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

> **NIH NIH R21** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2021 · $207,506

## Abstract

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.

## Key facts

- **NIH application ID:** 10194032
- **Project number:** 1R21EY032544-01
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Amy Elizabeth Millen
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $207,506
- **Award type:** 1
- **Project period:** 2021-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10194032

## Citation

> US National Institutes of Health, RePORTER application 10194032, A Study of Estrogen and Body Mass Index in Fuchs’ Endothelial Corneal Dystrophy (1R21EY032544-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10194032. Licensed CC0.

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