Gender and Cataract – The Role of Estrogen

There is evidence from epidemiologic data that cataract is more common in women than men. This is not solely due to a higher rate of cataract extraction in women, as is the case in the western world, but several population-based studies show that females have a higher prevalence of lens opacities, especially cortical. There is no firm evidence that lifestyle-related factors are the cause of this gender discrepancy. Focus has therefore been directed towards the role of estrogen in cataract formation. Although data on endogenous and exogenous estrogen involvement in cataractogenesis are conflicting, some studies have indicated that hormone therapy may decrease the risk of cataract and thus be protective. It has been hypothesized that the decrease in estrogen at menopause cause increased risk of cataract in women, i.e. not strictly the concentration of estrogen, but more the withdrawal effect. Estrogens are known to exert several anti-aging effects that may explain the longer lifespan in women, including metabolically beneficial effects, neuroprotection, preservation of telomeres and anti-oxidative properties. Since oxidative stress is considered important in cataractogenesis, studies have investigated the effects of estrogens on lens epithelial cells in culture or in animal models. Several investigators have found protection by physiological concentrations of 17β-estradiol against oxidative stress induced by H2O2 in cultured lens epithelial cells. Although both main types of estrogen receptors, ERα and ERβ, have been demonstrated in lens epithelium, most studies so far indicate that the estrogen-mediated protection in the lens is exerted through non-genomic, i.e. receptor-independent mechanisms, possibly through phosphorylation of extracellular signal-regulated kinase (ERK1/ERK2), a member of the mitogen-activated protein kinase (MAPK)-signaling pathway. Further studies are needed, both epidemiologic as to the role of hormone therapies, and laboratory studies regarding molecular estrogen-mediated mechanisms, in order to comprehend the role of estrogens on cataract formation.