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 using systemic menopausal hormone therapy found a slightly higher incidence of autoimmune disease among those taking estrogen alone than among those taking estrogen with a progestogen. The researchers stressed that the difference was small, the study cannot establish cause and effect, and it does not compare either treatment with no hormone therapy.

A retrospective study of 109,384 women using systemic menopausal hormone therapy found a slightly higher incidence of autoimmune disease among those taking estrogen-only therapy than among those taking estrogen with a progestogen. The findings, presented at the Menopause Society annual meeting, show an association—not proof that one regimen causes autoimmune disease—and the authors said the small difference does not warrant immediate treatment changes.

Researchers compared 54,692 women in each treatment group, matched on demographic and medical characteristics, including hysterectomy and surgical menopause. At least 180 days after starting therapy, composite autoimmune disease incidence was 4.9% with estrogen alone and 4.5% with estrogen-progestogen therapy. The reported hazard ratio was 1.076 (95% confidence interval 1.015–1.141; P=0.022).

Among 20 individual conditions assessed, the study reported statistically significant differences for systemic lupus erythematosus, psoriasis, psoriatic arthritis, multiple sclerosis and lichen sclerosus. The percentages were low in both groups. For example, multiple sclerosis was recorded in 0.2% of the estrogen-only group and 0.1% of the combined-therapy group; the estimates for psoriatic arthritis were 0.2% in each group, despite a higher hazard estimate in the estrogen-only group.

The researchers, medical student Hadia Saroya and Xuezhi (Daniel) Jiang, MD, PhD, of Drexel University College of Medicine, used records from the TriNetX U.S. Collaborative Network. The analysis included women ages 45 to 70 and excluded those with a prior autoimmune disease and several other conditions or exposures. It did not include women using vaginal estrogen.

Why the Small Difference Matters

The findings may help clinicians and patients discuss whether the type of hormone regimen is associated with differences in autoimmune diagnoses. The distinction matters because estrogen-only therapy is commonly used after hysterectomy, while estrogen-progestogen therapy is generally used when a patient needs endometrial protection. The study does not establish that switching treatments would reduce risk, and it does not show that either regimen raises risk compared with taking no hormone therapy.

Jiang told MedPage Today that the clinical message is to support informed discussions and individualized care, rather than immediate treatment changes. The absolute differences were small, and the authors cautioned that they may not be clinically meaningful. The results should be treated as a signal for further study, not as a basis for patients to start, stop or change prescribed therapy without speaking with a qualified healthcare professional.

How the Two Regimens Were Compared

Much previous research has treated menopausal hormone therapy as a single exposure, Jiang told MedPage Today. This study instead compared systemic estrogen-only therapy with estrogen-progestogen therapy, reflecting the different regimens used in clinical care. The researchers matched groups on measured characteristics and assessed diagnoses recorded at least 180 days after therapy began.

The report was presented as a poster at the Menopause Society annual meeting. The study was retrospective, meaning researchers analyzed existing health records rather than assigning participants to treatments. Earlier evidence has not pointed to a consistent effect: JoAnn E. Manson of Harvard Medical School told MedPage Today that the Women’s Health Initiative did not find a significant difference in rheumatoid arthritis risk or severity between women assigned postmenopausal hormone therapy or placebo. A separate randomized trial in women with lupus found no increase in severe flares, though it reported a small risk of more mild-to-moderate flares.

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

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

Limits of the Health Records Study

The retrospective design cannot show that the hormone regimen caused the differences, and residual confounding may remain despite matching. Diagnoses in electronic medical records can also be misclassified. TriNetX records did not provide information on the route of hormone administration, dosage or the specific estrogen and progestogen formulations used.

The report also cannot answer whether hormone therapy itself changes autoimmune disease risk: there was no group of women using no hormone therapy. The authors said it remains unknown whether results differ by age, when treatment begins, natural versus surgical menopause, underlying autoimmune susceptibility, or the use of micronized progesterone compared with synthetic progestins. The reported associations do not establish that risk is increased for every condition or for every patient.

Research Needed to Test the Association

The authors described the study as a starting point for prospective research, including studies comparing hormone therapy with no treatment and examining whether different formulations produce different results. Larger randomized trials could help test whether the associations persist when treatment is assigned and participants are followed under a planned protocol.

For now, the report is a conference presentation, and the supplied information does not establish whether a full peer-reviewed publication or further study has been scheduled. Patients considering menopause hormone therapy should discuss their individual circumstances and treatment options with a qualified healthcare professional; the study authors’ comments do not call for immediate changes to care.

Key Questions

What did the study find?

Among women using systemic menopausal hormone therapy, composite autoimmune disease incidence was 4.9% with estrogen-only therapy and 4.5% with estrogen-progestogen therapy. The retrospective study found an association, not proof that the treatment caused the difference.

Which autoimmune diseases had higher hazard estimates?

The study reported statistically significant higher hazards in the estrogen-only group for systemic lupus erythematosus, psoriasis, psoriatic arthritis, multiple sclerosis and lichen sclerosus. Absolute percentages were small, and the finding does not establish cause and effect.

Does this mean estrogen-only therapy causes autoimmune disease?

No. The study was retrospective and compared two hormone therapy regimens; it did not establish causation or compare either regimen with no hormone therapy.

Should patients change their hormone therapy?

The study authors said the findings support informed, individualized discussions rather than immediate changes. Anyone considering a change should speak with a qualified healthcare professional.

What research is still needed?

Researchers say prospective studies should compare hormone therapy with no treatment and assess whether findings vary by dose, route, formulation, age, timing of initiation, menopause type and underlying autoimmune susceptibility.

Source: rss