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COVID-19与月经不规则及异常子宫出血之间的关系：一项两样本孟德尔随机分析
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Abstract:
观察性研究发现，在2019冠状病毒大流行期间，女性月经不调、异常子宫出血的发病率较前增加，但没有研究证明两者之间存在因果关系。孟德尔随机化分析可以使用独立于混杂因素的遗传变异来获得因果关系的估计。我们旨在通过MR分析探讨COVID-19感染与异常子宫出血及月经不规则之间的因果关系。采用逆方差加权法(IVW)进行主要分析，并进行敏感性分析和多变量MR分析。结果发现，不同疾病程度的COVID-19患者与子宫内膜息肉存在因果关系，感染、患有严重的呼吸道疾病、住院患者的p值分别为0.0376、0.0298、0.00281，当COVID-19病毒感染进展到严重呼吸道疾病和住院阶段时，月经大出血的风险增大，p值分别为0.0432和0.0338。当接受MR-Egger回归法作为结果时，感染新冠肺炎病毒与宫颈息肉之间存在因果关系(p = 0.0490)，因新冠肺炎住院的患者得子宫内膜恶性肿瘤的风险增大(p = 0.0310)。我们进一步研究了COVID-19与可能导致月经不规则的激素之间的关系，发现COVID-19可以影响宿主雌二醇和前列腺素E2的表达(COVID-19感染与前列腺素E2 p = 0.011；COVID-19感染患有严重呼吸道疾病病例与雌二醇p = 0.005；COVID-19感染住院病例与雌二醇p = 0.027)。综上所述，不同程度的新冠肺炎感染增加了女性月经大出血、子宫息肉甚至子宫内膜恶性肿瘤的风险，新冠肺炎感染同样会导致女性雌二醇及前列腺素E2水平降低，这可能进一步影响女性月经。
Observational studies have identified a rise in the incidence of irregular menstruation and abnormal uterine bleeding among women during the COVID-19 pandemic. However, no studies have established a causal link between the two. Mendelian randomization analysis leverages genetic variation, which is independent of confounding factors, to estimate causality. Our aim was to explore the causal relationship between COVID-19 infection and abnormal uterine bleeding as well as irregular menstruation using MR analysis. The main analysis employed the variance inverse weighting method (IVW). Sensitivity analysis and multivariate MR analysis were also conducted. The results indicated a causal relationship between patients with varying disease severity and endometrial polyps, with p-values for patients with infection, severe respiratory disease, and hospitalization being 0.0376, 0.0298, and 0.00281, respectively. As COVID-19 virus infection progressed to severe respiratory disease and hospitalization stages, the risk of heavy menstrual bleeding increased, with p-values of 0.0432 and 0.0338, respectively. When the MR-Egger regression method was considered, there was a causal relationship between COVID-19 virus infection and cervical polyps (p = 0.0490), and the risk of endometrial malignancies in hospitalized patients due to COVID-19 also increased (p = 0.0310). We further investigated the relationship between COVID-19 and hormones that may cause menstrual irregularities. We found that COVID-19 can affect the expression of estradiol and prostaglandin E2 in the host (p = 0.011 for COVID-19 infection and prostaglandin E2; p = 0.005 for patients with severe respiratory disease and estradiol p; p = 0.027 for inpatients with COVID-19 infection and estradiol). In summary, varying degrees of COVID-19 infection
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