Examining Hormone Therapy's Link to Autoimmune Risks in Menopause

Researchers have recently identified a potential link between estrogen-only hormone therapy for menopausal women and a slight increase in the risk of autoimmune diseases. This finding underscores the importance of discussing hormone therapy options with patients, say experts.

Understanding the Study

At the 2026 Annual Meeting of The Menopause Society, Dr. Xuezhi Daniel Jiang, a professor at the Drexel University College of Medicine, presented results from a comprehensive retrospective study examining menopausal women aged 45 to 70. The aim was to explore associations between hormone therapy and the onset of autoimmune conditions.

According to Dr. Jiang, “Menopausal hormone therapy is a common treatment for disturbing menopausal symptoms and can involve estrogen alone or in combination with progestogen, depending on the individual’s uterine status.” He notes that both estrogen and progestogens can influence immune function, yet the distinction in autoimmune disease risk between various hormone therapy combinations is not well understood.

Research Findings

The study utilized data from the TriNetX U.S. Collaborative Network and involved a large cohort of 54,692 women receiving estrogen-only therapy as well as those receiving estrogen combined with progestogen. Notably, participants with pre-existing autoimmune diseases were excluded to focus on newly developed conditions following hormone therapy.

Women in the estrogen-only group had an average follow-up of 1,291 days, while those on the combined therapy were followed for an average of 1,241 days. The findings revealed a composite autoimmune disease incidence of 4.9% in the estrogen-only group compared to 4.5% in the estrogen and progestogen group, indicating a modest risk associated specifically with estrogen therapy (HR = 1.08; 95% CI, 1.02-1.14).

More detailed results showed the risk of systemic lupus erythematosus at 0.3% for the estrogen group versus 0.2% for the combination group, along with similar trends for rheumatoid arthritis, psoriasis, and multiple sclerosis. Dr. Jiang highlighted that these findings hint at a more complex relationship between hormones and different autoimmune conditions.

Limitations of the Study

While the substantial sample size is noteworthy for studying less common autoimmune conditions, the observational nature of this research and reliance on electronic health records pose challenges. Factors such as diagnostic inaccuracies and variations in medication adherence could influence the results.

Dr. Nanette F. Santoro, a specialist from the University of Colorado, emphasized the difficulty in accurately diagnosing autoimmune diseases using administrative databases, which may sacrifice some detail.

Moreover, Dr. Stephanie Faubion from the Mayo Clinic pointed out that, while this study generates valuable hypotheses regarding the impact of different hormone therapies on autoimmune diseases, it does not definitively establish causation. The analysis may reflect residual confounding related to the demographics of the study populations receiving each treatment.

Recommendations Moving Forward

Experts believe that increased awareness rather than immediate alarm should guide clinicians in light of these findings. Hormonal treatments must continue to be chosen based on their established benefits, risks, and the particular needs of each patient.

Dr. Jiang stresses the importance for rheumatologists to consider a patient's menopausal hormone therapy usage when treating newly diagnosed autoimmune conditions. He does not recommend altering hormone therapy solely based on this study's results.

Dr. Faubion concurred, noting that although these findings shouldn’t change current clinical practices, they highlight the need for ongoing research into how different hormone therapy formulations may interact with autoimmune processes. Future studies are vital to further clarify these relationships and enhance individualized treatment approaches for women.

In conclusion, while the study raises essential points regarding hormone therapy in menopausal women and autoimmune disease risk, it primarily serves as a starting point for further investigation rather than a basis for changing medical practice.