Among older women, the adrenal steroid dehydroepiandrosterone may attenuate declines in bone mineral density and modestly increase fat-free mass over 12 months when compared with placebo, according to findings from a pooled analysis published in Clinical Endocrinology.
“Because age-related decreases in androgens and estrogens contribute to the loss of BMD and muscle mass in older adults, maintaining youthful levels of DHEA may be an effective strategy for attenuating the rates of loss,” Catherine M. Jankowski, PhD, FACSM, an exercise physiologist and associate professor at the University of Colorado Anschutz Medical Campus, and colleagues wrote in the study background. “It has been postulated that DHEA therapy is safer than estrogen or testosterone therapy. The rationale for this is that DHEA [sulfate] circulates as an inactive prohormone that is converted to biologically active sex steroids in a tissue-specific, and presumably tissue-appropriate, manner.”
Jankowski and colleagues analyzed data from four single-site, double-blind, randomized controlled trials sponsored by the National Institute on Aging designed to assess the effects of DHEA sulfate therapy on BMD and body composition in adults aged 55 to 85 years not using sex hormone therapy (295 women). Low serum DHEA sulfate concentration was an inclusion criterion in two studies. Researchers merged data from the four studies into a central database and analyzed 12-month changes in BMD, body composition and circulating hormones and growth factors in response to oral DHEA therapy vs. placebo. Dose of DHEA therapy was 50 mg per day in three studies and 75 mg per day for men only in one study. In two studies, researchers also provided calcium and vitamin D supplements to participants. BMD was assessed via DXA at the proximal femur and lumbar spine at baseline and 12 months. Serum DHEA sulfate, estradiol, testosterone, sex hormone-binding globulin and insulin-like growth factor I concentrations were measured at baseline and 12 months following an overnight fast.
Effects on bone
Of the 468 cases with evaluable T-scores for BMD, 138 women and 98 men had low bone mass and 29 women and 11 men had osteoporosis.
The researchers found that the observed benefit of DHEA therapy on the lumbar spine BMD in older women and men combined across the four studies was driven by the beneficial effects in women. DHEA therapy was associated with increases or attenuated decreases in lumbar spine, total hip and trochanter BMD vs. placebo (P < .01 for all). There were no observed changes in BMD in men assigned to DHEA therapy.
“Unlike these pharmaceutical trials, the DHEA trials did not target women with osteoporosis, which may have contributed to the modest increases in BMD,” the researchers wrote.
In one of the four trials, the 12-month study was followed by 12 months of open-label treatment. In that study, women prescribed DHEA experienced a mean increase in lumbar spine BMD of 1.7% at 12 months and a further increase of 1.8% at 24 months, according to the researchers. Another 2-year intervention suggested more modest incremental responses to DHEA therapy in lumbar spine BMD in older women (mean, 0.6% at 1 year and 1% at 2 years).
In the two studies that also incorporated calcium and vitamin D supplementation, researchers observed no additional increases in BMD, they wrote.
Across trials, sex-specific effects of DHEA therapy on body composition included a 0.5-kg increase in fat-free mass in women and a decrease of 0.4 kg fat mass in men, the researchers wrote, adding that none of the trials controlled for exercise behavior, which might have explained some of the increase in fat-free mass in women taking DHEA.
“Combining DHEA therapy with resistance exercise that imparts mechanical strain to bone may promote greater increases in muscle mass and BMD rather than either intervention alone,” they wrote.
Men assigned DHEA did not experience an increase in fat-free mass, according to researchers, who added that the mechanisms underlying DHEA actions in human adipose tissue are unclear.
“It is possible that DHEA therapy could be a strategy to attenuate the decline in BMD in postmenopausal women who do not tolerate other treatments,” the researchers wrote. “The beneficial effects of DHEA replacement on body composition are to modestly increase [fat-free mass] in women and decrease [fat mass] in older men a reversal of the usual age-related trends in muscle and fat mass.”
The effects of long-term DHEA sulfate therapy on musculoskeletal health in men and women, as well as the safety profile of such supplementation, need further study, they wrote. – by Regina Schaffer
Disclosures: The authors report no relevant financial disclosures.