MELATONIN FOR AGE-RELATED SLEEP DISTURBANCE IN WOMEN

褪黑激素治疗女性年龄相关睡眠障碍

• 批准号: 6988861
• 负责人: PATRICIA J MURPHY
• 金额: $ 13.67万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6988861
• 关键词: aging; body temperature; circadian rhythms; clinical research; clinical trials; female; gonadotropins; hormone regulation /control mechanism; hormone therapy; hot flash; human subject; human therapy evaluation; luteinizing hormone; melatonin; menopause; patient oriented research; sex hormones; sleep; sleep disorders; slow release drug; women' s health

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.

描述（由申请人提供）：睡眠投诉在经历更年期过渡的妇女中急剧增加，并且这些投诉在绝经后不会停止。60岁以上的健康女性中，多达一半的人也报告睡眠中断，主要是以睡眠维持性失眠的形式。在多大程度上影响睡眠质量的生理变化，如昼夜节律的改变，体温调节，以及中年女性出现的性激素的重新调节，并随着年龄的增长而加剧，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的关系，以及研究治疗睡眠障碍的替代方法。该提案是一项竞争性继续研究，其最初的项目期旨在研究绝经后数年的女性，性激素谱和体温变量是否与客观测量的睡眠质量相关，如围绝经期女性所报告的那样。在这些年龄较大的绝经后妇女中，证实了性激素谱在衰老过程中保持显著改变，低雌二醇和高LH水平与睡眠质量差相关。此外，老年妇女在睡眠中比年轻的绝经前妇女有更多的LH脉冲，并且这些LH脉冲中的大部分与睡眠中的觉醒有时间上的关联。睡眠质量较差的绝经后妇女在夜间睡眠之前和期间的核心体温水平较高，并且在清醒和睡眠之间的核心体温下降平缓。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，老年人在LH脉冲幅度的节律中表现出相位提前，这对应于一天中睡眠通常最受干扰的时间。我们目前的目的是检验这一假设，即使用外源性褪黑激素可以改善围绝经期以及老年绝经后妇女的睡眠质量。褪黑激素可能是唯一适合治疗睡眠障碍的老年妇女，因为它的体温过低，催眠，和抗促性腺激素的性质。在迄今为止规模最大的褪黑激素治疗年龄相关睡眠障碍的系统性临床试验中，该研究将评估缓释褪黑激素与安慰剂对促性腺激素水平高、潮热和睡眠维持性失眠的女性的性激素水平、体温、昼夜节律幅度和睡眠质量的影响。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，并被视为开发安全有效的治疗更年期和衰老伴随的睡眠问题的第一步。