Risk Factors for Hot Flashes in Mid-Life Women

描述（由申请人提供）：潮热是美国妇女报告的最常见的围绝经期症状，也是妇女在绝经过渡期寻求医疗护理的主要原因，因此潮热造成了严重的公共健康问题。尽管潮热对公众健康的重要性，但人们对使妇女易患潮热的因素知之甚少。在上一个资助期间，获得了新的初步数据，表明肥胖增加了围绝经期潮热的风险。因此，本次更新申请的总体目标是研究肥胖增加潮热风险的机制。具体来说，拟议的工作将测试肥胖与潮热通过涉及早期卵巢衰竭，改变性类固醇激素水平，类固醇生成酶和类固醇激素受体的遗传多态性的机制。具体目标是确定：1）肥胖症与早期卵泡损失和性类固醇激素水平改变有关，2）肥胖症与编码合成和降解性类固醇的酶和/或对性类固醇有反应的受体的基因中的选定多态性有关，3）选定多态性与性类固醇激素水平有关，和4）肥胖和热潮红之间的关联是由早期卵泡损失、改变的激素水平和/或选择的遗传多态性介导的。为了完成这些目标，肥胖和非肥胖围绝经期妇女有和没有潮热将完成问卷调查，接受经阴道超声测量卵巢体积和卵泡数量，并提供血液样本，用于测量选定的性类固醇激素和类固醇生成酶和类固醇激素受体的遗传多态性。将使用适当的统计学检验比较肥胖和非肥胖女性的卵巢体积、卵泡数量、性类固醇激素水平和具有选定遗传多态性的几率。此外，将使用统计模型来确定肥胖和潮热之间的关联是否通过调整卵巢体积、卵泡数量、性类固醇激素水平和选定的遗传多态性而减弱。这项研究的结果将提供有关围绝经期潮热的危险因素的信息。反过来，这些信息可能有助于未来开发预防或治疗潮热的新策略。

DESCRIPTION (provided by applicant): Hot flashes pose a significant public heath problem because they are the most common perimenopausal symptom reported by women in the United States and the primary reason that women seek medical care during the menopausal transition. Despite the public health importance of hot flashes, little is known about the factors that predispose women to hot flashes. During the previous funding period, new preliminary data were obtained that indicate that obesity increases the risk of perimenopausal hot flashes. Thus, the overall goal of this renewal application is to examine the mechanism by which obesity increases the risk of hot flashes. Specifically, the proposed work will test the hypothesis that obesity is associated with hot flashes through mechanisms that involve early ovarian failure, altered sex steroid hormone levels, and selected genetic polymorphisms in steroidogenic enzymes and steroid hormone receptors. The specific aims are to determine whether: 1) obesity is associated with early ovarian follicle loss and altered levels of sex steroid hormones, 2) obesity is associated with selected polymorphisms in genes that encode enzymes that synthesize and degrade sex steroids and/or receptors that respond to sex steroids, 3) selected polymorph- isms are associated with sex steroid hormone levels, and 4) the association between obesity and hot flashes is mediated by early ovarian follicle loss, altered hormone levels, and/or selected genetic polymorphisms. To complete these aims, obese and non-obese perimenopausal women with and without hot flashes will complete questionnaires, receive transvaginal ultrasounds for measurement of ovarian volume and follicle numbers, and provide blood samples for measurement of selected sex steroid hormones and genetic polymorphisms in steroidogenic enzymes and steroid hormone receptors. Ovarian volume, follicle numbers, sex steroid hormone levels, and the odds of having selected genetic polymorphisms will be compared in obese and non-obese women using appropriate statistical tests. Further, statistical models will be used to determine whether the association between obesity and hot flashes is attenuated by adjustment for ovarian volume, follicle numbers, sex steroid hormone levels, and selected genetic polymorphisms. The results of this study will provide information about risk factors for perimenopausal hot flashes. In turn, this information may be useful for the future development of novel strategies to prevent or treat hot flashes.