Pharmacokinetics of dehydroepiandrosterone and its metabolites after long-term daily oral administration to healthy young men.

OBJECTIVE

To determine the effects of dehydroepiandrosterone (DHEA) supplementation on the pharmacokinetics of DHEA and its metabolites and the reproductive axis of healthy young men.

DESIGN

A prospective, randomized, double-blind, placebo-controlled pharmacokinetic study.

SETTING

General Clinical Research Center and laboratories at the Keck School of Medicine of the University of Southern California, Los Angeles, California.

PATIENT(S): Fourteen healthy men, ages 18-42 years.

INTERVENTION(S): Daily oral administration of placebo (n = 5), 50 mg DHEA (n = 4), or 200 mg DHEA (n = 5) for 6 months. Blood samples were collected at frequent intervals on day 1 and at months 3 and 6 of treatment.

MAIN OUTCOME MEASURE(S): Quantification of DHEA, DHEA sulfate (DHEAS), androstenedione, T, E(2), dihydrotestosterone (DHT), and 5alpha-androstane-3alpha-17beta-diol glucuronide (ADG). Physical examination, semen analysis, serum LH, FSH, prostate-specific antigen, and general chemistries were carried out.

RESULT(S): Baseline DHEA, DHEAS, and ADG levels increased significantly from day 1 to months 3 and 6 in the DHEA treatment groups but not in the placebo group. No significant changes were observed in pharmacokinetic values. Clinical parameters were not affected.

CONCLUSION(S): DHEA, DHEAS, and ADG increased significantly during 6 months of daily DHEA supplementation. Although the pharmacokinetics of DHEA and its metabolites are not altered, sustained baseline elevation of ADG, a distal DHT metabolite, raises concerns about the potential negative impact of DHEA supplementation on the prostate gland.