Effect of Hormone Replacement Therapy on Dry Eye Disease in Postmenopausal Women: A Systematic Review of Randomized Controlled Trials [ID 887]

INTRODUCTION: Dry eye disease (DED) disproportionately affects postmenopausal women, yet the role of hormone replacement therapy (HRT) in its treatment remains unclear. This systematic review synthesizes current evidence from randomized controlled trials (RCTs) to evaluate HRT’s efficacy on both subjective and objective DED outcomes. METHODS: We conducted a systematic review of RCTs assessing standardized HRT formulations (estrogen-only, combined estrogen–progesterone, or progesterone-only) in postmenopausal women (≥12 months amenorrhea). Comparators included placebo, no treatment, or alternative hormonal regimens. Primary outcomes included tear break-up time, Schirmer test scores, ocular surface staining, intraocular pressure, and self-reported DED symptoms. Studies involving premenopausal participants or significant ocular/systemic comorbidities were excluded. RESULTS: Nine RCTs (n=739) met inclusion criteria. Hormone replacement therapy demonstrated no significant effect across all five primary outcomes. Tear break-up time (n=343) and Schirmer scores (n=465) yielded standardized mean differences (SMDs) of 0.03 and −0.17, respectively, both nonsignificant. Ocular surface staining (n=85) also showed no effect (SMD −0.63). Symptom-based outcomes, including foreign body sensation (mean difference [MD] −4.83) and dryness (MD 0.47), were similarly null. All CIs crossed zero, with moderate to high heterogeneity ( I 2 =40–95%). CONCLUSIONS/IMPLICATIONS: Despite biologic plausibility, current RCT data do not support routine HRT use for DED management in postmenopausal women. Considerable heterogeneity highlights the need for standardized trial designs. Future research should explore personalized hormonal strategies that account for dosage, route, and hormonal composition to better inform gynecologic practice and ocular health.