Association of glaucoma diagnosis with sex hormone-related diagnoses and hormone-replacement therapy within a national U.S. database

OBJECTIVE: To understand the potential influence of gonadocorticoids on glaucoma susceptibility. METHODS: We conducted a retrospective cohort study using TriNetX, a multicentre federated health research network, to create cohorts of patients with sex hormone-related diagnoses, including those that lead to increased or decreased estrogen or testosterone states. These were compared with corresponding propensity score-matched control cohorts. Associations between sex hormone states and glaucoma diagnoses/procedures were assessed using standardized differences to identify imbalance. Glaucoma diagnoses were divided into 3 categories: glaucoma suspect, open-angle glaucoma, and narrow-angle glaucoma. Resulting risk ratios, 95% confidence intervals, and P values are reported. A significance level of 0.05 was assumed. RESULTS: Estrogen-deficient states (including bilateral oophorectomy, primary ovarian failure, and early menopause) showed mixed results. Bilateral oophorectomy (n = 24 798) was associated with a lower risk of glaucoma (P < 0.001), primary ovarian failure (n = 23 853) was not associated with risk of glaucoma, and early menopause (n = 256 043) was associated with an increased risk of glaucoma (P < 0.001). A testosterone-deficient state (male hypogonadism, n = 90 752) was not associated with risk of glaucoma. Increased estrogen (hormone-replacement therapy) (n = 41 144) and long-term estrogen use (n = 39 202) showed decreased risk of glaucoma diagnosis (P < 0.001). Long-term oral contraceptive use (n = 5795) was associated with a lower risk of glaucoma suspect diagnosis (P < 0.001). Increased testosterone (polycystic ovarian syndrome, n = 9181) was not associated with a diagnosis of glaucoma. CONCLUSIONS: Estrogen- and testosterone-deficient states in this study did not show a consistent pattern with glaucoma risk, whereas estrogen-replacement therapy and long-term estrogen use may confer protective effects.