Takeaways
- Hormone therapy was associated with a higher risk of autoimmune disease in postmenopausal women than expected.
- Jiang emphasized clinical vigilance and shared decision-making for patients with personal or family autoimmune histories.
- Further studies are needed to clarify how dosage, regimen, and timing of hormone therapy affect autoimmune disease risk.
At The Menopause Society 2025 Annual Meeting, Xuezhi Daniel Jiang, MD, PhD, professor of Obstetrics and Gynecology at Drexel University College of Medicine and practicing ob-gyn at Reading Hospital in Pennsylvania, discussed new findings examining whether menopausal hormone therapy influences the risk of autoimmune disease development.1,2
“Autoimmune diseases are far more prevalent in women than men,” Jiang said. “Women have, on average, a four- to fivefold higher risk of developing autoimmune disease compared to men.” He added that the menopause transition may further increase the risk later in life, prompting researchers to explore whether restoring estrogen through hormone therapy could lower this risk.
However, the study results were unexpected. “Our findings are kind of surprising—actually opposite to what we were expecting,” Jiang explained. “Our findings suggest that hormone therapy actually increases the risk of developing autoimmune disease in postmenopausal women compared to their counterparts.”
Clinical implications and the need for vigilance
Jiang emphasized that although these findings warrant attention, clinicians should not rush to change practice. “At this point, it’s too premature to draw any conclusion,” he said. “It’s too early to say hormone therapy is contraindicated in women with autoimmune disease, either with family histories or personal histories, because we really require more prospective study to look into this.”
Instead, he urged clinicians to exercise “clinical vigilance” when prescribing hormone therapy, especially in patients with a personal or family history of autoimmune conditions. “Clinicians probably need to discuss with patients, require shared decision-making, and educate patients regarding the symptoms of autoimmune disease,” Jiang said. He also recommended close monitoring for any new or worsening autoimmune symptoms during therapy.
Future research directions
According to Jiang, more research is needed to clarify how factors such as hormone formulation, dosage, and timing affect autoimmune disease risk. “We need more studies to look into different dosages and different regimens, like estrogen alone versus estrogen plus progestins,” he noted. “We also want to look at the time of initiation of hormone therapy to see if the timing hypothesis also applies to this subject.”
Jiang also suggested examining whether hormone therapy might worsen disease severity in women with existing autoimmune conditions or contribute to the onset of other autoimmune diseases.
Reflecting on lessons from the Women’s Health Initiative (WHI) study, he drew parallels between early misconceptions about hormone therapy and the evolving understanding of its risks and benefits. “The WHI findings in 2002 caused hormone therapy phobia,” he said. “But later, when we stratified the data by age, we realized that the timing hypothesis is true—if you initiate hormone therapy in early menopausal women, the benefits can outweigh the risks. Probably the same thing applies to autoimmune disease.”
He concluded that while the current findings raise important questions, “it’s too premature to say anything definitive. There’s no yes-or-no answer yet—it’s not set in stone.”