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the 80 per cent: why women dominate autoimmune disease diagnoses
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the growing number of autoimmune diseases, which develop when the body’s immune system plays friendly fire on healthy tissues it mistakes for foreign invaders, continues to be a point of interest for medical researchers. the complex diseases vary significantly in which tissues are attacked, making it difficult to reach a single consensus that drives them all.
that said, there is one thing researchers know without a doubt: women are disproportionately affected by these types of diseases. of all cases, 80 per cent are diagnosed in women.
while it’s not deemed a women’s health issue, with that many cases being found in women, they are a major focus of research in the women’s health space—even if that research is still “pretty scattered.”
“there’s not a solid body where you could just reliably have a collection of articles to really tell you these causes [of autoimmune disease],” said dr. tanya lee, a naturopathic doctor practising in toronto.
hormones and autoimmune disease in women
while medical researchers continue to hunt for answers, much of what exists has pointed to several areas of health that could play major roles in the discrepancy in the development of autoimmune disease among women and men.
one has to do with female hormones. the female immune system, specifically immune cells, is full of estrogen receptors that act as specialized proteins allowing estrogen to regulate the immune response.
with more estrogen in the body, these receptors can be activated at a higher rate.
“we naturally mount stronger immune responses, more rapid immune responses, a little bit more severe, so that could be playing into why women tend to be more prone to autoimmune disease because we may have just a stronger immune response,” said dr. lee. “lupus tends to be more estrogen-driven.”
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progesterone, another female hormone, is another potential culprit—but currently, the research has found its relation to autoimmune diseases only for specific types, such as multiple sclerosis (ms) and rheumatoid arthritis (ra).
research on ms and ra has found that lower levels of progesterone can lead to more symptoms in developed autoimmune diseases. so, while it’s not generally a direct cause, the swings that occur throughout the month in progesterone due to the menstrual cycle can heavily influence disease severity.
“women who have rheumatoid arthritis, what i’ve seen in practice, tend to flare more during their premenstrual time, and that is often corrected where we do see some balance between estrogen and progesterone,” said dr. lee.
while hormones certainly play their part, they cannot be used as a blanket cause because “every individual disease tends to have its own kind of mechanism of how it functions and how it responds to sex hormones.”
that said, there are some physiological facts that offer insight into why these hormones, specifically estrogen, could be part of the puzzle.
“if i had to be really general, we tend to kind of look at estrogen being a little more inflammatory and testosterone being more anti-inflammatory,” said dr. lee, who’s seen evidence from lupus trials that show using androgens to treat women with lupus can lead to better symptom outcomes.
“but again, it can’t just be applied to any, every person with lupus. you have to really do your due diligence in understanding whether or not this person’s a good candidate for this type of therapy,” she said.
other factors that play into hormonal shifts and changes, such as sleep, may also drive changes in immune function that lend to autoimmune disease development.
“something like a lack of sleep, like stress, lack of sleep, again these things could be tied into hormonal fluctuations like perimenopause,” said dr. lee. “they’re all going to play a role, again, on how your immune system functions. so, everything works together.”
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xx versus xy
women being prone to autoimmune disease may also come down to the very basics: their chromosomes. females have two xx chromosomes, whereas males have xy. the x chromosome determines a person’s sex, governs traits and bodily functions unrelated to sex, and has more “factors that influence white blood cells and innate immunity,” said dr. lee.
the x chromosome houses the highest concentration of immune-related genes, which could show why women have a stronger immune response. but when things go too far in the wrong direction, that overabundance can also drive the higher susceptibility of autoimmune disease.
some research suggests that one of the two x chromosomes, which is often shut down during fetal development to avoid overexpression of certain genes that could lead to issues, gets around the wall designed to protect the body. when that happens, genes become overactive, and they need somewhere to direct their tasks, such as healthy tissues.
the psychological aspect of autoimmune disease development
even though autoimmune disease is driven by a physiological response, newer research has examined psychological aspects of its development in women and found that there is some connection between repressive trauma and the onset of these diseases.
“the way women process stress could be generally different than the way men have been taught to process stress, and that could be playing a role,” said dr. lee. “we tend to hold things more in. we tend to not express our discomfort the same way.”
because of how women are conditioned to repress certain emotions and put others first, that toll of stress can add up within the body, showing up in a few different ways. the first has to do with the physical stress response triggering inflammation that drives overactivity within the immune system, which can end up turning on the body’s own tissues.
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hormones can also become dysregulated after continual suppression, which interferes with how well the body regulates the immune response. the effects are particularly strong in women who have had adverse experiences and high levels of mental stress or trauma in childhood, as research shows that these types of events show a distinct increased risk of the development of autoimmune disease.
“if you think about what autoimmune disease is, like your body attacking itself, and when we repress things … it’s kind of doing it at the same time; we’re not letting things outward, so it’s just kind of destroying us from the inside out,” said dr. lee.
the uniquely complex state of autoimmune disease
while the research continues regarding autoimmune disease in general, and in regard to women’s dominance in terms of the development of these diseases, getting to a one-size-fits-all answer isn’t possible.
these diseases, as well as the women who develop them, are all different, so presentation, development, severity and progression will all differ just as varied. even in research, dr. lee notes, it would be “really difficult to do a really focused study on one hormone and one outcome.”
“i think that kind of speaks to the nature of the multifactorial nature of autoimmune disease and just women’s bodies in itself,” she said. “everyone’s so different. i could have 10 people presenting with lupus, all women, perhaps all even in the same stage of life, but they’re all going to have different treatment plans depending on how they’re presenting their concerns.”
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