Estrogen-Only Hormone Therapy Linked to Slight Autoimmune Risk Increase
A retrospective study of more than 100,000 women found a slightly higher rate of autoimmune disease among those using estrogen-only menopausal hormone therapy than among those using combined estrogen-progestogen therapy. Five specific conditions showed higher hazards, but absolute differences were small and may not be clinically meaningful. The authors cautioned that the findings do not compare hormone users with nonusers and called for individualized discussions rather than immediate treatment changes.
This retrospective study used a U.S. database to compare women aged 45–70 who used systemic menopausal hormones, excluding those with prior autoimmune disease or certain immune treatments. Composite autoimmune disease occurred in 4.9% of estrogen-only users and 4.5% of combined-therapy users; five conditions—lupus, psoriasis, psoriatic arthritis, multiple sclerosis, and lichen sclerosis—showed higher hazard estimates.
The authors stressed that the absolute gaps were modest and that the design did not compare hormone users with nonusers. Outside experts said the results need replication in randomized trials, citing mixed prior evidence, including no significant rheumatoid arthritis difference in the Women’s Health Initiative and no severe lupus flares in another trial.
For menopausal women and their clinicians, this report could prompt more individualized discussions about hormone type, especially among those with autoimmune concerns or prior hysterectomy. Because the absolute gaps were modest and nonusers were not compared, it may create uncertainty rather than a clear reason to switch treatment. It could also encourage collaboration between menopause and rheumatology specialists and support calls for larger prospective studies, while patients may wish to avoid changing therapy without medical advice.