Testosterone Gel Provides Limited Gains

TOPLINE:

Compared with exercise alone, combining exercise training with testosterone gel application did not result in longer 6-minute walk distances (6MWDs) in older women with a recent hip fracture repair and persistent mobility impairments.

METHODOLOGY:

• Hip fractures are a significant public health issue, with up to 76% of patients in the United States experiencing functional loss despite rehabilitation.
• Researchers conducted a phase 3 clinical trial at eight US sites between December 2018 and August 2023 to evaluate the effects of exercise combined with topical testosterone therapy on functional outcomes in 129 women aged 65 years or older with a recent surgical repair of a nonpathologic fracture of the femur.
• Participants were randomly assigned to one of the three groups: Exercise plus 1% topical testosterone gel (n = 55; mean age, 79.4 years; 94.6% White population), exercise plus placebo gel (n = 54; mean age, 78.3 years; 90.7% White population), or enhanced usual care (n = 20; mean age, 83 years; 95.0% White population).
• Both exercise groups underwent a 24-week supervised, multimodal, high-intensity exercise program with progressive resistance training, whereas the enhanced usual care group was advised to independently perform low-intensity home-based exercise.
• The primary outcome was a change in the 6MWD from baseline to 24 weeks.

TAKEAWAY:

• At 24 weeks, the mean increase in the 6MWD was not significantly different among groups: 42.7 m, 40.5 m, and 37.7 m for the exercise plus topical testosterone gel, exercise plus placebo gel, and enhanced usual care groups, respectively.
• The change in physical performance at 24 weeks, measured using the Short Physical Performance Battery score, was significantly greater in the exercise plus topical testosterone gel group than in the exercise plus placebo gel group (P = .009).
• Among all participants, 11 (8.5%) had one or more serious adverse events during the intervention period, with the groupwise count being seven, three, and one for the exercise plus topical testosterone gel, exercise plus placebo gel, and enhanced usual care groups, respectively (P = .48).

IN PRACTICE:

“Among older women with a recent hip fracture repair and persistent mobility impairments, exercise training combined with topical testosterone therapy did not result in improvements in 6MWD compared with exercise training alone, although improvements in physical performance were observed,” the authors concluded. “Testosterone combined with exercise might benefit physical performance and mobility for short distances and warrants further study.”

SOURCE:

This study was led by Ellen F. Binder, MD, Division of General Medicine and Geriatrics, Washington University School of Medicine in St. Louis, Missouri. It was published online on May 15, 2025, in JAMA Network Open.

LIMITATIONS:

The enhanced usual care group’s protocol included low-intensity exercises, potentially leading to more exercise than anticipated. The findings cannot be generalized to immediate post–hip fracture recovery periods, patients with varying functional impairment levels, those with dementia, or individuals from racially and ethnically minoritized populations.

DISCLOSURES:

This clinical trial was supported by grants from the National Institute on Aging. Support at the Baltimore site was provided by the Baltimore Veterans Affairs Medical Center Geriatric Research, Education, and Clinical Centers. Multiple authors reported receiving grants, personal fees, employment, and internal research support from multiple institutes, foundations, and pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.