Association of reproductive factors with dementia: A systematic review and dose-response meta-analyses of observational studies

Associations between endogenous estrogen exposure indicators and risk of subtypes of dementia have been unclear. Databases (PubMed, EMBASE and Web of Science) were searched electronically on 1st July and updated regularly until 12nd November 2021. Observational studies of English language were selected if reported an effect estimate [e.g., odds ratio (OR), rate ratio (RR) or hazard ratio (HR)] and 95% CI for the association between any exposure (age of menarche, age at menopause, reproductive period, estradiol level) and any endpoint variable [all-cause dementia, Alzheimer's disease (AD), vascular dementia (VD), cognitive impairment (CI)]. Random-effects models and dose-response meta-analyses were used to calculate estimates and to show the linear/nonlinear relationship. PROSPERO CRD42021274827. We included 22 studies (475 9764 women) in this analysis. We found no clear relationship between late menarche (≥14 vs