DHEA Augmentation Of The Musculoskeletal Effects Of Exercise In Older Women: A Randomized Controlled Trial

Bone-loading exercise (Ex) is recommended to attenuate bone loss and increase muscle mass in postmenopausal women with low areal bone mineral density (aBMD). These adaptations to mechanical strain may be augmented by the anabolic hormonal effects of dehydroepiandrosterone (DHEA); this adrenal steroid declines with age and is the primary source of estrogen and testosterone in older women. Oral DHEA (50 mg/day) raises serum DHEA-sulfate (DHEAS) to young adult levels and increases aBMD and fat-free mass (FFM) in older women. PURPOSE: We determined whether the increases in lumbar (L; 2-4) spine aBMD and FFM in response to Ex (mechanical strain stimulus) and DHEA (hormonal stimulus) were greater than either Ex or DHEA alone. METHODS: Postmenopausal women (N = 144) with low bone mass or moderate osteoporosis (hip or spine T-score > = -3.0 and < -1.0) were randomized to Ex+DHEA, Ex+placebo (PL), or DHEA only. Ex was jumping and resistance training 3 days/week for 36 weeks; DHEA (50 mg) or PL was taken daily. Lspine aBMD and FFM were measured by DXA at baseline and week 36. Linear regression modelled for the a priori contrasts of Ex+DHEA vs Ex+PL and Ex+DHEA vs DHEA, for the 36-week changes (mean ± SD). Effect sizes are expressed as Cohen’s d. For context, historical cases (N = 77 women) represented no Ex+PL. RESULTS: Eighty participants (age 66 ± 5 years; 95% Non-Hispanic, 90% White) completed the intervention without pandemic disruption. The changes in Lspine aBMD were not different in Ex+DHEA (0.7 ± 3.7%; n = 28) relative to Ex+PL (0.4 ± 3.2%; n = 28; p = 0.70, d = 0.09) or DHEA only (0.9 ± 1.8%; n = 24; p = 0.84, d = -0.06). FFM increased more in Ex+DHEA (1.5 ± 1.7 kg) relative to DHEA (0.3 ± 1.2 kg; p = 0.002, d = 0.84) but not Ex+PL (1.0 ± 1.2 kg; p = 0.20, d = 0.33). Relative to historical cases, all conditions showed small to moderate increases in Lspine aBMD (-1.1 ± 4.5%; DHEA+EX, d = 0.43; EX+PL, d = 0.37; DHEA, d = 0.58) and moderate to large increases in FFM (-0.1 ± 0.7 kg; Ex+DHEA, d = 1.2; EX+PL, d = 1.1; DHEA, d = 0.4). CONCLUSION: Strain plus hormonal stimuli (Ex+DHEA) resulted in the largest increase in FFM whereas the hormonal stimulus of DHEA resulted in the largest increase in Lspine aBMD. All conditions opposed the decreases in Lspine aBMD and FFM with aging. Because the sample size was less than originally planned, these results should be interpreted cautiously. Supported by: NIH/NIA R01 AG053489; NIH/NAIMS R01 AR077924; NIH/NCATS Colorado CTSA UM1 TR004399; NIH/NIDDK P30 DK048520