Female reproductive factors in relation to risk of exfoliation glaucoma or glaucoma suspect.

PURPOSE Incidence studies have reported higher rates of exfoliation syndrome and glaucoma (XFG) in women, implicating female-specific factors. We evaluated associations between female reproductive factors and incident XFG. DESIGN Prospective cohort study of 121,098 females in the Nurses' Health Study (NHS; 1980-2018) and NHSII (1991-2019). METHODS Eligible participants were ≥40 years old, postmenopausal, had no history of XFG or cataract extraction, had data on reproductive factors, and reported ophthalmic examinations. Incident XFG or exfoliation glaucoma suspect (XFGS) cases (n=440 affected eyes) were confirmed with medical records. Per-eye Cox proportional hazards models were used to estimate multivariable-adjusted hazard ratios (MVHRs) and 95% confidence intervals (CIs). False discovery rate (FDR) was used to correct for multiple comparisons. RESULTS Overall, reproductive history indicative of a greater lifetime estrogen exposure was suggestively associated with higher XFG/XFGS risk. Each 1-year increase in age at menarche was associated with 9% lower risks (MVHR=0.91; 95%CI: 0.85, 0.97; FDR-corrected p-trend=0.047). Parity was not associated, longer durations of oral contraceptive use and breastfeeding were inversely associated, and earlier age at menopause and duration of menopausal hormone therapy was adversely associated, although no FDR-corrected p-trends were significant. Among those with high genetic susceptibility for XFG, surgical menopause (bilateral oophorectomy) was inversely associated with XFG/XFGS compared to natural menopause (MVHR=0.37; 95% CI: 0.15, 0.92; FDR-corrected p-interaction=0.0007). CONCLUSION Later age at menarche was associated with a lower XFG/XFGS risk. Surgical versus natural menopause was inversely associated with XFG/XFGS risk only among those with high genetic susceptibility. These results need confirmation.