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Oral Dehydroepiandrosterone for Adrenal Androgen Replacement: Pharmacokinetics and Peripheral Conversion to Androgens and Estrogens in Young Healthy Females after Dexamethasone Suppression

Department of Endocrinology, Medical University Clinic Wuerzburg (W.A., H.-G.J., F.C., M.R., B.A.), Wuerzburg; Jenapharm (D.H., M.O., M.E.), Jena; and Institute for Hormone and Fertility Research (H.M.S.), Hamburg, Germany

Address all correspondence and requests for reprints to: Wiebke Arlt, Department of Endocrinology, Medical University Clinic, Josef-Schneider-Str. 2, 97080 Wuerzburg, Germany.

Women with adrenal insufficiency suffer from chronic dehydroepiandrosterone (sulfate) [DHEA(S)] deficiency. To define a suitable dose for DHEA replacement, we studied the pharmacokinetics and biotransformation of orally administered DHEA in nine healthy female volunteers (mean age 23.3 ± 4.1 yr, mean body mass index 22.5 ± 1.8 kg/m²) with transient suppression of adrenal androgen secretion because of dexamethasone (dex) administration (4 x 0.5 mg/day for 4 days). Diurnal blood sampling was performed during the early follicular phase of four subsequent menstrual cycles (study period 1: baseline; study periods 2–4: dex + placebo, dex + 50 mg DHEA or dex + 100 mg DHEA in a randomized cross-over design). Dex induced not only a significant suppression of serum cortisol (to 8% of baseline) but also of DHEA (18%), DHEA(S) (16%), and androstenedione (26%), as well as of testosterone (28%), dihydrotestosterone (43%), and estrone (54%). Oral administration of 50 mg DHEA led to restoration of DHEA(S) baseline levels, whereas 100 mg induced supraphysiological concentrations [baseline vs. 50 mg DHEA vs. 100 mg DHEA: area under the concentration-time curve (AUC) 0–12 h DHEA: 280 ± 85 vs. 241 ± 73 vs. 383 ± 106 nmol/L x h; AUC 0–12 h DHEA(S): 89.1 ± 48.4 vs. 139.6 ± 43.5 vs. 213.3 ± 21.6 µmol/L x h). Serum concentrations of dihydrotestosterone and estrone were restored to baseline after 50 mg DHEA, whereas baseline testosterone and androstenedione levels were only achieved by administration of 100 mg DHEA. In conclusion, 50 mg DHEA seems to be a suitable replacement dose in females with adrenal insufficiency. Furthermore, the rapid and lasting conversion to potent androgens demonstrates a potential role of DHEA for androgen replacement in females in general.

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