Type Of Menopause Hormone Therapy Tied To Small Autoimmune Disease Risk

TL;DR

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A retrospective study of more than 100,000 women found a slightly higher rate of autoimmune disease among users of estrogen-only menopausal hormone therapy than among users of estrogen-progestogen therapy. The absolute difference was small, and the researchers said the findings do not show whether either regimen changes risk compared with no hormone therapy.

A retrospective study of more than 100,000 women found a slightly higher incidence of autoimmune disease among those taking estrogen-only menopausal hormone therapy than among those taking estrogen with a progestogen. The findings, presented at the Menopause Society annual meeting, show an association—not proof that the treatment caused disease—and researchers said the absolute difference was small.

Researchers compared 54,692 women in each treatment group, identified through the TriNetX U.S. Collaborative Network. Participants were ages 45 to 70 and used systemic menopausal hormone therapy. The study excluded women with prior autoimmune disease and several other conditions or exposures, including chemotherapy or immunotherapy, organ transplantation, HIV, and vaginal estrogen use. The researchers matched the groups on demographic and medical characteristics, including hysterectomy and surgical menopause.

At least 180 days after therapy began, the rate of the study’s combined autoimmune disease outcome was 4.9% in the estrogen-only group and 4.5% in the estrogen-progestogen group. The reported hazard ratio was 1.076 (95% CI 1.015-1.141; P=0.022). Among 20 individual conditions examined, the study reported statistically significant differences for systemic lupus erythematosus, psoriasis, psoriatic arthritis, multiple sclerosis, and lichen sclerosis. The individual rates were low, and some reported percentages were the same after rounding.

Medical student Hadia Saroya and Xuezhi (Daniel) Jiang, MD, PhD, of Drexel University College of Medicine, presented the results in a poster. The researchers described the analysis as a comparison between two types of hormone therapy; it did not include a group of women who used no hormone therapy. Its results therefore cannot establish whether either regimen raises or lowers autoimmune disease risk compared with no treatment.

A Small Difference, Not a Treatment Verdict

The findings may help clinicians and patients discuss whether the type of hormone therapy could be relevant to autoimmune disease, a group of conditions that is more common in women than men, according to Menopause Society medical director Stephanie Faubion. But the observed difference—4.9% versus 4.5% for the combined outcome—does not by itself show that switching treatments would prevent disease or that estrogen-only therapy caused the higher rate.

Hormone therapy decisions depend on a person’s health and treatment needs. Estrogen-progestogen therapy is generally used when endometrial protection is needed, while estrogen-only therapy is commonly used after hysterectomy. The study is not evidence that patients should change or stop prescribed therapy. Jiang said the practical message is to support informed discussion and individualized care, rather than immediate treatment changes.

Why Researchers Compared the Regimens

Much earlier research treated menopausal hormone therapy as a single exposure, Jiang told MedPage Today. This study instead compared estrogen-only therapy with estrogen-progestogen therapy, reflecting the different regimens used in clinical care. The researchers said estrogen and progesterone can affect immune function through different mechanisms, but the analysis does not explain why the groups differed.

Prior evidence has not produced a consistent picture. JoAnn E. Manson, MD, MPH, DrPH, of Harvard Medical School and a past Menopause Society president, said data from the Women’s Health Initiative did not show a significant difference in rheumatoid arthritis risk or severity between women assigned postmenopausal hormone therapy or placebo. A separate randomized trial involving women with lupus found no increase in severe flares with hormone replacement therapy, though it reported a small risk of increased mild-to-moderate flares. Those findings concern different populations and outcomes, so they do not directly confirm or refute this study.

“The clinical message is to encourage informed discussions and individualized care rather than immediate changes in treatment.”

— Xuezhi (Daniel) Jiang, study co-author, speaking to MedPage Today

Key Limits in the Available Evidence

The research was retrospective and observational, so differences between the groups may reflect factors the analysis did not measure or fully account for. Jiang cited possible residual confounding and misclassification in electronic medical records. The database lacked information on route of administration, dose, and the specific estrogen or progestogen formulations, which could affect how results are interpreted.

The study also cannot determine whether hormone therapy itself changes autoimmune risk because it did not compare users with women taking no hormone therapy. The reported associations do not establish causation, and the small absolute differences may not be clinically meaningful. It is also unclear whether the results vary by age, treatment timing, type of menopause, underlying autoimmune susceptibility, or whether natural micronized progesterone and synthetic progestins have different associations.

Prospective Studies Are the Next Test

The authors described the analysis as a starting point for prospective research that can compare hormone therapy with no treatment and track autoimmune outcomes more consistently. Future work could also examine specific hormone formulations, age and timing of initiation, surgical versus natural menopause, and pre-existing susceptibility to autoimmune disease.

For now, the findings have been presented as a meeting poster, and the source report does not establish whether they have been published as a full peer-reviewed study. Manson called for replication and large-scale randomized trials. Until stronger evidence is available, the results support discussion with a qualified healthcare professional rather than a blanket change in menopause hormone therapy.

Key Questions

What did the study find?

In this retrospective comparison, the combined autoimmune disease outcome occurred in 4.9% of estrogen-only users and 4.5% of estrogen-progestogen users. The study found an association, not proof that one regimen caused the difference.

Does this show that estrogen-only therapy causes autoimmune disease?

No. The study was observational, and factors not captured in the analysis could have influenced the results. Its authors said it does not establish whether either regimen changes risk compared with no hormone therapy.

Should patients change their hormone therapy because of this report?

The researchers said the findings should encourage individualized discussion, not immediate treatment changes. Patients should discuss decisions about prescribed hormone therapy with a qualified healthcare professional.

Which autoimmune conditions had higher reported rates?

The researchers reported statistically significant differences for systemic lupus erythematosus, psoriasis, psoriatic arthritis, multiple sclerosis, and lichen sclerosis. The reported percentages were low, and the study does not show that therapy caused these conditions.

What research is needed next?

The authors called for prospective research, including comparisons with women who do not use hormone therapy. Further work could test whether results differ by hormone formulation, dose, route, age, treatment timing, or menopause type.

Source: rss