Predictors of Early Menopause

描述（由申请人提供）：在西方人群中，大约10%的女性经历早期自然绝经，定义为45岁之前的绝经。由于卵巢功能过早停止会影响生育能力和计划生育，并增加患心血管疾病、骨质疏松症和其他慢性疾病的风险，因此提前绝经会显著影响女性的心理和身体健康。如果能够在生殖功能开始下降之前确定有提前绝经危险的妇女，将改善治疗和预防的选择。提前绝经的准确预测依赖于所有与风险相关的生化、生殖、饮食和生活方式因素的识别。需要同时评估多种危险因素的大型前瞻性研究，但很少进行。这些研究的发现不仅可以改善临床预测，而且可以深入了解早期绝经的风险是否可以改变，以及高危女性生殖功能的下降是否可以减缓。我们建议在护士健康研究II （NHS2）的成员中确定生化、生殖、饮食和生活方式因素与早期绝经风险的关系，这是一项正在进行的前瞻性研究，在1989年队列开始时对116,000名25-42岁的女性进行了研究。在24年的随访中，3500多名NHS2参与者经历了提前绝经，其中包括500名在绝经前15年提供血液样本的女性。在这个项目中，我们将首先评估抗雌激素激素（AMH）是否能预测提前绝经的风险，将500名自然提前绝经的女性的水平与500名48岁绝经的对照组的水平进行比较。其次，我们将通过前瞻性评估风险与以下因素的关系来扩大对早期绝经病因学的了解：1)炎症标志物，包括c反应蛋白、白细胞介素-6和肿瘤坏死因子α受体2水平；2)总和生物利用度25-羟基维生素D水平；3)生殖、饮食和生活方式因素。第三，我们将确定生物化学和行为因素本身是否与基线AMH水平和10-14年内AMH下降率相关。最后，我们将开发早期绝经的预测和病因模型，包括所有这些信息。我们在NHS2中的研究将是第一批前瞻性评估生化、生殖、饮食和生活方式因素如何共同与早期绝经相关的研究之一。来

DESCRIPTION (provided by applicant): Approximately 10% of women in Western populations experience early natural menopause, defined as menopause before age 45. Early menopause can significantly impact women's psychological and physical health, as the early cessation of ovarian function influences fertility and family planning, and increases risk of cardiovascular disease, osteoporosis and other chronic conditions. The ability to identify women at risk for early menopause prior to the onset of decline in reproductive function would improve options for treatment and prevention. Accurate prediction of early menopause is dependent upon the identification of all biochemical, reproductive, dietary and lifestyle factors that are importantly associated with risk. Large prospective studies evaluating multiple risk factors simultaneously are needed, but few have been conducted. Finding from these studies can not only improve clinical prediction but can provide insight into whether risk of early menopause is modifiable and declines in reproductive function in high-risk women can be slowed. We propose to determine how biochemical, reproductive, dietary and lifestyle factors are related to risk of early menopause among members of the Nurses' Health Study II (NHS2), an ongoing prospective study of 116,000 women, aged 25-42 at cohort inception in 1989. Early menopause was experienced by more than 3,500 NHS2 participants over 24 years of follow-up, including 500 women who provided a blood sample up to 15 years prior to menopause. In this project, we will first evaluate whether anti-M¿llerian hormone (AMH) predicts risk of early menopause, comparing levels in 500 women with early natural menopause to levels in 500 matched controls with menopause at e age 48. Second, we will expand knowledge of the etiology of early menopause by evaluating prospectively how risk is related to the following: 1) inflammation markers including C-reactive protein, interleukin-6, and tumor necrosis factor alpha receptor 2 levels; 2) total and bioavailable 25- hydroxyvitamin D levels; and 3) reproductive, dietary and lifestyle factors. Third, we will determine whether biochemical and behavioral factors are themselves associated with baseline AMH levels and rate of AMH decline over 10-14 years. Finally, we will develop prediction and etiologic models for early menopause that incorporate all of this information. Our study in the NHS2 will be among the first to evaluate prospectively how biochemical, reproductive, dietary and lifestyle factors collectively relate to early menopause. To our knowledge, it will be the first to investigate whether vitamin D and inflammatory factors are associated with risk of early menopause, and among the first to address whether women at high risk for early menopause may be able to slow early decline in reproductive function. This work is an important first step in developing novel interventions, which can then be tested in clinical trials. Results from this study may have important implications for fertility preservation and for improved prevention of cardiovascular disease and other chronic conditions in at-risk women.