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Effects of menstrual disorders and dysmenorrhea on cardiovascular disease: a Mendelian randomization study
Sijia Lai1, Qiubai Jin2, Dayang Wang1
1Institute of Cardiovascular Disease, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
Insights
This study confirms that menstrual disorders like irregular menses and dysmenorrhea causally increase cardiovascular disease (CVD) risk. These conditions can serve as early markers for identifying women needing timely intervention for CVD prevention.
Area of Science:
- Cardiovascular Medicine
- Reproductive Health
- Genetic Epidemiology
Background:
- Observational studies suggest links between menstrual disorders and cardiovascular disease (CVD).
- The causal relationship between menstrual disorders and CVD risk remains uncertain.
- This research investigates the potential causal impact of menstrual disorders on CVD development.
Purpose of the Study:
- To determine if menstrual disorders (excessive menstruation, irregular menses) and dysmenorrhea causally influence cardiovascular disease risk.
- To establish Mendelian randomization evidence for the association between menstrual disorders and various cardiovascular outcomes.
Main Methods:
- Utilized summary data from the FinnGen study for menstrual disorders and UK Biobank/meta-analysis for CVD.
- Employed the inverse-variance-weighted (IVW) method for Mendelian randomization analysis.
- Conducted sensitivity analyses using multiple methods to ensure robustness of findings.
Main Results:
- Excessive menstruation showed a causal link to higher atrial fibrillation risk but lower hypertension risk.
- Irregular menses was causally associated with increased risk of atrial fibrillation, hypertension, myocardial infarction, ischemic heart disease, and coronary heart disease.
- Dysmenorrhea was causally linked to higher risks of atrial fibrillation and cardioembolic ischemic stroke.
- After correction, irregular menses remained significantly associated with an elevated risk of myocardial infarction.
Conclusions:
- Confirmed a causal relationship between excessive menstruation, irregular menses, dysmenorrhea, and cardiovascular outcomes, independent of sex hormone levels.
- Highlighted irregular menses as a significant risk factor for myocardial infarction.
- Advocates for using these menstrual characteristics as markers to identify women at high risk for future CVD, prompting early clinical intervention for menstrual diseases.
Background:
Observational studies have demonstrated associations between menstrual disorders, dysmenorrhea, and cardiovascular disease (CVD). However, it remains unclear whether these associations are causal. This study is to investigate whether menstrual disorders and dysmenorrhea causally affect the risk of CVD.
Methods:
The summary data for menstrual disorders (excessive menstruation and irregular menses) and dysmenorrhea were obtained from FinnGen study, summary data for CVD were obtained from UK Biobank and meta-analysis. The inverse-variance-weighted method was mainly used in the Mendelian randomization for causality analysis. Sensitivity analyses were performed by several methods under different model assumptions.
Results:
Genetic liability to excessive menstruation was associated with higher risk of atrial fibrillation (odds ratio (OR), 1.078 [95% confidence interval (CI), 1.015-1.145]; P=0.014), but a lower risk of hypertension (OR, 0.994 [95% CI: 0.989-0.999]; P=0.016). Irregular menses was associated with higher risk of atrial fibrillation (OR, 1.095 [95% CI: 1.015-1.182]; P=0.02), hypertension (OR, 1.007 [95% CI: 1.000-1.013]; P=0.047), myocardial infarction (OR, 1.172 [95% CI: 1.060-1.295]; P=0.02), ischemic heart disease, (OR, 1.005 [95% CI: 1.000-1.010]; P=0.037) and coronary heart disease (OR, 1.004 [95% CI: 1.001-1.008]; P=0.026). Dysmenorrhea was associated with higher risk of atrial fibrillation (OR, 1.052 [95% CI: 1.014-1.092]; P=0.008) and Ischemic stroke (cardioembolic) (OR, 1.122 [95% CI: 1.002-1.257]; P=0.046). After Benjamini-Hochberg correction, irregular menses was associated with higher risk of myocardial infarction.
Conclusion:
We confirmed a causal relationship of excessive menstruation, irregular menses and dysmenorrhea on cardiovascular outcomes independent of sex hormone levels, with an emphasis on the link between irregular menses and myocardial infarction. These clinical features can be utilized as markers to identify women at higher risk of developing CVD in the future, recommending early clinical intervention of menstrual diseases.
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