Early menopause and premature ovarian insufficiency are associated with increased risk of dementia: A systematic review and meta-analysis of observational studies.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational cohort and case-control studies
PubMed 37393661 · doi:10.1016/j.maturitas.2023.107792
What was done
Authors searched PubMed, Scopus, and CENTRAL through August 2022 for observational studies evaluating the association between early menopause (EM) or premature ovarian insufficiency (POI) and dementia risk of any type. Study quality was evaluated using the Newcastle-Ottawa scale. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated, and heterogeneity was assessed using the I2 index.
What was found
Eleven studies were included (9 good quality, 2 fair quality; n = 4,716,862). Women with EM had an increased risk of dementia compared to those with normal age at menopause (OR 1.37, 95% CI 1.22-1.54; I2 93%). However, removing one large retrospective cohort study eliminated the statistically significant association (OR 1.07, 95% CI 0.78-1.48; I2 94%). Women with POI also showed an increased dementia risk (OR 1.18, 95% CI 1.15-1.21; I2 0%). Risk was most apparent in cohort studies and in women experiencing natural menopause.
Why it matters
This meta-analysis synthesizes evidence on whether premature or early cessation of ovarian function and estrogen decline increases dementia risk, finding suggestive links but highlighting sensitivity to study selection.
Limits
All included studies were observational. The analysis for early menopause demonstrated substantial heterogeneity (I2 > 90%) and lack of robustness after sensitivity analysis (exclusion of one large study rendered the finding non-significant). Specific dementia subtypes and confounding variables (such as hormone replacement therapy use) are not detailed in the abstract.
Cited by
- contradicts Loss of estrogen during menopause is not a cause of cognitive problems or Alzheimer's disease.