The Circadian Pattern of Melatonin and Its Positive Relationship with Progesterone in Women

Abstract

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.

Seasonal Variations of Melatonin Secretion in Young Females under Natural and Artificial Light Conditions in Fukuoka, Japan

“…There are several studies which observed an increase of the human serum melatonin level in the luteal phase compared to the follicular phase during the menstrual cycle (Arendt, 1978;Webley and Leidenberger, 1986). Opposite to this, Ito et al (1995) and Kivela et al (1988) reported no significant effect of the menstrual cycle on plasma or serum melatonin levels, but Kivela et al (1988) also found that the mean nighttime serum melatonin levels were significantly higher in winter than in summer during the follicular phase.…”

The Relationship of Nocturnal Melatonin to Estradiol and Progesterone in Depressed and Healthy Pregnant Women

“…In cycling women, Webley and Leidenberger 23 found that increased P 4 during the luteal vs. follicular menstrual phase was associated with significantly increased melatonin levels; furthermore, in women taking three-phase oral contraceptives, increased P 4 dosage also was associated with elevated total 24-hour melatonin exposure. Increased melatonin secretion in association with oral contraceptive use has been reported elsewhere.…”

Potential drug interactions with melatonin

“…Mean serum ethinyloestradiol levels following 30 mg administration were reported to be about 0.5 nM [53], which is much lower than the concentration that caused impairment in the metabolism of melatonin (1 M) in the current study so that at clinically relevant concentrations (< 10 nM) it is unlikely to impair the sulphate conjugation of exogenous melatonin. However, the much lower endogenous levels of melatonin may be impaired by 17α-ethinyloestradiol and such a mechanism may explain to some extent why melatonin levels during the night are higher in females taking oral contraceptives [54][55][56]. Since 17-ethinyloestradiol appeared to decrease the sulphate conjugation of 6-hydroxymelatonin, it would be advisable in studies assessing melatonin treatment to exclude volunteers that use oral contraceptives as it could influence their melatonin profiles.…”