Circadian Pattern of Plasma Melatonin Concentrations during Four Phases of the Human Menstrual Cycle

Abstract

The role of melatonin in human reproductive physiology remains obscure. Previous investigations of the nocturnal melatonin secretory pattern during the human menstrual cycle have yielded conflicting results and have been limited by incomplete characterization of the pertinent features of the circadian pattern such as magnitude, duration, or circadian position of the nocturnal increase, by incomplete assessments of ovarian secretion and menstrual cycle phase, or by both. In the present study, the circadian melatonin profile was characterized by obtaining plasma samples at hourly intervals from 10.00 to 17.00 h and at half-hourly intervals from 17.00 to 10.00 h in 10 women during four prospectively estimated menstrual phases: early follicular, late follicular, midluteal, and late luteal. Menstrual phases and ovarian function were confirmed by obtaining daily serum samples for LH, FSH, estradiol, and progesterone during the entire menstrual cycle. Eight women had ovulatory cycles with luteal lengths of greater than 11 days and with determinations of the circadian melatonin pattern during each menstrual phase. Despite gonadal steroid excursions characteristic of ovulatory cycles, consistent variations in plasma melatonin patterns by menstrual phase were not found. Daytime levels were at or below 43 pmol/l in all women and all but 2 women displayed prominent nocturnal elevations. While changes in the circadian pattern of melatonin secretion immediately preceding the LH surge cannot be excluded, the lack of consistent variation by menstrual cycle phase and the absence of clear circadian variation found in 2 women suggests that the secretory profile of melatonin is unaltered by fluctuations in gonadal steroids and that melatonin secretion may not be necessary for menstrual cyclicity to occur.

Plasma Melatonin Rhythm in Normal Puberty: Interactions of Age and Pubertal Stages

“…In fact, different results possibly might be obtained by frequent instantaneous blood sampling, rather than the constant withdrawal technique used in the present study. The results, however, are consistent with reports of studies in adults in differing environmental conditions (shift work, travel across time zones) and in various phy siologic or pathologic states (healthy subjects, phases of the menstrual cycle, depression, liver disease), in which visual inspection of the graphics or actual data suggest that the duration of the nocturnal surge is rather stable [34][35][36][37][38][39], Moreover, since human wake/sleep patterns are usually linked to light/dark cycles, we expected that later bedtimes might produce a shift toward later melatonin peak. Despite a significant trend for later bedtime with age, no significant shift in the time of melatonin peak was noted across age groups or along pubertal development, rendering unlikely the hypothesis that such a temporal al teration of the melatonin rhythm provides a signal for ini tiation of human puberty.…”

Plasma Melatonin Profile and Hormonal Interactions in the Menstrual Cycles of Anovulatory Infertile Women Treated with Gonadotropins

“…The plasma melatonin concentrations measured in this study are close to the values reported in patients suffering from anovulatory disorders who are on gonadotropin therapy [14] but are considerably higher than the values in normal subjects [10]. The variation in melatonin levels across the cycle was significant (F = 2.38; d.f.…”

“…Consequently, it has been implicated in the control of pubertal onset [2,3] and timing of ovulation [4,5] in humans, Melatonin levels were reported to fluctuate during the menstrual cycle [6] or pregnancy [7], and significant correlations with sex steroids have been reported [7][8][9]. The melatonin profile, however, varied among studies as reports indicating higher follicular levels [8], higher luteal levels [9] or no fluctuations [10] have appeared in the literature. These inconsistencies are possibly accounted for by differences in the background levels of gonadotropins and sex steroids that exist under a dynamic state of interplay during the menstrual cycle.…”

Melatonin and estrogen in breast cyst fluids

“…To our knowledge, this was the first study to identify melatonin in human BCF. Average intracystic melatonin concentrations (229 ± 25 pg/ml) were approximately 5-23 times greater than published daytime serum concentrations among pre-or post-menopausal women (approximately 10-50 pg/ml), and about 3-4 times greater than circulating nighttime concentrations (approximately 60-80 pg/ml) [44][45][46][47][48]. Furthermore, intracystic melatonin levels observed in this study were similar to those previously associated with inhibition of cancer cell growth in vitro (typically 1 nM or 232 pg/ml) [40][41][42].…”