Does Dehydroepiandrosterone Replacement Augment Gains in Lean Mass with Resistance Training in Older Adults?

The age-related declines in the adrenal production of dehydroepiandrosterone (DHEA) and its ester, DHEA sulfate (DHEAS), may limit the hypertrophic response of muscle to resistance exercise training (REX) in older adults. DHEAS may have direct anabolic effects mediated by systemic and/or tissue-specific mechanisms in a variety of tissues, including skeletal muscle, as well as indirect anabolic effects mediated by increases in serum insulin-like growth factor-1 (IGF-1). PURPOSE: We tested the hypothesis that DHEA replacement therapy in older women (W) and men (M) would augment REX-induced gains in fat-free mass (FFM) when compared with placebo therapy. METHODS: As part of a larger randomized controlled trial (R01 AG18857), 140 adults aged 60+ with low serum DHEAS (< 3.8 umol/L) were randomized to DHEA replacement (50 mg/day; DHEA) or placebo (PLAC) for 12 months. Eighteen participants (mean ± SD; age = 68 ± 7y; BMI = 26 ± 4 kg/m2), naïve to REX, agreed to continue study treatment (DHEA, 2W/3M; PLAC, 6W/7M) for an additional 6 months and to engage in REX (2 sets of 5–8 repetitions of 7 exercises performed at 80% of the one repetition maximum, 3d/wk). Muscle strength, fasted serum DHEAS and IGF-1, and body composition were measured before and after training. RESULTS: Before training, there were no significant differences between the groups in body composition or muscular strength (all P >0.66). Serum DHEAS (9.9 ± 0.7 vs 1.1 ±0.8 umol/L;P< 0.001) and IGF-1 (181 ±36 vs. 143 ± 45 ng/ml; P = 0.02) were significantly greater in the DHEA group throughout the intervention. In response to REX, there was a trend for the DHEA group to have greater gains in FFM than the PLAC group (2.6 ± 1.5 vs. 1.2 ± 1.4 kg; P = 0.07). There were no significant differences between groups in the loss of fat mass (DHEA, −2.0 ± 1.9; PLAC, −1.3 ±3.6 kg; P = 0.70) or the increase in muscle strength averaged across all exercises (DHEA, 37 ±12%; PLAC, 39 ± 18%;P = 0.83). CONCLUSION: The trend for greater gains in FFM in response to REX with DHEA replacement compared with PLAC suggests that raising serum DHEAS to youthful levels in older adults may promote anabolic mechanisms. Increased serum IGF-1 in response to DHEA replacement may mediate these hypertrophic effects. Future research will be needed to a) confirm these preliminary findings, b) determine the efficacy of combined DHEA and REX as a therapy to ameliorate sarcopenia, and c) further elucidate the systemic and tissue-specific mechanisms activated by DHEA replacement.