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

• 批准号: 10194032
• 负责人: Amy Elizabeth Millen
• 金额: $ 20.75万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10194032
• 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' 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' 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

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.

摘要 终末期Fuchs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唯一公认的可改变的危险因素是吸烟，4，5 关于FECD的可改变的危险因素存在最少的流行病学数据。FECD致盲得到矫正 然而，对于角膜移植，移植费用昂贵，供体组织有限，并发症 6，7与同龄男性相比，有一种 女性绝经后FECD患病率的增加。8，9我们假设较高的雌激素 暴露与FECD风险降低有关，从而解释了观察到的性别差异。到目前为止，没有 已发表的研究已经检验了内源性或外源性雌激素指标之间的关系。 暴露与FECD；BMI，循环雌激素水平的决定因素之一，10-12之间的相关性研究 和FECD是非常有限的。4，13研究结果表明，BMI和FECD13和 高BMI对FECD的保护作用。4利用25+年妇女健康行动的丰富资源 (WHI)研究，我们建议检查FECD与内源性和外源性之间的关系 雌激素暴露。WHI由观察性研究(OS)和临床试验组成，包括两项 激素治疗(HT)、单独使用雌激素或雌激素+孕激素的随机对照临床试验， 分别与安慰剂进行比较。14-17结果表明FECD，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识别出来。WHI有一个广泛的数据库， 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 在参加WHI OS的同一年或更早的年份参加联邦医疗保险的WHI OS女性样本 基线(1993-1998)(n=27,960)，以检查医疗保险索赔与事件结果之间的关联 表明1993-2017年FECD和(目标1)估计的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)，不同时间点的体重指数 在参与者成年后的整个过程中，并测量了2562名女性的血清雌二醇浓度 (27,960人中)。我们还建议(目标2)使用参加联邦医疗保险的WHI HT妇女的样本 随访期间(1993-2017)的时间(n=20,236)，以检查以下各项的医疗保险索赔之间的关联 1993-2017年间FECD的结果以及作为部分内容随机接受更年期激素治疗 两个HTS。这些数据将有助于我们对FECD中雌激素暴露和BMI的理解。这些发现 可能导致开发算法来识别FECD进展的高风险女性，并指导 努力进行未来的试验，评估旨在降低FECD风险和 进步。