Increases in Bone Mineral Density in Response to Oral Dehydroepiandrosterone Replacement in Older Adults Appear to Be Mediated by Serum Estrogens

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Abstract

Context:

The mechanisms by which dehydroepiandrosterone (DHEA) replacement increases bone mineral density (BMD) in older adults are not known.

Objective:

The aims were to determine the effects of DHEA therapy on changes in sex hormones and IGF-I and their associations with changes in BMD.

Design, Setting, and Participants:

A randomized, double-blinded, placebo-controlled trial was conducted at an academic research institution. Participants were 58 women and 61 men, aged 60-88 yr, with low serum DHEA sulfate (DHEAS) levels.

Intervention:

The intervention was oral DHEA 50 mg/d or placebo for 12 months.

Main Outcome Measures:

BMD and serum DHEAS, testosterone, estradiol (E2), estrone (E1), SHBG, IGF-I, and IGF binding protein 3 were measured before and after intervention. Free testosterone and estrogen (FEI) indices were calculated.

Results:

The average changes in hip and spine BMD (DHEA vs. placebo) ranged from 1.1 to 1.6%. Compared with placebo, DHEA replacement increased serum DHEAS, testosterone, free testosterone index, E1, E2, FEI, and IGF-I (all P < 0.001) and decreased SHBG (P = 0.02) in women and, in men, increased DHEAS, E1, FEI (all P < 0.001), and E2 (P = 0.02) and decreased SHBG (P = 0.037). The changes in total and regional hip BMD were associated with 12-month E2 (all P ≤ 0.001) and FEI (all P ≤ 0.013). The effects of DHEA treatment were eliminated by adjustment for 12-month E2.

Conclusions:

The significant increases in hip BMD in older adults undergoing DHEA replacement were mediated primarily by increases in serum E2 rather than direct effects of DHEAS.

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