Endocrinology: Melatonin potentiates testosterone-induced suppression of luteinizing hormone secretion in normal men

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Abstract
A total of 12 healthy adult men were recruited to investigate the effect of exogenous melatonin on the sensitivity of the hypothalamo-pituitary axis to sex steroid negative feedback. The experiment consisted of a double-blind, randomized cross-over trial during which all subjects received 100 mg oral melatonin or placebo at 1600 h for 14 days. Midway through each of the two treatments (day 8), 100 mg testosterone propionate i.m. (TP) was given at 0900 h. Blood samples for the measurement of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, testosterone and melatonin were taken at 0900 h on days 1, 3, 5, and daily from days 8–14. An additional blood sample was taken 8 h after the administration of testosterone. The interval between the melatonin and placebo treatment periods was 2 months. The oral administration of melatonin caused a pharmacological increase in the blood plasma concentration of melatonin which was maximum at 2 h and still above normal at 24 h. The daily treatment thus resulted in persistently high circulating levels of melatonin for 14 days. This treatment had no significant effect on the secretion of LH, FSH, prolactin or testosterone based on the first week of each study (melatonin compared with placebo). The injection of TP caused a rapid 3 to 4-fold increase in the plasma concentrations of testosterone which was at a maximum at 8 h and had returned to baseline within 4 days, with a similar pattern in both the melatonin and placebo periods. This dose of TP caused a decrease in the plasma concentrations of LH and FSH lasting 4 days; there was no change in the concentration of prolactin. The steroid-induced, time-dependent reduction in the plasma concentration of LH was significantly greater in the subjects receiving melatonin compared with placebo (analysis of variance P < 0.01); LH concentrations were suppressed to a greater extent and for one day longer during the administration of melatonin. This effect did not reach statistical significance for the changes in the plasma concentration of FSH. These results show that the sensitivity of the hypothalamo-pituitary axis to testosterone feedback is increased by pharmacological treatment with melatonin, and suggest novel strategies for the development of hormonal contraception in men.

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