Amplification of nocturnal melatonin secretion in women with functional secondary amenorrhoea: relation to endogenous oestrogen concentration

BACKGROUND AND OBJECTIVE: Although there is extensive evidence that melatonin inhibits gonadotrophin secretion in animals, there is a parity of data on the relation between melatonin and ovarian function in humans. The purpose of this study was to evaluate the relation between endogenous oestrogen concentrations and nocturnal melatonin secretion occurring in patients with secondary amenorrhoea (SA). DESIGN AND PATIENTS: Nocturnal serum melatonin concentrations were determined in 20 women with SA, 5 women with endometriosis showing normal menstrual cycles and 11 volunteers with normal menstrual cycles. MEASUREMENT: Serum melatonin concentrations were determined by high performance liquid chromatography with electrochemical detection. Differences in melatonin concentrations were examined by analysis of variance. RESULTS: Nocturnal melatonin concentrations in patients with SA were significantly higher than in normal women (P < 0.01 vs women with normal menstrual cycles). There were significant negative correlations between cummulative melatonin levels (between 2000 and 0800 h) and serum 17 beta-oestradiol (r = -0.561, p < 0.01) and between peak serum melatonin values and the serum 17 beta-oestradiol (r = -0.608, P < 0.01) in SA. Intravenous administration of a conjugated oestrogen (Premarin 20 mg) significantly suppressed nocturnal melatonin secretion (P < 0.05). A low oestrogen state, induced by long-term (3.5 months) GnRH agonist treatment (900 micrograms/day of buserelin acetate) of the women with endometriosis produced an increase in nocturnal melatonin secretion comparable to that found in SA women. CONCLUSION: Our findings suggest that elevated nocturnal melatonin secretion in women with secondary amenorrhoea may be related to their low oestrogen concentrations.