The largest glaucoma diagnosis postponement was seen in the early menopause group (3.6 years) and the smallest observed in the late menopause group (2.7 years). Photo: Schering. Click image to enlarge.

Researchers at Atlanta’s Emory University recently investigated ways in which estrogen may aid in delaying development of open-angle glaucoma. Their goal was to observe the association between hormonal therapy (HT) use and glaucoma diagnosis onset in postmenopausal women.

The retrospective study included veteran women with open-angle glaucoma from VA records spanning the years 2000 to 2019. HT users accounted for 1,926 individuals while 1,026 untreated women served as controls in the study. Researchers evaluated the impact of HT duration on age of glaucoma diagnosis and used multivariate analysis to determine which factors contributed to age at glaucoma diagnosis.

What the study researchers found was a linear relationship between age of glaucoma diagnosis and menopause in women with and without using HT; however, users typically had a later glaucoma diagnosis. At zero to two years, two to five years and greater than five years of HT use, glaucoma diagnosis was associated with delays of 2.2, 3.7 and 4.5 years, respectively. An interaction between HT duration and age of menopause diagnosis was also seen, with the impact of HT decreasing for later menopause age.

In the discussion section of their paper for Investigative Ophthalmology and Visual Science, the authors relay that under the multivariate analysis, age at menopause was the largest predictor for age of glaucoma diagnosis, followed by HT use, white descent and antihypertensive medication use. A secondary analysis further revealed that for each additional prescription-year of HT, there was an associated 0.2 year later age of glaucoma diagnosis.

They also explain that their data suggests age of menopause may modulate the protective HT effect on glaucoma diagnosis; the negative interaction term between menopause diagnosis age and HT use indicated the effect of HT on age of glaucoma diagnosis decreases with later age at menopause diagnosis.

There were also observed racial differences observed. The authors explain that while main predictive parameters like age at menopause, systemic antihypertensive medication use and HT use were consistent across all ethnicities, there was a trend suggesting HT use was associated with even greater delay in age of glaucoma diagnosis for Black and African-American patients; however, this was not statistically significant.

The authors further extend that these findings support the growing body of literature suggesting a protective role of estrogen in glaucoma pathogenesis. As they observe, “later diagnosis of glaucoma with longer HT durations and the modulating effect of age of menopause suggests that estrogen supplementation may directly influence the pathophysiological processes involved in glaucoma development and progression.” Prior preclinical studies have shown estrogen improved retinal ganglion cell survival and mitigated visual dysfunction after injury to these cells.

Clinically, future research is still needed to uncover the mechanisms underpinning this observed benefit of estrogen in glaucoma development and progression. Looking ahead toward this, the authors caution that “this is key given the potential risk of systemic use of HT; we need continued research to identify potential targets based on these hormonal pathways in the management of this sight-threatening disease, while minimizing the potential risks.”