Bhasin S, et al. - In the Physical Function Trial (PFT), one of seven Testosterone Trials (TTrials), the effect of testosterone on mobility, self-reported physical function, falls, and patient global impression-of-change (PGIC) was determined in older men with low testosterone concentrations, self-reported mobility limitation, and walking speed of less than 1.2 m/s. In addition, researchers determined differences in the effect of testosterone on mobility in accordance to baseline walking speed, mobility limitation, or other participant-level factors using data from the PFT and the overall TTrials study population. Findings revealed consistent improvement in self-reported walking ability, modest improvement in 6-minute walk test (6MWT) distance (across all TTtrials participants), but no effect on falls in relation to testosterone therapy. Baseline gait speed and self-reported mobility limitation, and changes in testosterone and hemoglobin concentrations seemed to influence the effect of testosterone on mobility measures.

Methods

• A total of 790 men aged 65 years or older and with an average of two total testosterone concentrations below 275 ng/dL (9.5 nmol/L) were included in the TTrials; among these, 390 reported mobility limitations and a walking speed below 1.2 m/s and were enrolled in the PFT.
• Researchers assigned participants (by minimization method) to 1% testosterone gel or placebo gel daily for 12 months; participants and study staff were masked to intervention allocation.
• An increase in 6MWT distance of 50 m or more was assessed as the primary outcome of the PFT.
• Data for absolute change in 6MWT distance and physical component of Short Form-36 (PF10), and for PGIC and falls were reported.
• They reported data for men enrolled in the PFT and those who were not, and for all men in TTrials.
• In addition, they reported data according to baseline walking speed and mobility limitation.
• They analyzed all patients who were allocated to treatment, had a baseline assessment, and at least one post-intervention assessment in a modified intention-to-treat population.

Results

• The TTrials were performed between April 28, 2011 and June 16, 2014.
• Of 790 TTrials participants, researchers allocated 395 to testosterone and 395 to placebo; among the 390 enrollees in the PFT, they allocated 193 to testosterone and 197 to placebo.
• The testosterone group displayed significantly more improvement in 6MWT distance vs the placebo group among all men in the TTrials, but not among those who were enrolled in the PFT; 6MWT distance improved with a treatment effect of 8.9 m among TTrials participants not enrolled in the PFT (95% CI 2.2–15.6; p=0.010), as reported previously.
• As reported previously, the testosterone group displayed more improved PF10 vs the placebo group in all men in TTrials and in men enrolled in the PFT; PF10 improved with an effect size of 4.0 among those not enrolled in the PFT (1.5–6.5; p=0.0019).
• Researchers noted significantly greater improvements in 6MWT distance (treatment effect 14.2 m, 6.5–21.9; p=0.0004) and PF10 (4.9, 2.2–7.7; p=0.0005) among testosterone-treated men with baseline walking speed of 1.2 m/s or higher vs placebo-treated men.
• Significantly more improvement in 6MWT distance (7.6 m, 1.0–14.1; p=0.0237) and PF10 (3.6, 1.3–5.9; p=0.0018) was evident among testosterone-treated men reporting mobility limitation vs placebo-treated men.
• In the testosterone group, men perceived improvement in their walking ability (PGIC) more frequently vs men in the placebo group; this was true for both for men enrolled in the PFT (effect size 2.21, 1.35–3.63; p=0.0018) and those not enrolled in the PFT (3.01, 1.61–5.63; p=0.0006).
• Changes in testosterone, free testosterone, dihydrotestosterone, and hemoglobin concentrations significantly correlated with changes in 6MWT distance.
• The two treatment groups of the TTrials displayed identical fall frequency during the intervention period (103 [27%] of 380 analyzed in both groups had at least one fall).