Adding topical testosterone treatment to a structured, high-intensity exercise program was no better than the exercise alone in helping older women recover from hip fracture, a randomized trial showed.
Mean change from baseline in 6-minute walk distance (6MWD) after 24 weeks was 42.7 m for 53 patients assigned to the testosterone treatment plus exercise, versus 40.5 m among 51 patients using a placebo in addition to exercise (P=0.96 after adjusting for covariates), according to Ellen F. Binder, MD, of Washington University in St. Louis, and colleagues.
Patients in a third arm, who received "enhanced usual care" -- instructions to perform exercises at home, plus some health education -- had average increases of 37.7 m in the 6MWD test (adjusted P=0.63 vs testosterone and structured exercise), the researchers reported in JAMA Network Open.
"These findings do not support prescribing testosterone therapy to women to enhance long-distance walking mobility after hip fracture," Binder and colleagues wrote.
However, in light of "some improvements" in scores on the Short Physical Performance Battery (SPPB), the investigators weren't ready to close the book on testosterone for hip fracture patients. "[T]estosterone combined with exercise might benefit physical performance and mobility for short distances and warrants further study," they concluded.
Binder's group had hoped to find a benefit for the testosterone therapy in this rigorous setting. Structured, intensive exercise is clearly effective in speeding recovery from hip fracture, but it seemed reasonable to suppose that adding an anabolic agent could "augment the effects of exercise on muscle function and thereby improve postfracture function," the researchers explained.
Testosterone therapy has been tested before in certain female populations, mainly as treatment for osteoporosis or diminished sex drive, Binder and colleagues noted. It has also been used in hip fracture patients, but with uncertain benefits; a 2014 Cochrane review found that the quality of those studies was too poor to support conclusions either way. Its authors thus called for more rigorous studies to settle the question.
That's what Binder and colleagues had in mind with the new trial, dubbed STEP-HI. They enrolled 129 women 65 and older with recent hip fracture repair procedures, with the initial plan of randomizing them 1:1:1 in double-blind fashion to the structured exercise program with a topical testosterone gel or similar-appearing placebo, or to "enhanced usual care." Partway through, however, the trial's data safety and monitoring board approved a plan to reduce the number assigned to usual care. Totals of 55 were in the group with active testosterone, 54 were in the placebo-gel group, and 20 had enhanced usual care. Seven patients didn't complete the study, primarily on account of COVID-19 pandemic restrictions, and were kept out of the efficacy analyses.
Mean patient age was about 80, and more than 90% were white. Roughly half were living alone. About 3 months had passed, on average, since their hip fracture repair before starting the trial.
The testosterone product was a generic 1.0% gel, with doses estimated to achieve serum levels of 110-160 ng/mL, somewhat above the normal reference range. Doses (pumps per application) were adjusted if blood tests showed significant deviation from the target range. To maintain blinding, whenever an active-treatment group member had a dosage adjustment, so did someone from the placebo group. All participants, including those assigned to enhanced usual care, also received oral calcium (1,000 mg/day) and vitamin D (2,000 IU/day) supplements.
The exercise program was conducted in person with staff supervision. It started with activities to improve balance, flexibility, and strength, with more intensive strength training added over time. Participants were also to perform specific exercises at home. Exercises included in enhanced usual care were low-intensity, with initial instructions given in person without further supervision, although staff called participants in this group each week to encourage compliance.
Change from baseline in 6MWD score was the trial's primary outcome. Secondary measures included the SPPB, hand grip strength, leg press weight, general hip function, and evaluations of overall function and health status.
Only SPPB among these secondary outcomes showed a significant advantage for the testosterone gel, with a mean increase from baseline of 1.5 points, versus 0.7 points in the placebo-plus-exercise group (adjusted P=0.009). However, the enhanced usual care group also saw a mean increase of 1.5 points.
Serum testosterone levels did increase as expected in the group using the active product, reaching just above 150 ng/mL by week 12, though this fell to about 115 ng/mL at week 24. In the other groups, testosterone levels remained at their initial low baseline throughout the study.
Eleven participants suffered serious adverse events in the study, seven of whom were in the active testosterone group. These events were possibly related to treatment in five patients, including four using testosterone; falls were the most common such event, the researchers indicated.
Limitations to the study included the possibility that some participants, especially those assigned to enhanced usual care, surpassed expectations for their at-home exercise. As well, this was not an "all-comers" trial and the results may not apply to patients whose baseline hip function is substantially better or worse than the included participants, nor to more racially/ethnically diverse populations.
Disclosures
The study was funded by the National Institute on Aging.
Binder reported relationships with Akros Pharma and Eisai. Co-authors reported relationships with Krog & Partners, Vitality Healthspan Foundation, Wolters Kluwer, Radius Health, Amgen, Solarea Bio, and Agnovos.
Primary Source
JAMA Network Open
Source Reference: Binder EF, et al "Combining exercise training and testosterone therapy in older women after hip fracture: The STEP-HI randomized clinical trial" JAMA Netw Open 2025; DOI: 10.1001/jamanetworkopen.2025.10512.
No comments:
Post a Comment
Note: Only a member of this blog may post a comment.