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 Delta5-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.


METHODS
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 (DXM) and following a stimulation test with adrenocorticotropic hormone (ACTH) (10 microg bolus). Serum levels of DHEA, DHEAS, androstenedione (Delta4-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/Delta4-A, DHEA/Delta4-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.


CONCLUSIONS
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.
Genazzani
Andrea R
AR
Department of Reproductive Medicine and Child Development, Division of Gynecology and Obstetrics, University of Pisa, Pisa, Italy. a.genazzani@obgyn.med.unipi.it
Pluchino
Nicola
N
Begliuomini
Silvia
S
Stomati
Massimo
M
Bernardi
Francesca
F
Pieri
Matteo
M
Casarosa
Elena
E
Palumbo
Marco
M
Genazzani
Alessandro D
AD
Luisi
Michele
M
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000284:Administration, Oral; D000311:Adrenal Glands / Q000187:drug effects* / Q000201:enzymology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000368:Aged; D003687:Dehydroepiandrosterone / Q000008:administration & dosage* / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause / Q000187:drug effects*; D013256:Steroids / Q000097:blood; D013997:Time Factors
D000276:Adjuvants, Immunologic; D013256:Steroids; D003687:Dehydroepiandrosterone; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone