regressions.