Abnormalities in androgens and ovarian markers in reproductive-age racially and ethnically diverse women in a prospective longitudinal cohort

前瞻性纵向队列中不同种族和民族的育龄女性雄激素和卵巢标志物的异常

• 批准号: 10930196
• 负责人: CATHERINE KIM
• 金额: $ 76.13万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-23 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10930196
• 关键词: 11-ketotestosterone; Address; Age; Androgens; Biological Assay; Black race; Blood Pressure; Blood Tests; Body Weight Changes; Body mass index; Cardiometabolic Disease; Cardiovascular Diseases; Characteristics; Contraceptive Usage; Coronary Artery Risk Development in Young Adults Study; Data; Data Collection; Diagnosis; Diagnostic; Educational workshop; Enrollment; Estrogens; Ethnic Origin; Ethnic Population; Event; Expert Opinion; Future; Glucose; Glucose Intolerance; Grouping; Heart; Hyperandrogenemia; Immunoassay; Infrastructure; Insulin Resistance; Intervention; Knowledge; Latina; Lipids; Longitudinal cohort; Machine Learning; Mass Spectrum Analysis; Measures; Menstruation; Methodology; Nature; Non-Insulin-Dependent Diabetes Mellitus; Not Hispanic or Latino; Obesity; Oral Contraceptives; Outcome; Ovarian; Ovary; Participant; Phenotype; Polycystic Ovary Syndrome; Postmenopause; Predictive Value; Prospective cohort; Questionnaires; Race; Recording of previous events; Reporting; Research Personnel; Resources; Risk; Risk Factors; Risk Reduction; Sampling; Serum; Sex Hormone-Binding Globulin; Socioeconomic Status; Techniques; Testosterone; United States National Institutes of Health; Visualization; Woman; Work; adjudication; androgenic; cardiometabolic risk; cardiometabolism; cardiovascular disorder risk; cigarette smoking; cohort; coronary artery calcification; ethnic diversity; genetic architecture; human old age (65+); improved; learning strategy; low socioeconomic status; middle age; mullerian-inhibiting hormone; novel; pill; population based; prospective; racial diversity; racial population; radiological imaging; reproductive; risk prediction; screening

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among reproductive-age women and characterized by hyperandrogenemia, irregular menses, and enlarged polycystic ovaries. The genetic architecture of PCOS also includes obesity and insulin resistance, and thus women with PCOS often have elevated body mass index (BMI) and glucose intolerance. In October 2021, the NIH convened a PCOS workshop; co-I Siscovick reported on knowledge gaps regarding PCOS and cardiovascular disease (CVD). First, best practices for identification of abnormal androgens, menses, and ovarian markers are unclear, particularly as women age. Cutpoints for abnormal values are arbitrary and based upon expert opinion; the predictive value of serum ovarian markers compared to radiographic markers is not accepted; and optimal tests for blood androgens is uncertain. Second, it is not understood how PCOS characteristics and subphenotypes differ by race and ethnicity; socioeconomic status (SES); and potentially modifiable factors such as BMI and oral contraceptive use (OCP). Third, it is unclear to what extent PCOS characteristics predict risk for cardiometabolic disease beyond standard risk factors. Similarly, it is unknown if PCOS subphenotypes confer different risks of cardiometabolic disease. These issues are best addressed using population-based prospective cohorts spanning reproductive age to older age, as such studies minimize biases in referral and ascertainment of outcomes. However, such studies are few. The Coronary Artery Risk Development in Young Adults Study (CARDIA) and the Dallas Heart Study (DHS) are two population-based, prospective, longitudinal cohorts which first sampled Black and white participants during their reproductive years (age 18-30 years in CARDIA, age 35-49 years in DHS) and have followed their cohorts to late middle age. The studies used identical questionnaires for ascertainment of menstrual history and exogenous estrogen use. Both studies have deeply phenotyped women with repeated measures of traditional and novel CVD risk factors, intermediate atherosclerotic markers including coronary artery calcification (CAC), adjudication of CVD events, and radiographic assessment of ovaries. Our team, consisting of PIs of these studies, and experts well-versed in the controversies of PCOS, will build upon this rich infrastructure. We will use existing data and samples from reproductive-age women in both studies (n=1163 in CARDIA, approximately half of whom were Black; n=827 in DHS, approximately two-thirds of whom were Black, 25% non-Hispanic white, and 10% Latina). We will measure androgenic metabolites including 11 oxy-androgens using state-of-the-art mass spectrometry and anti-Müllerian hormone (AMH) and sex hormone binding globulin (SHBG). We will apply machine learning strategies to generate cutpoints and PCOS groupings, compare these to conventional definitions and phenotypes, and examine associations by racial and ethnic group, SES, and OCP use. Finally, we will examine prospective associations with cardiometabolic risk, particularly events. No additional data collection is needed.

多囊卵巢综合症（PCOS）是育龄妇女中最常见的内分泌疾病， 其特征是高雄激素血症、月经不调和多囊卵巢增大。 PCOS 的结构还包括肥胖和胰岛素抵抗，因此患有 PCOS 的女性通常患有 体重指数 (BMI) 升高和葡萄糖不耐症 2021 年 10 月，NIH 召开了 PCOS 会议。 研讨会；共同主席 Siscovick 报告了有关 PCOS 和心血管疾病 (CVD) 的知识差距。 首先，识别异常雄激素、月经和卵巢标志物的最佳实践尚不清楚， 特别是随着女性年龄的增长，异常值的切点是任意的并且基于专家的意见； 与放射学标记物相比，血清卵巢标记物的预测价值未被接受，并且是最佳的； 其次，目前尚不清楚PCOS的特征和情况。 亚表型因种族和民族而异；社会经济地位（SES）和潜在的可改变因素； 第三，尚不清楚 PCOS 特征在多大程度上可以预测。 同样，PCOS 亚表型是否会导致心脏代谢疾病的风险超出标准危险因素。 这些问题最好通过基于人群的方法来解决。 前瞻性队列跨越育龄期至老年期，因为此类研究最大限度地减少了转诊和治疗方面的偏差 然而，此类研究很少。 成人研究 (CARDIA) 和达拉斯心脏研究 (DHS) 是两项基于人群的前瞻性纵向研究 首先对处于生育年龄（18-30 岁）的黑人和白人参与者进行抽样调查的队列 CARDIA，DHS 年龄为 35-49 岁），并跟踪他们的队列至中年后期。 两项研究均使用相同的问卷来确定月经史和外源性雌激素的使用情况。 通过反复测量传统和新型 CVD 危险因素，对女性进行了深入的表型分析， 中间动脉粥样硬化标志物，包括冠状动脉钙化 (CAC)、CVD 事件的判定、 我们的团队由这些研究的 PI 和精通的专家组成。 在 PCOS 的争议中，我们将利用现有的数据和样本。 两项研究中均来自育龄妇女（CARDIA 中 n=1163 人，其中大约一半是黑人； DHS 中的 n=827 人，其中大约三分之二是黑人、25% 非西班牙裔白人和 10% 拉丁裔）。 将使用最先进的质谱法测量雄激素代谢物，包括 11 种氧雄激素， 我们将应用机器学习。 生成切点和 PCOS 分组的策略，将它们与传统定义进行比较， 表型，并检查种族和族裔群体、SES 和 OCP 使用的关联。 与心脏代谢风险（特别是事件）的前瞻性关联不需要额外的数据收集。