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- Title
Increases in bone mineral density in response to oral dehydroepiandrosterone replacement in older adults appear to be mediated by serum estrogens.
- Authors
Jankowski, Catherine M; Gozansky, Wendolyn S; Kittelson, John M; Van Pelt, Rachael E; Schwartz, Robert S; Kohrt, Wendy M
- Abstract
<bold>Context: </bold>The mechanisms by which dehydroepiandrosterone (DHEA) replacement increases bone mineral density (BMD) in older adults are not known.<bold>Objective: </bold>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.<bold>Design, Setting, and Participants: </bold>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.<bold>Intervention: </bold>The intervention was oral DHEA 50 mg/d or placebo for 12 months.<bold>Main Outcome Measures: </bold>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.<bold>Results: </bold>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).<bold>Conclusions: </bold>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.
- Publication
Journal of Clinical Endocrinology & Metabolism, 2008, Vol 93, Issue 12, p4767
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/jc.2007-2614