Hormone Therapy and Autoimmune Disease: Early Findings Raise New Questions for Postmenopausal Care

Xuezhi Daniel Jiang, MD, PhD

Courtesy of Drexel University

Autoimmune diseases disproportionately affect women, with some estimates suggesting a four-fold higher risk compared with men. Menopausal transition further increases vulnerability, likely driven by hormonal shifts. For years, clinicians have speculated whether restoring estrogen levels through hormone therapy (HT) might help ease—or even prevent—autoimmune pathways in postmenopausal women. But new preliminary data presented at The Menopause Society (TMS) 2025 Annual Meeting suggest the relationship may be more complex than expected.

Using the TriNetX global health database, researchers led by Xuezhi (Daniel) Jiang, MD, PhD, a professor of obstetrics and gynecology at Drexel University College of Medicine and a practicing OB-GYN specializing in menopausal medicine, evaluated whether HT initiation in postmenopausal women altered their long-term autoimmune disease risk. The team found that rates of autoimmune disorders increased—not decreased—after starting HT, with elevated risk observed across most autoimmune conditions studied.

Patient Care® sat down with Jiang during the meeting to discuss the rationale behind the study, the unexpected findings, potential biological explanations, and how primary care physicians should interpret these early signals when counseling postmenopausal patients.

Jiang has spent his career in menopausal medicine and clinical research and now practices at Reading Hospital–Tower Health in Pennsylvania.

The following interview has been edited for style, clarity, and flow.

Patient Care: Dr Jiang, what motivated you to explore the relationship between menopausal hormone therapy and autoimmune disease?

Xuezhi (Daniel) Jiang, MD, PhD: Autoimmune diseases affect women far more than men, and the menopausal transition also increases that risk. I started thinking about why that happens and whether the hormonal changes—especially the decline in estrogen—contribute. That led me to wonder whether restoring estrogen through hormone therapy could potentially reduce autoimmune disease incidence in postmenopausal women.

To explore that question, we used the TriNetX database, which provides access to real-time, de-identified patient data from a large global population. This study is really just the beginning of that investigation.

Patient Care: Your findings were the opposite of what you expected. What did the data show?

Jiang: Yes, very surprising. Instead of seeing a protective effect, we found an increased risk of autoimmune diseases after women started hormone therapy. Out of 17 autoimmune diseases we examined, 15 showed increased risk.

We also looked at the duration of exposure—at 5, 10, and 20 years after starting HT—and the risk increased as the exposure time increased. The rise was not dramatic, but it was consistent. This was not what we anticipated, and we are still working to understand the underlying mechanisms.

Patient Care: Graves disease and autoimmune hepatitis did not show increased risk. What might explain those exceptions?

Jiang: Different autoimmune diseases have different estrogen sensitivities and different pathways. Graves disease tends to develop earlier in life—often between ages 30 and 50—so most postmenopausal women have already passed that risk window. Anyone diagnosed before starting hormone therapy was excluded from the study, so that could explain why we did not see an increase.

Autoimmune hepatitis has weak estrogen sensitivity and is also rare. It is often diagnosed by lab findings rather than symptoms, so it may be under-detected in electronic medical records. Without prospective data or access to individual patient histories, it's very hard to know for sure.

Patient Care: How should primary care clinicians and OB-GYNs integrate these findings into patient counseling on hormone therapy?

Jiang: First, I want to emphasize that I am a hormone therapy advocate and a menopausal medicine practitioner. I still believe hormone therapy is safe when used appropriately. These findings should raise awareness—not fear. We do not want hormone therapy phobia.

Many women are truly miserable during menopause and are excellent candidates for HT. Providers should not withhold treatment based on preliminary data alone.

Instead, clinicians should individualize care. Women with a family history of autoimmune disease or those with autoimmune conditions diagnosed before menopause may be higher-risk groups, and shared decision-making is key. Educate patients on symptoms such as arthralgia, rashes, or fatigue, and maintain clinical vigilance. HT is not one-size-fits-all, and these findings are too premature to change prescribing practice.

Patient Care: What research is needed next to help clarify the relationship between HT and autoimmune disease risk?

Jiang: Prospective studies are the ideal next step. Even retrospective studies based on large, multicenter datasets with access to individual patient data would help. One limitation of TriNetX is that you cannot easily access individual-level data, which makes it difficult to evaluate confounding factors.

To my knowledge, this is one of the first studies to examine this kind of association. We need more evidence to confirm the findings and to identify which patient populations may truly be at increased risk.