Clinical meaningfulness of the changes in muscle performance and physical function associated with testosterone administration in older men with mobility limitation

Abstract

Context: Testosterone in Older Men with Mobility Limitations Trial determined the effects of testosterone on muscle performance and physical function in older men with mobility limitation. Trial's Data and Safety Monitoring Board recommended enrollment cessation due to increased frequency of adverse events in testosterone arm. The changes in muscle performance and physical function were evaluated in relation to participant's perception of change.

Methods: Men aged 65 years and older, with mobility limitation, total testosterone 100-350 ng/dL, or free testosterone less than 50 pg/mL, were randomized to placebo or 10 g testosterone gel daily for 6 months. Primary outcome was leg-press strength. Secondary outcomes included chest-press strength, stair-climb, 40-m walk, muscle mass, physical activity, self-reported function, and fatigue. Proportions of participants exceeding minimally important difference in study arms were compared.

Results: Of 209 randomized participants, 165 had follow-up efficacy measures. Mean (SD) age was 74 (5.4) years and short physical performance battery score 7.7 (1.4). Testosterone arm exhibited greater improvements in leg-press strength, chest-press strength and power, and loaded stair-climb than placebo. Compared with placebo, significantly greater proportion of men receiving testosterone improved their leg-press and chest-press strengths (43% vs 18%, p = .01) and stair-climbing power (28% vs 10%, p = .03) more than minimally important difference. Increases in leg-press strength and stair-climbing power were associated with changes in testosterone levels and muscle mass. Physical activity, walking speed, self-reported function, and fatigue did not change.

Conclusions: Testosterone administration in older men with mobility limitation was associated with patient-important improvements in muscle strength and stair-climbing power. Improvements in muscle strength and only some physical function measures should be weighed against the risk of adverse events in this population.

Trial registration: ClinicalTrials.gov NCT00240981.

Figure 1.

The flow of participants through the TOM Trial is depicted. A two-stage screening process was used. Of 4,726 participants who underwent telephone screening, 1,240 were deemed eligible for further screening, 571 signed consent and were screened in person, 278 met eligibility criteria, and 209 were randomized. Participants with limited exercise tolerance or those at high risk of cardiovascular events underwent a modified testing protocol, which included unloaded 40-m walk test, Bassey’s leg power, physical activity, and self-reported measures (Group A). All others underwent a cardiopulmonary exercise tolerance test. Participants who demonstrated evidence of ischemia or exercise intolerance during exercise tolerance test were assigned to Group B and underwent loaded and unloaded walk and stair-climb, leg-press strength and power, and self-reported measures. Participants who underwent an exercise tolerance test without demonstrating ischemic changes underwent complete battery of tests, including loaded and unloaded walk and stair-climb, lift and reach, leg press and chest press, physical activity, and self-reported measures (Group C).

Figure 2.

The percent change from baseline in selected measures of muscle performance and physical function in testosterone and placebo arms of the trial. Data are mean and 95% confidence intervals. Estimates of mean treatment difference attributable to testosterone administration (Δ_TP) are presented along with 95% confidence intervals. These may be interpreted as estimates of difference (testosterone minus placebo) in proportionate change achieved over 6 months.

Figure 3.

Absolute treatment differences (testosterone vs placebo arms) are plotted for the primary and secondary outcomes in units normalized to the baseline standard deviation of measurement; point estimates (red) are accompanied by 95% confidence intervals.