A retrospective study of more than 5.4 million patients found that combined estrogen and progesterone therapy was associated with higher risks of developing several autoimmune conditions compared with progesterone-only treatment. The research, published in ACR Open Rheumatology, analyzed data from 89 health care organizations.

The analysis showed that patients receiving combined therapy had increased risk ratios for Sjögren disease (1.65), systemic sclerosis (1.2), rheumatoid arthritis (1.3), systemic lupus erythematosus (1.07), giant cell arteritis (1.28), Behcet disease (1.3), psoriatic arthritis (1.28), reactive arthritis (1.6), and ankylosing spondylitis (1.4). The data indicated a lower risk ratio (0.7) for antiphospholipid syndrome in patients receiving combination therapy.

The researchers at Jefferson Einstein Hospital examined 3,338,925 patients who received combined estrogen and progesterone therapy and 2,090,758 who received progesterone-only treatment. The study utilized 1:1 propensity score matching based on age, ethnicity, and additional criteria.

The investigation matched patients based on neoplastic disorders, immune checkpoint inhibitor use, and personal histories of venous embolism, thrombosis, and pulmonary embolism.

Study limitations included potential inaccuracies in electronic health records and inherent biases in health care database studies. The researchers stated that while the study established associations, it could not determine causation.

The authors called for prospective studies to examine underlying mechanisms and evaluate causality.

Conflict of interest disclosures can be found in the study.