Very short term dehydroepiandrosterone treatment in female adrenal failure: impact on carbohydrate, lipid and protein metabolism

Objective: In female adrenal insufficiency, dehydroepiandrosterone (DHEA) secretion is impaired and circulating androgen levels are severely reduced. We wanted to analyse the acute effects of physiological DHEA substitution on substrate metabolism. Design: We studied nine females with adrenal insufficiency after 9 days of oral DHEA replacement (50 mg/day) in a double-blind, placebo-controlled crossover study. Methods: Whole body and regional substrate metabolism was assayed in the basal state and during a euglycemic hyperinsulinemic glucose clamp by means of isotope dilution techniques (glucose, phenylalanine, tyrosine), indirect calorimetry and in situ lipolysis (microdialysis technique). Results: DHEA treatment normalized the levels of all androgens. Basal and insulin-stimulated total energy expenditure and rates of protein, lipid and glucose oxidation were unaffected by DHEA. Whole body turnover of glucose and protein were also unaffected by DHEA. Forearm breakdown of protein was reduced by insulin to the same extent after placebo and DHEA. Insulin sensitivity as expressed by the glucose infusion rate during the euglycemic clamp was similar after placebo and DHEA. Finally, the interstitial release of glycerol in adipose tissue was not significantly influenced by DHEA. Conclusions: Short-term oral DHEA replacement in women with adrenal insufficiency was not associated with measurable changes in total or regional substrate metabolism.