Associations between the incidence of Fuchs' endothelial corneal dystrophy and menopausal hormone therapy use and exposure to endogenous estrogen

Objectives: End-stage Fuchs' endothelial corneal dystrophy is a leading cause of corneal blindness, with a higher prevalence in females than in males. Few modifiable risk factors have been identified. We examined associations between menopausal hormone therapy use (never/past/current), duration of hormone therapy use, estimated lifetime exposure to endogenous estrogen, and serum estradiol with incident Fuchs' endothelial corneal dystrophy in a cohort of postmenopausal women. Study design: This was a prospective analysis in the Women's Health Initiative Observational Study. Main outcome measures: Incident cases of Fuchs' endothelial corneal dystrophy were identified from the Women's Health Initiative Observational Study baseline (1993–1998) through 2019 using Medicare claims data. Results: In 22,980 women, 1382 incident cases of Fuchs' endothelial corneal dystrophy (annualized incidence rate and 95 % confidence interval = 5.0 [4.8–5.3] cases per 1000 person-years) were identified. The adjusted hazard ratios and 95 % confidence intervals for Fuchs' endothelial corneal dystrophy were 1.02 (0.88–1.18) and 0.89 (0.79–0.997) for past and current hormone therapy use (vs. never use) at baseline, respectively. Adjusted hazard ratios (95 % confidence interval) were 0.90 (0.79–1.03) and 0.95 (0.84–1.08), p-trend = 0.36, for ≤10 and > 10 years, respectively, of hormone therapy use compared with no use; and the adjusted hazard ratio (95 % confidence interval) was 1.01 (0.88–1.15), p-trend = 0.87, for 46.7–59.0 versus 13.8–41.0 years of estimated lifetime exposure to endogenous estrogen. No statistically significant associations were observed with serum estradiol concentrations in a subset of participants. Conclusions: In this cohort of postmenopausal women, current hormone therapy use (vs. never use) showed evidence of protection against the development of Fuchs' endothelial corneal dystrophy; however, duration of hormone therapy use, estimated lifetime exposure to endogenous estrogen, or serum estradiol concentrations were not significantly associated with a decreased risk of Fuchs' endothelial corneal dystrophy.