More than 50 million individuals worldwide have AMD, and previous population-based studies have shown females are associated with a higher risk of getting this disorder. Some researchers have suggested sex differences in the pathophysiology of AMD might be attributable to variations in the levels of the hormone estrogen.

Hoping for more clarity on the matter, researchers from South Korea investigated the association between female reproductive factors and wet AMD risk in postmenopausal women using a nationwide population-based cohort of nearly 1.3 million postmenopausal women over the age of 50. This is the first cohort study in the Asian population and the largest cohort study ever to report the association between female reproductive factors and exudative AMD, the authors noted in their paper.

During a mean follow-up of 7.27 years, 4,086 patients were newly diagnosed with exudative AMD. The hazard ratio (95% confidence intervals) for wet AMD was 1.14 for a reproductive period ≥40 years compared to a reproductive period less than 30 years, and 1.72 for patients with five or more years of hormone replacement therapy (HRT) and 1.29 for those with two to five years of HRT vs. treatment-naïve patients.

“A longer reproductive period, which reflects a greater exposure to endogenous estrogen, was associated with a greater incidence of exudative AMD,” the authors concluded in their paper. “A history of HRT independently increased the risk of exudative AMD in post-menopausal women, which indicated that exogenous female hormone exposure was associated with a greater risk of exudative AMD. Taken together, the results of our study suggest that exogenous and endogenous female hormone exposure was associated with a greater risk of developing exudative AMD.”

This evidence is contrary to the existing literature, they added. 

The authors believe estrogen “may have a more complex influence, since it plays both beneficial and adverse roles in the pathogenesis of exudative AMD.” As an example of one of its protective roles, they noted that “aging accelerates oxidative stress to the RPE and leads to RPE apoptosis and degeneration, and estrogen itself has been shown to be a potent antioxidant, potentially lowering the oxidative stress of the RPE directly.” However, they also said some reports have found that estrogen could have a detrimental effect by promoting the development and increasing the severity of choroidal neovascularization, the key pathologic process of exudative AMD.

Hwang S, Woong Hang S, Han J, et al. Female reproductive factors and the risk of exudative age-related macular degeneration: a nationwide cohort study. Retina. [Epub ahead of print]. doi: 10.1097/IAE.0000000000003164