The Silent Crisis: Autoimmune Diseases in Women

Autoimmune diseases affect approximately 5-10% of the global population, with around 80% of these patients being women. So, what is an autoimmune disease? They occur when the body’s natural defense system cannot tell the difference between its own cells and foreign cells – causing it to mistakenly attack normal cells. Over 100 different autoimmune conditions exist, ranging from lupus and rheumatoid arthritis to Hashimoto’s thyroiditis and multiple sclerosis. Autoimmune diseases are chronic, debilitating and life-altering. Yet, they are often invisible and misunderstood.

Despite the multitude of the types of this disease, many share similar symptoms:

• Redness, heat, pain and swelling

• Fatigue

• Joint pain and stiffness

• Skin problems such as rashes

• Abdominal pain or digestive issues

• Recurring fever

• Muscle aches

• Shortness of breath

  
  

Troublingly, diagnosis is challenging because these symptoms are also present in a variety of other common conditions.

Imagine the life of Joanne. She seemed to have it all – a supportive family, a successful career and a dream to travel the world. But beneath this, she battled relentless fatigue, unexplained joint pain and rashes that dominated her face. Doctor after doctor dismissed her symptoms as stress or burnout, leaving her feel unseen and unheard. After many exhausting years, she finally received a diagnosis – lupus, an autoimmune disease that had quietly wreaked havoc on her body and mind. Joanne’s story reflects the sad reality for countless men and women.

However, why is it that 80% of autoimmune disease suffers are women in particular?

This diagram displays the most common autoimmune diseases, comparing the incidence of the disease in females to the incidence in males. The disparity is alarming and has long been a mystery. However, in recent years, scientists have begun to develop a variety of possible theories for the question - why are women disproportionately affected?

Hormonal Fluctuations

Research has found to suggest that many autoimmune diseases affect women during periods of extensive stress, such as pregnancy, or during a great hormonal change. It is widely known that pregnancy results in substantial hormonal and bodily changes and interestingly, the hormonal changes continue until at least a year post-pregnancy. These changes are likely to serve as a trigger for the development of autoimmune diseases. Furthermore, the foetus contains foreign antigens, which results in changes in the mother’s body that seek to suppress the maternal immune system to prevent the rejection of the foetus. It is due to this suppressed immune system that the development of autoimmune diseases may also be triggered.

Despite women’s greater susceptibility to autoimmune diseases having been recognised for more than 100 years, it is saddening that only recently attention and research has been focused on this issue. During such research, one interesting observation was that some of these conditions arise in women after key life transitions. For example, lupus and multiple sclerosis often first appear during the childbearing years and rheumatoid arthritis most commonly arises after menopause. So, you may wonder - what may puberty, pregnancy and menopause have in common? They involve great changes in the levels of the sex hormones - oestrogen, progesterone and testosterone. A connection can be drawn between hormones like oestrogen playing a significant role in the onset of autoimmune diseases, making it unsurprising that oral contraceptives and hormone-replacement therapy have been associated with an increased risk of lupus.

Interestingly, testosterone, which women produce at a smaller level than men, is also a crucial hormone in the twisted web of autoimmunity. The hormone has found to be largely immunosuppressive so it affects the responses of immune cells negatively, which may explain why men have lower incidences of autoimmune disease. According to a 2016 study, research has found that men with low testosterone because of a condition known as hypogonadism have a higher risk of developing lupus and rheumatoid arthritis.

Despite having greatly influential roles, hormones simply cannot be the whole story. Autoimmune diseases sometimes develop in childhood, long before hormones such as oestrogen and progesterone rise during puberty. Therefore, there must be other processes involved and in order to explore this, researchers are studying the primary biological difference between men and women: the second X chromosome.

XX chromosomes

Some researchers have related autoimmune conditions with the X chromosome and the process of X inactivation. Since females, normally, have two X chromosomes, they may possess a higher risk of autoimmune diseases, as compared to men because the X chromosome plays the critical role of containing many immune-related genes. The fact that women have two X chromosomes, while men have one X and one Y chromosome may be the key to understanding this problem.

In women, one X chromosome is inactivated in every cell very early in embryonic development. A Stanford Medicine-led study has highlighted the role of a molecule called Xist, which is responsible for silencing one of the two chromosomes in every female cell. However, in recent years, scientists have discovered that X inactivation does not fully occur the way that was previously understood. Studies indicate that approximately 12% of the genes on the supposedly inactivated X chromosome are still turned on, suggesting that the genes that escape inactivation can lead to higher expression levels of certain proteins in females compared to males. This overexpression may contribute to the development or exacerbation of autoimmune diseases.

Immune system variations

It has been long known in medical science that basic immune responses between men and women differ, with women having far greater antibody production, thus producing a more effective immune response. This manifests in usually milder infections in woman but tragically, leads to women being more prone to developing autoimmune diseases. Hormones like oestrogen, testosterone, and progesterone likely account for most of the differences in immune responses between men and women but the precise interaction between hormones and the innate immune response after infection is unfortunately poorly understood.  Perhaps, evolution may also contribute to the disproportion observed in autoimmunity. Research has suggested that stronger autoimmunity in women may give them a reproductive advantage by improving chances of a successful pregnancy, even if it ultimately comes at the cost of increased disease risk.

Continued issues within the healthcare system

All the discussion around the debilitating nature of these diseases is entirely futile if women are misdiagnosed from the onset. Crucially, women, in particular, frequently have their symptoms dismissed as stress which delays necessary diagnosis and leads to worsening tolls on their body and mind. Furthermore, historically, medical studies have neglected including females, leading to biased medical research where there is a lack of understanding of how diseases, including autoimmune diseases, manifest differently in women. It is crucial that awareness is raised about this issue and we advocate for more inclusive research, in the hope that future medical advancements prioritise women’s health and address these disparities.

To conclude, through the role of female hormones, X chromosomes and pregnancy in perhaps triggering autoimmune diseases, it seems as though biology is somehow conspiring against the female sex. However, through a more optimistic lens, one may argue that this is just a reflection of the importance of women for the survival of our species and the cost that comes with this.

Finally, our message to you is to never downplay your symptoms, if you feel that something is wrong, and you have noticed a change in your body – address it. Contact your doctor.

Donate!

• The Wren Project – offer free listening support, believing that no one should have to face autoimmune disease alone

• FAIR – fund research into autoimmune diseases, which has too often been overlooked

• Autoimmune Association – gather funds to support patients and advance research

Sources:

Hopkins Medicine – What Are Common Symptoms of Autoimmune Disease?

Stanford Medicine-led study

PubMed Central – Women and Autoimmune Diseases

PubMed Central – Prevalence of Autoimmune Disorders in Women

Scientific America – Why Nearly 80 Percent of Autoimmune Sufferers Are Female