Predictors of Early Menopause

早期更年期的预测因素

• 批准号: 8760173
• 负责人: ELIZABETH R BERTONE-JOHNSON
• 金额: $ 62.69万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-17 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8760173
• 关键词: 25-hydroxyvitamin D; Address; Affect; Age; Aging; Behavioral; Bioavailable; Biochemical; Biochemical Markers; Biological Preservation; Blood specimen; Breast Feeding; C-reactive protein; Chronic; Chronic Disease; Clinical; Clinical Trials; Contraceptive Usage; Development; Dietary Factors; Etiology; Family Planning; Fertility; Glycoproteins; High Risk Woman; Hormones; Inflammatory; Intake; Interleukin-6; Intervention; Isoflavones; Knowledge; Menopause; Mental Health; Modeling; Nurses' Health Study; Obesity; Omega-3 Fatty Acids; Oral Contraceptives; Osteoporosis; Ovarian; Ovulation; Participant; Physical activity; Plasma; Population; Prevention; Prospective Studies; Reproductive History; Risk; Risk Factors; Role; Smoking; Testing; Underweight; Vegetable Proteins; Vitamin D; Woman; Work; aged; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular risk factor; cohort; early experience; experience; follow-up; granulosa cell; high risk; human TNFRSF1A protein; improved; inflammatory marker; insight; lifestyle factors; member; novel; parity; physical conditioning; public health relevance; reproductive function; tumor necrosis factor alpha receptor

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.

描述（由申请人提供）：西方人群中约有10%的女性经历早期自然绝经，定义为45岁之前绝经。过早绝经会严重影响妇女的心理和身体健康，因为卵巢功能的过早停止会影响生育和计划生育，并增加患心血管疾病、骨质疏松症和其他慢性疾病的风险。如果能够在生殖功能开始下降之前确定有提前绝经风险的妇女，将改善治疗和预防的选择。早期绝经的准确预测取决于与风险重要相关的所有生化，生殖，饮食和生活方式因素的识别。需要同时评估多种风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，还可以深入了解早期更年期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。 我们建议确定生物化学，生殖，饮食和生活方式因素与护士健康研究II（NHS 2）成员中过早绝经的风险有关，NHS 2是一项正在进行的前瞻性研究，涉及116，000名年龄在25-42岁的女性，于1989年开始队列研究。在24年的随访中，超过3，500名NHS 2参与者经历了早期绝经，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，我们将首先评估抗苗勒管激素（AMH）是否预测早期绝经的风险，将500名自然绝经早期的妇女的水平与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展对绝经早期病因学的认识：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）总的和生物可利用的25-羟基维生素D水平; 3）生殖，饮食和生活方式因素。第三，我们将确定生化和行为因素本身是否与基线AMH水平以及10-14年内AMH下降率相关。最后，我们将开发结合所有这些信息的早期绝经的预测和病因模型。 我们在NHS 2的研究将是第一个前瞻性评估生物化学，生殖，饮食和生活方式因素如何共同与早期绝经有关的研究。到 根据我们的知识，这将是第一个调查维生素D和炎症因子是否与早期绝经风险相关的研究，也是第一个解决早期绝经高风险女性是否能够减缓生殖功能早期下降的研究。这项工作是开发新干预措施的重要第一步，然后可以在临床试验中进行测试。这项研究的结果可能对保持生育能力和改善高危女性心血管疾病和其他慢性疾病的预防具有重要意义。