Increased Risk of Rheumatoid Arthritis Among Patients With Endometriosis

A Nationwide Population-Based Cohort Study

Yu-Hao Xue; Liang-Tian You; Hsin-Fu Ting; Yu-Wen Chen; Zi-Yun Sheng; Yi-Dong Xie; Yu-Hsun Wang; Jeng-Yuan Chiou; James Cheng-Chung Wei


Rheumatology. 2021;60(7):3326-3333. 

In This Article

Abstract and Introduction


Objectives: Autoimmunity may play a role in endometriosis. The association between endometriosis and RA remains unknown. This study was conducted to identify any evidence for this relationship.

Methods: This 13-year, nationwide, population-based, retrospective cohort study analysed the risk of RA in a cohort of individuals with endometriosis. We investigated the incidence of RA among patients with endometriosis using data from the Longitudinal Health Insurance Database 2000, which is maintained by the Taiwan National Health Research Institutes. We used propensity scores to match comorbidities in the two cohorts. Kaplan–Meier analysis and Cox proportional hazard model were employed to analyse the association between endometriosis and RA among patients with different potential risks.

Results: Patients with endometriosis [adjusted hazard ratio (HR) 1.75, 95% CI 1.27, 2.41], aged ≥45 years (adjusted HR 1.50, 95% CI 1.06–2.13) and with autoimmune disease (adjusted HR 6.99, 95% CI 2.84–17.21) had a significantly higher risk of RA. The analyses also showed that when stratified by age, comorbidities and medication use, the risk of RA in patients with endometriosis was also higher than in those without endometriosis.

Conclusions: This 14-year, nationwide, population-based retrospective cohort study revealed that patients with endometriosis have a higher risk of RA. In the clinical management of patients with RA, rheumatologists should be especially mindful of the possibility of underlying endometriosis.


Endometriosis is a common gynaecological disease, that is characterized by abnormal growth of endometrial cells outside the uterus. It can result in discomfort, and in the most severe cases, even the use of an analgesic does not adequately reduce the pain. The most widely accepted hypothesis for the pathophysiology of endometriosis is the retrograde menstruation hypothesis, whereby endometrial fragments reaching the pelvis via transtubal retrograde flow implant onto the peritoneum and abdominal organs, proliferate, and cause chronic inflammation with formation of adhesions.[1–3] It has also been associated with infertility, although the mechanism is still not fully understood. In a systemic review, the first-degree relatives of women with severe endometriosis were found to have a six times greater risk for endometriosis than that of unaffected women.[2,4] The prevalence of the symptoms of endometriosis in women experiencing pain, infertility or both is as high as 35–50%.[2] The prevalence of endometriosis increases dramatically to as high as 25–50% in women with infertility, and 30–50% of women with endometriosis are infertile.[5] Moreover, women with endometriosis are at higher risk of developing ovarian cancer compared with the general female population, and they also may be at increased risk of breast cancer and other cancers, as well as autoimmune and atopic disorders.[3] In some patients with endometriosis, there is also a chronic local inflammatory process and presence of autoantibodies.[6] Furthermore, endometriosis shares similarities with several autoimmune diseases, such as elevation in levels of cytokines, decreased apoptosis and cell-mediated abnormalities.[7]

A prospective cohort study conducted as part of the Nurses' Health Study II showed that endometriosis was significantly associated with subsequent SLE and RA.[8] However, no population-based studies have been conducted in an Asian country. Thus, we conducted a long-term nationwide cohort study by analysing data from Taiwan's Longitudinal Health Insurance Database 2000 (LHID2000) to assess the association between endometriosis and the subsequent development of RA.