Hormone Replacement Therapies and Retinal Disease: A Systematic Review and Meta-analysis

Hormone-replacement therapy (HRT) is widely prescribed for menopausal symptoms, but its associations with major retinal diseases remain uncertain. We evaluated associations between systemic menopausal HRT and major retinal diseases in adults assigned female at birth. Retinal disease causes substantial irreversible vision loss in older women and clarifying ocular risks/benefits of HRT may inform counseling. Following a PROSPERO-registered protocol (CRD420251033644), we searched MEDLINE, Embase, Web of Science, and ClinicalTrials.gov from inception to April 29, 2025. Two reviewers screened records, extracted data, and assessed risk of bias, with a third reviewer resolving conflicts. Random-effects meta-analyses pooled maximally adjusted effect estimates for systemic (oral/transdermal) menopausal hormone therapy versus nonuse/placebo, and certainty of evidence was assessed with Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Forty-eight studies (3,843,057 women) were included. HRT was associated with lower odds of early AMD (OR 0.81, 95%CI 0.70–0.94; p=.006; I²=67.5%) and neovascular AMD (OR 0.38, 95%CI 0.28–0.51; p<.001; I²=0%), but not late AMD with geographic atrophy (OR 0.99, 95%CI 0.93–1.06; p=.868; I²=42.7%). There were no clear associations with retinal artery occlusion (HR 1.04, 95%CI 0.84–1.28; p=.735; I²=0%), retinal vein occlusion (HR 1.09, 95%CI 0.95–1.26; p=.203; I²=9.8%), or diabetic macular edema/diabetic retinopathy (OR 0.80, 95%CI 0.26–2.53; p=.71; I²=62%). Systemic menopausal HRT showed an inverse association with nAMD and early/intermediate AMD, with no clear associations for GA, retinal vascular occlusions, or DME/DR. Findings are hypothesis-generating and require confirmation in prospective studies.