Postmenopausal women who used estrogen hormone therapy (HT) had a modestly higher risk of developing a new autoimmune disease over the next 5-10 years than women who did not use HT, according to research presented at the annual meeting of The Menopause Society.

“These findings highlight the need for further prospective research to clarify the underlying mechanisms and temporal relationship between HT and autoimmune disease onset, and to support individualized risk-benefit evaluations in menopausal care,” wrote study author Xuezhi “Daniel” Jiang, MD, PhD, an ob/gyn at Reading Hospital and a professor of ob/gyn at Drexel University College of Medicine in Philadelphia.

Jiang told Medscape Medical News that it was a “preliminary finding on an understudied subject” that should be regarded as hypothesis-generating. 

Overall, the study found a 33% increased likelihood of any new autoimmune disease in those using HT compared to those not using HT (hazard ratio [HR] 1.33; 95% CI, 1.32-1.35; P < .001).

The conclusion is “set in stone” and causality cannot be determined based on this study, Jiang told Medscape Medical News. He emphasized that the absolute risk increases in autoimmune disease are small — less than 2% over 20 years of follow-up after HT — and that he remains an advocate for HT use in postmenopausal women without contraindications.

“The last thing I want to see is a second wave of HT phobia in the public after the WHI study,” Jiang said, referencing the misconceptions and fear about HT that arose after poor communication and interpretations about the Women’s Health Initiative study in the early 2000s. 

HT remains a safe and effective tool for menopausal symptom relief for women who use it appropriately, Jiang said. Individualized care with shared decision-making is especially important in women with a personal or family history of autoimmune diseases while further evidence develops on a link between HT and autoimmune risk.

Stephanie Faubion, MD, MBA, director of the Mayo Clinic Center for Women’s Health in Jacksonville, Florida, told Medscape Medical News that these findings “should not change practice in any way,” reiterating that the study was observational and cannot determine causation. 

“Having said that, women with existing lupus may need to avoid menopausal hormone therapy,” Faubion said, in part because it may exacerbate disease and because the presence of antiphospholipid antibodies may increase the risk for blood clot. “Women with other autoimmune diseases, like autoimmune thyroid disease and autoimmune adrenal disease (Addison’s), do not need to avoid estrogen,” she said. For other conditions, such as scleroderma, not much data exist to guide practice.

The researchers analyzed data from over 3.5 million patients in the TriNetX Global Health Research Network who had a diagnosis of menopause. They identified 889,413 women who used HT and 2,646,652 women who did not, so they matched those who used HT 1:1 to those who didn’t, on the basis of age, ethnicity, and comorbidities, including obesity, type 2 diabetes, hypertension, and major depressive disorder. 

Patients with a preexisting diagnosis of an autoimmune disease were excluded, and the researchers then calculated the incidence of new autoimmune diagnoses at 5 years, 10 years, and lifetime after an index date of initiating HT.

The matched cohorts of a combined 1,778,826 women were an average 60 years old. The researchers found that 6.7% of women who used HT had a new autoimmune disease diagnosis at 5 years, compared to 5.3% of those not using HT. At 10 years, 8.6% of HT users and 6.7% of non-HT users had a new autoimmune diagnosis, and across the full postmenopausal period, 9% of women receiving HT and 7.1% of women not using HT had an incident autoimmune disease diagnosis.

The researchers calculated that women who took HT had a 29% higher risk of developing an autoimmune disease within 5 years (risk ratio [RR], 1.29; P < .0001), a 28% higher risk within 10 years, and a 27% increased risk across the postmenopausal period (P < .0001 for both). 

The only autoimmune diseases for which no statistically significant increase occurred in those prescribed HT were Graves disease and autoimmune hepatitis. The risk varied from a 3% increase for psoriasis (P < .037) to a 2.9 times greater risk for lichen sclerosus (P < .0001). 

“Estrogen has complex pro- and anti-inflammatory effects depending on the cells involved and the doses and concentrations of estrogen being studied,” said Faubion, emphasizing the complexity of the topic and the need for additional study.

The research did not use external funding, and Jiang had no disclosures. Faubion had no disclosures. 

Tara Haelle is a science/health journalist based in Dallas.