CONTEXT: While recent studies suggest that exogenous estrogen treatment could help reduce age-related cognitive decline and delay the onset of dementia, this has not been found consistently. Few studies have considered the influence of life-time estrogen exposure which may have an independent effect on cognition and/or modulate treatment response. OBJECTIVE: The aim of this study was to examine whether factors related to estrogen exposure across the life-time were associated with cognitive function in postmenopausal women. DESIGN: A battery of cognitive tests were administered at baseline and at 2 and 4 years of follow-up to evaluate cognitive performance among a population-based cohort of 996 French women aged 65 years or older, who were recruited as part of the ESPRIT study. Detailed reproductive histories were also obtained. Logistic regression models, controlling for an extensive range of potential confounding factors, were generated to determine whether hormone-related factors across a woman's lifetime were associated with poor cognitive performance in later life. RESULTS: Age at first menses was negatively associated with performance on the tasks of visual memory and psychomotor speed, while a longer reproductive period was associated with better verbal fluency. Likewise, women who had their first child at a young age performed significantly worse on each of these tasks, as well as on a measure of global cognitive function. The results also suggest that current hormone therapy may be beneficial for a number of cognitive domains, however, in multivariate analysis, women performed significantly better on the task of visual memory only. In contrast, in analysis adjusted for baseline cognitive performance and a range of other factors, none of the reproductive variables were associated with a decline in cognitive performance or the incidence of dementia during the 4-year follow-up period. CONCLUSIONS: In addition to hormone therapy, certain hormone-related events across the lifetime are also associated with cognitive functioning in later life. They were not observed in this study to modulate dementia risk; however, this should be verified over a longer follow-up period. Further studies will also be required to determine whether lifetime hormonal exposure may modify women's response to hormone therapy after the menopause.