MELATONIN FOR AGE-RELATED SLEEP DISTURBANCE IN WOMEN

描述（由申请人提供）：在经历更年期过渡的女性中，睡眠抱怨急剧增加，并且这些抱怨在绝经后不会停止。在60岁以上的健康女性中，多达一半的人也报告睡眠中断，主要表现为睡眠维持性失眠。影响睡眠质量的生理变化，如昼夜节律的改变、体温调节和性激素的再调节，在中年妇女中出现并随着年龄的增长而加剧，在多大程度上仍然知之甚少。很明显，需要进一步了解这些生理变化与老年妇女睡眠问题之间的关系，同时也需要研究治疗睡眠障碍的其他方法。最初的项目期间，本提案是一个竞争性的延续，旨在检查绝经后数年的女性，性激素特征和体温变量是否与客观测量的睡眠质量有关，就像对围绝经期妇女的报道一样。在这些年龄较大的绝经后妇女中，性激素谱在衰老过程中仍有显著变化，低雌二醇和高黄体生成素水平都与睡眠质量差有关。此外，老年女性在睡眠中比年轻、绝经前的女性有更多的黄体生成素脉冲，而且这些黄体生成素脉冲大多数是暂时与从睡眠中醒来有关的。睡眠质量较差的绝经后妇女在夜间睡眠前和睡眠期间的身体核心温度水平都较高，在清醒和睡眠之间的核心温度下降幅度不大。最后，一项单独的研究在没有睡眠的情况下检查性激素的昼夜节律，发现老年人的LH脉搏振幅节律有一个阶段的提前，这与一天中睡眠通常最中断的时间相对应。我们目前的目的是测试使用外源性褪黑素可以改善围绝经期妇女以及年龄较大，绝经后妇女的睡眠质量的假设。褪黑素可能是唯一适合治疗睡眠障碍的老年妇女，因为它的低温，催眠和抗促性腺激素的性质。在迄今为止最大的系统性临床试验中，褪黑素治疗与年龄相关的睡眠障碍，该研究将评估缓释褪黑素与安慰剂对性激素水平、体温、昼夜节律振幅和高促性腺激素水平、潮热和睡眠维持性失眠女性的睡眠质量的影响。这项研究将增加我们对导致睡眠障碍的几个生理因素的理解，并被视为开发一种安全有效的治疗更年期和衰老伴随的睡眠问题的第一步。

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.