Influence of oral dehydroepiandrosterone (DHEA) on urinary steroid metabolites in males and females

Oral dehydroepiandrosterone (DHEA replacement therapy may have a multitude of potential beneficial effects anti exerts its action mainly via periphera l bioconversion to androgens land estrogens). A daily dose of 50-mg DHEA ha s been shown by us and others to restore low endogenous serum DHEA concentr ations to normal youthful levels followed by an increase in circulating and rogens and estrogens. As the hepatic first-pass effect may lead to a non ph ysiological metabolism of DHEA after oral ingestion we studied the influenc e of two single DHEA doses (50 and 100 mg) on the excretion of steroid meta bolites in 14 elderly males [age 58.8 +/- 5.1 years (mean +/- SEM)] with en dogenous DHEAS levels < 1500 ng/ml and in 9 healthy females (age 23.3 +/- 4 .1 years) with transient suppression of endogenous DHEA secretion induced b y dexamethasone (dex) pretreatment (4 x 0.5 mg/day/4 days). Urinary steroid profiles in the elderly males were compared to the steroid patterns found in 15 healthy young men (age 28.9 +/- 5.1 years). In the females the result s were compared to their individual baseline excretion without dex pretreat ment. Urinary steroid determinations were carried out by semiautomatic capi llary gas-liquid chromatography. In both genders DHEA administration induce d significant increases in urinary DHEA (females: baseline vs. 50 me vs. 10 0 mg: 361 +/- 131 vs. 510 +/- 264 vs. 1531 +/- 587 mu g/day; males: placebo vs. 50 mg vs. 100 mg: 431 +/- 154 vs. 1173 +/- 309 vs. 4751 +/- 1059 mu g/ day) as well as in the major DHEA metabolites androsterone (A) and etiochol anolone (Et). Fifty mg DHEA led to an excretion of DHEA and its metabolites only slightly above baseline levels found in young females and in young me n, respectively, whereas 100 mg induced clearly supraphysiological values. After 50 mg DHEA the ratios of urinary DHEA metabolites (A/DHEA, Et/DHEA) w ere not significantly different between elderly males vs, young male volunt eers and young healthy females versus their individual baseline levels. In conclusion, an oral dose of 30 to 50 mg DHEA restores a physiological urina ry steroid profile in subjects with DHEA deficiency without evidence for a relevant hepatic first-pass effect on urinary metabolites. (C) 2000 Elsevie r Science Inc. All rights reserved.