Menopausal age does not affect ventricular structure and function: a Mendelian randomization study.

Area of Science:

• Cardiovascular Science
• Reproductive Endocrinology
• Genetic Epidemiology

Background:

• Observational studies suggest a link between age at natural menopause (ANM) and cardiac ventricular characteristics.
• The causal nature of this association remains undetermined.
• Understanding this relationship is crucial for cardiovascular health in postmenopausal women.

Purpose of the Study:

• To investigate the potential causal effect of age at natural menopause (ANM) on ventricular structure and function.
• To differentiate between causal links and mere associations using robust genetic methods.

Main Methods:

• Employed Mendelian randomization (MR) analysis utilizing genome-wide association summary statistics.
• Primary analysis used the inverse variance weighted (IVW) method, complemented by MR-Egger, weighted median, and weighted mode.
• Sensitivity analyses were performed to ensure the robustness and reliability of the findings.

Main Results:

• The primary IVW MR analysis found no statistically significant causal association between ANM and any of the 16 assessed ventricular structures or functions.
• Consistent results were observed across all complementary MR methods.
• Sensitivity analyses confirmed the stability of the results, with no evidence of heterogeneity or horizontal pleiotropy.

Conclusions:

• This Mendelian randomization study provides strong evidence that age at natural menopause does not causally impact ventricular structure or function.
• The observed correlations in prior observational studies are likely due to confounding factors, such as shared upstream cardiovascular risk factors or pleiotropic genetic effects.
• These findings suggest that interventions targeting menopause timing are unlikely to directly alter cardiac ventricular characteristics.