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by: Megan Kelly, CNP

DID YOU KNOW THAT AUTOIMMUNE DISEASE IS 10X MORE PREVALENT IN WOMEN THAN IN MEN?

This is how out of whack the ratios (women:men) are in specific autoimmune diseases:

  • Hashimoto’s 10:1
  • Lupus 9:1
  • Primary Biliary Cirrhosis 9:1
  • Antiphospholipid Syndrome 9:1
  • Sjogren’s 9:1
  • Autoimmune Hepatitis 8:1
  • Graves’ 7:1
  • Scleroderma 3:1
  • Rheumatoid Arthritis 2.5:1
  • Multiple Sclerosis 2:1
  • Myasthenia Gravis 2:1
  • Autoimmune Thrombocytopenia Purpura 2:1

There are many theories as to why this is the case.

It is most likely due to the intricacy of female hormone balance. Puberty, pregnancy and menopause are all implicated in increased vulnerability to the development of autoimmune disease.

Estrogen’s role is complex as it seems to suppress Th1 dependant autoimmune diseases, while potentiating Th2 mediated autoimmune disease.

Testosterone may also be helping the men out a little bit. Turns out it provides immunosuppresive and anti-inflammatory effects, which keeps the immune system from overreacting and prevents molecular mimickery prompted attacks.

There also appears to be a difference in immune system function between men and women as well as specific environmental triggers that impact the divergent rates of autoimmunity between genders.

Let’s look a little closer at each of these theories, shall we?

ESTROGEN

As mentioned above, estrogen dominance suppresses the activity of the Th1 inflammatory cytokines such as IL-12, TNF-alpha and IFN-gamma, whereas they stimulate the production of TH2 inflammatory cytokines, such as IL-10, IL-4, and TGF-beta. This may explain why estrogen suppresses and potentiates TH1- and TH2-mediated diseases, respectively.

To clarify, Th1 cells are helper cells that are active in what is considered your “cell-mediated” immunity, which is meant to deal with infections by viruses and certain bacteria. They are your body’s first line defence against pathogens and tend to be pro-inflammatory. They tend to be involved in the development of organ-specific autoimmune diseases, including Celiac disease, Hashimoto’s, Multiple Sclerosis and Psoriasis when they become overactive.

Fantastic! So because women generally have more estrogen, we should be able to avoid these types of autoimmune diseases, right?

Well, as I mentioned, Th2 cytokines are potentiated by estrogen. Th2- mediated autoimmune disease tend to be more systemic, including Lupus, Scleroderma, and Ulcerative Colitis. So, women with estrogen dominance (commonly brought upon by the birth control pill, the accumulation of environmental and dietary estrogens or other systemic failings like a poor microbiome diversity) are at a higher risk for developing these autoimmune diseases.

Now, to complicate things further, the way that estrogen suppresses Th1 autoimmunity may be a double edged sword, especially as we begin to consider the hormone fluctuations that women experience throughout their lifetimes.

As mentioned, puberty, pregnancy and menopause are all implicated in increased vulnerability to the development of autoimmune disease.

During puberty, girls experience large fluctuations in estrogen levels. During pregnancy, women experience very high levels of estrogen, followed by a large drop-off upon giving birth. During peri-menopause, women experience those same fluctuations, followed by a large drop off once they are in menopause.

What we are seeing is a sort of “bounce-back” mechanism with the Th1 immune system. Essentially, when it is suppressed due to high estrogen levels and then that estrogen drops off, the Th1 cytokines bounce back in an exaggerated manner, leaving the female vulnerable to intense inflammation and development of Th1 autoimmune diseases during that time.

So, a large part of the reason that women are much more likely to develop autoimmune disease is not because we have too much estrogen or too much progesterone. It is that there is a delicate balance that needs to be maintained between the two and when we go through these large fluctuations, which naturally occur in our lifecycles, our immune systems are dramatically impacted and left vulnerable.

The best things that we can do to reduce the extremity of these hormonal fluctuations and protect ourselves from the dramatic impact that has on the immune system, is to support all elements of healthy hormone production and balance.

A FEW QUICK CONSIDERATIONS FOR KEEPING HORMONES SUPPORTED AND BALANCED:

  • Take care of your adrenal glands by reducing stress, getting enough vitamin C and consuming plenty of minerals (even sodium, but especially magnesium) throughout the day. Your adrenals are responsible for the production of estrogen after we transition to menopause so the healthier they are, the better they will be at producing enough estrogen to avoid the dramatic drop-off most of us experience.
  • Support your liver by consuming plenty of cruciferous and sulphurous vegetables like broccoli, cauliflower, cabbage, kale, onions and garlic. These contain compounds that help to up-regulate the liver’s pathway of detoxification that is responsible for eliminating excess hormones. This is a large part of how we maintain balance, especially when certain hormones are being over or under produced during puberty, pregnancy and menopause. You may also consider supporting your liver with supplemental milk thistle, a powerful hepatic stimulant and protector.
  • Support your gut microbiome by consuming fermented foods, avoiding excess sugar/carbohydrate, eating plenty of fruits and vegetables, drinking tea, and taking a probiotic supplement if needed See your nutritionist and naturopath for guidance here. I also recommend avoiding chronic antibiotic use as much as possible, reducing your use of NSAIDS and consider that the birth control pill may also negatively affect the gut microbiome AND contribute to hormone imbalance in the long run. Your gut microbiome is filled with beneficial bacteria, partially responsible for metabolizing hormones. They play a role in maintaining that important balance.
  • Support digestion by consuming plenty of fibre and water so that the excess, broken down hormones that have been funnelled into the bowels for elimination can be bound and eliminated via the bowels. Constipation may lead to the reabsorption of excess hormones and promote imbalance.

TESTOSTERONE

Not only do we have a higher baseline of estrogen than men, but we also have a lower baseline of testosterone, which, as it turns out, may have a protective effect against the development of autoimmune disease.

As mentioned, testosterone seems to have immunosuppresive and anti-inflammatory effects, which keeps the immune system from overreacting and prevents the molecular mimickery prompted attacks seen in autoimmune disease.

The anti-inflammatory effects of testosterone seem to be primarily in the humoral (antibody mediated) and cellular components of the immune system. Again, these tend to be the elements of the immune system that are overactive in autoimmunity.

Testosterone deficiency, on the other hand, is associated with increases in pro-inflammatory biomarkers like c-reactive protein (CRP), interleukin-6 (IL-6) and tumour necrosis factor (TNP-alpha). These are all heavily implicated in the development and progression of autoimmune disease. Once again, this leaves women at a higher risk..

This creates a good case for women to do small things that can naturally increase testosterone in a healthy way.

A FEW THINGS THAT BOOST TESTOSTERONE HEALTHFULLY, INCLUDE:

  • Exercise and weight lifting
  • Avoid crash dieting and consume a health balance of protein, fat and carbohydrates
  • Minimize stress and reduce cortisol levels with meditation, yoga and plenty of sleep
  • Get enough vitamin D from the sun or (especially if you’re Canadian like me!) high-quality supplementation. See your naturopath for more guidance as there is a tolerable upper level for vitamin D, beyond which you can experience symptoms. 
  • Make sure the diet is nutrient dense and consult with your ND to see if a high-quality multivitamin might be helpful. Vitamins A, C, E, and the full B-Complex as well as zinc are particularly important.
  • Consult with your ND regarding adaptogens such as Maca and Ashwagandha

THE MALE VS. FEMALE IMMUNE SYSTEM

Not only are there inherent differences in our hormonal systems, but our immune systems have stand alone differences as well.

Compared to females, most males exhibit relative immune suppression. This seems to be linked to male sexual activity. Meanwhile, women show greater immunocompetence, which may be an evolutionary encoded adaptation due to our responsibility in gestating and protecting future family members. This translates to improved resilience in the face of potentially pathogenic threats.

Women generally demonstrate enhanced immune reactivity, differential resistance to target organ damage and differences in magnitude or responsiveness of immune cells. For these reasons, the incidence and severity of parasitic infections is higher in men compared to women.

This increased activity in the female immune system may seem like a good thing. However, when it comes to autoimmune disease, wherein the immune system becomes overactive and loses the ability to differentiate between pathogen and self, this actually leaves us at higher risk.

This is why I would strongly recommend that women with autoimmune disease or with a history of autoimmune disease in their family, taking a preventative stance, avoid the use of powerful immune stimulants. These include echinacea, some algae like chlorella and spirulina, as well as some medicinal mushrooms. We do not want to simulate the immune system if it is in self-attack mode.

ENVIRONMENTAL VARIABLES

The final reason that the rate of autoimmune disease is much higher in women, may be the elevated exposure to environmental toxins found in feminine care products. For example, organic solvents, such as those found in nail polish, are linked to the development of autoimmune disease. Additionally, several chemicals commonly found in cosmetics are significantly correlated with onset of the autoimmune condition PBC.

It may seem like an unlikely cause, but the amount of daily chemical exposure that women face even before they leave the house every morning is extreme. In some, it may be the straw that broke the immune system’s back. I believe it is well worth it to start to make the switch to all natural beauty & skin care products. I would recommend checking out the EWG’s Skin Deep Database, where they have done the work of testing most of the widely available cosmetics on the market for safety and quality assurance and provided a ranking for you so that you can make the best choice for you!

CONCLUSION

There are several variables that make women more vulnerable to autoimmune disease. Our delicate hormone balance, lower levels of testosterone, fortified immune systems and elevated exposure to environmental toxins put us at a much higher risk than men, who do not have to battle against those factors.

The good news is, there are many factors within our control. Many of the recommendations made throughout the article can make an enormous difference toward prevention but also maintenance of remission from an autoimmune disease.

Although there is much that is out of our control, we still have so much power to determine our own health. We just have to take every step we can and be a little more careful than our male counterparts have to be. Totally unfair, I know, but we are warriors. If anyone can handle the challenge, it’s a woman.

If you’re looking for additional support in managing your autoimmune disease, please feel free to book a free meet and greet with one of our naturopaths and/or myself (Megan Kelly, CNP). All of our naturopaths have years of experience. I am the in-clinic nutritionist and have also been working with autoimmune disease as my specialty for years. I have additional certifications as an autoimmune paleo coach and would be happy to walk you through how you can use food to manage your autoimmune disease ongoing. I have both Celiac Disease & Hashimoto’s Thyroiditis. I have overcome both without the use of medications and I understand what it’s like to be at a low and feel helpless up against these diseases. You are not alone. You are strong and you can fight this.

Please share this article with anyone who might benefit from understanding this information.

SOURCES

Ceovic, Romana, et al. “Psoriasis: Female Skin Changes in Various Hormonal Stages throughout Life–Puberty, Pregnancy, and Menopause.” BioMed Research International, Hindawi Publishing Corporation, 2013, www.ncbi.nlm.nih.gov/pmc/articles/PMC3888685/.

Danesh, Melissa, and Jenny E Murase. “The Immunologic Effects of Estrogen on Psoriasis: A Comprehensive Review.” International Journal of Women’s Dermatology, Elsevier, 14 May 2015, www.ncbi.nlm.nih.gov/pubmed/28491968.

Dayoub, Ousama, et al. “Estrogen Receptor α/HDAC/NFAT Axis for Delphinidin Effects on Proliferation and Differentiation of T Lymphocytes from Patients with Cardiovascular Risks.” Scientific Reports, Nature Publishing Group UK, 24 Aug. 2017, www.ncbi.nlm.nih.gov/pubmed/28839227.

Salem, Mohamed Labib. “Estrogen, a Double-Edged Sword: Modulation of TH1- and TH2-Mediated Inflammations by Differential Regulation of TH1/TH2 Cytokine Production.” Current Drug Targets. Inflammation and Allergy, U.S. National Library of Medicine, Mar. 2004, www.ncbi.nlm.nih.gov/pubmed/15032646.

Vásárhelyi, Barna, and Tivadar Tulassay. “Endocrine Factors Determining Immune Polarization during Perinatal Transition.” Klinische Padiatrie, U.S. National Library of Medicine, Sept. 2017, www.ncbi.nlm.nih.gov/pubmed/28746946.

Xiang, Yang, et al. “Physiological Low-Dose Oestrogen Promotes the Development of Experimental Autoimmune Thyroiditis through the up-Regulation of Th1/Th17 Responses.” Journal of Reproductive Immunology, U.S. National Library of Medicine, Apr. 2018, www.ncbi.nlm.nih.gov/pubmed/29454161.