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Sunday, May 8, 2016

Female Reproductive Disorders, Diseases, and Costs of Exposure to Endocrine Disrupting Chemicals

The main finding of our study is that EDC exposure may contribute to causation of fibroids and endometriosis, with associated costs in the EU of approximately €1.41 billion annually. This suggests that prevention of exposures to DDE and phthalates alone would substantially reduce disease and disability among European women while decreasing health care expenditures and other social costs.

We applied a conservative approach to the difficult task of attributing disease burden and costs of EDC exposure in the female, focusing on 2 of the most common female conditions that are also among the most straightforward in terms of assessing the role of EDCs in etiology. It is important to note that our approach has several limitations that almost certainly result in a substantial underestimation of attributing disease burden. First, our analysis focused only on adult exposures. Despite the growing body of experimental data linking EDC exposure during fetal development with reproductive aberrations in the adult (74), and aside from the iatrogenic effects on offspring of prescribing DES to pregnant women, there are no epidemiological data known to us linking fetal exposure to reproductive abnormalities in adult women. Furthermore, reliance upon animal model studies is complicated by species-specific differences in biology and sensitivity to and/or clearance of EDCs, necessitating careful assessment of animal model findings for human relevance. Fetal exposure, however, has the potential to affect reproduction by multiple routes (eg, by interfering with the development of the brain, reproductive tract, and ovary), and likely poses the greatest risk to female reproductive health. Although the 20- to 30-year gap between exposure and the recognition of reproductive impairment (or even longer in terms of diagnoses such as premature menopause) presents challenges in establishing etiologic links, ongoing birth cohort studies around the globe provide hope for updating the burden of disease and cost estimates presented here in the near future. Nevertheless, the absence of existing studies of fetal and periconceptional exposures which are important windows of exposure prevented inclusion of attribution for these exposures, and represents a major limitation of this analysis presented here, one that likely underestimates attributable disease burden.

Second, our analysis only focused on specific reproductive tract disorders. Because characterizing the effects of exposures on the developing ovary remains a formidable research challenge, the panel elected to focus on 2 major reproductive tract abnormalities, fibroids and endometriosis. Although it is highly appropriate to focus on these extremely important uterine tract health deficits, PCOS, infertility and pregnancy complications also affect a considerable number of women, have major cost implications and are increasingly linked to EDC exposures. Thus, it is important to recognize that the cost burdens calculated in this analysis do not represent all, or even most, of the reproductive costs associated with human female exposure. Exposure of the mother during gestation can lead to poorer health and function of the offspring, and also will have considerable cost implications in terms of maternal stress-induced illness and lost productivity due to child-care burdens. Indeed, given the importance of the uterine environment and of postnatal maternal care, using disease management costs alone provides an incomplete assessment of cost burden. Further, the cost analysis of the 2 gynecological disorders was limited to health care costs and lost work time directly associated with disease treatment, and did not take into account the increasingly reported associations between infertility, gynecological disorders, gravid diseases, or other later onset adulthood diseases. Important examples include a higher risk of autoimmune disorders and cancer for women with endometriosis, a higher risk of gestational diabetes and metabolic or cardiovascular disease among women with PCOS, and a greater risk of cancer among infertile women in comparison with unaffected women (18–25). Thus, even this attempt to restrict the analysis of cost burden to 2 specific reproductive tract disorders must be considered an underestimate of the exposure-associated cost burden from an overall health perspective.

Finally, this analysis does not represent the cost to female reproductive health of exposure to all EDCs. For reasons of extensive data gaps already outlined, we only quantified attributable burden for 2 classes of EDCs, DDEs and phthalates. Many other EDCs with similar modes of action likely adversely affect female health and function. The polycyclic aromatic hydrocarbons represent a large and ubiquitous class of chemicals with extensive exposure profiles. These compounds act via an extensive range of mechanisms and receptors, including the aryl hydrocarbon and estrogen receptors and have been associated with adverse outcomes in offspring (85) and have known effects on reproductive organs (87). Thus, analysis of the burden imposed by exposure only to DDEs and phthalates is a further source of potential underestimation of the health burden and cost implications of EDC exposure.

Despite the complexities of the field and the numerous caveats outlined above, the present analysis provides some evidence of the health care burden imposed by the 2 most common female reproductive tract disorders, endometriosis and fibroids. If, as we suggest, our analysis provides a conservative estimate that represents the “tip of the iceberg,” the greater than €1.41 billion per annum cost estimated for the clinical management of 2 reproductive tract diseases associated with exposure to 2 EDCs suggests that new measures to prevent EDC exposure might have considerable personal and economic benefits.


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