Sex and Sex Hormone Factors Influencing Acute Alcohol Effects on Sleep Physiology

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Rates of heavy drinking and Alcohol Use Disorder (AUD) are increasing in women at an alarming pace. Such drastic increases in drinking will have a significant negative impact on women’s health. Unfortunately, until recently heavy drinking has been considered a male-oriented problem, and consequently research on alcohol- related harms in women has been minimal. One specific aspect of women’s health that may be negatively affected by alcohol is sleep. Numerous studies in men show that although alcohol has an initial sedative effect, it leads to frequent awakenings and impaired rapid eye movement sleep in the second half of the night. Preliminary evidence suggests that women experience similar impairment, and that they may be even more sensitive to alcohol-disrupted sleep than men. Further, in the general population, women are at greater risk for insomnia and sleep disturbances than men, in part because women’s sleep is sensitive to fluctuations in ovarian hormones. Hormonal influences on sleep are especially pronounced in older women of late reproductive age. However, the influence of sex and sex hormones on alcohol-disrupted sleep across the reproductive lifespan in women is unknown. Here, we will determine the influence of sex, menstrual cycle phase, and sex hormones on alcohol-disrupted sleep in adults across the reproductive age range for women. Healthy women and men (age 21-45) will complete two pairs of experimental sessions in which they receive a dose of alcohol (target BrAC = 100mg%, intravenous) or placebo (saline) one hour prior to eight hours of polysomnographically-monitored sleep in the lab. Women will complete one alcohol-placebo session pair during the mid-follicular phase of the menstrual cycle and one pair during the late luteal phase. Men will complete two session pairs at matched intervals. Participants will also complete two 5-day at-home monitoring periods of naturalistic sleep and alcohol consumption patterns during the mid-follicular and late luteal phases. Sleep and alcohol use will be assessed with actigraphy, daily sleep and wake diaries, and alcohol wrist sensors. We hypothesize that women will show greater disruption of sleep following alcohol than men and that alcohol-disrupted sleep, measured in lab with polysomnography and at-home with actigraphy, will be more pronounced in the late luteal phase compared to the mid-follicular phase. We also expect that estradiol will be negatively associated with alcohol-disrupted sleep, whereas progesterone will be positively associated with alcohol-disrupted sleep. This study will provide essential information regarding alcohol effects on sleep across the reproductive age span in women, and critically, how these effects are moderated by sex, menstrual cycle, and fluctuations in sex hormones. Findings will directly inform future interventions aimed at reducing alcohol consumption and the negative impacts of alcohol on sleep in women. Given the wide-ranging impact of sleep on other areas of function, including cognition, stress, and well-being, such interventions will have a substantial positive impact on women’s health.