medwireNews: Using topical testosterone alongside an exercise training program does not improve 6-minute walking distance (6MWD) versus exercise alone in older women recovering from a hip fracture, show results of the phase 3 STEP-HI study.
Ellen Binder (Washington University School of Medicine, St Louis, Missouri, USA) and co-investigators say their findings “do not support prescribing testosterone therapy to women to enhance long-distance walking mobility after hip fracture.”
The study included 129 women aged 65 years or older (mean age 79.3 years) with a recent surgical repair of a nonpathologic femur fracture who were randomly assigned to receive exercise training plus topical 1.0% testosterone gel (n=55), exercise training plus placebo gel (n=54), or enhanced usual care (n=20).
All the women were community dwelling after discharge from rehabilitation and were given vitamin D and calcium supplements to take daily. Those in the two exercise groups underwent a 24-week supervised, multimodal high-intensity exercise program that included progressive resistance training twice weekly at a dedicated exercise facility. Participants in the exercise groups were also expected to perform home exercises on 3 additional days per week.
Individuals in the enhanced usual care group took part in a self-administered, low-intensity, exercise program at home, and a staff-led monthly health education session.
The researchers report in JAMA Network Open that, at baseline, the mean 6MWD was 279.6 m in the exercise plus testosterone group, 236.4 m in the exercise plus placebo group, and 219.7 m in the enhanced usual care group. At 24 weeks, this increased by 42.7 m, 40.5 m, and 37.7 m, respectively, with no significant difference in improvement among the three groups.
Binder et al note that the 95% confidence interval for the 2.2 m difference in 6MWD between the two exercise groups ranged from −21.2 m to 25.5 m.
“These confidence bounds mean that we are 95% certain that the difference in efficacy between exercise plus placebo gel and exercise plus topical testosterone gel is at most 25.5 m,” the authors remark. “Since a large clinically meaningful difference is approximately 50 m, this finding establishes with a high degree of confidence that there is not a large clinically important benefit associated with adding testosterone to exercise insofar as the primary outcome is concerned.”
Secondary analyses revealed a significantly greater improvement in Short Physical Performance Battery Score at 24 weeks in women prescribed exercise plus topical testosterone gel than in those given exercise plus placebo gel, at 1.5 versus 0.7 points. Furthermore, the difference of 0.8 points between the two arms “is within the range considered to be clinically meaningful and suggests an independent effect of testosterone therapy on physical performance,” say the investigators.
They also found, in a post-hoc analysis, that 39.5% of 38 women in the testosterone arm who required a walker or cane to perform the 6MWD at baseline did not require an assistive device at 24 weeks. By comparison, the rate was 17.1% of 41 women in the exercise plus placebo gel group, a significant difference.
“The improvements in SPPB score and assistive device use suggest that testosterone therapy may have more benefits for strength and functional movements rather than endurance activities, such as the 6MWD,” say Binder and co-authors.
The also offer potential explanations for a lack of improvement in 6MWD with testosterone: “First, the 24-week treatment period, the target testosterone level, and/or the timing of the interventions may have been insufficient to induce the hypothesized changes in muscle strength or function necessary to improve long-distance walking. Second, the anabolic effects of testosterone may not have been strong enough to exceed the improvements in long-distance walking achieved through exercise training alone.”
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