Abstract
SummaryBackgroundAssociations between endogenous estrogen exposure indicators and risk of subtypes of dementia have been unclear.MethodsDatabases (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.FindingsWe included 22 studies (475 9764 women) in this analysis. We found no clear relationship between late menarche (≥14 vs <14 years) and dementia, CI in categorical meta-analysis compared to a J-shape relationship in dose-response meta-analyses. Later menopause (≥45 vs <45 years) was consistently associated with a lower risk of all-cause dementia (pooled RR: 0.87, 95%CI: 0.78–0.97, I2=56.0%), AD (0.67, 0.44–0.99, I2=78.3%), VD (0.87, 0.80–0.94) and CI (0.82, 0.71–0.94, I2=19.3%) in categorical meta-analysis, showing similar results in dose-response meta-analyses. An inverse relationship between longer reproductive duration (≥35 vs <35 years) and dementia was observed in dose-response meta-analysis. In addition, estradiol levels after menopause were inversely correlated with the risk of AD and CI.InterpretationIn this study, later menopause and longer reproductive period were associated with a lower risk of dementia, while the relationship for menarchal age was J-shaped. There was an inverse relationship between higher postmenopausal estrogen levels and risk of AD and CI. Longitudinal study are needed to further explore the association between life-time estrogen exposure and risk of subtypes of dementia.FundingStart-up Foundation for Scientific Research in Shandong University.
Highlights
Sex differences have been shown in the epidemiology of dementia.[1]
We found no clear relationship between late menarche (≥14 vs
Longitudinal, repeat measure designs are needed to examine the association between life-time estrogen exposure and risk of subtypes of dementia using direct measure of serum level of endogenous estrogen before and after menopause
Summary
Previous studies have shown inconsistent findings on the associations between age at menopause, length of reproductive period and risk of dementia. We included both preand postmenopausal estrogen exposures in the present review, providing a life-course perspective into understanding the relationship between endogenous estrogen exposure and subtypes of dementia. Later menopause and longer reproductive period were associated with a lower risk of dementia, while the relationship for menarchal age was J-shaped. Higher concentration of endogenous estradiol after menopause was linked to lower risk of AD and CI. Longitudinal, repeat measure designs are needed to examine the association between life-time estrogen exposure and risk of subtypes of dementia using direct measure of serum level of endogenous estrogen before and after menopause
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