Phthalate exposure and hot flashes in midlife women

潮热造成了重大的公共卫生问题，因为他们是最常见的围月经期 美国妇女报告的症状和妇女寻求医疗保健的主要原因 在更年期过渡期。尽管潮热在女性生活中的重要性， 这种症状的危险因素我们对195名女性（年龄45-54岁）的初步数据表明， 邻苯二甲酸酯暴露与潮热风险增加有关。具体而言，更高 个人护理产品（PCP）中常见的邻苯二甲酸酯浓度与 增加曾经有过潮热的风险，在过去30天内有过潮热，以及频繁的潮热。 此外，我们的初步数据表明，邻苯二甲酸酯代谢物水平的增加与 窦卵泡数量减少，这是女性潮热的一个已知危险因素。因此，这一总体目标 应用是通过检验尿邻苯二甲酸酯代谢物 浓度与潮热有关，并探讨其与潜在机制的关系 低雌激素水平和卵巢功能衰竭引起的潮热。为了验证这一假设，我们建议 完成以下具体目标：1）前瞻性地确定尿中邻苯二甲酸酯水平是否 代谢物与随后的潮热有关，2）确定邻苯二甲酸酯的尿水平是否 代谢产物与低雌激素和雄激素水平有关，3）确定尿中的 邻苯二甲酸酯代谢物与卵泡损失有关，4）探索是否观察到任何 尿邻苯二甲酸酯代谢物与潮热之间的关联是由卵巢卵泡损失介导的 和/或低水平的性类固醇激素为了完成这些目标，我们将使用尿液和血液样本， 经阴道超声数据，和潮热的历史，已获得782名妇女（年龄 45-54岁）参加中年妇女健康研究。尿液样本将被 测量邻苯二甲酸酯代谢物，并对血样进行以下测量： 性类固醇激素水平以及抗苗勒管抗体和β-半胱氨酸B水平。经阴道超声数据 将用于确定窦卵泡计数和卵巢体积。统计分析将 进行评估尿邻苯二甲酸酯水平，激素水平，窦卵泡数量， 和卵巢体积。此外，将进行统计分析，以检查低性类固醇是否 激素水平、窦卵泡计数减少或卵巢储备不足介导了 邻苯二甲酸酯代谢物和潮热。这项研究的结果将有助于更好地了解 潮热的危险因素以及环境化学物质与潮热相关的机制 对妇女的不良生殖后果。这可能导致制定预防战略， 女性潮热的新疗法

Hot flashes pose a significant public health 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 importance of hot flashes in a woman's life, little is known about the risk factors for this symptom. Our preliminary data from 195 women (aged 45-54 years) suggest that phthalate exposures are associated with an increased risk of hot flashes. Specifically, higher concentrations of phthalates commonly found in personal care products (PCPs) were associated with an increased risk of ever having hot flashes, having hot flashes in the past 30 days, and frequent hot flashes. Further, our preliminary data suggest that increased levels of phthalate metabolites are associated with reduced antral follicle counts, a known risk factor for hot flashes in women. Thus, the overall goal of this application is to extend our preliminary analysis by testing the hypothesis that urinary phthalate metabolite concentrations are associated with hot flashes and explore their associations with potential mechanisms of hot flashes that involve low estrogen levels and ovarian failure. To test this hypothesis, we propose to complete the following specific aims: 1) prospectively determine whether urinary levels of phthalate metabolites are associated with subsequent hot flashes, 2) determine whether urinary levels of phthalate metabolites are associated with low estrogen and androgen levels, 3) determine whether urinary levels of phthalate metabolites are associated with ovarian follicle loss, and 4) explore whether any observed associations between urinary phthalate metabolites and hot flashes are mediated by ovarian follicle loss and/or low levels of sex steroid hormones. To complete these aims, we will use urine and blood samples, transvaginal ultrasound data, and hot flashes histories that have been obtained from 782 women (aged 45-54 years) who participated in the Midlife Women's Health Study. The urine samples will be subjected to measurements of phthalate metabolites and the blood samples will be subjected to measurements of sex steroid hormone levels as well as anti-Müllerian and inhibin B levels. Transvaginal ultrasound data will be used to determine antral follicle counts and ovarian volume. Statistical analyses then will be conducted to assess correlations between urinary phthalate levels, hormone levels, antral follicle numbers, and ovarian volume. Further, statistical analyses will be conducted to examine whether low sex steroid hormone levels, reduced antral follicle counts, or small ovarian reserve mediate the association between phthalate metabolites and hot flashes. The results of this study will provide a better understanding of the risk factors for hot flashes and the mechanisms by which environmental chemicals are associated with adverse reproductive outcomes in women. This may lead to the development of preventive strategies and new treatments for hot flashes in women.