Objective: To determine the effect of administering 6 months of oral postmenopausal DHEA therapy on serum DHEA, DHEAS, and T levels and on physiologic endpoints including lipoproteins and insulin-like growth factor-I (IGF-T). Design: Randomized, double-blind, parallel trial. Setting: Academic referral practice. Patient(s): Thirteen normal-weight or overweight, healthy, nonsmoking, postmenopausal women. Intervention(s): Administration of oral micronized DHEA (25 mg/d). Main Outcome Measure(s): Monthly fasting 23 hours postdose levels of serum DHEA, DHEAS, T, lipoproteins, IGF binding protein-3 (IGFBP-3), and liver function tests. Morphometric indices by dual-energy x-ray absorptiometry (percent body fat; lean body mass), immune indices, and insulin sensitivity. Result(s): Levels of DHEA, DHEAS, and T all rose into premenopausal ranges, but after 6 months, levels of DHEA T did not differ from baseline or placebo. At 3 months, the ratio of IGF-I to IGFBP-3 rose by 36.1% +/- 12.7%, but it to placebo values by 6 months. High-density lipoprotein and apolipoprotein A1 levels declined. Conclusion(s): Patients appeared to tolerate 6 months of DHEA therapy well. Given the small study size, no significant differences in morphometric indices, immune indices, or insulin-sensitizing properties were observed, significant attenuation of bioavailability occurred. Supplementation with DHEA increased IGFI/IGFBP-3 levels at months and decreased high-density lipoprotein and apolipoprotein A1 levels at 6 months. (Fertil Steril(R) (C) 1998 by American Society for Reproductive Medicine.).