The Menstrual Cycle and Sleep

Women show a dramatic increase in sleep disturbance when they approach menopause (i.e., during the transition to peri-menopause to menopause) (Baker et al 2018). Self-reported sleep complaints in the midlife years are more likely during the premenstrual week and during the first few days of menstruation compared to other times of the cycle. For example, the Study of Women’s Health Across the Nation (SWAN), which included women in their late reproductive years and women entering the menopausal transition, reported that self-report sleep disturbance varied with cycle phase, being more likely to occur during the late luteal and early follicular phases of the menstrual cycle. 18 After controlling for cycle day and other confounders, poorer sleep quality was associated with hormonal factors, although relationships differed depending on reproductive stage: higher levels of a progesterone metabolite, pregnanediol glucuronide, in urine were related to more trouble sleeping in the perimenopausal group, and higher urine FSH levels were related to more sleeping complaints in the premenopausal group. 18 Menstrual cycle-related changes may impact sleep more prominently with advancing age: although hormone levels were not measured, a large actigraphy study of late-reproductive aged women in SWAN, found a 5% decline in sleep efficiency and a 25-minute decrease in total sleep time in the premenstrual week relative to the prior week 27 and a small PSG study found that women in the menopausal transition who were still cycling had more awakenings and arousals, as well as less N3 sleep in the luteal phase compared to the follicular phase 40 - effects that are not observed in most studies of younger women. While there was no change in slow wave EEG activity, the upper frequency range of sleep spindles significantly increase in the luteal phase compared with the follicular phase. 40 Interestingly, midlife women with insomnia showed a blunted rise in sigma EEG activity in the luteal phase, possibly reflecting a weaker influence of the menstrual cycle on sleep EEG in the presence of insomnia. 40 Further investigation is necessary to examine distinct trajectories of sleep disturbance across the menstrual cycle in the context of sex hormone levels, menopausal symptoms, and age.

Sleep duration, timing, and quality can influence the reproductive system and particular sleep stages are also important for reproductive maturity: During puberty, LH is released in a pulsatile fashion during N3, playing a critical role in reproductive regulation. 106 , 107 In adultood, the direction of this relationship changes in the early follicular phase, with sleep inhibiting LH secretion, which may be necessary for recruitment of ovarian follicles. 108 There are reports of associations between short sleep duration and altered menstrual cycles. Women reporting < 6 h sleep were more likely to report abnormal (short or long) menstrual cycle lengths 109 . There has been a larger body of work investigating the impact of shiftwork on reproductive function in women, given the typical disrupted sleep and circadian patterns in this group, as reviewed in detail elsewhere. 110 In general, observational studies have provided evidence for reproductive disturbances such as menstrual irregularity and subfertility in women shift workers. 111 For example, a 2014 meta-analysis of 4 studies involving 28,479 women suggested that shift workers experience higher rates of infertility. 112 Similarly, a meta-analysis of 4 studies involving 71,681 women suggested that shift workers experience higher rates of menstrual disruption (cycles less than 25 days or greater than 31 days) compared to non-shift workers. 112 Some evidence suggests that shift work, particularly night-shift work, may lead to fertility problems and increased risk for miscarriage, however the effect size is uncertain. 113 Meta-analyses of the literature investigating the association between various working conditions and fetal and maternal health concluded that shiftwork poses minimal risk to the female reproductive system 114 and that there is insufficient evidence for clinicians to advise restricting shiftwork in reproductive-age women. 112 However, several professional bodies on health and safety state that shift work, particularly night shift work, may increase risk for menstrual cycle disruption or pregnancy complications. The nature of the relationship between shiftwork and reproductive health remains unclear, but it could relate to increased stress, disrupted circadian rhythms and/or sleep, which influence reproductive hormone secretion, particularly LH and FSH. In vitro fertilization (IVF) is a widely used assisted reproductive technology, as it offers a solution for infertility and other reproductive issues. Emerging work has begun to examine the impact of sleep on IVF outcomes since sleep can affect various physiological processes that play a role in the success of the treatment, such as hormone regulation, immune function, and stress levels. Sleep disturbances are commonly reported throughout the IVF treatment process. 115 A pilot study of 22 women that used subjective and objective measures found that almost half of the group has short actigraphic TST (< 7 hours) at baseline, and this percentage remained high across IVF treatment until post-embryo transfer. Daytime sleepiness was also common in the group and increased significantly from baseline to stimulation. 116 There was a trend for a positive association of TST with oocytes retrieved in this small sample, suggesting that sleep duration may be an important factor for IVF success. Another study using actigraphy 117 showed an association between shorter sleep duration and higher rates of implantation failure. Poor sleep quality may be a risk factor for adverse IVF embryo transfer, 118 while good sleep quality has been associated with successful outcomes in IVF treatments, including higher rates of clinical pregnancy and live birth. 118 It should be acknowledged, however, that the association between sleep and reproductive function may be bidirectional. Disturbed sleep may interfere with fertility but, the distress associated with infertility can also contribute to a poor sleep quality and shorter sleep. 119 Reschini and colleagues 120 examined sleep quality and psychological health (i.e., infertility related distress and symptoms of anxiety and depression) in women undergoing IVF treatment. While results showed that only sleep quality was linked with IVF treatment success, they concluded the association between poor sleep quality and lower chances of pregnancy were mediated by a poorer psychological health. Further longitudinal studies of larger samples of women preparing for and undergoing IVF are required to fully understand the role of sleep in the success of IVF outcomes.

Aspects of sleep and circadian rhythms are altered in association with the hormonal changes of the menstrual cycle, with negative effects on sleep most evident in the presence of menstrual-associated disorders. The magnitude of effect varies, particularly for self-reported sleep quality, which worsens in some, but not all, women when premenstrual symptoms emerge. For research purposes, effects of menstrual cycle phase should be kept in mind when data are collected, and ideally, phase should be documented. There are diverse menstrual cycle profiles such that inter-subject variability needs to be accounted when studing sleep. When comparing women with men, women of reproductive age should be studied in the follicular phase before there is potential influence from the rise in progesterone. Women's lives are marked by significant hormomal fluctuations during (i.e., menstrual cycle) and across (i.e., puberty, menopause) their reproductive years that affect sleep, which can have consequences for their physical, mental and emotional wellbeing. Sleep is an essential behavior that needs to be prioritized in the context of women´s health. Providing women with menstrual health education, necessary resources, and psychosocial support to manage the effects of hormonal changes can help them navigate potential challenges to sleep that may accompany these transformative phases.

Most women have menstrual cycle lengths between 21-30 days, with menses lasting <7days. 2 The menstrual cycle is divided into a pre-ovulatory follicular phase and post-ovulatory luteal phase, with onset of menstrual flow marking the beginning of a new cycle (Day 1) ( Figure 1 ). During the follicular phase, follicle-stimulating hormone and luteinizing hormone (LH) are released from the anterior pituitary and act on the ovaries to initiate development of several primary follicles, which produce estrogens, principally estradiol. At the end of the follicular phase, estrogen levels rise, triggering a peak in LH. Ovulation occurs 12-16 hours later, around day 14. Following ovulation, the corpus luteum develops, producing progesterone and estrogen, which peak 5-7 days after ovulation before declining (in the absence of implantation), resulting in endometrial breakdown and menstruation. Estrogen and progesterone receptors are widely distributed throughout the central nervous system (CNS), including the basal forebrain, hypothalamus, dorsal raphe nucleus, and locus coeruleus. 3 , 4 These areas are also involved in sleep regulation, and fluctuations in ovarian steroids across the menstrual cycle can modulate sleep. Indeed, work in rodents shows that sleep patterns fluctuate in concert with natural fluctuations of ovarian steroids and ovariectomy eliminates these fluctuations in sleep, with effects dependent on time of day. 5 , 6 While ovarian steroids’ mechanisms of action on sleep regulation are not completely clear, both sleep- and wake-promoting areas of the CNS are sensitive to the effects of estrogen. Ovarian steroids can also influence circadian rhythms, including of sleep-wake activity, through direct or indirect effects on the master pacemaker – the suprachiasmatic nucleus. The mechanistic framework is therefore in place for menstrual cycle-related changes in reproductive hormones to influence sleep and circadian rhythms.

From menarche or first menstrual period, to menopause that signals the end of reproduction, women experience monthly variations in hormones that regulate reproduction. These hormones have widespread effects outside their direct reproductive functions, including influences on regulating mood, body temperature, respiration, autonomic nervous system, and sleep. This review updates a prior review from 2018, 1 delving into the complex relationship between the menstrual cycle and sleep, focusing on perceived sleep quality, objective measures of sleep continuity and sleep architecture, as well as sleep-related physiological changes in homeostatic and circadian regulation of body temperature and heart rate, at different phases of the menstrual cycle. We discuss sleep disturbances in the context of the menstrual cycle across the reproductive years, and also consider relationships between sleep and infertility, use of oral contraceptives, and menstrual-associated disorders, including polycystic ovary syndrome, premenstrual dysphoric disorder, and dysmenorrhea.