Dehydroepiandrosterone replacement therapy in older adults: 1- and 2-y effects on bone.

Randomized, placebo-controlled trial in sedentary, nonsmoking adults aged 65 to 75 years. The active DHEA group included 56 randomized participants in year 1, with the cohort evenly split by sex (28 men and 28 women); a subset entered a 2-year open-label extension.

Oral DHEA 50 mg/day was given daily for 12 months in the randomized phase, with all participants also receiving vitamin D 16 µg/day (650 IU) and calcium 700 mg/day. A subset continued into a 2-year open-label extension with DHEA 50 mg/day.

DHEA improved lumbar spine bone mineral density in older women, but not in men, while hip and whole-body BMD did not change in either sex. In year 1, women receiving DHEA had a 1.8 ± 0.4% increase in lumbar spine BMD versus no change with placebo, and men had a 1.7 ± 0.3% increase with DHEA versus 1.1 ± 0.3% with placebo. Over 2 years, spine BMD gains were maintained or increased in women, including 3.6 ± 0.7% in women on 2 years of DHEA and 2.1 ± 0.7% in women who crossed over from placebo. In women, DHEA also increased IGF-1, estradiol, and total testosterone, while HDL decreased by 4.5 mg/dL.

Effects were sex-specific, limiting generalizability to men. The randomized phase was only 12 months, and the 2-year extension was open-label, reducing certainty about longer-term effects. The active-arm sample was modest, and the report does not indicate that the study was powered for multiple subgroup or biomarker outcomes.