To investigate the possible role of melatonin in the regulation of the human menstrual cycle, the circadian pattern of melatonin was determined in the follicular and luteal phases of 10 normal women. Four-hourly sampling was used to derive a melatonin index which described the total exposure to melatonin for 24 h. This sampling procedure adequately represented the circadian melatonin output and demonstrated that pulses of melatonin secretion, inconsistent with a measured half-life of 47 min, did not exist. A significant increase (P less than 0.001) in the melatonin index was found in the luteal phase compared to that in the follicular phase. To investigate the influence of exogenous progestins on the melatonin pattern, repeated 24-h profiles were measured in 8 women taking the 3-phase contraceptive pill. There was a significant increase (P less than 0.01) in the melatonin index associated with an increase in the dose of progestin. These results are consistent with a positive relationship between melatonin and progesterone and suggest that changes in the circadian pattern of melatonin secretion, rising during the luteal phase with a fall before ovulation, may act as a modulator of cyclicity.
PIP: 10 normal women participated in a study designed to investigate the possible role of melatonin in the regulation of the human menstrual cycle. The circadian pattern of melatonin was determined in the follicular and luteal phases of the study subjects who had conventional life styles and normal sleep/wake rhythms. Also investigated was the influence of exogenous steroids on the circadian pattern of melatonin, using subjects who were taking a 3-phase oral contraceptive (OC). Initially, 2 studies were performed to determine the frequency of sampling necessary to define the circadian profile of melatonin and to determine the relevance of that sampling frequency to the half-life of melatonin. 3 routes of administration were employed: 2 mg melatonin as a 0.04% solution in corn oil containing 2% ethanol, taken orally as a suspension in 50 ml milk; 2 mg melatonin in an 8% solution of ethanol in a nasal spray; and 2 mg melatonin in 250 mg ascorbic acid, taken orally in a gelatin capsule. A program of 4-hourly sampling was adopted. The 10 healthy women ranged in age from 20-40 years and had normal menstrual cycles. A circadian pattern of serum melatonin concentrations was observed in all study subjects. Figure 1 shows the 24-hour profiles of melatonin in 1 woman studied in the follicular and luteal phases of her menstrual cycle. The concentrations of melatonin in samples taken at intervals of 15 minutes for a 24-hour period indicated that episodic release did not take place. The increase in the melatonin index from the follicular to the luteal phase was highly significant for the group as a whole. The investigation of other aspects of the circadian pattern of melatonin showed a significant increase in the luteal phase compared to the follicular phase in peak serum melatonin concentrations, estimated from data at 4-hourly intervals. The mean duration of elevation was 11.6 +- 0.8 h in the luteal phase and 10.7 +- 0.7 h in the follicular phase. All subjects had a single peak concentration, at either 2400 or 0400 h. A change in the melatonin index was found in the 8 women using the 3-phase OC pill when sampled at 2 times during the cycle. A significant increase in the melatonin index was associated with an increase in the dose of progestin, either from no progestin intake to a low-dose or from a low-dose to a higher dose.