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Gender Bias in Autoimmune Diseases: How Humans and Disease Discriminate

Written by Jessica Lopez, Edited by Olivia N. McCollum

Background

Autoimmune diseases are debilitating and painful conditions where the immune system targets the body’s tissues.1 These conditions occur in women up to four times more than in men.2 In spite of these findings, many immunotherapy options responsible for treating autoimmune diseases have decreased efficacy in women.1 Raising awareness of autoimmune diseases in relation to women can lead to increased inclusion of women in clinical research, thereby improving understanding and developing more effective treatments. As autoimmunity is the leading cause of death for young women, intervention and increased research can help save and improve lives.


Etiology

Autoimmune diseases partly arise due to a genetic dysfunction that interferes with the interaction between multiple genes.3 These gene variants that cause the dysfunction are connected to their respective autoimmune disease.3 Additionally, most of these variants are located in the same regions on chromosomes, leading researchers to believe there is a “common cause” to autoimmune disorders.3 While genetics increases the likelihood of developing an autoimmune disease, the majority of autoimmune cases develop from the presence of the variant, as well as a trigger for the disease to appear.3 These triggers can vary, be environmental, or due to gene interaction with the environment.3 Some hormones, viruses, bacteria, and many more can trigger autoimmunity.3 As there are many possible triggers, there is no complete profile and thus understanding of all the environmental influences.3


Biological differences

There are many biological differences between the sexes, and many have been proposed as causes for why autoimmune diseases tend to afflict women. Sex hormones dictate much of the immune response, as many sex hormones are receptors for immune cells.4 Specifically, estrogen has been shown to increase proinflammatory cytokines after infection, meaning infections in women can escalate to autoimmune activation.4 


Another in particular, antibody amount, has been investigated to possibly play a role.2 Women have much higher levels of autoantibodies (serum antibodies that attack the own body) than men, and autoantibodies are linked to most autoimmune diseases.2 Specifically, more serum antibodies (found in blood serum) are linked to a higher prevalence of autoimmune disease.2 As increased antibodies in women are theorized to function as extra defenses for offspring, it would appear difficult for autoimmunity to develop later in life.2 However, autoantibodies can appear years before the disease appears.2 Thus, Rheumatoid Arthritis, a disease common in older women, possibly occurs due to autoantibodies causing the disease years after the autoantibodies were created.2 Thus, the origin of autoimmunity is possibly linked to the evolutionary need to keep offspring safe, a duty falling primarily on women.


Human Gender Bias

Humans also can introduce bias into the research of diseases, inhibiting progress in the research field, ultimately affecting the patients in need of the treatments. Namely, the exclusion of women from the studies of many diseases has greatly impacted the research that is used to make therapies.1 Even with the inclusion of women in NIH studies, there is little use of parameters to measure the differences between sexes.1 Thus, immunotherapies are created with little regard to the effects on women.1 Specifically, immunotherapies that suppress the immune response for Rheumatoid Arthritis have greater negative effects on women.1


Treatment

New treatment methods, such as immunomodulatory biologic drugs, are an innovative way to treat autoimmunity. As proinflammatory cytokines (linked to a possible cause of autoimmunity) increase due to estrogen from an infection, immunomodulatory biologic drugs can block these cytokines.5 Specifically, they work by containing TNF-α blockers that limit the proinflammatory response from the infection.5

References


  1. Klein SL, Morgan R. The impact of sex and gender on immunotherapy outcomes. Biology of Sex Differences. 2020;11(1). doi:https://doi.org/10.1186/s13293-020-00301-y

  2. Kronzer VL, Bridges SL, Davis JM. Why women have more autoimmune diseases than men: an evolutionary perspective. Evolutionary Applications. 2020;14(3). doi:https://doi.org/10.1111/eva.13167

  3. Karopka T, Fluck J, Mevissen HT, Glass Ä. The Autoimmune Disease Database: a dynamically compiled literature-derived database. BMC Bioinformatics. 2006;7(1). doi:https://doi.org/10.1186/1471-2105-7-325

  4. Fairweather D, Rose NR. Women and Autoimmune Diseases. Emerging Infectious Diseases. 2004;10(11):2005-2011. doi:https://doi.org/10.3201/eid1011.040367

  5. Moorman CD, Sohn SJ, Phee H. Emerging Therapeutics for Immune Tolerance: Tolerogenic Vaccines, T cell Therapy, and IL-2 Therapy. Emerging Therapeutics for Immune Tolerance: Tolerogenic Vaccines, T cell Therapy, and IL-2 Therapy. 2021;12. doi:https://doi.org/10.3389/fimmu.2021.657768

As this article discusses sex differences in autoimmune disease prevalence and treatment, the terms “women” and “females” are used. Sex in terms of male and female refers to biological attributes such as chromosomes, hormones, and reproductive anatomy. Thus, the term “female” is used in this article when referring to biological attributes relevant to autoimmune diseases. Gender in terms of women and men refers to socially and culturally constructed identities and roles. In this article, “woman” is used when referring to populations or social contexts where gender influences social outcomes. 


The authors affirm that gender identity is diverse, including transgender, nonbinary, and gender-expansive individuals, who may have health experiences that differ from those included in sex-based or gender-based experiments and analyses. The intention of this article is to highlight the limitations of current research practices while also respecting all gender identities. Future research should strive to conduct inclusive experiments and analyses that recognize both biological sex and gender identity as significant determinants of health.


This post is not a substitute for professional advice. If you believe that you may be experiencing a medical emergency, please contact your primary care physician, or go to the nearest Emergency Room. Results from ongoing research are constantly evolving. This post contains information that was last updated in December 2025.


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