A Study of Estrogen and Body Mass Index in Fuchs’ Endothelial Corneal Dystrophy

福克斯内皮性角膜营养不良中雌激素和体重指数的研究

基本信息

批准号：
10427350
负责人：
Amy Elizabeth Millen
金额：
$ 23.81万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10427350
关键词：
Adult Affect Age Age at Menarche Benefits and Risks Blindness Body mass index Cadaver Cell Survival Clinical Trials Cornea Corneal Endothelium Corneal dystrophy Data Databases Development Elderly Endothelial Cells Enrollment Epidemiology Estradiol Estrogens Fee-for-Service Plans Follow-Up Studies Fuchs&apos Endothelial Dystrophy Future Health Health behavior High Risk Woman Hormonal Individual Intervention Keratoplasty Lead Life Life Expectancy Link Measures Medical Medicare Medicare claim Menopause Observational Study Operative Surgical Procedures Outcome Participant Pathway interactions Placebos Population Postmenopause Pregnancy Prevalence Prevention Prevention strategy Progestins Proxy Publishing Randomized Randomized Clinical Trials Randomized Controlled Clinical Trials Regimen Reproductive History Research Research Design Resources Risk Risk Factors Role Running Sampling Serum Smoking Therapy trial Time Tissue Donors Transplantation United States Woman Women&apos s Health aged algorithm development base cost demographics epidemiologic data epidemiology study follow-up high body mass index hormone therapy improved men modifiable risk population based protective effect reproductive hormone sex disparity sight restoration trial design

项目摘要

ABSTRACT End-stage Fuchs' endothelial corneal dystrophy (FECD), typically occurring after the 7th decade of life, is a leading cause of corneal blindness.1-3 The only well-established modifiable risk factor for FECD is smoking,4,5 and minimal epidemiologic data exists on modifiable risk factors for FECD. Blindness from FECD is corrected with corneal transplantation, however, transplantation is costly, donor tissue is limited globally, complications can arise, and surgery is not always desired in the elderly.6,7 Compared to men of similar age, there is an increase in the prevalence of FECD after menopause in women.8,9 We hypothesize that higher estrogen exposure is associated with reduced risk of FECD, thus explaining this observed sex disparity. To date, no published studies have examined associations between endogenous or exogenous measures of estrogen exposure and FECD; studies on associations between BMI, one determinant of circulating estrogen levels,10-12 and FECD are very limited.4,13 Study results have shown both no association between BMI and FECD13 and a protective effect of high BMI on FECD.4 Using the rich resource of the 25+ year Women's Health Initiative (WHI) study, we propose to examine the association between FECD and endogenous and exogenous estrogen exposure. The WHI consists of an Observational Study (OS) and Clinical Trials, including two randomized, controlled clinical trials of hormone therapy (HT), estrogen-alone or estrogen plus progestin, each compared to placebo.14-17 Outcomes indicative of FECD, including endothelial corneal dystrophy and corneal transplant, can be identified from Medicare claims data. The WHI has an extensive database on participants' demographics, reproductive history, health behaviors and health outcomes. We propose to use a sample of WHI OS women enrolled in Medicare during the same year or earlier as their enrollment in WHI OS baseline (1993-1998) (n=27,960) to examine the association between Medicare claims for incident outcomes indicative of FECD from 1993-2017 and (Aim 1) estimated lifetime endogenous estrogen exposure, menopausal hormone therapy use and duration (exogenous estrogen exposure), BMI at different time points throughout a participants' adult life, and measured serum estradiol concentration in a subset of 2,562 women (of the 27,960). We also propose (Aim 2) to use a sample of the WHI HT women enrolled in Medicare some time during follow-up (1993-2017) (n=20,236), to examine the association between Medicare claims for outcomes indicative of FECD from 1993-2017 and randomization to menopausal hormone therapy as part of the two HTs. Such data will inform our understanding of estrogen exposure and BMI in FECD. These findings could lead to development of algorithms to identify women at higher risk for FECD progression, and guide endeavors for future trials that may evaluate hormonal interventions aimed at reducing FECD risk and progression.

抽象的终末期福克斯内皮性角膜营养不良 (FECD)，通常发生在 7 岁以后，是一种角膜失明的主要原因。1-3 FECD 唯一确定的可改变危险因素是吸烟，4,5 关于 FECD 可改变危险因素的流行病学数据很少。 FECD 导致的失明得到纠正然而，对于角膜移植来说，移植成本高昂，供体组织在全球范围内有限，并发症也较多可能会出现，并且老年人并不总是需要手术。6,7 与同龄男性相比，存在女性绝经后 FECD 的患病率增加。8,9 我们假设较高的雌激素水平暴露与 FECD 风险降低相关，从而解释了观察到的性别差异。迄今为止，没有已发表的研究检查了内源性或外源性雌激素测量之间的关联暴露和FECD； BMI（循环雌激素水平的决定因素之一）之间关联的研究，10-12 和 FECD 非常有限。4,13 研究结果表明 BMI 和 FECD13 之间没有关联高BMI对FECD的保护作用。4利用25+年妇女健康倡议的丰富资源 (WHI) 研究中，我们建议检查 FECD 与内源性和外源性之间的关联雌激素暴露。 WHI 由观察性研究 (OS) 和临床试验组成，其中包括两项激素治疗（HT）、单独雌激素或雌激素加孕激素的随机对照临床试验，每项均与安慰剂进行比较。14-17 表明 FECD 的结果，包括内皮性角膜营养不良和角膜移植，可以从医疗保险索赔数据中确定。 WHI 拥有广泛的数据库参与者的人口统计、生育史、健康行为和健康结果。我们建议使用一个在加入 WHI OS 的同一年或更早加入 Medicare 的 WHI OS 女性样本基线 (1993-1998) (n=27,960) 检查医疗保险索赔与事件结果之间的关联指示 1993-2017 年的 FECD 和（目标 1）估计终生内源性雌激素暴露，更年期激素治疗的使用和持续时间（外源性雌激素暴露），不同时间点的BMI 在参与者的整个成年生活中，测量了 2,562 名女性的血清雌二醇浓度（27,960 人中）。我们还建议（目标 2）使用参加 Medicare 的 WHI HT 女性样本随访期间（1993-2017）（n=20,236）的时间，以检查医疗保险索赔之间的关联结果表明 1993 年至 2017 年 FECD 和随机化至绝经期激素治疗作为两个 HT。这些数据将帮助我们了解 FECD 中的雌激素暴露和体重指数。这些发现可能会导致开发算法来识别 FECD 进展风险较高的女性，并指导努力开展未来的试验，评估旨在降低 FECD 风险的激素干预措施，以及进展。