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，也是妇女在更年期过渡期间寻求医疗保健的主要原因，因此构成了一个重大的公共卫生问题。尽管潮热对公共健康很重要，但人们对女性易患潮热的因素知之甚少。在之前的资助期间，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，这项更新应用的总体目标是研究肥胖增加潮热风险的机制。具体来说，这项工作将验证肥胖与潮热有关的假说，其机制涉及卵巢早衰、性类固醇激素水平改变、类固醇生成酶和类固醇激素受体的遗传多态性。具体目的是确定是否：1)肥胖与卵巢早期卵泡丢失和性类固醇激素水平改变有关，2)肥胖与编码合成和降解性类固醇和/或对性类固醇有反应的受体的酶的基因的选择性多态性有关，3)选择性多态性与性类固醇激素水平有关，4)肥胖和潮热之间的关联是由卵巢早期卵泡丢失、激素水平改变介导的，和/或选择的遗传多态性。为了完成这些目标，肥胖和非肥胖的有或没有潮热的围绝经期妇女将完成问卷调查，接受经阴道超声检查以测量卵巢体积和卵泡数量，并提供血液样本以测量选定的性类固醇激素和类固醇激素生成酶和类固醇激素受体的遗传多态性。将使用适当的统计测试比较肥胖和非肥胖妇女的卵巢体积、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，统计模型将用于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。这项研究的结果将为围绝经期潮热的危险因素提供信息。反过来，这些信息可能对未来预防或治疗潮热的新策略的发展有用。

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.