The relationship between menopause and autoimmune disease is a women’s health issue that can no longer be ignored. Autoimmune diseases affect women far more often than men, with women accounting for approximately 80% of cases. Hormonal fluctuations during perimenopause and menopause — particularly declining estrogen levels — are associated with an increase in certain immune cells and antibodies that may worsen or contribute to disease onset.

Rheumatoid arthritis, lupus, Sjögren’s syndrome, and psoriatic arthritis are among the autoimmune conditions linked to menopause. Declining estrogen levels during this transition can increase inflammation and reduce the effectiveness of immune regulation. Although hormone therapy use in postmenopausal women has been associated with a higher incidence of certain autoimmune conditions, it has also emerged as an important tool for symptom management and improving quality of life when appropriately monitored.

Why Women?

Why women are affected more often and more severely by autoimmune disease is something physicians, scientists, and researchers are still studying, but working theories have emerged.

“A primary reason for the increased prevalence of autoimmune diseases in women, based on research, is the effect of hormones like estrogen,” says DeLisa Fairweather, Ph.D., a professor of medicine and immunology at Mayo Clinic in Jacksonville, FL, whose research focuses on sex differences in chronic inflammatory diseases.

Dr. Fairweather explains that these hormones are associated with an increase in certain immune cells and antibodies, which can then damage the body’s own tissues. Genes located on the X chromosome (of which women have two) can also lead to a dysregulated immune response.

Dr. Fairweather is also an author of newer research that challenges the oft-cited statistic that 80% of autoimmune diagnoses occur in women, finding the number closer to 67%. While still much higher than men, it is lower than previously thought.

Past research, she maintains, relied on less accurate methods, like studying the prevalence of an individual autoimmune disease and projecting what that would mean for all autoimmune disorders. Fairweather’s study also looks at 105 autoimmune diseases, a much wider lens on the issue.

The 20 most common autoimmune diseases — including rheumatoid arthritis, psoriasis, autoimmune thyroiditis, multiple sclerosis, systemic lupus erythematosus (SLE) — are more prevalent in women than in men, and researchers believe the reasons are multifactorial.

Mariko Ishimori, M.D., a rheumatologist at Cedars-Sinai in Los Angeles, points out that there are chromosomal, hormonal, and immune system responses that differ between men and women, starting with the fact that women have two X chromosomes (XX), while men have one (XY).

“You only need one copy of an X chromosome, but women have two,” Dr. Ishimori explains. “The body has mechanisms to try to silence one copy.”

This inactivation process is critical because it regulates genes expression. Overexpression — which does happen as some genes escape inactivation —can lead to harmful effects, contributing to inflammation and causing autoimmune dysfunction.

Further Risks

Dr. Ishimori acknowledges the role that hormones such as estrogen play in autoimmune disease onset, and explains that, ironically, the strong female immune system may contribute to increased autoimmune vulnerability.

“Generally, women at every age group have more powerful immune systems than men,” she says, adding that a more robust immunity also makes women more likely to develop autoimmune disease.

Autoimmune conditions can also carry broader health implications beyond the diseases themselves. Dr. Ishimori points out that inflammation associated with autoimmune conditions can lead to blood vessel damage, atherosclerosis, and an increased risk of heart attack and stroke.

While these conditions can increase inflammation in both men and women, women with rheumatoid arthritis (RA), lupus, or systemic sclerosis are 50% more likely to die of cardiovascular disease than men with the same conditions, according to research published in Circulation: Cardiovascular Quality and Outcomes. Researchers cite several factors behind this disparity, including differences in disease severity, inequity in treatment access, and the under-recognition or cardiovascular risk in women.

Dr. Ishimori has also stated that the inflammation associated with autoimmune disease may contribute to mental health conditions like depression — an observation increasingly supported by research.

Studies published in BMJ Mental Health found that the risk for developing a mood disorder such as depression, bipolar disorder, or anxiety is an average of 47.6% higher for women compared to men across a wide range of autoimmune conditions.

Why do women seem to be more vulnerable to this phenomenon? The study authors hypothesize that hormonal and chromosomal differences in women may trigger an immune system response that more strongly affects mental health.

Once again, Dr. Ishimori has particular insight on the subject, observing that regardless of sex, the strain of having a chronic, lifelong condition can’t be overlooked.

“It’s difficult to wrap your mind around,” she says, “and it can be anxiety provoking and lead to depression in some patients when there’s sadness or hopelessness that things won’t get better.” Additionally, symptoms of autoimmunity like fatigue can make it hard to participate in life activities that bring joy.

Finding Solutions

The overall odds of developing autoimmune disease are approximately one in 20, but the relative odds for women are significantly higher. Addressing these issues begins with greater awareness, earlier intervention, and improved education for both clinicians and patients.

Understanding how hormones impact the immune system and disease presentation, especially the hormone fluctuation associated with menopause, is the first step toward preventing, alleviating, or altering the course of autoimmune disease. Personalized precision-based approaches may help clinicians better support women through this important life stage while preserving quality of life and long-term vitality.

For clinicians advancing the future of women’s health — including physicians, NPs, PAs, OB-GYN clinicians, functional medicine providers, hormone specialists, and longevity practitioners — continued education is essential. The A4M Women’s Health Summit, taking place in San Antonio in October 2026, offers an in-depth exploration of the hormonal, metabolic, and longevity-focused factors shaping women’s health today.

More than a traditional conference, the event is designed to provide practical clinical insight, real-world strategies, and forward-thinking perspectives that clinicians can apply directly to patient care. 

Menopause represents a significant transition in a woman’s life — one that can also serve as a catalyst for greater awareness, proactive intervention, and renewed focus on long-term health. Understanding the potential risks is critical, but equally important is equipping women with the tools, strategies, and support needed to preserve vitality, resilience, and wellness for years to come.

Sources:

Women and Autoimmune Disease by the Numbers

The Impact of Menopause on Autoimmune and Rheumatic Diseases