Dry Eye Disease Across the Menopausal Transition: A Systematic Review and Meta-Analysis

Abstract BACKGROUND/OBJECTIVES: Dry eye disease (DED) disproportionately affects women, and hormonal changes across the menopausal transition have been proposed as contributors. This prospectively registered (PROSPERO: CRD420261390285) systematic review and meta-analysis examined whether the odds of prevalent DED differs between premenopausal, perimenopausal, and postmenopausal women. SUBJECTS/METHODS: MEDLINE, Embase, and Cochrane Library were searched to September 17, 2025. Sixteen observational studies met inclusion criteria, of which ten provided extractable data for meta-analysis. Study designs were cross-sectional, and no randomized studies were identified. The analyses compared postmenopausal women with (1) combined premenopausal and perimenopausal women, (2) perimenopausal women alone, and (3) strictly premenopausal women. Risk of bias was assessed using ROBINS-E. Random-effects Mantel-Haenszel models generated pooled odds ratios (ORs) comparing the odds of prevalent DED across menopausal stages. RESULTS: Postmenopausal women had significantly higher odds of prevalent DED than pre/perimenopausal women (OR 2.05, 95% CI 1.28–3.31, p = 0.003; I²=82%). Compared with strictly premenopausal women, postmenopausal women had higher odds of prevalent DED (OR 2.42, 95% CI 1.23–4.75, p = 0.010; I²=82%). The comparison with perimenopausal women showed a nonsignificant association in the same direction (OR 1.32, 95% CI 0.79–2.18, p = 0.287; I²=88%). Non-pooled studies supported increased DED burden with advancing menopausal stage. Overall certainty of evidence was low due to residual confounding, cross-sectional designs, and substantial heterogeneity. CONCLUSIONS: DED appears more prevalent in postmenopausal women than in earlier reproductive stages, although heterogeneity and confounding limit causal inference. Longitudinal studies with standardized menopausal staging and definitions are needed to clarify hormonal and age-related contributions.