Endometriosis linked to higher risk of autoimmune diseases

Endometriosis linked to higher risk of autoimmune diseases | Image Credit: © Alena - © Alena - stock.adobe.com.

Shared biological mechanisms leads to increased risks of osteoarthritis, rheumatoid arthritis, and multiple sclerosis among patients with endometriosis, according to a recent study published in Human Reproduction.¹

Questioning the origin of endometriosis

While retrograde menstruation has been considered as the origin of most endometrial deposits leading to endometriosis, the presence of these symptoms in many menstruating individuals has led to questions about why only some endometrial cells can adhere to peritoneal surfaces. There is a link with aberrant immune response, leading to studies assessing potential increased odds of autoimmune disorders.²

“By leveraging [genome-wide association studies] data, it is possible to explore how shared genetic risk factors contribute to the pathophysiology of these conditions, paving the way for a deeper understanding of their interconnected mechanisms and informing potential clinical diagnostic and therapeutic strategies,” wrote investigators.¹

The study was conducted to assess links between endometriosis and 31 immunological disorders. Data was obtained from the UK Biobank, which includes approximately 500,000 individuals aged 40 to 69 years between 2006 and 2010. Questionnaires were used to collect data on socioeconomic status, behavior, family history, and medical history.

Identification of cases and immunological conditions

During follow-up, disease and death registries were assessed in conjunction with hospital admission records and primary care data to determine cause-specific morbidity and mortality. Biological samples collected from participants included blood, urine, and saliva.

Self-reported questionnaire data and hospital records were analyzed to identify endometriosis cases and immunological conditions. Categories of immunological conditions included autoinflammatory conditions, classical autoimmune conditions, and a combination of autoinflammatory and autoimmune conditions.

Age at recruitment and menarche, ancestry, menopausal status, body size, body mass index, parity, fat distribution, smoking and alcohol use, infertility, and comorbidities were reported as cofounders. A cohort study design and a cross-sectional analysis test were conducted to assess phenotypic associations.

Significantly elevated risk of immunological conditions in endometriosis

When including factors linked with endometriosis and immunological diseases, none had a significant influence on the effects size of association of over 5%. Overall, the risk of having an immunological condition was significantly increased among women with endometriosis vs those without endometriosis, with a hazard ratio (HR) of 1.32.

For classic autoimmune diseases, autoinflammatory diseases, and mixed-pattern disease, HRs of 1.41, 1.29, and 1.88, respectively, were reported among women with endometriosis. Significant associations were reported for rheumatoid arthritis, coeliac disease, and osteoarthritis, with HRs of 1.57, 1.99, and 1.31, respectively.

Cohort analyses also highlighted a significant link to psoriasis, with an HR of 1.67. In comparison, the cross-sectional analyses found odds ratios of 1.62 for systemic lupus erythematosus and 1.66 for gout. However, insufficient case numbers prevented these links from being assessed in the cohort analyses.

Overall, the risk of having at least 1 immunological disease was increased by 14% among women with endometriosis vs those without endometriosis. Additionally, the risk of having at least 2 immunological diseases was increased by 21% among this population, and the risk of at least 3 by 30%.

Genetic correlation suggests shared pathways

These associations did not significantly change when stratifying by gynecological surgery, menopausal status, or hormone replacement therapy use. Further evaluations were conducted to determine whether these immunological conditions linked to endometriosis shared a genetic correlation with the condition.

The analysis identified significant genetic sharing for osteoarthritis, rheumatoid arthritis, and multiple sclerosis. This highlighted a potential genetic basis shared by endometriosis and certain immunological conditions through common biological pathways.

“Clinically, our results highlight the importance of awareness among treating physicians about the increased risk of such comorbidities,” wrote investigators.

References

1. Shigesi N, Harris HR, Fang H, et al. The phenotypic and genetic association between endometriosis and immunological diseases. Human Reproduction. 2025;40(6):1195-1209. doi:10.1093/humrep/deaf062
2. Eisenberg VH, Zolti M, Soriano D. Is there an association between autoimmunity and endometriosis? Autoimmun Rev. 2012;11:806–814.