Autoimmune activity in the pathogenesis of polycystic ovarian syndrome (PCOS) has been questioned for multiple decades. In a research letter published in The Lancet in 1999, authors Fénichel, et al., examined circulating antiovarian antibodies in thirty-four women with anovulation meeting PCOS diagnostic criteria against a control group. Their study found positive antiovarian antibodies in fifteen of the thirty-four PCOS women (44%), and the mean ratios of these antibodies were significantly higher for women with PCOS than for the control group. The authors concluded that “high concentrations of antiovarian antibody found in a group of PCOS suggest that an immune reaction is associated to PCOS.1”
Following this, in 2000, Ali, et al., reported similar findings in Obstetrics & Gynecology. Their study also showed a statistically significant higher mean ratio of antiovarian antibodies in patients with PCOS as compared to controls. Further, they also determined that the specificity of antiovarian antibodies was significantly higher in women who also had positive antinuclear antibodies.2
Research in this area has expanded in the last decade, as PCOS has become increasingly common. Recent estimates suggest that up to 12% of women in the United States have PCOS. Also of interest is the strong link between PCOS and Hashimoto’s Thyroiditis (HT), with HT being about 3 times more common in women with PCOS, further suggesting a role of autoimmune activity. Much of the research on autoimmunity in PCOS has been done in the context of HT, and anti-TPO antibodies have been found to be present in up to 26% of women with PCOS.3
An imbalance between estradiol and progesterone has been investigated as playing a role in potential autoimmune activity in PCOS. Progesterone, which is typically low in patients with PCOS, is generally considered immunosuppressant and can downregulate the production of autoimmune antibodies, as well as inflammatory cytokines produced by circulating autoantibodies. Estradiol, on the other hand, is generally proliferative and immunostimulatory. In a 2015 study of eighty-six reproductive-aged women with PCOS, increased estradiol and estradiol/progesterone ratio appeared to be directly involved in high anti-TPO levels in PCOS patients.3
Interestingly, as researchers continue to study PCOS as an autoimmune disease, there is also evidence that the presence of PCOS itself increases a person’s risk of developing other autoimmune diseases. A 2020 review article by Hu, et al., discusses alterations in immune system activity as a result of PCOS. They conclude that a dysregulation in the hormonal and immune microenvironment, and chronic low-grade inflammation due to these alterations, results in production of autoantibodies, increasing risk of autoimmune disease development.4
Hormonal imbalance in the PCOS state can cause infertility, insulin resistance, cardiovascular problems, increased risk of certain cancers, and more. A newer concept, and as discussed above, is that this hormonal dysregulation may also exacerbate the autoimmunity of PCOS and increase the risk of developing other autoimmune diseases. Identifying and addressing hormonal imbalance in PCOS or suspected PCOS patients is therefore a fundamental part of any treatment approach.
