Our Children At Risk

HORMONE DISRUPTORS: EMERGING EVIDENCE OF A FUTURE THREAT

What are Hormones?

Hormones are the natural chemical messengers of our bodies. Secreted into our bloodstream in carefully measured amounts by the endocrine glands, these chemicals then bind to special receptors in different parts of the body and thereby control and adjust many body functions. Thyroid hormone adjusts our metabolic rate, thereby affecting appetite, temperature, and even normal turnover of hair and skin. In the fetus, thyroid hormone strongly influences normal brain development. Infants born of mothers with low thyroid hormone levels almost always suffer from severe mental retardation. Estrogen, secreted primarily by the ovaries, influences the menstrual cycle, fertility, pregnancy, and crucial stages in infant development. Testosterone, secreted by the testes and the adrenal glands, influences sperm development, sexual functioning, and even behavior.

There is increasing evidence that some chemicals found in the environment may interfere with our bodies' complex and carefully regulated hormonal messenger system. The significance of this chemical interference is not yet clear. Nonetheless it is important to be aware of emerging science about hormone disruption in order to be prepared to take action.

The DES Story

A synthetic chemical that mimics natural estrogen came into widespread medical use in the 1950s. The chemical, diethylstilbesterol (DES), was widely used as a "morning-after" pill and during pregnancy to prevent miscarriage. In this manner several million women were exposed to a powerful synthetic estrogen. At that time most people did not realize that chemicals can cross the placenta and that what the mother took during pregnancy would actually enter the fetus. It wasn't until the 1970s, after nearly three decades of DES use, that the terrible side effects of the drug began to be recognized.

Girls born of women who took DES as prescribed during pregnancy were born apparently normal. Yet in their teens and twenties many of these girls developed a rare vaginal cancer; others were found to have abnormalities of the reproductive tract.^[153] In many cases these DES-daughters were found to be infertile, while those who were fertile were more likely to suffer a miscarriage or an ectopic pregnancy. Other studies have suggested immunologic and neuro-behavioral abnormalities in women exposed to DES in utero.^[154] While the effects on the sons of the exposed women have been less clear, there is evidence that they have an increased risk of undescended testicles, have small penises, and poor sperm function.^[155]

The lessons of DES are twofold. Both doctors and pregnant women are much more cautious about any drug use during pregnancy because we now know that many chemicals can cross the placenta and that the fetus is more susceptible to adverse effects from exposure than the adult. The second lesson is that synthetic chemicals can mimic natural hormones and can thereby cause severe, unpredictable effects many years, or even a generation, later.

What Chemicals May Be Involved?

Only a small number of chemicals have been conclusively shown to cause adverse effects in humans via an endocrine mechanism. These known human hormone disruptors are DES, DDT, PCBs, and dioxin.^[156] DDT is known to mimic estrogen, while its major breakdown product, DDE, interferes with androgen (testosterone) function. Polychlorinated biphenyls (PCBs) have been found to mimic estrogen and interfere with thyroid hormone. Dioxin interferes with sex hormone function via a complex and indirect route.

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Pesticides Known or Suspected to be Endocrine Disruptors

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Herbicides:
2,4,5-T*	Amitrole	Nitrofen*
2,4-D	Atrazine	Trifluralin
Alachlor	Metribuzin

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Fungicides:
Benomyl	Maneb	Vinclozolin
Fenarimol	Metiram	Zineb
Mancozeb	Tributyltin	Ziram

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Insecticides:
Aldicarb	Endosulfan	Methomyl
Aldrin*	Endrin*	Methoxychlor
Carbaryl	Fenvalerate	Mirex*
Chlordane*	Heptachlor*	Parathion*
Dicofol	Kepone*	Pentachlorophenol
Dieldrin*	Lindane	Permethrin
DDT/DDE*	Malathion	Toxaphene*

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Fumigants:
DBCP*

*Banned

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Though banned, DDT and PCBs persist in the environment, where they accumulate in the fat of living things. Dioxin has not been banned because it is primarily an unwanted by-product of combustion. Incinerators and paper bleaching processes produce most of the dioxin in our environment today.

We do not know for sure how many other chemicals may have effects on our hormones. At this time there is no series of tests that chemicals can undergo to determine if they may disrupt hormones. The EPA is working to establish such a series of tests, but the tests will not be widely used for several years. Meanwhile, individual scientists are reporting that a number of other common chemicals may have effects on hormones, particularly on estrogen. The suspect chemicals include a fairly long list of common pesticides, as well as chemicals used in plastics. Many plasticizers, including the alkyl phenols, bisphenol A, and the phthalates, all of which are in widespread use today, have been shown to interact with the estrogen receptor. Many of these chemicals have also been shown to stimulate growth of estrogen-sensitive breast cancer cells in the laboratory. Although these chemicals are all weaker, molecule for molecule, than natural estrogen, there is some cause for concern and a clear and urgent need for more information.

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Industrial Chemicals Known or Suspected to be Endocrine Disruptors

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Bisphenol A	Manganese
Butylhydroxyanisole (BHA)	Mercury
Cadmium	Polybrominated biphenyls (PBB's)
Dioxins	Polychlorinated biphenyls (PCB's)
Furans	Penta- to Nonyl-phenols
Hexachlorobenzene	Phthalates
Lead	Styrene

Polychlorinated Biphenyls (PCBs) and Children

The presence of significant levels of contamination in the Great Lakes ecosystem, and the presence of adverse health effects in animals feeding on fish from these lakes, raises the question of what human health effects may arise from eating Great Lakes fish. A study designed to answer this question was initiated in the early 1980s. A group of new mothers who ate fish from the Great Lakes either just prior to pregnancy or during pregnancy were selected. New mothers who were similar to the fish eaters in most other ways but who ate no Great Lakes fish were used as a comparison group. Maternal blood and breast milk, as well as umbilical cord blood samples, allowed the researchers to accurately measure levels of PCBs in the mothers and infants. The infants were then followed with examinations just after birth, at seven months, at four years, and most recently at eleven years of age.

As infants, the exposed children were smaller and had disproportionately small head size compared to expectations for their age and birthweight, as well as compared to the average head size of the unexposed infants.^[157] At seven months the exposed infants had less preference for novelty and had deficits in visual recognition memory. ^[158] At four years of age the exposed children remained thinner and had lower activity levels compared to the unexposed children; the effect on activity level was particularly correlated with postnatal PCB exposures via breast milk.^[159] Even at eleven years there were significant neurological differences between the exposed and unexposed children. Compared with the unexposed children, the most highly exposed children were three times as likely to have low average IQ scores and twice as likely to be at least two years behind in reading comprehension.^[160]

The results of these studies in the Great Lakes region are consistent with other studies done in the U.S. and throughout the world on children exposed to PCBs.^[161] Because PCBs are known to interfere with thyroid hormone, and because thyroid hormone is critical for normal fetal brain development, it is not surprising that this class of hormone-disrupting chemicals would be responsible for such significant health effects in exposed children. Although the health effects of PCBs are not yet as well understood as the effects of lead, they are similar chemicals in certain respects: both persist in the environment and in the body; both are easily passed from mother to fetus; and both interfere in significant ways with the normal and full development of the human brain.

Future Directions

Hormones regulate the basic functions of our lives and are particularly critical in ensuring reproductive function and proper growth and development. Interference with the normal hormone balance would be a very serious problem with implications for human reproduction, fetal development, neurobehavioral function, and cancer causation. A few chemicals are now known to interfere with hormones. Fortunately most of these are banned, though they persist in our environment. Two major questions must be answered: How many of the chemicals in our environment can affect hormone systems? And are the observed increasing trends in breast, prostate, and testicular cancer as well as the possible declining trend in sperm counts and increasing incidence of male genital abnormalities due to exposure to hormone disruptors? Much more scientific work needs to be done in this emerging area of research. Only after science has clarified some of these important questions can we say how great a threat endocrine disruptors may be for our own and future children.