Sex differences in sleep: impact of biological sex and sex steroids

Abstract

Men and women sleep differently. While much is known about the mechanisms that drive sleep, the reason for these sex differences in sleep behaviour is unknown and understudied. Historically, women and female animals are underrepresented in studies of sleep and its disorders. Nevertheless, there is a growing recognition of sex disparities in sleep and rhythm disorders. Women typically report poorer quality and more disrupted sleep across various stages of life. Findings from clinical and basic research studies strongly implicate a role for sex steroids in sleep modulation. Understanding how neuroendocrine mediators and sex differences influence sleep is central to advancing our understanding of sleep-related disorders. The investigation into sex differences and sex steroid modulation of sleep is in its infancy. Identifying the mechanisms underlying sex and gender differences in sleep will provide valuable insights leading to tailored therapeutics that benefit each sex. The goal of this review is to discuss our current understanding of how biological sex and sex steroids influence sleep behaviour from both the clinical and pre-clinical perspective.

Keywords: oestrogens; progesterone; sleep; sleep circuits; testosterone; ventrolateral preoptic area.

Figure 1.

Prevalence of insomnia complaints by sex and age in a general population. Sleep disorders among women are a significant public health issue: sleep complaints such as insufficient sleep and insomnia are more prevalent in women. This sex difference in insomnia emerges after puberty, suggesting that hormonal events underlying puberty may be involved. Adapted from [1] and based on [47,58,60]. (Online version in colour.)

Figure 2.

Comparison of hypnograms representing typical sleep patterns in humans and rodents. Human sleep is monophasic and normally consists of three to five cycles of the sleep stages throughout the night. Longer bouts of NREMS stage N3 or SWS occur earlier in the night while REMS increases in duration and frequency as the night progresses. Rodent sleep is polyphasic, with wake, NREMS and REMS occurring throughout the light and dark phases. More sleep is acquired in the light phase, while the dark phases consist of consolidated periods of wake. (Online version in colour.)

Figure 3.

Oestradiol may act to consolidate and enhance sleep–wake activity to the appropriate time of day. Under normal sleep conditions, oestradiol administered to ovariectomized adult rats increases spontaneous total sleep (NREM and REM) in the light phase while suppressing total sleep in the dark phase, resulting in more consolidated wake bouts (not shown). Data redrawn from [108]. Following a 6-h bout of sleep deprivation (SD), oestradiol facilitated REM recovery sleep in the light phase allowing a return to baseline levels in the dark phase. In contrast, control SD females exhibited increased REM sleep throughout the dark phase [125]. Asterisks represent statistically significant differences between the treatment groups (significance level set at 0.05). Ovx, ovariectomized. (Online version in colour.)

Figure 4.

Simplified diagram of projections from sleep-regulating nuclei and potential sites of oestradiol action. Sleep-active neurons are present in the ventrolateral preoptic area (VLPO) and median preoptic nucleus (MnPN). Inhibitory projections from the VLPO and MnPN innervate the major arousal nuclei including the tubermammillary nucleus (TMN), the dorsal raphe nucleus (DRN), the locus coeruleus (LC) and the lateral hypothalamus (LH). MRN, median raphe nucleus. (Online version in colour.)