Women's sleep in health and disease

Sleep, 2009

Hormones and Behavior, 2013

Sleep disturbances are commonly associated with menopause. Hormone replacement therapy is often used to treat various menopausal symptoms, but its efficacy for improving sleep is a matter of debate. We addressed this question by using a rodent model of ovarian hormone loss and replacement in midlife. Middle-aged female rats were ovariectomized and implanted with capsules containing estradiol with or without progesterone, or oil. After two weeks, sleep/wake states were recorded polygraphically during a 24-h baseline period, followed by 6 h of sleep deprivation in the second half of the light phase, and a 24-h recovery period. During the baseline dark phase, hormone treatments increased wakefulness, and decreased non-rapid eye movement sleep (NREMS) by shortening NREMS episodes; however, NREMS EEG delta power or energy (cumulative power) was unaffected by combined hormones. Following sleep deprivation, all the groups showed NREMS and rapid eye movement sleep (REMS) rebounds, with similar relative increases from respective baseline levels. The increases in NREMS EEG delta power/energy during recovery were enhanced by combined hormones. These results from middle-aged ovariectomized rats indicate that replacement with estrogen with or without progesterone reduces baseline NREMS without affecting sleep intensity, particularly during the dark (active) phase, whereas following sleep deprivation the same hormone treatments do not affect the ability to increase NREMS or REMS, but treatment with both hormones, in particular, enhances the intensity of recovery sleep. These results support the usefulness of ovariectomized middle-aged rats as a model system to study the biological effects of hormone replacement on sleep regulation.

Medical Clinics of North America, 2004

In the last decade, more research interest has focused on the sleep of women across the life cycle. A significant body of literature has endorsed the view that the sleep of women differs in many respects from that of men. Beyond gender differences, however, are questions about sleep within cohorts of women. For example, in adult women ages 20-45 years, there are women with regular menstrual cycles, women taking oral contraceptives, pregnant and lactating women, and women entering menopause. Given that each of these states is associated with a unique hormonal environment, it is important to determine whether there are clinically significant differences in the sleep of women in these phases of life. This article presents what is known currently about the sleep of women from adulthood through menopause and provides recommendations for evaluation and treatment.

Physiology & Behavior, 2011

Sleep complaints such as insufficient sleep and insomnia are twice as prevalent in women. Symptoms of sleep disruption are often coincident with changes in the gonadal hormone profile across a women's lifespan. Data from a number of different species, including humans, nonhuman primates and rodents strongly implicate a role for gonadal hormones in the modulation of sleep. In female rats, increased levels of circulating estradiol increase wakefulness and reduce sleep in the dark phase. In this study, we asked whether this reduction in sleep is driven by estradiol-dependent reduction in sleep need during the dark phase by assessing sleep before and after sleep deprivation (SD). Ovariectomized rats implanted with EEG telemetry transmitters were given Silastic capsules containing either 17-β estradiol in sesame oil (E2) or sesame oil alone. After a 24-hour baseline, animals were sleep-deprived via gentle handling for the entire 12-hour light phase, and then allowed to recover. E2 treatment suppressed baseline REM sleep duration in the dark phase, but not NREM or Wake duration, within three days. While SD induced a compensatory increase in REM duration in both groups, this increase was smaller in E2-treated rats compared to oils, as measured in absolute duration as well as by relative increase over baseline. Thus, E2 suppressed REM sleep in the dark phase both before and after SD. E2 also suppressed NREM and increased waking in the early-to mid-dark phase on the day after SD. NREM delta power tracked NREM sleep before and after SD, with small hormone-dependent reductions in delta power in recovery, but not spontaneous sleep. These results demonstrate that E2 powerfully and specifically suppresses spontaneous and recovery REM sleep in the dark phase, and suggest that ovarian steroids may consolidate circadian sleep-wake rhythms.

Journal of Neuroendocrinology, 2006

The effect of circulating oestrogen deficiency on sleep regulation and locomotor activity was investigated in aromatase cytochrome P450 deficient mice (ArKO) and wild-type (WT) controls. Sleep was recorded in 3-month old mice during a 24-h baseline day, 6-h sleep deprivation (SD) and 18-h recovery, and activity was recorded at the age of 3, 9 and 12 months. In mice deficient of oestrogen, the total amount of sleep per 24 h was the same as in WT controls. However, in ArKO mice, sleep was enhanced in the dark period at the expense of sleep in the light phase, and was more fragmented than sleep in WT mice. This redistribution of sleep resulted in a damped amplitude of slow-wave activity (SWA; power between 0.75-4.0 Hz) in non-rapid eye movement sleep across 24 h. After SD, the rebound of sleep and SWA was similar between the genotypes, suggesting that oestrogen deficiency does not affect the mechanisms maintaining the homeostatic balance between the amount of sleep and its intensity. Motor activity decreased with age in both genotypes and was lower in ArKO mice compared to WT at all three ages. After SD, the amount of rest in 3-month old WT mice increased above baseline and was more consolidated. Both effects were less pronounced in ArKO mice, reflecting the baseline differences between the genotypes. The results indicate that despite the pronounced redistribution of sleep and motor activity in oestrogen deficient mice, the basic homeostatic mechanisms of sleep regulation in ArKO mice remain intact.

Journal of Neuroscience, 2011

While much is known about the mechanisms that underlie sleep and circadian rhythms, the investigation into sex differences and gonadal steroid modulation of sleep and biological rhythms is in its infancy. There is a growing recognition of sex disparities in sleep and rhythm disorders. Understanding how neuroendocrine mediators and sex differences influence sleep and biological rhythms is central to advancing our understanding of sleep-related disorders. While it is known that ovarian steroids affect circadian rhythms in rodents, the role of androgen is less understood. Surprising findings that androgens, acting via androgen receptors in the master "circadian clock" within the suprachiasmatic nucleus, modulate photic effects on activity in males point to novel mechanisms of circadian control. Work in aromatase-deficient mice suggests that some sex differences in photic responsiveness are independent of gonadal hormone effects during development. In parallel, aspects of sex differences in sleep are also reported to be independent of gonadal steroids and may involve sex chromosome complement. This a summary of recent work illustrating how sex differences and gonadal hormones influence sleep and circadian rhythms that was presented at a Mini-Symposium at the 2011 annual meeting of the Society for Neuroscience.

Brain Research, 1996

Previously, we reported that paradoxical sleep (PS) is sexually dimorphic in mice and rats. Since some early studies indicate that PS is suppressed during proestrus night, it is important to know whether the estrus cycle and accompanying circulating ovarian hormones could explain the sexual dimorphism of PS. To examine this, sleep patterns of male rats were compared with those of normal cycling female rats and ovariectomized females in a 12:12 h light/dark cycle. Slow wave sleep and total sleep time are indistinguishable between the males, cycling females and ovariectomized females. However, normal males display significantly more PS than cycling females during both daytime and nighttime (average of all estrus stages). On the other hand, while ovariectomy has no visible effect on daytime sleepthe sexual dimorphism of PS is unchanged by ovariectomy-during nighttime, ovariectomy produces a selective increase of PS, eliminating the sex difference during the night. In sum, normal cycling females show no change in daytime sleep patterns across the estrus cycle, but have significantly less PS during proestrus nights than during metestrus and diestrus nights. The results indicate that the sex difference in nighttime PS is due to the suppression of PS by ovarian hormones during proestrus and, to a less extent, estrus nights. The sex difference in daytime PS, on the other hand, appears to be independent of circulating ovarian hormones.

Sleep, 2011

Female Reproductive Hormones and Sleep Homeostasis-Deurveilher et al MATERIALS AND METHODS We used the same data base as in our previous report 17 to perform additional analyses of sleep architecture. The details of surgery, experimental design, experimental procedures, and sleep/ INTRODUCTION Increasing evidence suggests that the ovarian hormones estradiol and progesterone not only control reproductive functions and behaviors but also influence a diverse range of physiological and psychological processes, including mood, sensory, and cognitive functions. 1-3 Sleep is no exception: alterations of sleep patterns are associated with changing levels of endogenous estradiol and progesterone such as occur during the menstrual cycle, pregnancy, and menopause. 4-6 Sleep patterns also change in response to hormonal treatments, such as oral contraceptive use in young women 7,8 and hormone replacement therapy in menopausal women. 9-11 While inadequate sleep is becoming increasingly common and can impair human health and performance, 12-14 relatively little is known about whether and how endogenous or exogenous female sex hormones influence recovery from sleep loss. 15,16 To determine how female sex hormones modulate spontaneous (baseline) sleep and sleep recovery after sleep loss, we previously used a rodent model of hormonal loss and replacement in a paradigm involving gentle handling to generate acute (6 h) sleep deprivation. 17 We used subcutaneous steroid implants to produce stable, physiological levels of estradiol and progesterone in adult ovariectomized (OVX) rats in order to evaluate effects on baseline and recovery sleep in similar stable hormonal conditions. This approach is not possible in normally cycling females because of the changing estradiol and proges

ChronoPhysiology and Therapy, 2014

Sleep disorders such as insomnia, sleep-related breathing disorders, circadian rhythm disorders, and sleep-related movement disorders are a significant public health issue, affecting approximately 40 million people in the US each year. Sleep disturbances are observed in both men and women, though prevalence rates often differ between the sexes. In general, research suggests that women more frequently report subjective complaints of insomnia, yet show better sleep than men when evaluated on objective measures of sleep. Men are more likely to be diagnosed with obstructive sleep apnea than women, though rates of obstructive sleep apnea increase after menopause and may be generally underdiagnosed in women. Although circadian rhythm disorders are equally prevalent in men and women, studies find that women typically have earlier bedtimes and exhibit altered temperature and melatonin rhythms relative to men. Lastly, movement disorders appear to be more prevalent in women than men, presumably due to higher rates of anemia and increased risks associated with pregnancy in women. Although gonadal hormones would be expected to play a significant role in the development and/or exacerbation of sleep disturbances, no causal link between these factors has been clearly established. In large part, the impact of hormones on sleep disturbances is significantly confounded by factors such as psychiatric, physical, and lifestyle concerns, which may play an equal or greater role in the development and/or exacerbation of sleep disturbances than do hormonal factors. Current standard of care for persons with sleep disorders includes use of psychological, pharmacologic, and/or medical device supported interventions. Hormonal-based treatments are not typically recommended given the potential for long-term adverse health effects. In sum, there is a substantial need for more comprehensive studies focused on elucidating the impact of hormones on sleep. Such studies should reveal sex-specific differences in sleep, which could lead to enhanced interventions for sex-specific sleep disturbances.

International Journal of Endocrinology, 2010