Pharmacokinetics of dehydroepiandrosterone and its metabolites after long-term oral dehydroepiandrosterone treatment in postmenopausal women.
OBJECTIVE
Some postmenopausal women use over-the-counter dehydroepiandrosterone because of its purported beneficial effects. Although without major inherent androgenic activity, it is metabolized to potent androgens and estrogens. We investigated the pharmacokinetics of dehydroepiandrosterone and its relevant metabolites after prolonged treatment of postmenopausal women with 25 mg/d of dehydroepiandrosterone.


METHODS
Twenty healthy postmenopausal women were randomized to either 25 mg/d of dehydroepiandrosterone or placebo for 6 months. Frequent blood samples were obtained over 24 hours on day 1 and after 3 and 6 months.


RESULTS
Mean baseline androgen levels at day 1 and month 3 in the treated group (seven evaluable women) were the following: dehydroepiandrosterone, 1.82 and 3.56 ng/mL; dehydroepiandrosterone sulfate, 0.96 and 3.37 microg/mL; 5-androstene-3beta,17beta-diol, 0.32 and 0.66 ng/mL; androstenedione, 0.50 and 0.86 ng/mL; testosterone, 17.9 and 28.7 ng/dL; dihydrotestosterone, 6.91 and 17.4 ng/dL; and 3alpha-androstanediol glucuronide, 2.66 and 10.7 ng/mL, respectively; these increases were significant. Small changes (-6% to 16%) were observed from month 3 to month 6. Nonsignificant increases were observed in baseline estrone and estradiol levels and in Cmax and AUC0-24h values for the androgens and estrogens from day 1 to months 3 and 6 of treatment. Sex hormone-binding globulin levels were unchanged, but free testosterone increased significantly from day 1 to month 3. Baseline hormone levels did not increase in the placebo group (six evaluable women). Changes in baseline values over time differed significantly between the groups for all hormones except estrone and estradiol.


CONCLUSIONS
In postmenopausal women treated orally with a commonly available dose of dehydroepiandrosterone, the daily exposure (AUC) of dehydroepiandrosterone and its principal androgenic metabolites was found to be similar during 6 months of treatment despite increased serum baseline concentrations of these androgens.
Stanczyk
Frank Z
FZ
Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. fstanczyk@socal.rr.com
Slater
Cristin C
CC
Ramos
Diana E
DE
Azen
Colleen
C
Cherala
Ganesh
G
Hakala
Charles
C
Abraham
Guy
G
Roy
Subir
S
D000368:Aged; D003687:Dehydroepiandrosterone / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood / Q000187:drug effects*; D013997:Time Factors; D016896:Treatment Outcome
D003687:Dehydroepiandrosterone