MELATONIN FOR AGE-RELATED SLEEP DISTURBANCE IN WOMEN

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DESCRIPTION (provided by applicant): Sleep complaints increase dramatically among women experiencing the menopause transition, and these complaints do not cease post-menopause. Up to half of otherwise healthy women over age 60 report disrupted sleep as well, primarily in the form of sleep maintenance insomnia. To what extent physiological changes that influence sleep quality, such as alterations in circadian rhythmicity, thermoregulation, and reregulation of sex hormones that emerge in middle-aged women and are exacerbated with increasing age, remain poorly understood. It has become clear that further understanding of how these physiological changes relate to sleep problems in older women is needed, as are investigations of alternative approaches to treating the sleep disturbance. The initial project period for which this proposal is a COMPETING CONTINUATION sought to examine, in women several years beyond menopause, whether sex hormone profiles and body temperature variables were associated with objectively measured sleep quality, as had been reported for perimenopausal women. In these older postmenopausal women, it was confirmed that sex hormone profiles remained significantly altered in aging, and that both low estradiol and high LH levels were associated with poor sleep quality. Also, older women had more LH pulses during sleep than did young, premenopausal women, and are large majority of these LH pulses were temporally associated with awakenings from sleep. Postmenopausal women with poorer sleep quality had higher body core temperature levels both prior to and during nocturnal sleep, and a blunted drop in core temperature between wakefulness and sleep. Finally, a separate study examining circadian rhythms of sex hormone profiles in the absence of sleep revealed that older individuals exhibit a phase advance in the rhythm of LH pulse amplitudes, which corresponds to the time of day that sleep is typically most disrupted. Our current aim is to test the hypothesis that sleep quality can be improved using exogenous melatonin in perimenopausal as well as older, postmenopausal women. Melatonin may be uniquely appropriate for treating sleep disturbance in aging women, because of its hypothermic, soporific, and antigonadotropic properties. In the largest systematic clinical trial to date of melatonin for age-related sleep disturbance, the study will evaluate the effects of slow release melatonin versus placebo on sex hormone levels, body temperature, circadian rhythm amplitude, and sleep quality in women who have high gonadotropin levels, hot flashes, and sleep maintenance insomnia. The study will increase our understanding of several physiological factors that contribute to sleep disturbance, and is viewed as an initial step toward developing a safe and effective treatment for sleep problems that accompany both menopause and aging.