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Dehydroepiandrosterone Supplementation and Bone Turnover in Middle-Aged to Elderly Men

Department of Growth and Development (A.J.K.), and the Department of Medicine and Physiology and Division of Endocrinology at the VA Medical Center (B.H.), University of California at San Francisco, California 94143-0438

Address all correspondence and requests for reprints to: Dr. Arnold Kahn, Department of Growth and Development, University of California-San Francisco School of Dentistry, 707 Parnassus Avenue, D-1018, San Francisco, California 94143-0438. E-mail: . olbones{at}itsa.ucsf.edu

Abstract

In the present placebo-controlled, double-blind study, we assessed the effect of dehydroepiandrosterone (DHEA) supplementation (90 mg orally/d) on bone turnover in 43 healthy men, 56–80 yr old. Placebo or steroid was given for 6 months, followed by a 1-month washout period and then a further 6 months of the opposite agent. Serum samples were collected at baseline 3, 6, 7, and 13 months and assayed for procollagen peptide, bone-specific alkaline phosphatase, and osteocalcin, all markers of bone formation. Measurements were also made of serum cortisol, DHEA/DHEA-S, E2 and free and total T. First void, fasting urine was collected at baseline, 6, 7, and 13 months and assessed for deoxypyridinoline, a marker of bone resorption. Mean serum DHEA and DHEA-S levels in treated men were increased approximately 3-fold (2.2 ng/ml to 6 ng/ml) and 4.5-fold (1000 ng/ml to 4500 ng/ml), respectively, after 6 months and returned to baseline after washout. Similarly, circulating E2 concentrations were also increased 1.4-fold (from 16–23 pg/ml; P < 0.001), a finding not observed with any other measured hormone. Bone marker levels remained remarkably constant at each sampling interval; procollagen peptide at approximately 8.0 ng/ml; bone-specific alkaline phosphatase at approximately 21.0 U/liter; deoxypyridinoline at 4.5 nmol/mmol Cr. Osteocalcin showed a transient reduction from approximately 10.2- 6.2 ng/ml, P < 0.005 to P < 0.001, at 3 months, but this decline was observed in both treated and controls. Stratifying the marker levels by age or baseline DHEA/DHEA-S levels did not affect the findings. We conclude that oral DHEA does not affect bone turnover in middle-aged to elderly men when used for a 6-month period at doses targeted to restore circulating levels of the steroid to that seen in young adults.

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