The association of female reproductive factors with glaucoma and related traits: A systematic review

TOPIC: This systematic review summarizes the existing evidence for the association between female reproductive factors (age at menarche, parity, oral contraceptive (OC) use, age at menopause, and postmenopausal hormone (PMH) use) and intraocular pressure (IOP) or open-angle glaucoma (OAG). CLINICAL RELEVANCE: Understanding the association between female reproductive factors and glaucoma may shed light on disease pathogenesis and aid clinical prediction and personalized treatment strategies. Importantly, some factors are modifiable which may lead to new therapies. METHODS: Two reviewers independently extracted articles in Medline, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials databases to identify relevant studies. Eligibility criteria included studies with human subjects over 18 years of age; a measured exposure of at least one of the following: age at menarche, parity, OC use, age at menopause, PMH use; a measured outcome of either IOP or OAG; a cohort, case-control, cross-sectional or randomized-controlled trial design; and a reported measure of association including hazard, risk or odds ratio or mean difference with associated confidence intervals. RESULTS: We included a total of 27 studies. Substantial differences in study design, exposure and treatment levels, treatment duration and variable reporting precluded meaningful quantitative synthesis of the identified studies. Overall, relatively consistent associations between PMH use and lower IOP were identified. With respect to OAG, estrogen-only PMH use may be associated with lower OAG risk and this association may be modified by race. No significant associations were found with combined estrogen + progesterone PMH use. No strong associations between parity, or age at menarche and glaucoma were found, but a younger age at menopause was associated with increased glaucoma risk, and adverse associations were identified with longer duration of OC use, though no overall association with OC use was found. CONCLUSION: The association between PMH use and lower IOP/OAG risk is a potentially clinically relevant and modifiable risk factor and should be investigated further, although this needs to be interpreted in the context of a high risk of bias across included studies. There is a need for future research examining associations with IOP specifically, and how the relationship between genetic factors and OAG risk may be influenced by female reproductive factors