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Dehydroepiandrosterone Reduces Serum Low Density Lipoprotein Levels and Body Fat but Does not Alter Insulin Sensitivity in Normal Men^*

JOHN E. NESTLER, CORNELIUS O. BARLASCINI, JOHN N. CLORE and WILLIAM G. BLACKARD

Division of Endocrinology and Metabolism, Medical College of Virginia/Virginia Commonwealth University Richmond, Virginia 23298

Address all correspondence and requests for reprints to: John E. Nestler, M.D., Division of Endocrinology and Metabolism, Medical College of Virginia, MCV Station, Box 111, Richmond, Virginia 23298.

To assess the effects of dehydroepiandrosterone (DHEA) on body fat mass, serum lipid levels, and tissue sensitivity to insulin, five normal men were given placebo and five normal men were given oral DHEA [1600 mg/day (554.7 mmol/ day)] for 28 days in a randomized, double blind study. In the DHEA group serum DHEA-S levels rose 2.5- to 3.5-fold, and mean (±SEM) serum androstenedione rose from 4.3 ± 0.6 to 8.6 ± 1.2 nmol/L (P < 0.004, by paired t test), but serum total testosterone, free testosterone, sex hormone-binding globulin, estradiol, and estrone levels did not change.

In the DHEA group the mean percent body fat decreased by 31%, with no change in weight. This suggests that the reduction in fat mass was coupled with an increase in muscle mass. DHEA administration also resulted in a fall in mean serum total cholesterol concentration (4.82 ± 0.21 vs. 4.48 ± 0.29 nmol/L; P < 0.05), which was due almost entirely to a fall of 7.5% in mean serum low density lipoprotein cholesterol (3.21 ± 0.11 vs. 2.97 ± 0.14 nmol/L; P < 0.01). No changes in anthropometric parameters or serum lipid levels occurred in the placebo group. Tissue sensitivity to insulin, assessed by the hyperinsulinemic-euglycemic clamp technique, did not change in either the placebo or DHEA groups.

These results suggest that in normal men DHEA administration reduces body fat, increases muscle mass, and reduces serum low density lipoprotein cholesterol levels. Tissue sensitivity to insulin was unaffected by short term DHEA administration.

^* This work was supported in part by NIH Grants AM-07428 and RR-00065.

Recipient of a Clinical Associate Physician award from the NIH.

Received July 6, 1987.

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