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Autoimmune diseases occur when the body’s immune system mistakenly attacks its own healthy cells, tissues, and organs. These diseases affect millions of people worldwide, with a much higher prevalence observed in females compared to males. Autoimmune diseases are influenced by many factors, including genetics, hormones, and environmental triggers. The interplay of these elements contributes to the development of autoimmune diseases. In this article, we’ll look at possible explanations for why autoimmune diseases are more prevalent in females.

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Autoimmune diseases were first described more than 50 years ago. In simple terms, an autoimmune disease is when the body’s immune system mistakenly attacks its own healthy cells, organs, and tissues. Normally, the immune system acts as a defense mechanism to protect the body from harmful substances like bacteria, viruses, and toxins. However, in the case of an autoimmune disease, the immune system fails to recognize the difference between the body’s own cells and foreign invaders, leading to the production of autoantibodies and an inflammatory immune response.

This response can result in damage to various organs and tissues, causing a range of symptoms and health complications. It’s estimated that there are more than 100 different autoimmune diseases, including Hashimoto’s thyroiditis – one of the more common autoimmune diseases – and Graves’ disease, two diseases that affect thyroid function. In addition to Hashimoto’s thyroiditis and Graves’ disease, some of the other more common autoimmune diseases in the U.S. include:

• Lupus
• Rheumatoid Arthritis
• Type 1 Diabetes
• Multiple Sclerosis
• Myasthenia Gravis
• Inflammatory Bowel Disease
• Crohn’s Disease
• Psoriasis
• Scleroderma
• Addison Disease
• Celiac Disease
• Dermatomyositis
• Pernicious Anemia
• Sjögren’s Syndrome
• Psoriatic Arthritis

Each autoimmune disease has specific characteristics and effects on the body. The exact cause of autoimmune diseases is not fully understood, but a combination of genetic predisposition and environmental factors is believed to play a role. Managing autoimmune diseases typically involves reducing inflammation and modulating the immune response through medications and lifestyle changes, and treating medical conditions and symptoms resulting from the disease.

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Autoimmune diseases are a common and growing health concern worldwide. It is estimated that between 5% to 10% of the global population suffers from some form of autoimmune disease. According to the Autoimmune Association, over 50 million Americans are estimated to have one or more autoimmune diseases.

Autoimmune diseases affect individuals of both sexes, but evidence suggests that they are far more prevalent in females than males. According to a study published in the Journal of Autoimmunity, females are generally at a higher risk of developing autoimmune diseases, with a female-to-male ratio ranging from 2:1 to 9:1, depending on the specific condition. Additionally, the American Autoimmune Related Diseases Association (AARDA) reports that approximately 80% of people suffering from autoimmune diseases are women, and autoimmune diseases are among the leading causes of death and disability in young women.

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It’s important to acknowledge that there is no one-size-fits-all answer to why females are at higher risk than males. But let’s explore some of the critical risk factors that are thought to create a higher risk of autoimmune diseases in women, including:

• Hormonal changes
• Genetics
• Chromosomes
• Immune response
• Environmental factors
• Evolution

Hormonal changes

One factor that could potentially explain the higher prevalence in females is the role of sex hormones. Estrogen, a hormone predominantly found in females, has been implicated in modulating the immune and autoimmune response. It is suggested that estrogen may enhance immune responses, leading to a greater risk of developing autoimmune diseases. Conversely, testosterone, the hormone found in higher levels in males, may protect against autoimmune disorders. However, the relationship between sex hormones and autoimmune diseases is complex and not yet fully understood.

Genetics

Genetics also play a crucial role in the development of autoimmune diseases. Specific genes are known to be associated with an increased risk of developing autoimmune disorders, as they have a role in regulating the immune system and its responses. Variations in these genes can increase the risk of developing autoimmune diseases and a higher risk of autoimmune disease in families. Research suggests that women are more likely to inherit these genes, making them more vulnerable to autoimmune diseases.

X chromosome inactivation

Females have two X chromosomes, and males have one X and one Y chromosome. To prevent gene overexpression on the X chromosome and balance the gene expression, one of the X chromosomes is randomly inactivated in each cell in females.

The X chromosome, however, contains many genes involved in the immune system and autoimmunity. X chromosome inactivation is when one of the two X chromosomes in female cells is randomly inactivated to maintain proper gene dosage. However, this inactivation process can also influence the risk of autoimmune diseases in females. Specifically, it’s theorized that X chromosome inactivation leads to uneven expression of the X-linked genes involved in immune regulation. If one X chromosome carries a defective or overactive immune-related gene, it can contribute to an imbalance in immune response, increasing the risk of autoimmune diseases in females. Further research is needed to fully understand the complex relationship between X chromosome inactivation and autoimmune diseases.

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Immune response

Another potential explanation lies in the differences in the immune response between males and females. It has been observed that females generally display a more robust immune response than males. This heightened immune response can increase the risk of developing autoimmune diseases as the immune system becomes more prone to attacking the body’s own tissues. The reasons for these gender-based immune response differences are not entirely clear but may be influenced by a combination of genetic, hormonal, and environmental factors.

Microchimerism

Microchimerism is a fascinating phenomenon that has intrigued scientists for many years. It refers to the presence of a small number of cells from one individual within another individual. These cells can be of different types, including immune, stem, or even whole organ cells. While microchimerism can occur naturally in various circumstances, such as during pregnancy or after organ transplantation, researchers have found a potential link between microchimerism and autoimmune disease.

The relationship between microchimerism and autoimmune disease is complex and not yet fully understood. However, several studies have suggested that microchimerism may play a role in both the development and modulation of autoimmune diseases.

The microchimerism theory of autoimmunity is that fetal cells the mother acquires during pregnancy can persist in her body for many years, sometimes even decades. These fetal cells can contain unique genetic material that differs from the mother’s own DNA. It is believed that these cells may contribute to the development of autoimmune diseases by triggering an immune response against the mother’s tissues.

The best study linking microchimerism to autoimmune disease in women is a prospective, blinded study of fetal microchimerism in women with primary Sjogren’s syndrome (PSS). The study investigated naturally acquired microchimerism in autoimmune disease and was a prospective, blinded study of fetal microchimerism in women. The study used a quantitative assay to test for male DNA in women with PSS and healthy women who had given birth to at least one son. Levels of DNA were significantly higher in women with PSS compared with healthy women.

A more recent study out of the Fred Hutchinson Cancer Center added to the understanding, reporting that microchimerism can trigger rheumatoid arthritis in mothers who carry their child’s cells.

Furthermore, microchimerism has been observed in patients with certain autoimmune diseases. For example, 2012 research published in the journal Chimerism found evidence of fetal microchimeric cells in the blood and thyroid glands of women with Hashimoto’s disease. Another study found that microchimerism is far more common in women with Hashimoto’s than those with nodular goiter.

These findings suggest that fetal microchimerism may play a role in developing Hashimoto’s disease, although the exact mechanisms are still unclear.

Environmental factors

It’s vital to consider the impact of environmental triggers on the development of autoimmune diseases. These triggers can include infections, exposure to certain chemicals, viral, bacterial, fungal infections, and psychological stress. Research has shown that females may be more susceptible to these triggers, potentially contributing to this population’s higher prevalence of autoimmune diseases.

Evolutionary perspective

Evolution plays a part in explaining why females are more susceptible to autoimmune diseases. Throughout history, females have played the primary role in reproduction and childcare, requiring a robust immune system to protect themselves and their offspring. Women’s immune systems may also be more likely to produce antibodies that protect against some infections and increase the risk of autoimmune diseases.

This need for a robust immune system led to the development of specific genetic traits and hormonal differences in females, making them more prone to autoimmune disorders. Additionally, hormones like estrogen can affect the immune response, potentially making females more susceptible to these diseases. Understanding the evolutionary basis for this susceptibility can help researchers and medical professionals develop targeted treatments and prevention strategies for female patients.

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Additionally, evidence suggests that diagnostic biases and healthcare disparities may also play a role in the observed gender disparity in autoimmune diseases. Historically, autoimmune diseases have been predominantly studied in women, leading to a potential underreporting and underdiagnosis in males. This underestimation of autoimmunity in men may, in turn, contribute to the perception that autoimmune diseases are more prevalent in females.

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While Hashimoto’s disease can affect both males and females, it is significantly more prevalent in females. In fact, it is estimated that women are around eight times more likely to develop Hashimoto’s disease than men. Several factors contribute to the higher prevalence of this condition in females, including hormonal, genetic, and immunological factors.

Hormonal factors

One of the main reasons why Hashimoto’s disease is more common in females is the influence of female hormones. Estrogen, the primary female sex hormone, modulates the immune system. It is believed that estrogen may enhance immune responses, making women more susceptible to developing Hashimoto’s. Additionally, fluctuations in hormone levels during the menstrual cycle, pregnancy, and menopause can trigger or exacerbate flare-ups in the symptoms of Hashimoto’s disease.

One of the ways estrogen influences the risk of Hashimoto’s disease is through its effect on the immune system. Estrogen can modulate immune responses, and imbalances in estrogen levels may lead to an overactive immune system. In individuals with a predisposition to autoimmune diseases like Hashimoto’s, this overactive immune response can result in the immune system attacking the thyroid gland, leading to inflammation and subsequent damage.

Estrogen may also impact Hashimoto’s disease by affecting the thyroid itself. Studies have shown that estrogen can interfere with the synthesis and utilization of thyroid hormones, essential for regulating metabolism and other bodily functions. This interference can disrupt the delicate balance of thyroid hormones, leading to imbalances that contribute to the development of Hashimoto’s disease.

Estrogen can also influence the gut microbiome, which is crucial to immune function and overall health. Imbalances in the gut microbiome can lead to increased intestinal permeability, also known as “leaky gut syndrome.” When the gut becomes leaky, toxins and undigested food particles are allowed into the bloodstream, triggering immune responses and potentially leading to autoimmune conditions like Hashimoto’s disease. Estrogen can affect the gut microbiome composition, potentially exacerbating leaky gut and increasing the risk of autoimmune diseases.

Genetic factors

Genetics also play a crucial role in the development of Hashimoto’s disease. Studies have shown that specific genes increase the risk of developing autoimmune thyroid diseases. These genes are more commonly found in females, which could explain the higher prevalence of Hashimoto’s disease in women.

Research has shown that there is a genetic component to Hashimoto’s disease. Studies have also found that individuals with a family history of autoimmune diseases, such as rheumatoid arthritis, type 1 diabetes, and lupus, are more likely to develop Hashimoto’s. Having a first-degree relative, such as a parent or sibling, with Hashimoto’s significantly increases the risk of developing the condition.

Immunological factors

The immune system is complex and delicate, and it is responsible for protecting the body against foreign invaders. In the case of Hashimoto’s disease, the immune system mistakenly targets the thyroid gland as if it were a threat. The exact cause of this immune response is still not fully understood. However, it is believed that a combination of genetic predisposition and environmental factors could trigger the immune system’s attack on the thyroid gland.

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Environmental factors

Various environmental factors may contribute to the risk of developing Hashimoto’s disease in women. However, the specific relationship between these factors and the gender disparity in prevalence is not yet clear. These factors include

• Iodine deficiency or excess
• Exposure to environmental toxins, such as heavy metals like mercury and lead and pesticides
• Exposure to endocrine-disrupting chemicals found in plastics, cosmetics, and cleaning agents
• Chronic stress
• Cigarette smoking
• Infections, such as Epstein-Barr virus (EBV) and Yersinia enterocolitica

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It’s clear that autoimmune diseases – including autoimmune thyroid diseases – are more prevalent in females compared to males. The factors contributing to this gender disparity are complex and multifactorial. Sex hormones, genetics, chromosomal changes, immune response differences, microchimerism, environmental triggers, and potential diagnostic biases all likely play a role. Further research is needed to understand the mechanisms underlying this disparity. Understanding these factors is crucial not only for treating and managing autoimmune diseases but also for early detection, prevention, and improved healthcare outcomes for those affected.

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