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Randomized Controlled Trial
. 2008 Dec;93(12):4767-73.
doi: 10.1210/jc.2007-2614. Epub 2008 Sep 23.

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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Free PMC article
Randomized Controlled Trial

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

Catherine M Jankowski et al. J Clin Endocrinol Metab. .
Free PMC article

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 (E(2)), estrone (E(1)), 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, E(1), E(2), FEI, and IGF-I (all P < 0.001) and decreased SHBG (P = 0.02) in women and, in men, increased DHEAS, E(1), FEI (all P < 0.001), and E(2) (P = 0.02) and decreased SHBG (P = 0.037). The changes in total and regional hip BMD were associated with 12-month E(2) (all P <or= 0.001) and FEI (all P <or= 0.013). The effects of DHEA treatment were eliminated by adjustment for 12-month E(2).

Conclusions: The significant increases in hip BMD in older adults undergoing DHEA replacement were mediated primarily by increases in serum E(2) rather than direct effects of DHEAS.

Figures

Figure 1
Figure 1
Serum markers of bone resorption (CTX) and formation (BAP) before intervention (top panels) and changes in response to 12 months of DHEA or placebo therapy (bottom panels). Values are mean ± se. *, Different from change in placebo group, P < 0.05.

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