Department of Reproductive Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
National Research Institute for Family Planning, Beijing, China.
Front Endocrinol (Lausanne). 2024 Aug 2;15:1328403. doi: 10.3389/fendo.2024.1328403. eCollection 2024.
Endometriosis is a chronic inflammatory disease of women during their reproductive years. The relationship between the severity and location of endometriosis and menstruation, ovulation, reproductive function, and mode of delivery remains unclear.
We explored the association between the various phenotypes of endometriosis and menstruation, ovulation, reproductive function, and mode of delivery, using two-sample Mendelian randomization (MR) and summary data on endometriosis stages and locations from the FinnGen consortium and women's menstruation, ovulation, reproductive function, and mode of delivery from OpenGWAS and ReproGen. Inverse-variance weighting was used for the primary MR analysis. In addition, a series of sensitivity analyses, confounding analyses, co-localization analyses, and multivariate MR analyses were performed.
MR analysis showed a negative effect of moderate to severe endometriosis on age at last live birth (OR = 0.973, 95% CI: 0.960-0.986) and normal delivery (OR = 0.999, 95% CI: 0.998-1.000; values for endpoint were excluded), ovarian endometriosis on age at last live birth (OR = 0.976, 95% CI: 0.965-0.988) and normal delivery (OR = 0.999, 95% CI: 0.998-1.000; values for endpoint were excluded), and fallopian tubal endometriosis on excessive irregular menstruation (OR = 0.966, 95% CI: 0.942-0.990). Bidirectional MR analysis showed that age at menarche had a negative causal effect on intestinal endometriosis (OR = 0.417, 95% CI: 0.216-0.804). All MR analyses were confirmed by sensitivity analyses, and only the genetic effects of moderate to severe endometriosis on normal delivery and age at last live birth were supported by co-localization evidence.
Our findings deepen the understanding of the relationship between various types of endometriosis and menstruation, ovulation, reproductive function, and mode of delivery and clarify the important role of moderate to severe endometriosis.
子宫内膜异位症是一种发生于育龄期妇女的慢性炎症性疾病。子宫内膜异位症的严重程度和位置与月经、排卵、生殖功能和分娩方式之间的关系尚不清楚。
我们使用 FinnGen 联盟的子宫内膜异位症各表型与月经、排卵、生殖功能和分娩方式的双样本 Mendelian 随机化（MR）以及 OpenGWAS 和 ReproGen 的女性月经、排卵、生殖功能和分娩方式的汇总数据，探讨了各种子宫内膜异位症表型与月经、排卵、生殖功能和分娩方式之间的关系。主要的 MR 分析采用了逆方差加权法。此外，还进行了一系列敏感性分析、混杂因素分析、共定位分析和多变量 MR 分析。
MR 分析显示，中重度子宫内膜异位症与末次活产年龄（OR=0.973，95%CI：0.960-0.986）和自然分娩（OR=0.999，95%CI：0.998-1.000；终点值被排除在外）呈负相关，卵巢子宫内膜异位症与末次活产年龄（OR=0.976，95%CI：0.965-0.988）和自然分娩（OR=0.999，95%CI：0.998-1.000；终点值被排除在外）呈负相关，输卵管子宫内膜异位症与月经过多（OR=0.966，95%CI：0.942-0.990）呈负相关。双向 MR 分析显示，初潮年龄对肠子宫内膜异位症有负向因果关系（OR=0.417，95%CI：0.216-0.804）。所有的 MR 分析都通过敏感性分析得到了证实，只有中重度子宫内膜异位症对自然分娩和末次活产年龄的遗传效应得到了共定位证据的支持。
本研究加深了对各种类型的子宫内膜异位症与月经、排卵、生殖功能和分娩方式之间关系的认识，明确了中重度子宫内膜异位症的重要作用。
