New Theories Explaining Why Women are More Susceptible to Autoimmune Disease than Men

Although autoimmune disease (AD) affects both genders, women are at an overwhelming disadvantage. Of the approximate 8% of the population affected by AD, a whopping 78% of those cases are women (NCBI). The National Institutes of Health has officially designated autoimmune disease as a major women’s health issue.

Autoimmunity in and of itself is very complicated, with more than 80 diseases under its umbrella. The rate at which AD affects women over men, is no exception to the complexity of understanding this group of diseases. Through recent studies, scientists have found evidence to support three significant theories to explain why women are so greatly affected by AD compared to men.

Testosterone levels protect men 
According to researchers at the University of Gothenburg, there is a link between the male sex hormone testosterone and protection against autoimmune diseases. Men are generally more protected than women, who only have one-tenth as much testosterone. Their study confirmed that this hormone reduces the number of B cells, a type of lymphocyte that releases harmful antibodies. Testosterone suppresses the protein BAFF, which makes the harmful B cells more viable. Therefore, women don’t benefit from the same protection against these B cells. 

These findings support those of a previous study showing the link between varying levels of BAFF and systemic lupus erythematosus (SLE), an autoimmune disease that affects nine women for every one man. Lupus is one of the most common autoimmune diseases among women.

Skin
Perhaps one of the most interesting findings was uncovered in a study at The University of Michigan three years ago. Researchers discovered that women carry more of a molecular switch, called VGLL3, in their skin than men do. In 2019, further research pointed to evidence showing that having too much VGLL3 in skin cells pushes the immune system into overdrive, leading to a “self-attacking” autoimmune response that can extend beyond the skin, also attacking internal organs.

The same gene expression-level changes in skin cells with extra VGLL3 are also seen in autoimmune diseases such as lupus. It is still not known why women have more VGLL3 in their skin than men. However, men with lupus do show the same VGLL3 pathway activated as in women with lupus.

“The Pregnancy Compensation Hypothesis” and hormones 
The idea behind this theory is that a woman’s immune system evolves to support the heightened need for protection during pregnancy. According to Melissa Wilson, PhD and senior author of a study conducted at Arizona State University, reduced pregnancy rates in today’s modern, industrialized societies means women’s immune systems don’t have the reproductive challenges they are meant to stand up against. These changes in the reproductive ecology of women makes them more susceptible to autoimmune disease because immune surveillance is heightened. 

Furthermore, results from the study concluded that due to a more sedentary lifestyle in modern society, an overabundance of calories supports greater amounts of the female hormone estradiol. Maintaining such high levels of hormones can trigger the onset of autoimmune diseases. So not only do men get protection from AD with their higher levels of testosterone, but women have increased risk of AD due to higher levels of estradiol, thus widening the gap of AD in men versus women.

There is still so much to learn about autoimmune disorders, especially with the various types of diseases being categorized as autoimmune-related. Scientists do know that some of the highest risk factors of AD include genetics, environmental factors, lifestyle and even prior infection. But newer findings, especially those discussed here, suggest that simply being female puts you at higher risk for AD, with lupus seemingly at the top of the list.

Interestingly, a multitude of autoimmune diseases present some of the same early signs, including:

• Skin rashes, itchiness or flakiness

• Fatigue

• Rapid weight gain or loss

• Digestive tract issues

• Joint pain

• Swelling/Bloating

• Lack of focus

• Abdominal pain

If you or any women in your life suffer from any of these symptoms without an identified, underlying cause, seeking the advice of a health care professional and medical testing should be considered. Cyrex Laboratories, a leader in advanced clinical testing, offers several screens for the detection of autoimmune-related reactivities. The Array 5 – Multiple Autoimmune Reactivity Screen™ is one of their comprehensive tests offered to measure predictive antibodies, some of which can appear up to 10 years before the clinical onset of disease. This groundbreaking test can help alert at-risk patients in time to stop the development of actual disease in some cases.

Preventative medicine is the best medicine, which is why symptoms should never be ignored. Taking control of your medical wellbeing through smart lifestyle practices, healthy eating and regular physical exams can help you live your best life and prevent disease. Finally, it is important for women to understand how their bodies work, the unique health risks they are susceptible to, and protocols for optimal health.

Dr. Chad Larson, NMD, DC, CCN, CSCS, is advisor and consultant on Clinical Consulting Team for Cyrex Laboratories. Larson holds a Doctor of Naturopathic Medicine degree from Southwest College of Naturopathic Medicine and a Doctor of Chiropractic degree from Southern California University of Health Sciences. He is a Certified Clinical Nutritionist and a Certified Strength and Conditioning Specialist. He particularly pursues advanced developments in the fields of endocrinology, orthopedics, sports medicine, and environmentally-induced chronic disease.