Indecent Exposures: EDCs and Women’s Health

The evidence is stacking up against endocrine-disrupting chemicals and their link to a variety of female reproductive problems. Reducing these problems is going to take more than simply washing fresh produce and avoiding certain pre-packaged foods.

According to the recent Introduction to Endocrine Disrupting Chemicals (EDCs): A Guide For Public Interest Organizations and Policy Makers published jointly by the Endocrine Society and IPEN, almost 100% of the world’s population has detectable amounts of EDCs — phthalates (plasticizers), bisphenol A (BPA), polychlorinated biphenyls (PCBs), etc., in their bodies — chemicals that did not even exist prior to the 20th century.

“Studies on human populations show associations between the presence of certain chemicals and higher risks of certain endocrine disorders such as impaired fertility, diabetes and obesity, and cardiovascular disorders,” says Andrea C. Gore, PhD, professor at the University of Texas at Austin and lead author of the guide. “Chemicals that interfere with hormone actions — even at low doses — are particularly detrimental when exposures happen during development. This ‘developmental origin of health and disease’ hypothesis is absolutely critical to consider.”

“Studies on human populations show associations between the presence of certain chemicals and higher risks of certain endocrine disorders such as impaired fertility, diabetes and obesity, and cardiovascular disorders. Chemicals that interfere with hormone actions — even at low doses — are particularly detrimental when exposures happen during development. This ‘developmental origin of health and disease’ hypothesis is absolutely critical to consider.” — Andrea C. Gore, PhD, professor at the University of Texas, Austin

For women, EDCs can be especially tricky substances, impairing reproductive functions across the life cycle, from causing problems with development of the oocyte pool to inducing early puberty to increasing rates of miscarriage and infertility. “We know this from animal studies in the lab, from research on wildlife that have been exposed to EDCs (especially pesticides), and from population studies in humans,” Gore says. “Along with reproductive function are increases in reproductive cancers — breast, ovarian, and endometrial cancers are on the rise and are associated with EDC exposures.”

Early Menopause and EDC Exposure

In “Persistent Organic Pollutants and Early Menopause in U.S. Women,” published online in PLoS ONE, study authors led by Amber R. Cooper, MD, MSCI, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Washington University in St. Louis, Barnes-Jewish Hospital, St. Louis, Mo., sought to determine whether earlier age of menopause is also associated with EDC exposure. Although menopause timing might not seem like the gravest potential negative health impact from EDC exposure, in fact, it could have far-reaching individual and population-wide effects. Earlier menopause not only reduces a woman’s fertility but also puts her at risk for earlier cardiovascular disease and osteoporosis development. On a societal scale, decreased fecundity raises difficult questions for human reproduction.

Thus, to more fully elucidate this problem, Cooper and her research team surveyed National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2008 to evaluate the serum or urine levels of dioxins/furans, phytoestrogens, phthalates, PCBs, phenolic derivatives, organophosphate pesticides, surfactants, and polycyclic aromatic hydrocarbons (PAHs) in 31,575 U.S. menopausal women older than age 30 years with intact reproductive organs. Of the eight categories of EDCs studied, 111 individual chemicals were analyzed, 15 of which demonstrated a significant association with loss of ovarian function. Specifi cally, women with the highest levels of `-hexachlorocyclohexane; mirex; p,p’- dichlorodiphenyldichloroethylene; 1, 2, 3, 4, 6, 7, 8-heptachlorodibenzofuran; mono-(2-ethyl-5-hydroxyhexyl) and mono-(2-ethyl-5-oxohexyl) phthalate; and PCB congeners −70, −99, −105, −118, −138, −153, −156, −170, and −183 experienced menopause 1.9 to 3.8 years earlier than those with lower levels. It’s important to bear in mind, according to Cooper, that “we looked at everyday exposures across the United States, not experimental conditions. We need to be aware that these EDCs are in our everyday life, even if banned in the past, and they may be having an untoward effect on our ovaries, reproductive health, and overall well-being.” The team also found that increasing serum or urine EDCs is associated with earlier ages of menopause, not just high absolute levels. Another strength of their approach is the number of lenses through which they made their observations, first examining the highest levels of EDC exposure, then considering the dose-response relationship as both a continuous log-transformed variable and as a continuous variable based on decile of EDC level, and, finally, performing a secondary analysis of the 15 suspicious chemicals in a younger cohort of women to confirm their findings.

The team suggests several possible causes for the ovarian insufficiency, such as damage to the follicular pool happening over time, in utero exposure preventing development of adequate numbers of oocytes, and premature depletion of the follicular pool from recruitment of excess follicles. Although the causal mechanism has yet to be pinned down, Cooper says, “The bottom line is, I hope that this study increases awareness and promotes future research. It shows an association between increasing environmental exposures and earlier age at menopause, earlier than what has been linked with tobacco smoke in past studies. It does not prove cause and effect but warrants much more research.”

Cleaning Up Our Acts

“It is surprisingly difficult to determine the extent of ‘known exposures’ because most of us are exposed to various chemicals throughout our lives,” Gore says. “Most of them are not overtly toxic, but the cumulative effects of exposures to mixtures of many chemicals at low doses but often of unknown identity, is hard to quantify.” Yet given the profound biochemical disruptions they are linked to, finding some way to mitigate the effects of pervasive exposures seems imperative. “At this point, identifying and minimizing risk is the best we can do. Research is very important for trying to arrive at new therapies, so by understanding the mechanisms by which the chemicals act in our bodies, we will someday be able to do more efficient interventions,” Gore says.

“We need to be aware that these EDCs are in our everyday life, even if banned in the past, and they may be having an untoward effect on our ovaries, reproductive health, and overall well-being.” — Amber R. Cooper, MD, MSCI, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Washington University in St. Louis, and Barnes-Jewish Hospital, St. Louis, Mo.

In the meantime, as she says, “avoiding exposure in the first place is, of course, the best case scenario.” Because diet is the primary route for chemical exposure, “cleaning up” the food source is a good place to start. Exposure avoidance can mean advising patients to make simple lifestyle changes such as eating fresh rather than processed foods for obvious — and not so obvious — reasons. “Food contact materials such as cans, packaging, and plastic bottles, are not intended to leach chemicals into food and beverages, but this can happen, especially at hot temperatures (e.g., hot cars, microwaving, and heating food, etc.). Even if you’re careful not to let your plastic water bottle get hot, you don’t know whether it was transported across the country in an un–air-conditioned truck that sat out in the summer heat. Th e bottle may be nice and cool when you buy it at the supermarket, but leaching could have happened earlier,” Gore explains.

Physicians should also prompt patients to be aware of the contents of other household chemicals, such as toiletries, she says. Furthermore, “keeping our homes clean and plugging holes under the sink reduces pests and minimizes the need for spraying with pesticides. Th ere are also organic alternatives to chemical pest control.”

 

— Horvath is a freelance writer based in Baltimore, Md. She wrote
about the myths of pediatric thyroid cancer in the June issue.

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