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Menstrual Cycle · Cycle Disorders

Effects of menstrual disorders and dysmenorrhea on cardiovascular disease: a Mendelian randomization study

Lai S, Jin Q, Wang D, Li T, Wang X

Frontiers in endocrinology, 15, 1302312, 2024
DOI 10.3389/fendo.2024.1302312 PMID 38375191 PMC PMC10875084

RRM Academy Synopsis

Genetic liability to irregular periods links to heart attack risk

Genetic liability to irregular menses was linked to higher heart attack risk in a Mendelian randomization study of European-ancestry data. Heavy and painful periods had other links at first. After correction, only the irregular menses link to heart attack held.

Key Findings

  • Irregular menses, by genetic liability, was associated with higher risk of myocardial infarction (OR 1.172, 95% CI 1.060-1.295; P=0.02). The association held after Benjamini-Hochberg correction (P=0.034).
  • Atrial fibrillation was associated with all three exposures. Odds ratios were 1.078 (95% CI 1.015-1.145) for excessive menstruation, 1.095 (95% CI 1.015-1.182) for irregular menses, and 1.052 (95% CI 1.014-1.092) for dysmenorrhea.
  • Dysmenorrhea was associated with higher risk of cardioembolic ischemic stroke (OR 1.122, 95% CI 1.002-1.257; P=0.046). Excessive menstruation showed lower hypertension risk (OR 0.994, 95% CI 0.989-0.999; P=0.016).
  • Irregular menses also showed higher hypertension risk (OR 1.007, 95% CI 1.000-1.013; P=0.047). Its link to coronary heart disease had an OR of 1.004 (95% CI 1.001-1.008; P=0.026).
  • Menstrual exposure data came from FinnGen. Excessive menstruation had 36,824 cases and 107,564 controls. Irregular menses had 17,228 cases and 179,322 controls. Dysmenorrhea had 6,976 cases and 107,564 controls.

Interpretation

Mendelian randomization uses gene variants as a natural experiment, so the estimates reflect lifelong genetic liability. Only the irregular menses and myocardial infarction link passed correction. The other links were nominal, and several odds ratios sit close to 1. The analysis used European-ancestry data only. The dysmenorrhea group had the smallest sample and included a few other pelvic pain conditions. The authors say the dysmenorrhea analyses should be replicated in larger datasets. They conclude the results support a causal link and advise early clinical intervention for menstrual disorders.

RRM Context

The authors start from a premise that restorative reproductive medicine shares. Regular periods reflect a working hypothalamus-pituitary-ovary axis. Diaz and colleagues made the same case in 2006 by proposing the menstrual cycle as a vital sign. A restorative approach reads an irregular cycle as a clue to its cause. Suppressive medications override the cycle and hide that clue.

Our editorial summary of this paper, not the article's abstract.

Abstract

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.

Topics

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Related research

Menstrual Cycle › Cycle Disorders › Dysmenorrhea
Sijia Lai, Qiubai Jin, Dayang Wang, Tianli Li, Xian Wang
S Lai, Q Jin, D Wang, T Li, X Wang
PMID 38375191 38375191 DOI 10.3389/fendo.2024.1302312 10.3389/fendo.2024.1302312 Lai et al. 2024, Lai 2024

Keywords

FinnGen, Mendelian randomization, cardiovascular disease, dysmenorrhea, menstrual disorders

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