Women Are More Prone to Autoimmune Diseases: But Do We Know Why?

Women's Day 2022: From genetic and hormones to placenta, here are some of the theories scientists have come up with.

In 2017, pop star Selena Gomez underwent a kidney transplant after suffering complications from lupus, a rare autoimmune disease.

As it happens, lupus is notoriously difficult to diagnose. It is also 8 times more common in women than in men.

Simply put, an autoimmune disease is any condition where your body's defense system turns on itself.

This can happen if your immune system goes into overdrive, or gets confused between your body's own cells and foreign bodies.

While there is no official data in India, according to the US National Stem Cell Foundation, more than 4 percent of the world's population has an autoimmune disease.

But, that's not all.

Apart from lupus, whether its multiple sclerosis, rheumatoid arthritis, Crohn’s disease, psoriasis, Hashimoto's disease, or one of the eighty other types of known autoimmune conditions, if you're a woman, you likely have a higher risk of developing one of these.

In fact, so strong is the gender bias of autoimmune diseases that women are twice as likely to develop them as men.

This conclusion, though, is mostly observational, and the why of is still one of the biggest medical mysteries. One reason for this is that we aren't quite sure why autoimmune diseases happen in the first place.

There have been different theories, of course, from genes to the placenta, a number of different scientific inquiries have thrown up different answers.

The Clues in the Placenta

Considering autoimmune diseases generally present themselves during reproductive ages between 15 and 55 in women, some researchers think the female reproductive system may have an answer.

In 2019, a study conducted by researchers at the School of Life Sciences in Arizona State University in the US put forth the interesting theory of 'pregnancy compensation hypothesis' (PCH).

"We propose that the ancestral immune system was strongly shaped by the requirement to compensate for unique immune regulation during pregnancy."

The research authors

Basically, the study authors suggested that a female's immune system became dormant during pregnancy, so it doesn't attack and destroy the fetus. So in some sense the placenta provided a pushback to the immune system which tended to ramp up as a result.

This might have worked well for our ancestors, argue the researchers of the study, but in the modern age when women are having kids fewer and far apart, the lack of a frequent pushback from the placenta sends the immune system into an overdrive in the reproductive years.

This isn't the first time someone has looked to the 'lady parts' for answers to illnesses dominant in women. In Ancient Greece, Hippocrates—considered the father of modern medicine—also believed women's illnesses stemmed from the uterus.

Dr Vineeta Bal, an Immunologist, and researcher at the Indian Institute of Science Education and Research (IISER Pune) doesn't fully buy into this theory.

Speaking to FIT, she says, "even women who have never been pregnant are somewhat more susceptible to autoimmune diseases. Thus, placenta alone may not explain this association."

However, she doesn't deny that the placenta could have some role to play.

"It may be one of the many reasons why women are more susceptible than men."

Dr Vineeta Bal, Immunologist, and researcher at the Indian Institute of Science Education and Research (IISER Pune)

Dr Bal goes on to explain, "The development of full-fledged placenta and growing of a foetus which has 50 percent mismatch with the mother's transplantation antigens (called HLA), may imply that the immunosuppression exercised locally by the placenta during pregnancy, suppressive cytokines and other immune components such as regulatory T cells (Tregs) may make women more prone to the break in autoimmune pathology in the long run."

Maybe She’s Born With It

"Women do generally tend to have a higher risk of autoimmune diseases. It could be caused by multiple factors including genetic reasons," Dr Satish Koul, Director of Internal medicine, Fortis Memorial Research Institute, Gurugram tells FIT.

Many researchers in the past have considered this. In fact, genetics and hormonal changes are two of the strongest contenders as far as theories for the causes of autoimmune diseases go.

One theory is that this is due to the double X chromosomes that females have as opposed to one X and one Y chromosome in males.

According to some researchers, the X chromosome has codes for more immune related and immune regulatory genes, and having a larger number of these could increase the chances of a larger number of mutations occurring.

What about the 'female' hormones of estrogen and progesterone?

"While female hormones are one obvious candidate to explain the difference there is no concrete evidence that estrogen/progesterone are actively contributing to the pathology," says Dr Vineeta Bal.

According to Dr Koul, the root cause is more likely a combination of reasons wherein a family history of autoimmune diseases, and other environmental factors could also up the risk of these conditions in some women.

The Losing Hand

Instead of more granulated data for diseases and drugs, this discrepancy between female and male illnesses has further led to the exclusion of female variables from scientific studies.

An article published in the Guardian brings to lights how male mice are preferred for animal trials of medical research, even when studying women's conditions. The reason? Inconvenient hormonal fluctuations.

via GIPHY

This comes in the way of a potentially nuanced understanding of not just autoimmune diseases but also differences in the development of heart issues, and neurocognitive issue like dementia and alzheimers in men and women.

Even though women are more likely to develop autoimmune diseases, they also struggle to get a diagnosis and medical aid due to the gaping gender gap in medicine.

Women's pain and symptoms are more likely to be dismissed, and misdiagnosed with psychiatric conditions. This is especially true for women suffering from chronic pain.

Understanding and decoding autoimmune diseases and its impact on women becomes more important now than ever with the world seeing an unexplained yet consistent rise in cases of autoimmune diseases.