Endometriosis and Autoimmunity: Evidence from a Nationwide Cohort

Large cohort maps the autoimmune footprint of endometriosis

Key Points

Highlights :

• Large-scale, population-based cohort evidence strengthens the association between endometriosis and multiple autoimmune diseases.
• The risk of autoimmune comorbidity rises with endometriosis, pointing toward shared immune dysregulation.

Importance :

• Understanding systemic associations of endometriosis is crucial, as autoimmune comorbidities may complicate diagnosis, management, and long-term health outcomes.
• There is a need for heightened clinical vigilance and potential screening strategies for autoimmune conditions in women with endometriosis.

What's done here :

• Researchers analyzed a nationwide cohort of women with endometriosis, linking clinical registry data to identify co-occurring autoimmune diseases.
• Associations were quantified across a wide spectrum of autoimmune conditions, using multivariable models to adjust for confounders.
• This unique study is one of the largest and most comprehensive analyses to date exploring the endometriosis–autoimmunity link using a two-year diagnosis period.

Key features :

• Women with endometriosis showed a significantly higher incidence of autoimmune diseases compared with matched controls.
• The association was consistent across several autoimmune conditions, suggesting a broad pattern rather than isolated links.
• Findings support the hypothesis of shared pathophysiological pathways such as chronic inflammation, hormonal-immune interactions, and genetic predisposition.

Strengths and Limitations:

• Strenghths are, very large sample size and national registry design ensure robust statistical power; comprehensive assessment of a wide range of autoimmune diseases; and longitudinal follow-up that provides strong evidence for temporal associations.
• Limitations are: observational design (causality cannot be established); possible detection bias (women with endometriosis may undergo more frequent medical evaluation, increasing the likelihood of autoimmune diagnosis);; and the lack of mechanistic data limiting interpretation of biological pathways.

From the Editor-in-Chief – EndoNews

"This study delivers one of the most compelling population-level signals to date that endometriosis is not only a gynecologic disease, but a systemic one. By leveraging two of the largest U.S. healthcare databases, the authors demonstrate that women with endometriosis are consistently at higher risk of developing a wide range of autoimmune conditions — from rheumatoid arthritis and lupus to multiple sclerosis and thyroid autoimmunity. The scale of the study, encompassing over 1.5 million women, makes the associations difficult to dismiss as chance or bias alone.

What makes these findings striking is not only the breadth of autoimmune comorbidities but also the coherence of the biological rationale: chronic inflammation, immune dysregulation, and shared hormonal–immune pathways likely underpin this overlap. The results remind us that endometriosis may serve as both a marker and a mediator of systemic immune vulnerability.

For clinicians, the message is practical: women with endometriosis deserve heightened vigilance for autoimmune symptoms, and multidisciplinary care should not be delayed when red flags arise. For researchers, the study sets a new benchmark and poses urgent questions — are there common genetic or molecular signatures linking these diseases? Can early identification of autoimmune risk alter the trajectory of endometriosis or vice versa?

The authors are careful to note that causation cannot yet be proven, and surveillance bias may contribute. Still, the consistency, statistical strength, and plausibility of these findings mark this as a pivotal contribution. In the broader view, this work reframes endometriosis from a localized pelvic disorder into a disease with systemic immune implications — and that shift may ultimately transform both how we diagnose and how we care for millions of women worldwide.

Lay Summary

Endometriosis has long been suspected to share biological pathways with autoimmune disorders. Smaller studies have hinted at this connection, but strong large-scale evidence has been limited. Now, Dr.Elhadad's team from Columbia University, New York, have addressed this gap in a pioneering cohort study published in NPJ Women’s Health.

The team analyzed two of the largest U.S. health insurance databases, the Merative MarketScan Commercial Claims and Encounters (CCAE) and the Merative Multi-State Medicaid (MDCD), covering over 30 million individuals annually. They identified more than 332,000 women with endometriosis and compared them to over 1.2 million women without the condition. This unprecedented dataset allowed for a comprehensive evaluation of the relationship between endometriosis and autoimmune diseases.

The results were striking. Women with endometriosis were significantly more likely to be diagnosed with a wide range of autoimmune conditions within a two-year window, including rheumatoid arthritis, Hashimoto’s thyroiditis, systemic lupus erythematosus, multiple sclerosis, Sjögren’s syndrome, pernicious anemia, myositis, Graves’ disease, and type 1 diabetes. The risk was consistently elevated across both databases, reinforcing the reliability of the findings.

Globally, around 8% of people live with autoimmune disorders, and nearly 80% of these patients are women. The overlap with endometriosis underscores possible shared immunopathogenic mechanisms, such as chronic inflammation, immune dysregulation, hormonal–immune interactions, and genetic susceptibility. By highlighting these associations, the study offers critical insights into the systemic nature of endometriosis.

The strength of this research lies in its scale, design, and ability to link endometriosis with multiple autoimmune conditions across diverse populations. Still, as an observational study, it cannot prove causality or determine which disease develops first. Detection bias may also play a role, since women with endometriosis tend to receive more frequent medical care.

Despite these limitations, this study provides some of the strongest evidence to date that endometriosis is associated with an increased risk of autoimmune disease. It emphasizes the need for clinicians to remain vigilant for these comorbidities in women with endometriosis and calls for further research to unravel the biological mechanisms behind this striking overlap.

Research Source: https://pubmed.ncbi.nlm.nih.gov/40547362/