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Abstract Background Glaucoma is a complex multivariate disorder characterized by retinal ganglion cell (RGC) loss and optic nerve degeneration. Evidence suggests the role of estradiol (E2) and the etiology of glaucoma. Therefore, this present study evaluates the association between estrogen-signaling pathways and the risk of open-angle glaucoma (OAG). Results Meta-analysis was performed from available studies that investigated intraocular pressure (IOP) in patients treated with or without hormone replacement therapy (HRT) and studies that evaluated the associations between estrogen receptor (ER) polymorphisms and the risk of OAG. The pooled result showed that HRT had a positive effect in lowering IOP. Moreover, ERβ polymorphisms showed a significant association with the risk of OAG. Conclusion This report supports the notion that estrogen-signaling pathways play a pivotal role in the development of OAG.