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. 2024 Feb 5:15:1302312.
doi: 10.3389/fendo.2024.1302312. eCollection 2024.

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

Sijia Lai #  1 , Qiubai Jin #  2 , Dayang Wang  1 , Tianli Li  3 , Xian Wang  1
Affiliations

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

Sijia Lai et al. Front Endocrinol (Lausanne). .

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.

Keywords: FinnGen; Mendelian randomization; cardiovascular disease; dysmenorrhea; menstrual disorders.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) Schematic overview of the study design (B) Mendelian randomization analysis assumptions ①Relevance assumption. ②Exclusion restriction. ③Independence assumption. IVW, inverse-variance-weighted; EM, excessive menstruation; IM, irregular menses; AF, atrial fibrillation; HT, hypertension; MI, myocardial infarction; IHD, ischemic heart disease; CHD, coronary heart disease; IS, ischemic stroke (cardioembolic).
Figure 2
Figure 2
Significant and nominal significant causal associations of excessive menstruation, irregular menses and dysmenorrhea on cardiovascular disease. After Benjamini-Hochberg correction, the IVW method indicated that irregular menses was associated with higher risk of myocardial infarction. IVW, inverse-variance-weighted. .
Figure 3
Figure 3
Plots of Mendelian randomization estimates showing the causal effects of genetically predicted menstrual disorder and dysmenorrhea on cardiovascular disease. (A) Scatter plot from genetically predicted IM on MI; (B) Funnel plot from genetically predicted IM on MI; (C) Leave-one-out plot from genetically predicted IM on MI. IM, irregular menses; MI, myocardial infarction.
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