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J Clin Endocrinol Metab. 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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  • 1Division of Geriatric Medicine, University of Colorado Denver, mail stop B179, Room 8111, 12631 East 17th Avenue, Aurora, Colorado 80045, USA.

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.

PMID:
18812486
[PubMed - indexed for MEDLINE]
PMCID:
PMC2626446
Free PMC Article
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