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; 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.

抽象的 终阶段富克斯的内皮角膜营养不良（FECD）通常发生在生命的第7个十年之后，是一个 角膜失明的主要原因。1-3FECD唯一建立的可修改风险因素是吸烟，4,5 关于FECD的可修改风险因素，存在最小的流行病学数据。 FECD的失明被纠正 然而，随着角膜移植的成本，供体组织在全球范围内受到限制，并发症 可以出现，老年人并不总是需要手术。6,7与年龄相似的男性相比 女性更年期后的FECD患病率增加。8,9我们假设雌激素较高 暴露与降低FECD的风险有关，从而解释了这种观察到的性别差异。迄今为止，没有 已发表的研究检查了雌激素内源或外源性测量的关联 暴露和粪便；研究BMI之间的关联，循环雌激素水平的决定因素为10-12 4,13研究结果表明，BMI和FECD13和A之间没有关联 高BMI对FECD.4的保护作用，使用25年以上妇女健康计划的丰富资源 （whi）研究，我们建议检查粪便与内源性和外源性之间的关联 雌激素暴露。 WHI由一项观察性研究（OS）和临床试验组成，包括两个 激素治疗（HT），雌激素或雌激素加孕激素的随机对照临床试验， 每个与安慰剂相比。14-17的结果指示了粪便，包括内皮角膜营养不良和 角膜移植，可以从Medicare索赔数据中识别。 WHI在 参与者的人口统计学，生殖历史，健康行为和健康成果。我们建议使用 在同一年或较早的时候，他们参加了Medicare的妇女的样本 基线（1993-1998）（n = 27,960），以检查事件结果的医疗保险索赔之间的关联 指示1993 - 2017年的FECD和（AIM 1）估计的终身内源性雌激素暴露， 更年期激素治疗和持续时间（外源性雌激素暴露），在不同时间点BMI 在参与者的成人生活中，并在2562名女性中测量了血清雌二醇浓度 （27,960）。我们还建议（AIM 2）使用Medicare的Whi HT妇女的样本 随访期间（1993-2017）（n = 20,236），检查Medicare索赔之间的关联 结果表明1993 - 2017年的FECD，并随机与更年期激素疗法作为一部分 两个HTS。此类数据将为我们对雌激素暴露和FECD中的BMI的了解。这些发现 可能导致算法的发展，以识别出较高的FECD进展风险的女性，并指导 努力进行以后的试验，这些试验可能评估旨在降低FECD风险和的荷尔蒙干预措施 进展。