Association Between Endometriosis and Autoimmune Thyroid Disease Using a Multicenter Observational Medical Outcomes Partnership (OMOP) Common Data Model

Vollständiger Abstract

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Background: Endometriosis affects approximately 6–10% of women of reproductive age—an estimate that varies substantially with the diagnostic standard applied—and is increasingly recognized as a systemic inflammatory disease. Growing evidence implicates shared immunological pathways between endometriosis and autoimmune thyroid disease, yet large-scale real-world evidence from standardized multi-site data remains limited. We evaluated the association between endometriosis and newly recorded autoimmune thyroid disease using federated Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) data from 12 Korean hospitals. Methods: We conducted a propensity score (PS)-matched cohort study using OMOP-CDM version 5.3 data from 12 Korean tertiary academic medical centers. Women aged 18–60 years with a first recorded endometriosis diagnosis were matched 1:1 to controls without endometriosis on age, calendar year, hypertension, and selected Charlson comorbidity index components. Site-specific Cox proportional hazards models, fitted to patient-level records locally at each institution, estimated hazard ratios (HRs) for newly recorded autoimmune thyroid disease, defined as Hashimoto’s thyroiditis or Graves’ disease. Pooled estimates were derived using DerSimonian–Laird random-effects meta-analysis; leave-one-out meta-analysis, meta-regression on site-specific follow-up ratio, and an E-value were used to assess robustness. Results: After 1:1 PS matching, 71,619 women with endometriosis and 71,619 matched controls were included. Mean follow-up was 2693 days in the endometriosis group and 1677 days in the control group. A directionally positive but statistically inconclusive association was observed between endometriosis and autoimmune thyroid disease (pooled HR 1.22, 95% CI 0.97–1.53; p = 0.090; I2 = 38.2%). Seven of twelve sites reported HRs above 1.0, including two sites reaching individual statistical significance: AUMC (HR 1.38, p = 0.030) and KHUH (HR 2.69, p < 0.001). The pooled HR remained above 1.0 in all 12 leave-one-out iterations (range 1.17–1.31); omission of KHUH reduced I2 to 6.6%. Site-specific follow-up imbalance was not associated with the site-specific log HR (meta-regression p = 0.887). The E-value for the point estimate was 1.74. Conclusions: In this multi-site OMOP-CDM analysis, endometriosis showed a directionally positive but statistically inconclusive association with newly recorded autoimmune thyroid disease. The confidence interval is compatible with both no association and a clinically meaningful increase in risk, and the findings are hypothesis-generating rather than confirmatory. They do not support any change in the clinical evaluation of women with endometriosis. Further validation is warranted using standardized outcome definitions, thyroid autoantibody measurements, and thyroid function tests.