Role of Ovarian Hormones in the Modulation of Sleep in Females Across the Adult Lifespan

Abstract

Ovarian hormones, including 17β-estradiol, are implicated in numerous physiological processes, including sleep. Beginning at puberty, girls report more sleep complaints than boys, which is maintained throughout the reproductive life stage. Sleep problems are exacerbated during the menopausal transition, evidenced by greater risk for sleep disorders. There is emerging evidence that menopause-associated hormone loss contributes to this elevated risk, but age is also an important factor. The extent to which menopause-associated sleep disturbance persists into postmenopause above and beyond the effects of age remains unknown. Untreated sleep disturbances have important implications for cognitive health, as they are emerging as risk factors for dementia. Given that sleep loss impairs memory, an important knowledge gap concerns the role played by menopause-associated hormone loss in exacerbating sleep disturbance and, ultimately, cognitive function in aging women. In this review, we take a translational approach to illustrate the contribution of ovarian hormones in maintaining the sleep-wake cycle in younger and middle-aged females, with evidence implicating 17β-estradiol in supporting the memory-promoting effects of sleep. Sleep physiology is briefly reviewed before turning to behavioral and neural evidence from young females linking 17β-estradiol to sleep-wake cycle maintenance. Implications of menopause-associated 17β-estradiol loss is also reviewed before discussing how ovarian hormones may support the memory-promoting effects of sleep, and why menopause may exacerbate pathological aging via effects on sleep. While still in its infancy, this research area offers a new sex-based perspective on aging research, with a focus on a modifiable risk factor for pathological aging.

Keywords: fragmented sleep; menopause; menstrual cycle; sleep disorders; slow-wave sleep; spindles.

Figure 1.

Summary of sleep physiology/stages, associations with memory, and changes related to hormonal milieu. Illustrations on the left depict EEG activity associated with each of the four stages of sleep (American Academy of Sleep Medicine (4)), and include definitions. Note that sleep staging is also conducted using concurrent EMG and EOG recordings. The right panel summarizes memory and hormone findings for rodents, nonhuman primates, and humans, denoted with blue symbols. AD = Alzheimer’s disease; E2 = 17β-estradiol; EEG = electroencephalography; EMG = electromyography; EOG = electrooculography; NREM N1-3= nonrapid eye movement stages 1-3; OVX = ovariectomized; P = progesterone; SWA = slow-wave activity; SWS = slow-wave sleep; REM= rapid eye movement.

Figure 2.

Summary of hormone levels across different reproductive states in women, and known effects on memory and sleep. Left panel summarizes findings in women of reproductive age (with normal ~28-day cycles), the middle panel for women in perimenopause, and the right panel for women in postmenopause. The top bar summarizes hormone levels during the 3 reproductive states, with menopausal symptoms, memory findings and sleep disorder prevalence underneath. Specific findings with respect to how sleep is measured are presented in the middle and lower bars. Thick colored bars within each cell indicate higher levels of symptoms/memory/sleep parameters, and colored dots indicate incomplete/unknown information. E2 = 17β-estradiol; EEG = electroencephalography; EMG = electromyography; EOG = electrooculography; FSH = follicle stimulating hormone; N3 = nonrapid eye movement stages 1-3; OVX = ovariectomized; P = Progesterone; SWA = slow-wave activity; SWS = slow-wave sleep; REM= rapid eye movement; RLS = restless legs syndrome; WASO = waking after sleep onset.