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Women, Autoimmune Diseases and the Demographic Transition

The incidence of autoimmune diseases has tripled in the past few decades, and they cost the United States more than $100 billion each year. Additionally, an autoimmune disease typically lasts for the person’s lifetime, and there are no known cures, which further put a major financial burden on the health care system.

Current estimates show that 5-8% of people have autoimmune diseases worldwide, and it is estimated that over 23 million Americans suffer from them. Some contribute this to our society becoming “too clean.” According to this “hygiene hypothesis,” lack of exposure to beneficial microorganisms prevents normal development of the immune system. Another interesting feature is that women are much more likely to suffer from autoimmune diseases in men.

Three times as many women as men have autoimmune diseases. For certain conditions, such as Hashimoto’s thyroiditis and systemic lupus erythematosus (SLE), the disparity is as bad as 10:1 and 9:1, respectively. One study revealed that 93% of Addison’s patients are women, 88% of Graves’ patients, 94% of Sjogren’s patients and 88% of SLE patients. Autoimmune diseases are among the leading causes of death in young and middle-aged women in the United States. However, there are some that are more common in men, such as Goodpasture’s syndrome (3:1 men), but there are much fewer autoimmune diseases that exhibit this trend.

One explanation for this gender disparity is the role that pregnancy plays in autoimmune disease. For example, in some autoimmune diseases, women’s immune systems form reactions to fetal cells, some of which persist after pregnancy. Several reports have shown that cells containing Y chromosomes can be found throughout a woman’s body when she has a boy, which is known as fetal microchimerism. Furthermore, a study by Nelson et al. showed that greater amounts of microchimerism were seen in women with scleroderma compared to controls. However, the disparity between men and women has only become an issue in recent decades. Therefore, it is unlikely solely due to immune reactions to lingering fetal cells. Another theory for why women are more likely to get autoimmune diseases includes hormonal differences. This does not explain the increasing disparity because when men have the disease, their disease is just as severe as women who have it.

I believe one possible explanation may be our changing culture in the post-industrial era. According to the Bureau of Labor Statistics, more women are entering the workforce and fewer are staying home. Women are going to school for longer than ever before. They are having kids less frequently and later in life. Most autoimmune diseases develop in adolescence or early adulthood, so this may be a critical period in a person’s life for developing autoimmune diseases. In our era, more and more women are becoming pregnant after this period in their lives.

The decreased number of pregnancies may also be a problem, as regulatory T-cells (Tregs) are upregulated during pregnancy (Aluvihare et al., Somerset et al., Santner-Nanan et al.), and Tregs are known to promote tolerance and prevent the development of autoimmune diseases. These Tregs have also been shown to infiltrate fetal lymph nodes and induce tolerance to maternal antigens. This change in the role of women has also been hypothesized as an explanation for the increase in ovarian and endometrial cancers in recent decades. During pregnancy and breast-feeding, women stop ovulating for about 12 months, so the ovarian and endometrial walls do not need to proliferate like they would during menstruation.

More research needs to be done on this issue in order for us to better understand and prevent autoimmune diseases.

Ryan Denu Ryan Denu (7 Posts)

Contributing Writer

University of Wisconsin School of Medicine and Public Health

Ryan is a Class of 2019 MD/PhD student at the University of Wisconsin School of Medicine and Public Health. He graduated in May 2012 from the University of Wisconsin-Madison with a BS in molecular biology. He enjoys thinking and writing about health care policy and bioethics, and is also an avid tennis player, instructor, coach, umpire, and fan.