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 I and at months 3 and 6 of treatment. Main Outcome Measure(s): Quantification of DHEA, DHEA sulfate (DHEAS), androstenedione, T, E,, 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 I 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.