Why are autoimmune diseases more common in women?

Autoimmune diseases are like friendly fire in the body.

While our immune system normally helps defend against infections, when we have an autoimmune disease, it mistakenly recognizes our own tissue as an intruder, seeking and destroying it.

These disorders, which can target any part of the body, are far more common in women than men. As many as 70% to 80% of people with autoimmune diseases are female, with the percentages being higher for some specific conditions. For example, among people with Sjogren’s syndrome, which affects the glands that make saliva and tears, 95% are women.

Examples of autoimmune diseases

There’s a long list of autoimmune disorders and diseases. Some of them, and the main areas of the body they affect, include:

• Autoimmune hepatitis: the liver
• Type 1 diabetes: the pancreas, leading to reduced insulin
• Multiple sclerosis: the nervous system
• Myositis: muscles
• Myasthenia gravis: nerves and muscles
• Rheumatoid arthritis: joints
• Juvenile idiopathic arthritis: joints
• Sjogren’s syndrome: glands that makes saliva and tears
• Lupus: many organs and systems
• Hashimoto’s thyroiditis: the thyroid
• Vasculitis: blood vessels
• Celiac disease: the small intestine, as a reaction to eating gluten

The danger of autoimmune diseases

Every part of the body can be a target of an autoimmune disease. If a vital organ is attacked, the disease can be life-threatening.

Why are women more prone to autoimmune diseases?

In general, genetics play a large role in the risk of developing autoimmune diseases in both men and women. Environmental factors also play a role in both sexes. However, there are other major factors that increase the tendency for these diseases in women:

Estrogen

The female hormone estrogen boosts the function of T and B immune system cells. This can be an advantage in fighting infections but problematic in people with other factors that make them more likely to have autoimmune diseases.

Estrogen levels are the highest during pregnancy, and some autoimmune diseases are more common in women during childbearing years in general and during pregnancy in particular.

X chromosome inactivation

Chromosomes carry our DNA and genetic information. Males have one X chromosome and a much smaller Y chromosome. Females have two copies of the X chromosome.

Normally in females, one of the two X chromosomes becomes inactivated, leading to both males and females expressing one X chromosone gene. However, the complex system that makes this happen has many protein components that tend to become targets of the immune system, which can lead to autoimmune disease.

Additional X chromosomes

All females have two X chromosomes, compared with a single X chromosome in males. In some rare circumstances, some males and some females have more copies of the X chromosome than normal. These people are more likely to have certain autoimmune diseases. Having more than one copy of a X chromosome gene that is functional is referred to as the “X chromosome dose effect.” This phenomenon becomes critically important when it involves certain genes that heighten the function of the immune system.

An example of this is that males who have two copies of the X chromosome and a Y chromosome (Klinefelter’s syndrome) are more likely to have lupus when compared with men with one X and one Y chromosome. Also, women with three copies of the X chromosome are almost three times as likely to have lupus and/or Sjogren’s syndrome when compared with women who have two X chromosomes.

As discussed above, most of the genes on additional X chromosomes become inactivated as part of normal biology. But some chromosomes avoid this inactivation, such as the gene referred to as “toll-like receptor 8,” which is important in the development of lupus.

The female immune system and autoimmune diseases

Women can create a more robust immune response to infection than men. This provides an advantage in fighting infection but could promote an autoimmune disease in a person who has genetic susceptibility.

Puberty, pregnancy, menopause and autoimmune diseases

Because of the effects of estrogen and hormones described above, when females hit puberty or are pregnant, they are more at risk for autoimmune diseases such as lupus. The risk of developing disease or experiencing a flare reduces after menopause.

Hormonal birth control and autoimmune diseases

For some women with severe disease, such as those with lupus, estrogen-containing hormonal birth control is avoided due to the risk of increased estrogen exposure. However, most women can safely use some form of birth control in consultation with their rheumatologist and Ob/Gyn.

Decreasing risk for autoimmune diseases

Environmental factors are the major risk factors that can be controlled. For example, exposure to ultraviolet rays can be associated with lupus and juvenile dermatomyositis, which affects children’s skin and muscles. Pesticides and organic mercury have been linked to rheumatoid arthritis. Certain medications can trigger some autoimmune conditions.

When to see a doctor for an autoimmune disease

Any lasting symptoms — such as fatigue, weight loss, rashes, weakness or joint pain — that are associated with morning stiffness should be taken seriously. And a clue may be multiple symptoms that seem to start at the same time.

What to ask your doctor

It’s important to start early with conversations about the link between hormones and autoimmunity, and the potential impact on disease course and treatment.

It’s also important to discuss reproductive health history and family planning with your doctor. For most women, birth control can be used, and pregnancy can be achieved with careful planning involving the patient, rheumatologist and Ob/Gyn.

Treating autoimmune diseases

Treatment should be tailored to the individual and the extent of organ involvement. For patients with mild symptoms and without major organ involvement, the use of drugs that control the immune response without immunosuppression (like hydroxychloroquine), along with treating of symptoms, may be sufficient.

If major organs are affected, immunosuppressive and biologic drugs that target certain parts of the immune system are used.

Autoimmune diseases in men

Since most of these diseases are less common in men, it sometimes takes longer for doctors to recognize the possibility that the patient has an autoimmune condition. Risk factors are mostly genetic predisposition to the disease and environmental factors.