Guest post by Rashmi Kudesia M.D., M.Sc.
Over the past half-century or so, human exposure to chemicals in nearly all aspects of contemporary life – food, body products, household products, and other environmental exposures – has expanded exponentially. Increasingly, individuals in both the scientific and general populations are voicing concern over the health impacts that may be generated by lifelong exposure to such chemical agents, and effort is being placed on identifying those of greatest health concern. At this point, it is accepted that certain pollutants may impact endocrine, or hormonal, functions in the body, and some, for example bisphenol A, have been shown in some studies to also impact weight and cardiac health. Though the data is still in a nascent phase, given the centrality of weight, insulin function and reproductive hormones in these theories and in PCOS, researchers have started investigating the possible role of chemical exposures on PCOS. Here we will review some of the data published so far.
One of the first, and most widely-known agents, is bisphenol A (BPA). BPA is known to interfere with the normal levels and function of androgens (the “male hormones”, characteristically elevated in PCOS). Studies done in rodent models have shown that BPA exposure results in a PCOS-type syndrome in the rats, as well as dysregulating insulin function. In 2011, Kandaraki and colleagues published a human study that included 71 European women who met the strict National Institutes of Health criteria for PCOS. This means that these women had irregular or absent ovulation, and symptoms or bloodwork indicating high androgen levels. They were compared to 100 women without PCOS, matched by age and body mass index (a parameter that takes into account height and weight). They found that the PCOS women had higher levels of BPA, and this was true whether the PCOS women were lean or obese. Higher BPA levels were also associated with higher androgen levels and a greater degree of insulin resistance in the PCOS women. This provocative study suggested that environmental exposure to BPA may play a role in the main symptoms of PCOS.
In 2015, another study, published by Akin and colleagues, demonstrated a similar finding in Turkish adolescent girls with PCOS. They compared 112 girls aged 13-19 with PCOS to 61 girls without PCOS. This study used the more lenient Rotterdam criteria (requiring at least 2 out of 3 criteria: irregular or absent ovulation, high androgen levels, or polycystic-appearing ovaries on ultrasound). They also found that BPA levels were correlated to androgen levels, and hirsutism (excess facial and/or body hair).
Other studies, however, have not shown a similar association. A study of Han Chinese women seeking infertility treatment, by Yang and colleagues, demonstrated an association between PCOS and other pollutants, but not BPA. They noted that this conflicted with the findings of the 2011 study, as did the authors of a U.S. study (Vagi and colleagues), that also found no association between PCOS and BPA in women diagnosed by NIH criteria. However, both of these studies also investigated a variety of other chemical exposures and highlighted possible roles for polychlorinated biphenyls (PCBs), as well as other pollutants, including organochlorine pesticides, perfluorinated compounds (PFCs) and polycyclic aromatic hydrocarbons (PAHs).
Finally, both the Vagi study, as well as another by Hart and colleagues, demonstrated that phthalates, a class of chemicals that have been shown to have anti-androgen action (thereby possibly causing birth defects and issues for exposed boys/men), may actually decrease the PCOS prevalence, presumably by correcting the elevated androgen environment in PCOS women. The Vagi study looked at women, and the Hart study at adolescents, with PCOS and demonstrated that increasing serum phthalate levels were associated with a lower rate of PCOS.
So, what to make of all of this? First, as mentioned at the outset, this literature is still in its infancy. Environmental exposures are difficult to study, as it is almost impossible to isolate the effects of a single chemical, or class of chemicals, and to control for exposure during gestation, infancy and childhood, and adult life. If indeed any of these chemicals can increase or decrease the chance of developing PCOS, it has certainly not yet been determined when the vulnerable times might be – must exposure occur very early in development, or can adult women newly exposed also develop effects? Further, given the ubiquity of these chemicals, methods of avoidance are also not yet well-explicated. As additional difficulties in assessing the possible link, it may be that the risk is specific to certain types of PCOS (Rotterdam versus NIH criteria, or in lean or obese PCOS women), or geographically-determined exposures (the levels of various chemicals and exposures likely varies throughout the world).
Certainly, more research is needed to try to identify how we can best keep ourselves safe and limit exposure to endocrine-disrupting chemicals. In the meantime, choosing the cleanest lifestyle one can seems as though it could only be neutral-to-beneficial in terms of health effects; though of course the cost of the freshest, most organic, most natural food and products cannot be ignored, and, sadly, is simply not within reach for many women and families in our country. For now, the most evidence-based recommendation would be to do what is possible in terms of limiting environmental exposures, not overly stress about the rest that cannot be changed, and to speak with your doctor about any specific exposure concerns you may have. Earlier this year, the American Society for Reproductive Medicine convened an entire conference around this topic, the Environment and Reproductive Science Summit, so hopefully momentum is building to further address and clarify these concerns!
Dr. Kudesia is a board-certified Reproductive Endocrinology and Infertility specialist, practicing at Houston IVF in Houston, Texas. She joined Houston IVF in 2018 after practicing in New York City, where she was named a “New York Super Doctors Rising Star” in 2016 and 2017.
After completing her Baccalaureate degree in Biology & Medicine magna cum laude from Brown University, she received her M.D. with honors from the Duke University School of Medicine, where she was selected into a clinical research training program co-sponsored by the National Institutes of Health. Her residency training in Obstetrics & Gynecology at the New York Hospital-Weill Cornell Medical Center was followed by subspecialty training in Reproductive Endocrinology and Infertility (REI) at the Albert Einstein College of Medicine-Montefiore Medical Center, alongside a Masters’ of Science degree in Clinical Research Methods. She subsequently served as a Clinical Assistant Professor at the Icahn School of Medicine at Mount Sinai, as well as the Research Rotational Director for the REI fellowship, and Medical Director of the Brooklyn office of the Reproductive Medicine Associates of New York.
Dr. Kudesia is a Fellow of the American College of Obstetricians and Gynecologists, and an active member of the American Society for Reproductive Medicine (ASRM), Society for Reproductive Endocrinology and Infertility, Androgen Excess & Polycystic Ovary Syndrome Society, and American Medical Association (AMA). She has served in multiple local and national leadership roles in organized medicine, including her current positions as Secretary of the ASRM Women’s Council Executive Board and the ASRM delegate to the AMA Young Physicians’ Section.
Dr. Kudesia has also presented scientific research at national and international conferences, and has received multiple awards and grants for her work. She has published peer-reviewed articles and book chapters, including in leading journals such as Fertility & Sterility and the American Journal of Obstetrics & Gynecology, as well as editing a theme issue on reproductive medicine for the American Medical Association Journal of Ethics. Her current areas of focus include improving in vitro fertilization cycle prognosis, polycystic ovary syndrome, LGBT fertility, and fertility awareness, counseling, and access to care. She actively promotes women’s health and wellness on social media via Twitter, Facebook, and Instagram.