Sex-specific effects of dehydroepiandrosterone (DHEA) on bone mineral density and body composition: A pooled analysis of four clinical trials

Objective: Studies of dehydroepiandrosterone (DHEA) therapy in older adults suggest sex-specific effects on bone mineral density (BMD) and body composition, but the ability of a single study to reach this conclusion was limited. We evaluated the effects of DHEA on sex hormones, BMD, fat mass and fat-free mass in older women and men enrolled in four similar clinical trials. Design: Pooled analyses of data from four double-blinded, randomized controlled trials. Participants: Women (n = 295) and men (n = 290) aged 55 years or older who took DHEA or placebo tablet daily for 12 months. Measurements: Twelve-month changes in BMD, fat mass, fat-free mass and serum DHEA sulphate (DHEAS), (17)estradiol, testosterone and insulin-like growth factor-1 (IGF-1). Results: Women on DHEA had increases (mean ± SD; all P < 0.001 vs placebo) in DHEAS (231 ± 164 µg/dL), testosterone (18.6 ± 20.9 µg/dL), (17)estradiol (8.7 ± 11.0 pg/mL) and IGF-1 (25.1 ± 52.3 ng/mL), and men had increases in DHEAS (269.0 ± 177 µg/dL; P < 0.01), (17)estradiol (4.8 ± 12.2 pg/m; P < 0.01) and IGF-1 (6.3 ± 41.4 ng/mL; P < 0.05). Women on DHEA had increases in lumbar spine (1.0% ± 3.4%) and trochanter (0.5% ± 3.8%) BMD and maintained total hip BMD (0.0% ± 2.8%); men had no BMD benefit and a decrease in fat mass (−0.4 ± 2.6 kg; all P < 0.01 vs placebo). Conclusions: Dehydroepiandrosterone therapy may be an effective approach for preserving bone and muscle mass in women. Key questions are (a) the extent to which longer duration DHEA can attenuate the loss of bone and muscle in women, and (b) whether DHEA has a more favourable benefit-to-risk profile for women than oestrogen therapy.