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The most abundant human steroids, dehydroepiandrosterone (DHEA) and its sulfate ester DHEAS, may have a multitude of beneficial effects, but decline with age. DHEA possibly prevents immunosenescence, and as a neuroactive steroid it may influence processes of cognition and memory. Epidemiological studies revealed an inverse correlation between DHEAS levels and the incidence of cardiovascular disease in men, but not in women. To define a suitable dose for DHEA substitution in elderly men we studied pharmacokinetics and biotransformation of orally administered DHEA in 14 healthy male volunteers (mean age, 58.8 ± 5.1 yr; mean body mass index, 25.5 ± 1.5 kg/m2) with serum DHEAS concentrations below 4.1 μmol/L (1500 ng/mL). Diurnal blood sampling was performed on 3 occasions in a single dose, randomized, cross-over design (oral administration of placebo, 50 mg DHEA, or 100 mg DHEA). The intake of 50 mg DHEA led to an increase in serum DHEAS to mean levels of young adult men, whereas 100 mg DHEA induced supraphysiological concentrations [placebo vs. 50 mg DHEA vs. 100 mg DHEA; area under the curve (AUC) 0–12 h (mean ± sd) for DHEA, 108 ± 22 vs. 252 ± 45 vs. 349 ± 72 nmol/L·h; AUC 0–12 h for DHEAS, 33 ± 9 vs. 114 ±. 19 vs. 164± 36 μmol/L·h]. Serum testosterone and dihydrotestosterone remained unchanged after DHEA administration. In contrast, 17β-estradiol and estrone significantly increased in a dose-dependent manner to concentrations still within the upper normal range for men[ placebo vs. 50 mg DHEA vs. 100 mg DHEA; AUC 0–12 h for 17β-estradiol, 510 ± 198 vs. 635 ± 156 vs. 700 ± 209 pmol/L·h (P &amp;lt; 0.0001); AUC 0–12 h for estrone, 1443 ± 269 vs. 2537 ± 434 vs. 3254 ± 671 pmol/L·h (P&amp;lt; 0.0001)]. In conclusion, 50 mg DHEA seems to be a suitable substitution dose in elderly men, as it leads to serum DHEAS concentrations usually measured in young healthy adults. The DHEA-induced increase in circulating estrogens may contribute to beneficial effects of DHEA in men.

Biotransformation of Oral Dehydroepiandrosterone in Elderly Men: Significant Increase in Circulating Estrogens