The effect of estrogen on Alzheimer's Disease (AD) risk has received substantial research and media attention, especially in terms of hormone replacement therapy. But reproductive history is also an important modifier of estrogenic exposure, and deserves further investigation. Importantly, there is wide variation in reproductive patterns that modifies estrogen exposure during the reproductive span, which previous AD studies have not incorporated into their calculations. We measured degree of Alzheimer's-type dementia in a cohort of elderly British women, and collected detailed reproductive and medical history information, which we used to estimate number of months with estrogen exposure and number of months with menstrual cycles. Using Cox proportional-hazards models, we find that longer duration of estrogen exposure may have a protective effect against AD risk, such that for every additional month with estrogen, women experienced on average a 0.5% decrease in AD risk (N=89, p=0.02). More menstrual cycles may also have a protective effect against AD risk, although this result was of borderline statistical significance (p21 at first birth, and more months in lifetime spent pregnant had protective effects against AD risk. ; Psychoneuroendocrinology, 2013 vol. 38(12) pp. 2973-82 Cumulative estrogen exposure, number of menstrual cycles, and Alzheimer's risk in a cohort of British women Fox, M; Berzuini, C; Knapp, LA The effect of estrogen on Alzheimer's Disease (AD) risk has received substantial research and media attention, especially in terms of hormone replacement therapy. But reproductive history is also an important modifier of estrogenic exposure, and deserves further investigation. Importantly, there is wide variation in reproductive patterns that modifies estrogen exposure during the reproductive span, which previous AD studies have not incorporated into their calculations. We measured degree of Alzheimer's-type dementia in a cohort of elderly British women, and collected detailed reproductive and medical history information, which we used to estimate number of months with estrogen exposure and number of months with menstrual cycles. Using Cox proportional-hazards models, we find that longer duration of estrogen exposure may have a protective effect against AD risk, such that for every additional month with estrogen, women experienced on average a 0.5% decrease in AD risk (N=89, p=0.02). More menstrual cycles may also have a protective effect against AD risk, although this result was of borderline statistical significance (p21 at first birth, and more months in lifetime spent pregnant had protective effects against AD risk. Copyright © 2013 Elsevier Ltd. All rights reserved. Type: Journal article PMID: 24064221 | DOI Full Text (full-text online)