SynthesisSystematic reviews2026
Insights into the relationship between menopausal timing and risk of cardiovascular disease: a systematic review and meta-analysis of Mendelian randomization analyses.
Synthesis in Systematic reviews, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Authors and funding
5 authors.
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Abstract
backgroundCardiovascular disease (CVD) is the leading cause of death and imposes a substantial burden on women's health. Early onset of menopause, as a unique trait of reproductive aging, has been associated with a higher risk of adverse cardiovascular events in traditional observational studies. However, the findings yielded from Mendelian randomization (MR) studies were inconsistent. This systematic review aimed to (1) synthesize existing evidence on the relationship between genetically determined menopausal timing and CVD risk and (2) assess the methodological quality of the included MR studies.
methodsA systematic literature search was conducted in PubMed, EMBASE, and Web of Science from their inception to June 2025, supplemented by manual searches of the reference lists from retrieved studies and other sources. MR studies using genetic variants as instrumental variables to infer causality between menopausal timing and the risk of cardiovascular-related outcomes were included. The risk of bias of included studies was assessed based on three core MR assumptions and other potential sources of bias. Meta-analyses pooled the inverse-variance weighted-derived odds ratios (ORs) from individual studies using random-effects (RE) models.
resultsSeventeen articles were included in the systematic review, with study populations predominantly of European ancestry. Cardiovascular outcomes of interest included coronary artery disease, ischemic and hemorrhagic stroke, atrial fibrillation, heart failure, hypertension, ventricular structure and function, and cardiometabolic traits. Meta-analyses showed that genetically determined menopausal timing was not significantly associated with the risk of coronary heart disease (OR = 0.97; 95% CI, 0.87-1.07; P = 0.52; I
conclusionsThe findings from our study do not support a causal relationship between menopausal timing and CVD risk. It is recommended that future Mendelian randomization studies incorporate participants from diverse ancestries, explore gene-environment interactions, and rigorously address potential sources of bias. SYSTEMATIC REVIEW REGISTRATION: The study protocol was prospectively registered with PROSPERO (CRD420251058908).
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