Estrogen replacement therapy and cognitive decline in older community women

The purpose of this study was to evaluate the cross-sectional and longitudinal association of oral estrogen replacement therapy (ERT) and cognitive function in an older, nondemented sample of women.

In a prospective cohort of 9651 white women aged 65 years and older enrolled in the Study of Osteoporotic Fractures, a modified Mini-Mental Status Exam (mMMSE), and digit symbol substitution and Trails B tests were administered twice, 4 to 6 years apart. History and current use of oral ERT was documented. Age, educational attainment, and activity limitations were the primary covariates in the analyses; in addition, stroke and depression scores were adjusted in subsets of women with available data.

Current and past users of ERT had better initial scores on the mMMSE than did never users, P < .05 and .001, respectively, with better scores for current estrogen hormone users being most apparent among the older and less educated women. The percentages of women scoring < or = 23 of a possible 26 on the mMMSE were 14.3 for current users, 14.5 for past users, and 20.5 for never users, P < .001. However, only past users exhibited smaller declines upon retesting in mMMSE and Trails B performance, P < .05, than did never users. Educational attainment predicted both initial test scores and change scores and was, next to age, the most powerful predictor of cognitive function.

Current oral ERT does not protect against age-related declines in cognitive function in older nondemented women, whereas formal education does protect, even though it had been completed many years earlier. The influence of education in late-life on cognitive function should be tested.