Dehydroepiandrosterone Replacement Administration: Pharmacokinetic and Pharmacodynamic Studies in Healthy Elderly Subjects1

Dehydroepiandrosterone (DHEA; 50 and 25 mg) and placebo tablets were orally administered daily to 24 healthy aging men and women (67.8 ± 4.3 yr) for 8 days according to a balanced incomplete block design. Nine blood tests on both the first and eighth days allowed the measurement of DHEA, its sulfate DHEAS, and metabolites: testosterone, 5α-androstan-3α,17β-diol glucuronide, estradiol, and estrone. Relatively low background levels of DHEA(S) were observed, and with the reestablishment of“ young” levels, four important results were obtained. 1) Blood DHEA had an apparent terminal half-life of more than 20 h, the same order of magnitude as that of blood DHEAS, a result explainable by back-hydrolysis of the large amount of DHEAS formed after oral administration of DHEA, a mechanism providing long-lived unconjugated DHEA and metabolites. 2) The metabolic conversion of DHEAS to DHEA was significantly greater in women than in men. 3) No accumulation of steroids was observed. 4) No worrying transformation to androgen and estrogen was recorded; indeed, the limited increased estradiol in aged women could be predicted to be beneficial. These results suggested that daily oral administration of DHEA (25/50 mg) is safe in elderly subjects. The 50-mg dose was chosen for a 1 yr, double blind, placebo-controlled trial of daily oral administration of DHEA in 60- to 80-yr-old individuals (DHEAge).