Influence of exogenous melatonin on catecholamine levels in postmenopausal women prior and during oestradiol replacement

OBJECTIVE In young individuals melatonin administration reduces circulating norepinephrine. Some effects of melatonin are reduced in elderly women and are modulated by gonadal steroids, Accordingly, the influence of melatonin on catecholamine levels was investigated in postmenopausal women without and with oestradiol replacement. DESIGN Prior to and after 2 months of transdermal oestradiol (50 mu g/day), women were studied on two consecutive days, on which they received placebo or 1 mg of melatonin orally in a randomised and double-blind fashion. PATIENTS Fourteen healthy postmenopausal women, MEASUREMENTS Resting levels of epinephrine and norepinephrine and their responses to both a cold stimulus, performed by placing a hand in a basin of water and ice for 2 minutes, and to 10 minutes of upright position (upright test), RESULTS Prior to oestradiol, melatonin did not modify baseline or stimulated catecholamine levels, In contrast, during oestradiol, melatonin tended to reduce, although not significantly, baseline norepinephrine levels (P=0.053), and significantly reduced peak values (P=0.0061) and integrated norepinephrine response (P=0.0076) to the cold stimulus. Responses of norepinephrine to the upright test were not modified, while those of epinephrine were increased (P=0.042). During, but not prior to oestradiol replacement, modifications induced by melatonin (melatonin day-placebo day) in the norepinephrine response to the cold (r(2) = 0.457; P = 0.0079) and the upright (r(2)=0.747; P=0.0001) tests were linearly and inversely related to the responses of the placebo day. CONCLUSIONS Melatonin does not modulate adrenergic activity in postmenopausal women without hormone replacement therapy. Oestradiol replacement restores the capability of melatonin to modulate adrenergic activity, particularly the norepinephrine response to stimuli.