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Progestogen, when used in hormone therapy, is recognized for its benefits in protecting the uterus. A new study suggests that its addition limits the increased risk of composite autoimmune disease associated with estrogen-only therapy. Results of the study were presented at the 2026 Annual Meeting of The Menopause Society in San Diego, Oct. 20–24, 2026.

Previous research has demonstrated an association between menopausal hormone therapy and increased autoimmune disease risk. However, the effect of progestogen on this risk remains unclear.

A new large-scale study sought to compare incident autoimmune disease risk between women receiving systemic estrogen-only and systemic estrogen-plus-progestogen therapy. Outcomes included composite and 20 individual autoimmune diseases occurring 180 days or more after menopausal hormone therapy initiation.

The study used the TriNetX US Collaborative Network and included nearly 110,000 menopausal women who were grouped based on one-to-one propensity score matching.

Results showed that systemic estrogen-only therapy was associated with a modestly increased hazard of composite autoimmune disease compared with estrogen-plus-progestogen therapy (4.9% vs. 4.5%; hazard ratio, 1.08; 95% confidence interval, 1.02–1.14).

Significantly higher hazards were observed in the estrogen-only cohort for systemic lupus erythematosus, rheumatoid arthritis, psoriasis, psoriatic arthritis, multiple sclerosis and lichen sclerosus. No significant differences were observed for other autoimmune diseases.

Although significant associations were observed for selected autoimmune diseases, absolute event rates and risk differences were small. The researchers suggest that prospective studies are needed to further clarify the immunologic effects of different menopausal hormone therapy formulations.

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