Melatonin enhances cortisol levels in aged women: Reversible by estrogens

The administration of melatonin increases cortisol levels in postmenopausal women. Aging and hypoestrogenism are believed to impair the regulation of the hypothalamo-pituitary-adrenal axis and may participate in the determination of this altered response. In this study the implications of hypoestrogenism were tested. Seven postmenopausal women were studied. At 08.00 hr for 2 consecutive days, each woman received randomly and in a double blind fashion a pill of placebo or melatonin (100 mg). Serum melatonin and cortisol levels were evaluated at 20 min intervals, for 48 hr. Measurements were performed in the same subjects both during no estrogen supplementation and at least two cycles of conjugated estrogens administration (0.625 mg/day). During estrogen supplementation, postmenopausal women showed slightly lower cortisol levels at lunch and early night (20.00-01.00 hr). The onset of the nocturnal melatonin rise was not modified, but that of cortisol was delayed of about 60 min (P<0.02). The administration of melatonin elicited a marked increase in daytime cortisol levels in postmenopausal women (P<0.02), but this stimulus completely disappeared during estrogen administration. Mean nighttime (20.00-08.00 hr) cortisol levels were not modified by daytime administration of melatonin. The present data reveal that in aged postmenopausal women, reversal of hypoestrogenism, resulting from supplemental estrogens, may improve the regulation of the hypothalamopituitary-adrenal axis.