Zu Yizheng, Xie Yi, Zhang Huale, Chen Lichun, Yan Shihan, Wang Zhenna, Fang Zhuanji, Lin Shunhe, Yan Jianying
College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University Fujian Maternity and Child Health Hospital, Fuzhou, Fujian Province, People's Republic of China.
Fujian Clinical Research Center for Maternal-Fetal Medicine, Fuzhou, Fujian Province, People's Republic of China.
Int J Womens Health. 2025 Mar 27;17:923-935. doi: 10.2147/IJWH.S508174. eCollection 2025.
Endometriosis has been hypothesized to increase the risk of preeclampsia (PE) and eclampsia, although the exact mechanism of this relationship is not clear. This study aimed to further explore the potential association between endometriosis and PE/eclampsia through Mendelian randomization (MR) and confirm these findings in a retrospective cohort study.
A two-sample MR study was performed using genetic variants associated with endometriosis from the Finnish database, with outcome data for PE and eclampsia from the UK Biobank. Subgroup analyses were conducted based on endometriosis severity (American society of reproductive Medicine (ASRM) stages I-II and III-IV) and anatomical location (uterus, ovary, deep infiltrating endometriosis). Additionally, a retrospective cohort study was conducted to further assess the association, adjusting for confounding factors such as age, Body Mass Index (BMI), dysmenorrhea, history of uterine surgery, and adenomyosis. Multivariate logistic regression was used to analyze the risk of PE/eclampsia based on endometriosis severity.
MR using the Inverse Variance Weighted method found a meaningful association between advanced endometriosis (ASRM stages III-IV) and PE/eclampsia (p = 0.008), while no significant associations were observed for lower stages or endometriosis in the uterus and ovary. In the retrospective cohort, the initial association between the revised American Fertility Society (r-AFS) score and PE/eclampsia (OR: 1.02, 95% CI: 1.01-1.03, p < 0.001) weakened after adjusting for confounders. Significant risk factors identified included age (OR: 1.20, 95% CI: 1.10-1.30, p < 0.001), dysmenorrhea (OR: 2.72, 95% CI: 1.31-5.76, p = 0.008) and adenomyosis showing the strongest association (OR: 9.96, 95% CI: 5.00-20.06, p < 0.001).
The findings suggest a potential relationship between advanced endometriosis and the risk of PE/eclampsia. However, other clinical factors such as age, dysmenorrhea, and adenomyosis appear to contribute more significantly to the risk. Further studies are needed to confirm these findings and clarify the underlying mechanisms.
虽然子宫内膜异位症与子痫前期（PE）和子痫之间关系的确切机制尚不清楚，但已有假说认为子宫内膜异位症会增加患PE和子痫的风险。本研究旨在通过孟德尔随机化（MR）进一步探讨子宫内膜异位症与PE/子痫之间的潜在关联，并在一项回顾性队列研究中证实这些发现。
利用来自芬兰数据库中与子宫内膜异位症相关的基因变异进行两样本MR研究，并采用来自英国生物银行的PE和子痫结局数据。基于子宫内膜异位症的严重程度（美国生殖医学学会（ASRM）I-II期和III-IV期）和解剖位置（子宫、卵巢、深部浸润性子宫内膜异位症）进行亚组分析。此外，进行了一项回顾性队列研究以进一步评估这种关联，并对年龄、体重指数（BMI）、痛经、子宫手术史和子宫腺肌病等混杂因素进行了校正。采用多因素逻辑回归分析基于子宫内膜异位症严重程度的PE/子痫风险。
采用逆方差加权法的MR研究发现，晚期子宫内膜异位症（ASRM III-IV期）与PE/子痫之间存在有意义的关联（p = 0.008），而较低分期或子宫及卵巢子宫内膜异位症未观察到显著关联。在回顾性队列中，校正混杂因素后，修订后的美国生育协会（r-AFS）评分与PE/子痫之间的初始关联（OR：1.02，95%CI：1.01-1.03，p < 0.001）减弱。确定的显著风险因素包括年龄（OR：1.20，95%CI：1.10-1.30，p < 0.001）、痛经（OR：2.72，95%CI：1.31-5.76，p = 0.008）和子宫腺肌病，后者显示出最强的关联（OR：9.96，95%CI：5.00-20.06，p < 0.001）。
研究结果提示晚期子宫内膜异位症与PE/子痫风险之间存在潜在关系。然而，年龄、痛经和子宫腺肌病等其他临床因素似乎对风险的影响更为显著。需要进一步研究来证实这些发现并阐明潜在机制。
