Effects of menstrual cycles on the human circadian clock

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On the day of the estrous cycle during which blood levels of estradiol are high, female hamsters start their nocturnal activity phase earlier, This change in the locomotor activity rhythm throughout the estrous cycle may be caused by a direct effect of estrogen and progesterone on the circadian clock. However, it has not been reported that human females show a menstrual variation in circadian rhythms. We examined the effects of the menstrual cycle on circadian rhythms in 6 healthy women and 6 women with premenstrual syndrome (PMS). We measured circadian rhythms of wrist activity and temperature as well as plasma concentration of melatonin in the follicular phase (FP) and luteal phase (LP). In healthy women and PMS women, there was no menstrual change in circadian rhythms in sleep and temperature. However, the onset of the nocturnal melatonin rise was delayed by about 1 hr in the LP in PMS women although no phase shift was observed in healthy women. Therefore, estrous changes in circadian rhythm as observed in rats may be inhibited in human females. We observed a PMS woman who showed alternative phase shifts in the sleep, temperature and melatonin rhythms in the menstrual cycle : progressive phase advances in the follicular phase and phase delays in the luteal phase in a way similar to hamsters. We speculated that disturbance of the inhibition mechanism might be involved in this subject. To clarify the etiology of this disease, we examined the effects of 17β-estradiol (E2) on the expression of an interneuronal gap junction gene connexin-32 mRNA in the suprachiasmatic nucleus (SCN), the site of the circadian clock. E2 increased connexin-32 mRNA in the SCN. Dysfunction of interneuronal communication in the SCN bay be involved in the mechanism of this disease since we have shown that gap junction couple neurons in the rat SCN.