Testosterone therapy is being investigated for its potential role in reducing adiposity in older women — particularly those who have had a hip fracture. Recovery in this population is determined not only by mobility and bone health but also by the redistribution of appendicular adipose tissue into metabolically harmful visceral depots.

New research found that adding testosterone to structured exercise significantly altered fat distribution, decreasing the proportion of visceral adipose tissue (VAT) over a 6-month period, although it didn't reduce overall adiposity.

"We found that older women recovering from hip fracture who were randomly assigned to take part in a structured exercise program and used a topical testosterone gel experienced selective reductions in VAT, compared to those who completed the exercise program using a placebo gel, despite no differences in total adipose tissue throughout the body," Jacob Earp, PhD, assistant professor of kinesiology, College of Agriculture, Health and Natural Resources, University of Connecticut, told Medscape Medical News.

Since visceral adipose tissue has a "disproportional effect on metabolic health, our findings suggest that supplemental testosterone therapy in older women recovering from hip fracture could promote a healthy redistribution of adipose tissue, if paired with a structured exercise program," he said.

The study was published online in Obesity Pillars.

Adiposity and Aging

In both men and women, aging is associated with increases in total body adiposity and adipose redistribution from more innocuous subcutaneous stores into the metabolically stressful visceral compartment, which increases the risk of many obesity-related illnesses, the authors wrote.

This process, which is linked with decreases in sex hormones (estrogen and progesterone in women and testosterone in men), is "rapidly compounded" in older women after they sustain a hip fracture.

"Hip fractures are devastating injuries that most older adults don't ever recover from," Earp said.

In older men, testosterone therapy paired with exercise has been shown to enhance physical function, reduce visceral adipose, and improve body composition, he said. This made testosterone-exercise therapy an "attractive intervention" to study in older women, he said.

Research into the effects of testosterone in older women is limited, the researchers noted. 

Their study was a sub-analysis of the previously published STEP-HI Randomized Clinical Trial, led by Ellen Binder, MD, professor of medicine, Division of General Medicine and Geriatrics, Washington University School of Medicine in St Louis, who is a co-author of the current paper. The trial found that the testosterone-exercise regimen in women after a hip fracture didn't lead to significant improvement in long-distance mobility, compared to exercise plus a placebo or enhanced usual care.

The current study focused on fat distribution, rather than mobility. The researchers hypothesized that both exercise groups would experience a reduction in total and visceral adipose tissue, but women receiving testosterone therapy would experience a greater reduction in visceral adipose tissue and a "healthier pattern" of adipose distribution.

Changes in total, appendicular, and visceral adipose tissue mass and percentage of total adipose tissue in each region were measured using dual x-ray absorptiometry.

Effects on Visceral Adiposity

Women (age ≥65 years) who were recovering from a recent hip fracture were randomly assigned to receive either supervised exercise therapy plus topical testosterone gel (n=35 , mean age 79) or supervised therapy plus placebo gel (n=31, mean age 76) for a 6-week period.

No significant between-group differences were found for changes in total, appendicular, or visceral adipose tissue measured in grams, or in appendicular adipose tissue as a percentage of total fat.

However, testosterone therapy was associated with a significant relative change in visceral adipose tissue as a percentage of total adipose tissue (-10.57% vs 3.51%; P = .004).

The finding indicates that concerns that testosterone might increase visceral fat in older women weren't warranted, Earp said. "In fact, the opposite was true," he said.

Older women taking testosterone — for example, to combat loss of sexual desire — "should not be immediately concerned about experiencing a 'male pattern of fat distribution,'" Earp said. However, he cautioned, "more research is needed to expand this to other populations and determine if these effects are contingent upon also engaging in exercise."

The authors noted some study limitations, including lack of pre-fracture data, absence of a non-exercise control group, and the use of DXA scans, rather than CT or MRI, to assess adipose measurements. Longer-term data regarding health outcomes (eg, 5-year survival, rehospitalization rate, or incidence of major cardiac events) are necessary to objectively assess this intervention, they said. 

Too Early for Clinical Practice

The study is "an intriguing signal-generating study with strong research methodology," endocrinologist Florencia Halperin, MD, MMSc, chief medical officer, Form Health, told Medscape Medical News.

However, "after 6 months of exercise and treatment in this study, there were no differences in total body fat scores between the testosterone and placebo groups," noted Halperin, who is former medical director of the Program for Weight Management, Brigham and Women's Hospital, Boston. "This underscores that the effect size here was limited."

Similarly, in the "parent STEP-HI study, the addition of testosterone to exercise led to greater improvements in some physical performance tests, but no difference in important outcomes like the 6-minute walk distance, leg-press strength, and limb lean mass," she said. "So, while the direction of the findings in this study is consistent with physiology, the clinical impact of the interventions was very modest."

Moreover, the current study was small and the "outcomes are somewhat narrow," Halperin said.

"Larger and longer-term trials with broader consideration of possible adverse consequences are needed before this approach could be considered in clinical practice," she said.

This work is supported in part by grants from the National Institute on Aging and Baltimore Veterans Affairs Medical Center Geriatric Research, Education, and Clinical Centers. Earp and co-authors and Halperin declare no relevant financial relationships. 

Batya Swift Yasgur MA, LSW is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).