Evidence for Menopause as a Sex-Specific Risk Factor for Glaucoma

Abstract

Glaucoma is a leading cause of irreversible blindness worldwide and is characterized by progressive loss of visual function and retinal ganglion cells (RGC). Current epidemiological, clinical, and basic science evidence suggest that estrogen plays a role in the aging of the optic nerve. Menopause, a major biological life event affecting all women, coincides with a decrease in circulating sex hormones, such as estrogen. While 59% of the glaucomatous population are females, sex is not considered a risk factor for developing glaucoma. In this review, we explore whether menopause is a sex-specific risk factor for glaucoma. First, we investigate how menopause is defined as a sex-specific risk factor for other pathologies, including cardiovascular disease, osteoarthritis, and bone health. Next, we discuss clinical evidence that highlights the potential role of menopause in glaucoma. We also highlight preclinical studies that demonstrate larger vision and RGC loss following surgical menopause and how estrogen is protective in models of RGC injury. Lastly, we explore how surgical menopause and estrogen signaling are related to risk factors associated with developing glaucoma (e.g., intraocular pressure, aqueous outflow resistance, and ocular biomechanics). We hypothesize that menopause potentially sets the stage to develop glaucoma and therefore is a sex-specific risk factor for this disease. Graphical Abstract

A Histomorphometric and Computational Investigation of the Stabilizing Role of Pectinate Ligaments in the Aqueous Outflow Pathway

“…Finally, although sex differences are likely important in glaucoma [27,54], due to the scarcity of female samples in our data set, we did not consider sex as a biological variable in our analysis.…”

“…Hence, future investigations should consider other mouse strains (and species) to better elucidate the role of PL in aqueous outflow. Finally, although sex differences are likely important in glaucoma (Douglass et al, 2023; Lee et al, 2021), due to the scarcity of female samples in our data set, we did not consider sex as a biological variable in our analysis. Therefore, caution is advised interpreting these results for both sexes.…”

Awareness and Knowledge of Glaucoma and Its Associated Risk Factors Among Adult Population in the Jazan Region, Saudi Arabia

“…Primary angle-closure glaucoma (PACG) is the most common type of glaucoma in Asia, with recognized risk factors such as ethnicity, age, refractive error, sex, and family history. It is also the most common type of glaucoma in the United States, Europe, Africa, and Australia [ 6 ]. It is estimated that glaucoma, including OAG and ACG, will affect approximately 80 million people worldwide by 2020.…”

Association of Exercise Intensity with the Prevalence of Glaucoma and Intraocular Pressure in Men: A Study Based on the Korea National Health and Nutrition Examination Survey

“…Since IOP is a major risk factor for glaucoma, the association between exercise and IOP should also be analysed to understand the association between exercise and glaucoma. Sex-based differences in PA behaviour may affect exercise types and covariates [ 14 ], and there is evidence that menopause is a sex-specific risk factor for glaucoma [ 15 ]. Moreover, according to one study [ 7 ], vigorous PA has a positive association with the prevalence of glaucoma in men (OR = 6.05, 95% CI: 1.67–21.94), whereas another study indicates that vigorous PA protects male runners from glaucoma [ 16 ].…”