A new EU study reports on a growing body of evidence suggesting that exposures to endocrine-disrupting chemicals (EDCs), particularly diphenyldichloroethene and phthalates, contribute to the development of the most common reproductive disorders in women, endometriosis and uterine fibroids.
The study, “Female Reproductive Disorders, Diseases, and Costs of Exposure to Endocrine Disrupting Chemicals in the European Union“ (DOI: http://dx.doi.org/10.1210/jc.2015-2873), is co-authored by Patricia A. Hunt of the Washington State University’s School of Molecular Biosciences, and Leonardo Trasande, an associate professor at the New York University School of Medicine Department of Pediatrics. It was published in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.
Part of a series of economic analyses calculating the combined healthcare and economic costs attributable to specific EDC exposures within the European Union (EU), this study reported that endometriosis and fibroids experienced by hundreds of thousands of women accounts for roughly €1.4 billion (about $1.6 billion) annually in healthcare expenditures and lost earning potential. Previous studies in the series examined costs associated with infertility and male reproductive dysfunctions, birth defects, obesity, diabetes, cardiovascular disease, and neurobehavioral and learning disorders found that endocrine-disrupting chemical exposure may be costing the EU upwards of €157 billion ($173 billion) a year.
To assess the economic burden of EDC exposures, the scientists convened a global expert panel tasked with adapting existing environmental health cost models, based on the Institute of Medicine’s 1981 approach to assessing the contribution of environment factors in causing illness in referencing the body of established, peer-reviewed literature. The panel used the Intergovernmental Panel on Climate Change weight-of-evidence characterization to evaluate evidence for causation probability, exposure-response relationships, and reference levels and biomarker data based on studies in peer-reviewed media to represent European exposure and approximate disease burden as it occurred in 2010. Their cost-of-illness estimates drew on multiple peer-reviewed sources, and were carried out from a societal perspective — including direct costs (e.g., treatment costs) and indirect costs such as productivity loss. The study’s economic analysis included direct costs of hospital stays, physician services, and other medical costs. The researchers also calculated estimates of indirect costs such as lost worker productivity associated with these disorders.
Study co-authors report that the most robust data associating EDC exposure with female reproductive disorders exist for 1) diphenyldichloroethene-attributable fibroids, and 2) phthalate-attributable endometriosis in Europe. In both cases, the strength of epidemiological evidence was rated as low and the toxicological evidence moderate, with an assigned probability of causation of 20 percent to 39 percent. Across the EU, attributable cases were estimated to be 56,700 and 145,000 women, respectively, incurring total cumulative economic and healthcare costs potentially reaching €163 million and €1.25 billion, and the investigators suggest these public health costs be considered as the EU contemplates regulatory action on EDCs, which are a broad category of chemical compounds widely used in consumer products, electronics, and agriculture.
The Endocrine Society, the world’s oldest and largest organization of scientists devoted to hormone research and physicians who care for people with hormone-related conditions, celebrating its centennial in 2016, notes that EDCs have been associated with a diverse array of health effects, including infertility, cancer, birth defects and metabolic disease, and that the European Union is taking the lead on regulating these chemicals, through legislation such as REACH (Registration, Evaluation, Authorization and Restriction of Chemicals) and regulations on pesticides and biocides. They observe that the outcome of these policy discussions will be crucial not only for consumer and public health protection in the EU, but will also set scientific and policy precedents for other national policies and for a coordinated global approach to regulating these chemicals.
Uterine fibroids are benign tumors associated with infertility and other gynecological health problems, while endometriosis is an often painful disorder in which endometrial tissue that normally forms the lining of the uterus develops elsewhere in the body. Both conditions are common, with as many as 70 percent of women reportedly affected by at least one of the disorders.
The Endocrine Society points to research linking development of uterine fibroids and endometriosis to exposure to chemicals found in pesticides, cosmetics, toys, and food containers. Older studies suggest a byproduct of the pesticide DDT, a chemical known as DDE, can raise the risk of developing uterine fibroids, and that another group of chemicals called phthalates, which are found in plastic products and cosmetics, have been linked to a growing risk of endometriosis.
EDCs like DDT and phthalates are believed to contribute to health problems by mimicking, blocking, or otherwise interfering with the function of hormones, disrupting the signaling system the body uses to determine how cells develop and grow. This is particularly critical in unborn children, because chemical exposures during key points in their development can increase risk of health problems later in life.
“The data shows that protecting women from exposure to endocrine-disrupting chemicals could substantially reduce rates of disease and lower health care and other social costs of these conditions,” says Journal of Clinical Endocrinology & Metabolism study corresponding author and NYU Langone Medical Center associate professor of Pediatrics, Environmental Medicine & Population Health, Leonardo Trasande, MD, MPP.
“Although endometriosis and 56,700 cases of uterine fibroids these two gynecological conditions affect millions of women worldwide, we recognize that this analysis only reflects the tip of the iceberg,” Dr. Trasande notes in an Endocrine Society release. “A growing body of evidence suggests EDC exposure is linked to a broader range of female reproductive problems, including polycystic ovary syndrome, infertility and pregnancy complications. These disorders also place a significant cost burden on women, their families and society as a whole.
An accidental chemical exposure in the animal facility at Washington State University led to a new avenue of research for the lab of the study’s first author, Patricia A. Hunt. Inadvertent exposure of the Hunt lab’s mice to the estrogen mimic, bisphenol A (BPA), from damaged caging materials (polycarbonate cages and water bottles) led to realization that environmentally relevant doses of BPA cause meiotic disruption and aneuploidy in mice, and current studies are focusing on determining the reproductive effects of exposure to chemicals with estrogenic activity during different developmental time points.
Also a study co-author and a University of Washington associate professor of Pediatrics, Sheela Sathyanarayana specializes in pediatric environmental medicine and practices general pediatrics at Harborview Medical Center in Seattle. Dr. Sathyanarayana’s research interests focus on exposures to EDCs, including phthalates and bisphenol A, and their impact on reproductive development. In addition, she has given several invited talks on endocrine disruptors and their potential impact on human health. Currently, Dr. Sathyanarayana is the center director and clinical director for The Infant Development and Environment Study (TIDES), which is a multi-center cohort study of phthalate exposures in pregnancy and health outcomes in children, and she was named Outstanding New Investigator within the University of Washington Center for Ecogenetics and Environmental Health (CEEH). She also currently serves as chair for the US Environmental Protection Agency’s Children’s Health Protection Advisory Committee and serves on the National Academies of Sciences, National Research Council Committee on Endocrine-Related Low Dose Toxicity.
Paul A. Fowler of the University of Aberdeen, in the United Kingdom, and a co-author notes that since breakthrough epidemiological studies of the 1980s it has been clear that adult human health is dependent upon fetal development and fetal programming (early life programming), observing that dysfunctional changes in the fetus can be attributed to maternal cigarette smoking or environmental pollutant exposure, with an individual’s health trajectory likely to depend upon the pollutant burden carried at birth. He observes that fetal pollutant exposure has clear adverse effects on development, but little is known about levels of fetal exposure to real-life complex pollutant cocktails and developmental consequences, and that this fundamental lack of knowledge has resulted in a major impasse to developing strategies for reducing fetal pollutant burdens and predicting likely health outcomes. But while scientific data are limited and often indirect (i.e. animal models or surrogates of exposure), all studies suggest that fetal pollutant exposure affects lifelong health outcomes and, thereby, impacts on the general economy.
A paper titled “EDC-2: The Endocrine Society’s Second Scientific Statement on Endocrine-Disrupting Chemicals” (DOI: http://dx.doi.org/10.1210/er.2015-1010), co-authored by the University of Texas at Austin’s Andrea C. Gore, PhD, notes that the Society’s first Scientific Statement in 2009 provided a wake-up call to the scientific community about how environmental endocrine-disrupting chemicals (EDCs) affect health and disease.
Paper co-authors observe that five years later a substantially larger body of literature has solidified our understanding of plausible mechanisms underlying EDC actions and how exposures in animals and humans — especially during development — may lay the foundations for disease later in life. We now have much stronger knowledge about how EDCs alter gene-environment interactions via physiological, cellular, molecular, and epigenetic changes, producing effects in exposed individuals as well as their descendants.
In this second Scientific Statement, the co-authors reviewed the literature on a subset of topics for which the translational evidence is strongest: 1) obesity and diabetes, 2) female reproduction, 3) male reproduction, 4) hormone-sensitive cancers in females, 5) prostate, 6) thyroid, and 7) neurodevelopment and neuroendocrine systems. Their inclusion criteria for studies were those conducted predominantly in the past five years and deemed to be of high quality, based on appropriate negative and positive control groups or populations, adequate sample size and experimental design, and mammalian animal studies with exposure levels in a range that was relevant to humans. The investigators also focused on studies using the developmental origins of health and disease model. No report was excluded based on a positive or negative effect of the EDC exposure, and the co-authors report that the bulk of results across the board strengthen evidence of endocrine health-related actions of EDCs. They conclude that based on this more complete understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability, researchers, physicians, and other healthcare providers are better equipped to guide regulators and policymakers.
The Endocrine Society’s Scientific Statement on EDCs, EDC-2 can be found here.
The Endocrine Society’s “Introduction to Endocrine Disrupting Chemicals (EDCs): A Guide for Public Interest Organizations and Policy-makers” can be downloaded through this link.
The Endocrine Society
Journal of Clinical Endocrinology & Metabolism