If you are a woman with autoimmune disease, chances are you already know that 80% of people diagnosed with autoimmune disease are women. The question has long been held about why women suffer more from autoimmune disease than men. Even though there has been research and speculation over the years, a study published in February sheds a lot more light on the question.
Gender awareness
Throughout this article you will see me refer to women and men. This is not to dismiss the importance of gender identity but rather simplify some concepts. I do firmly believe that gender is a construct, it’s fluid, and should be defined by individuals. However, for simplicity of explanation, I use “woman” to refer to someone with XX chromosomes in this article. This is regardless of how they present or gender identity. Man is defined in this post as someone with XY chromosomes at birth. The goal is to make these complex topics as simple as possible and do not represent a denial or dismissal of other gender identities.
I do this with deep respect and reverence for people that do not fit the binary categories. This is not meant as a demonstration of disrespect, but rather an intentional decision to bring things to the basics for ease of explanation. You will also notice there are multiple variations of the XX/XY chromosome combinations we will also not discuss in depth. As with the gender binary constructs, the goal is keeping things simple, as research continues to emerge.
What is autommimune disease
Sources cite anywhere from 7 million to 50 million people suffering from up to 150 different autoimmune diseases. Of these people, up to 85% are women. The numbers vary depending on source, metric, and also the autoimmune diseases being measured. This makes it extra challenging for the regular person trying to find their way among the noise. The reasons women bear the brunt of autoimmune disease is a growing question, though. Things such as: Gender, genetics, hormonal immune system functionality, hormonal fluctuations, and environmental factors all play a role. Recent advancements in genetic and molecular biology continue to reveal why these conditions disproportionately affect women. The Stanford study discussed highlights the role of the X chromosome itself, as a factor for why women disproportionately suffer from autoimmune disease.
The gender disparity in autoimmunity
So what exactly is autoimmune disease? The United States NIH explains it like this:
A healthy immune system defends the body against disease and infection. But if the immune system malfunctions, it mistakenly attacks healthy cells, tissues, and organs. Called autoimmune disease, these attacks can affect any part of the body, weakening bodily function and even turning life-threatening.
This pattern is consistent with all autoimmune conditions. What is more interesting is that depending on the disease, the ratio between men and women is even higher. For example, Sjogren’s Syndrome affects 99% women and Lupus (SLE) affects approximately 92% women. This is partly why numbers vary about what percentage of women impacted over men varies, too. These estimates are all conservative, because getting a diagnosis for autoimmune disease can take years and multiple doctors. It’s likely that many people aren’t aware they have autoimmune disease, further complicating the situation. Given the significant gender gap in autoimmunity we would be foolish not to investigate underlying biological mechanisms.
Hormonal influence across a woman’s life
When studying the comparison between the two dominant sexes (XX/XY), it’s important to recognize the hormonal variations for women. While both boys and girls experience puberty, women also experience significant hormonal shifts such as pregnancy, and menopause. Men don’t experience these same dramatic shifts, even though at the end of our lives, we have similar levels of hormones, similar to before we all went through puberty. Of course, men experience things like andropause, but it’s not the same “change of life,” most women experience.
These hormonal shifts have profound effects on the immune system. For instance, estrogen levels, which increase during puberty and pregnancy, modulate immune activity. This modulation can sometimes lead to an imbalance, increasing the risk of triggering an autoimmune response. Estrogen, known to enhance immune response, can be protective in some contexts. However, it may exacerbate autoimmunity when regulation fails, resulting in a harmful rather than protective effect. It would be easy to say that hormones are the reason that women suffer more from autoimmune disease than men, but that’s an incomplete story.
Xist and the X chromosome
Research published in 2024 by the Stanford School of Medicine and lead researcher Dr. Diana R. Dou, attempt to shed more light on the question. Why DO women suffer more from autoimmune disease than men, anyways? One of the most significant recent discoveries in autoimmune research is the role of the X chromosome. Specifically, a molecule called Xist (X-inactive specific transcript). Xist is crucial for X-chromosome inactivation, a process where one of the two X chromosomes in females is largely silenced to prevent over-expression of X-linked genes. I like to think of this as a governor on your car accelerator. It’s there to prevent you from going to fast, so you don’t get hurt. The Xist molecule governs gene expression, so you don’t have two chromosomes trying to do the same thing. In this case, Xist keeps one foot on the accelerator instead of 2.
The issue presents when the “governor” is not operating correctly. Instead of deactivating the extra chromosome, it allows both chromosomes to operate at full speed, breaking the governor. Researchers theorize that the activation of both chromosomes cause the production of autoantibodies targeting the body’s own tissues, resulting in autoimmunity.
In experiments, researchers introduced the Xist gene into male mice, which typically do not need to silence an X chromosome, because there is only one copy of X. Remember, males are XY and females are XX. Researchers saw that when activated, it led to autoimmune responses in these mice, mimicking those seen in females. This clearly demonstrated the relationship between the Xist-mediated silencing malfunction, to the development of autoimmune diseases. This is an incredible finding because it shows our genes have a built-in safety to turn off extra genes, so we don’t double down on something unnecessarily. The drawback is autoimmune disease, when it doesn’t work as expected. The question of what breaks this governor still remains.
Recent advances and future directions
The implications of these findings extend beyond a better understanding of autoimmunity’s biological foundation. It also opens up new avenues for therapeutic interventions aimed at modulating Xist activity and the expression of genes on the X chromosome. Much more research is required, but we have a new leaf to turn over in the quest to reverse autoimmune disease. If I were to predict, future research may likely explore how hormonal states, environmental factors, and individual genetic makeup interact with the mechanisms controlled by Xist, to influence autoimmunity. In other words, what causes this function to not work as expected.
It looks like this could be a trigger for autoimmune disease, but questions still remain. If genes sketch the outline and lifestyle colors it in, how do we stay in the lines. We need further exploration into the environmental and hormonal triggers that might lead to X chromosome reactivation. Specifically around preventative strategies, interventions, or treatments to address the potential triggers. Additionally, understanding how individual variations in Xist activity and other genetic factors contribute to autoimmunity could pave the way for personalized medicine approaches. This has great potential for reducing the incidence, or severity of these conditions, in women.
Why Do Women Suffer From Autoimmune Disease More Than Men
This still doesn’t fully answer the question “why” women have more autoimmune disease, but we are much closer. Although, the constellation of factors clearly show why women are more susceptible. Besides our risk being much higher due to more X chromosomes, our hormonal differences play a factor. The endocrinological differences alone make us much more susceptible to environmental influences. There is still so much to learn, but this most recent study further elucidates some of the biological functions behind autoimmune diseases. Specifically, why it impacts women four times more than men, on average. As research progresses, the hope is to translate these findings into effective strategies that prevent, manage, and potentially cure autoimmune diseases. Women have enough to deal with so any opportunity to improve the quality of life for millions of affected women worldwide, is welcomed.
Are you struggling with autoimmune disease and not finding many answers? That’s exactly why I started Pomona Wellness. It took 10 doctors and multiple diagnoses before I got on a path to true recovery. I have been there and I know how lonely it can feel, but YOU ARE NOT ALONE. I manage my autoimmune disease, rather than it managing me, and you can too. If you want to learn more, let’s chat. Otherwise, you can learn more about autoimmune disease and wellbeing on the Wellspiration blog. Until then, I’m wishing you abundant health and limitless joy.
Medical Disclaimer:
These statements have not been evaluated by the Food and Drug Administration (FDA). Information provided in this blog post is for educational and informational purposes only and should not be considered as medical advice. The content is not intended to be a substitute for professional medical advice, diagnosis, treatment, cure or prevention of any disease. Always seek the advice of your physician or another qualified healthcare provider with any questions you may have regarding a medical condition.
Resources
- Autoimmune Diseases – National Institute of Health
- Bruce Goldman. (2024) “Stanford Medicine-led study shows why women are at greater risk of autoimmune disease.” Stanford Medicine News Center. https://med.stanford.edu/news/all-news/2024/02/women-autoimmune.html
- Diana R. Dou, et al. (2024) “Xist ribonucleoproteins promote female sex-biased autoimmunity.” 50 Cell. Article| Volume 187, Issue 3, P733-749. https://www.cell.com/cell/fulltext/S0092-8674(24)00002-3#%20
- F. Angum, T. Khan, J. Kaler, et al. (May 13, 2020) The Prevalence of Autoimmune Disorders in Women: A Narrative Review. Cureus 12(5): e8094. https://DOI.org/10.7759/cureus.8094
- Fairweather, D., & Rose, N. R. (2004). Women and autoimmune diseases. Emerging infectious diseases, 10(11), 2005–2011. https://doi.org/10.3201/eid1011.040367
- Melinda Wenner Moyer. (2021) “Why Nearly 80 Percent of Autoimmune Sufferers Are Female.” Scientific American. https://www.scientificamerican.com/article/why-nearly-80-percent-of-autoimmune-sufferers-are-female
- Maunil K. Desai. (2019). “Autoimmune Disease in Women: Endocrine Transition and Risk Across the Lifespan.” https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2019.00265/full
- Vanessa L. Kronzer, et al. (2020) “Why women have more autoimmune diseases than men: An evolutionary perspective.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980266/pdf/EVA-14-629.pdf.