Sex Differences in the Pharmacokinetics of Dehydroepiandrosterone (DHEA) after Single‐ and Multiple‐Dose Administration in Healthy Older Adults

The pharmacokinetics of exogenously administered DHEA have not been well characterized despite its increasing use in therapeutic and research investigations. The purpose of this study was to evaluate the pharmacokinetics of DHEA and its sulfated metabolite (DHEA‐S) after single‐ and multiple‐dose oral administration of DHEA 200 mg. Healthy older adult volunteers (7 women, 6 men) ages 65 to 79 years were studied on five visits separated by 1 week. Subjects received daily administration of placebo (days 1 to 7), DHEA 200 mg (days 8 to 22), and placebo (days 23 to 29). Blood samples were collected over 24 hours on days 1, 8, 15, 22, and 29 for DHEA and DHEA‐S determinations by RIA. Pharmacokinetic parameter estimates were calculated by noncompartmental methods. Administration of DHEA 200 mg resulted in higher DHEA Cmax,AUC, and overall concentrations in women than in men (p <0.03); DHEA‐S parameter estimates were similar between men and women. Following a single dose of DHEA 200 mg, DHEA concentrations increased 5‐ to 6‐fold in both men and women, and DHEA‐S concentrations increased 5‐fold in men and 21‐fold in women relative to endogenous concentrations. The results of this study indicate that the pharmacokinetics of DHEA differ between older men and women.