Influence of sex on sleep regulatory mechanisms.

The ability of biological sex and sex-driven characteristics to alter sleep states may contribute to gender disparities in sleep disorders. Sex influences sleep-wake amount, the daily timing of the sleep-wake cycle, and the ability to restore sleep after extended wakefulness. Several lines of evidence suggest that in mammals, reproductive hormones are responsible for the effects of sex on sleep and may have organizational and activational influences on sleep regulatory mechanisms. In humans, exogenously administered estrogens and progestins generally enhance sleep amount and continuity, whereas androgens appear to have a positive impact on rapid eye movement (REM) sleep but disrupt sleep consolidation. In rodent studies, however, female reproductive hormones appear to enhance wakefulness, and male gonadal hormones reinforce sleep. Rodent studies have also revealed that neonatal exposure to reproductive hormones organizes adult sleep-wake architecture. This paper reviews how sex and reproductive hormones interact with circadian and homeostatic sleep regulatory mechanisms in humans and animal models. We examine the organizational and activational nature of these interactions and also review how these interactions change with advancing age. Finally, we discuss the potential for genetic sex to influence sleep states. It is our hope that a better understanding of the mechanisms through which sex influences sleep-wake states will lead to improvements in the design of studies that examine gender disparities in sleep-wake disorders.