Autoimmune disease risk may differ by menopausal hormone therapy formulation

A large observational study of nearly 110,000 menopausal women found that systemic estrogen-only menopausal hormone therapy was associated with a modestly higher hazard of composite autoimmune disease than systemic estrogen-plus-progestogen therapy. The analysis, which used data from the TriNetX US Collaborative Network, also identified significantly higher hazards for six individual autoimmune diseases among women receiving estrogen-only therapy. The researchers said the findings were hypothesis-generating, and the absolute differences in event rates were small.

Researchers compared women receiving systemic estrogen-only therapy with women receiving systemic estrogen-plus-progestogen therapy after one-to-one propensity score matching. Outcomes included composite autoimmune disease and 20 individual autoimmune diseases recorded 180 days or more after hormone therapy began. For composite autoimmune disease, the estimated event proportions were 4.9% in the estrogen-only group and 4.5% in the estrogen-plus-progestogen group.

The corresponding hazard ratio was 1.08, with a 95% confidence interval of 1.02 to 1.14. These results indicate a small association between estrogen-only treatment and the measured rate of newly recorded composite autoimmune disease, but they do not establish that either formulation causes autoimmune disease. The disease-specific analysis found significantly higher hazards among women receiving estrogen-only therapy for systemic lupus erythematosus, rheumatoid arthritis, psoriasis, psoriatic arthritis, multiple sclerosis and lichen sclerosus.

No significant differences were observed for the other autoimmune diseases included in the study. The news release did not provide separate event counts, absolute risk differences or effect estimates for each individual disease, so the size of those associations cannot be evaluated from the reported results. The comparison was also limited to systemic hormone therapy formulations; the evidence supplied does not address other routes, doses, durations or hormone products.

Progestogen is included in hormone therapy to protect the uterus, and the study was designed to determine whether adding it changes the autoimmune-disease association associated with menopausal hormone therapy. The results suggest that the presence of progestogen may limit the increased hazard associated with estrogen alone. For composite autoimmune disease, the reported event proportions differed by 0.4 percentage points.

The release did not state follow-up duration or present absolute risk differences for the six conditions with higher hazards, limiting interpretation of their clinical significance. The researchers said prospective studies are needed to clarify the immunologic effects of different menopausal hormone therapy formulations. “Our findings suggest that the autoimmune disease risk associated with menopausal hormone therapy may differ by hormone formulation,” said Dr.

Xuezhi Daniel Jiang, lead author and professor of obstetrics and gynecology at Drexel University College of Medicine. She emphasized that estrogen-only therapy was associated with only a modestly higher risk than estrogen-plus-progestogen therapy and that the absolute differences were small. Dr.

Stephanie Faubion, medical director for The Menopause Society, said studies like this are important for informing future prospective investigations of the association between hormone therapy and autoimmune diseases, which are more common in women than in men. The study, titled “Incident autoimmune disease risk in systemic estrogen versus estrogen-progestogen menopausal hormone therapy,” was scheduled for presentation at The Menopause Society’s 2026 Annual Meeting in San Diego on October 20–24, 2026. The supplied news release reported no conflicts of interest.

Because the evidence did not include the full paper, details such as matching variables, eligibility criteria, follow-up duration, sensitivity analyses and complete disease-specific results were unavailable. The supported conclusion is therefore limited: among the matched cohort, systemic estrogen-only therapy was associated with slightly higher measured hazards for composite and selected autoimmune diseases than systemic estrogen-plus-progestogen therapy, but the absolute differences were small, causality was not demonstrated and prospective investigation is required.

Subject of Research: Comparison of incident autoimmune disease hazards between systemic estrogen-only and estrogen-plus-progestogen menopausal hormone therapy

Article Title: Autoimmune disease risk may differ by menopausal hormone therapy formulation

Article References: Autoimmune disease risk may differ by menopausal hormone therapy formulation. Original publication (Bibliographic details unavailable.)

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Keywords: menopause, hormone therapy, autoimmune disease, estrogen, progestogen, observational study, TriNetX, systemic lupus erythematosus, rheumatoid arthritis, psoriasis, Autoimmune, disease