Long-term low-dose oral administration of dehydroepiandrosterone modulates adrenal response to adrenocorticotropic hormone in early and late postmenopausal women

Objective. The aging process is associated with a decline in the circulating Delta(5)-androgen dehydroepiandrosterone (DHEA) and its sulfate ester, dehydroepiandrosterone sulfate (DHEAS). The present study aimed to evaluate the effects of a long-term (12 months) oral DHEA administration (25 mg/day) on adrenal function, before and after 3, 6 and 12 months of treatment. Method. Postmenopausal women belonging to two age groups, 50-55 years (n= 10) and 60-65 years (n = 10), were studied. Adrenal function was assessed in basal conditions, after suppression with dexamethasone (DYM) and following a stimulation test with adrenocorticotropic hormone (ACTH) (10 mu g bolus). Serum levels of DHEA, DHEAS, androstenedione (Delta(4)-A), allopregnanolone, 17-hydroxyprogesterone (17-OHP) and cortisol were measured and the effects of DHEA supplementation on specific adrenal enzymatic pathways were evaluated by calculating precursor/product ratios (17-OHP/cortisol, 17-OHP/ Delta(4)-A, DHEA/Delta(4)-A and DHEA/DHEAS). Results. DHEA supplementation annulled the age-related differences in DHEA and DHEAS levels and induced a marked increase in all steroids, except for cortisol, after 3-6 months of treatment. Serum cortisol levels decreased from the 3rd month, both in younger and older subjects. DHEA supplementation did not affect DXM-induced suppression of adrenal steroidogenesis. During the treatment period all adrenal androgens and progestins showed a significant increase in their response to ACTH, while the cortisol response decreased significantly. The results suggest a significant DHEA-induced change in adrenal enzymatic activities, as also evidenced by the change in precursor/product ratios during therapy. Conclusion. Chronic DHEA administration is capable of modifying circulating levels of androgens and progestins in both early and late postmenopausal women by modulating the age-related changes in adrenal function.