Why Women Get Autoimmune Diseases More Often—And Why Your Sex Matters for Treatment

Women account for the majority of autoimmune disease cases worldwide, with biological sex playing a fundamental role in disease risk, severity, and how patients respond to medications. Autoimmune diseases—conditions where the immune system mistakenly attacks the body's own tissues—affect approximately 10% of the global population, yet women are disproportionately affected across nearly every type. A comprehensive review published in January 2026 in Naunyn-Schmiedeberg's Archives of Pharmacology reveals that sex differences in autoimmunity stem from multiple biological mechanisms, including sex hormone effects, genetic factors, and immune system variations that remain largely overlooked in clinical treatment approaches.

Why Do Women Develop Autoimmune Diseases at Higher Rates?

The gender gap in autoimmune disease is striking and consistent. Data from China show that women were almost twice as likely to be diagnosed with an autoimmune disease compared to men. This female predominance appears across multiple conditions and metrics—not just in how many people get sick, but also in age of onset, disease severity, and overall disease burden.

The disparity varies by condition. For systemic lupus erythematosus (SLE), a serious inflammatory disease affecting joints, skin, and organs, women account for 89% of cases compared to just 11% in men. Rheumatoid arthritis shows a 52% to 48% female-to-male split, while multiple sclerosis affects women at a rate of 41% compared to 59% in men. Even conditions traditionally thought of as male-dominant, like ankylosing spondylitis, show a 38% female prevalence versus 62% male.

The biological mechanisms driving these differences operate at multiple levels within the body. Sex hormones—particularly estrogen and testosterone—play immunomodulatory roles, meaning they actively shape how the immune system functions. Additionally, the X chromosome carries genes that influence immune responses, and women have two X chromosomes compared to men's one, creating different patterns of gene expression. Environmental and lifestyle factors, including smoking, infections, and the composition of gut bacteria, interact with these biological sex differences to further influence autoimmune risk.

What Are the Key Biological Mechanisms Behind Sex-Driven Autoimmunity?

Understanding why sex matters for autoimmune disease requires looking at several interconnected biological systems:

• Sex Hormone Effects: Estrogen and testosterone circulate at different levels in women and men and directly influence immune cell function, inflammation regulation, and the body's ability to tolerate its own tissues without attacking them.
• X Chromosome Gene Dosage: Women carry two X chromosomes while men carry one, leading to differences in how many copies of immune-related genes are expressed and potentially escaping normal X-chromosome inactivation patterns.
• Innate and Adaptive Immune Responses: Sex-specific differences exist in how quickly the immune system detects threats and how it generates long-term immune memory, affecting both initial immune activation and sustained inflammatory responses.
• Epigenetic Regulation: Chemical modifications that control which genes are turned on or off in immune cells differ between sexes, influencing pathways that normally prevent the immune system from attacking the body.

These mechanisms don't operate in isolation. The review emphasizes that "recognizing sex as a fundamental biological variable is essential for advancing the understanding of autoimmune diseases and for the development of more effective, tailored therapeutic strategies." Yet current clinical practice often treats autoimmune disease the same way regardless of patient sex.

How Does Sex Affect Treatment Response and Drug Safety?

Perhaps most concerning for patients is that sex differences extend directly into how medications work. Women and men show variability in drug efficacy—meaning the same medication may work better or worse depending on biological sex—as well as differences in safety profiles and immune-related adverse events. Despite this reality, most clinical trials and drug development research fail to stratify results by sex, leaving physicians without clear guidance on personalized treatment approaches.

The global burden of autoimmune disease continues to grow. For rheumatoid arthritis specifically, projections for 2019 through 2030 show women experiencing an age-standardized incidence rate of 18.23 per 100,000 people compared to approximately 8.34 per 100,000 in men, with these trends expected to persist. Systemic lupus erythematosus shows even starker disparities, with women experiencing an age-standardized incidence rate of 8.82 per 100,000 people versus 1.53 per 100,000 in men.

The current gaps in sex-stratified clinical research represent a significant public health challenge. Women bear the greater disease burden, yet treatment protocols developed without accounting for sex-specific biology may be less effective or carry unexpected safety risks. Moving forward, recognizing sex as a fundamental biological variable—not merely a demographic category—is essential for developing therapies that actually work for the populations most affected by these chronic, often debilitating conditions.