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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. Author: Jankowski CM, Gozansky WS, Kittelson JM, Van Pelt RE, Schwartz RS, Kohrt WM. Journal: J Clin Endocrinol Metab; 2008 Dec; 93(12):4767-73. PubMed ID: 18812486. 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.[Abstract] [Full Text] [Related] [New Search]