Endometriosis, Infertility, and Risk of Stroke

项目总结/摘要 子宫内膜异位症是一种慢性妇科疾病，其特征是炎症水平升高和异常的 当子宫样组织植入子宫外时发生的免疫功能。妇女 子宫内膜异位症是在一个两倍的风险增加不孕症和子宫内膜异位症的诊断占20-50%的所有 不孕症诊断最近的研究表明，妇女子宫内膜异位症以及妇女 不孕症可能会增加日后患心血管疾病和其他慢性疾病的风险。当前 然而，研究具有这些生殖因素的妇女的长期健康轨迹的方法， 仅限于生育治疗的登记研究，随访时间短， 子宫内膜异位症尽管女性的负担不成比例，但中风与以下因素的关系研究尤其不足： 子宫内膜异位症和不孕症。此外，很少有研究调查子宫内膜异位症在 存在和不存在不孕症，这可能具有独立或协同作用。我们的建议结合了 来自116，429名参与护士健康研究II的参与者的广泛表型数据， 30年的随访以及生物样本，以解决现有文献中的这些差距。具体地说， 我们的建议将涉及：1）子宫内膜异位症、不孕症和中风（总的，出血性， 和缺血性中风（目的1））; 2）研究子宫内膜异位症，不孕症， 中风因绝经年龄和绝经过渡模式而异（目标2）; 3）生物学 子宫内膜异位症、不孕症和中风之间的潜在联系（抗苗勒管激素 [AMH]、炎症[白细胞介素-6和高敏C反应蛋白]、脂质[高密度脂蛋白、低密度脂蛋白]、 密度脂蛋白，总胆固醇]和脂肪因子[瘦素，脂联素]（目标3））。这些目标代表了一个 研究子宫内膜异位症和不孕症作为中风风险标志的严格和有效的机会， 妇女这项建议是了解子宫内膜异位症，不孕症， 和中风负担以及这些关联背后的机制，并将提供形成 病因学、预防、管理和治疗的未来研究。

Project Summary/Abstract Endometriosis is a chronic gynecology disease characterized by increased levels of inflammation and aberrant immune function that occurs when endometrial-like tissue implants outside the uterus. Women with endometriosis are at a two-fold increased risk of infertility and endometriosis diagnoses represent 20-50% of all infertility diagnoses. Recent research has suggested that women with endometriosis as well as women with infertility may be at an increased risk of cardiovascular and other chronic diseases later in life. The current approach to studying the long-term health trajectory of women with these reproductive factors, however, has been limited to registry studies of fertility treatment with short durations of follow-up and insufficient details on endometriosis. Despite a disproportionate burden in women, stroke is particularly understudied in relation to endometriosis and infertility. Moreover, very few studies have investigated the role of endometriosis in the presence and absence of infertility, which may have independent or synergistic effects. Our proposal combines extensive phenotypic data from 116,429 participants in the Nurses' Health Study II collected prospectively over 30 years of follow-up as well as biologic samples to address these gaps in the existing literature. Specifically, our proposal will address: 1) the relationship between endometriosis, infertility, and stroke (total, hemorrhagic, and ischemic stroke (Aim 1)); 2) investigate whether the relationship between endometriosis, infertility, and stroke varies by age at menopause and mode of menopausal transition (Aim 2); and 3) the biological pathways underlying the association between endometriosis, infertility, and stroke (anti-mullerian hormone [AMH], inflammation [Interleukin-6 and high sensitivity-C Reactive Protein], lipids [high-density lipoprotein, low- density lipoprotein, total cholesterol] and adipokines [leptin, adiponectin](Aim 3)).These aims represent a rigorous and efficient opportunity to investigate endometriosis and infertility as a marker of risk of stroke in women. This proposal is a first-step toward understanding the association between endometriosis, infertility, and stroke burden and the mechanisms underlying these associations, and will provide insights that shape future research into etiology, prevention, management, and treatment.