It was one of the big health scares of the '90s. "The Estrogen Complex," Newsweek dubbed it in 1994: "Sperm counts down, [animal] penises shriveled... It may be from chemical pollutants in water and food." "Environmental estrogens," found in pesticides and other industrial chemicals, were blamed for both reducing men's sperm counts and increasing women's risk of breast cancer. Last year's book "Our Stolen Future," which pushed that thesis, created quite a media splash.
Lawmakers responded: In a pair of 1996 laws, the Safe Drinking Water Act and the Food Quality Protection Act, Congress mandated that the Environmental Protection Agency develop screening and testing guidelines for endocrine disruptors, the chemical family that includes estrogens. But new evidence raises serious questions about the hypotheses on which these laws are based.
Signaling PathwaysEndocrine systems in humans and animals are highly regulated signaling pathways in which specific hormones, such as estrogens, are synthesized and delivered to various target tissues, where they bind hormone receptors and trigger a wide range of responses. Endogenous estrogens (those produced by the body itself) are necessary for the development of the female reproductive tract and secondary sex organs, and are also important in maintaining the integrity of the bone structure and cardiovascular systems. They may also influence brain degeneration and Alzheimer's disease.
A woman's lifetime exposure to estrogens is the most well-characterized risk factor for both breast and endometrial cancer. Moreover, both sons and daughters of women who took the potent estrogenic drug diethylstilbestrol (DES) during pregnancy exhibit high incidences of some serious health problems.
The Press's Ignominious RoleThe current scientific and regulatory focus on environmental estrogens--also called xenoestrogens--and other hormonally active chemicals was based in part on the experience with DES. Recent reports raised scientific concerns about the potential global threat of endocrine disruptors on human health. In 1992 a group from the University of Copenhagen published a paper that analyzed 61 sperm-count studies from laboratories around the world and concluded "that sperm density has declined appreciably during 1938-1990"--by more than 40%. Soon after, the British journal Lancet published an article hypothesizing that a world-wide decline in male reproductive capacity may be related to exposure to estrogens and other endocrine disruptors. At about the same time, two studies on a small number of breast cancer patients in the northeastern U.S. reported higher levels of organochlorine pollutants (PCBs or DDE) in the patients than in a control group of women not suffering from breast cancer. It was hypothesized that estrogenic pollutants may contribute to the increased incidence of breast cancer.
One of the most intriguing studies was a paper by scientists at Tulane University in New Orleans. They reported in the June 1996 issue of Science that mixtures of some weakly estrogenic chemicals were up to 1,600 times more active than the compounds alone. These reports, coupled with research showing that exposure to various endocrine-disrupting pollutants was associated with reproductive problems in wildlife--including decreased penis sizes in alligators living in a contaminated Florida lake--galvanized scientific and public concern about environmental estrogen.
But some scientists--including me--were skeptical. We pointed out that the human diet contains significant quantities of estrogenic chemicals--including phytoestrogens in fruits, vegetables and nuts, which have generally been associated with health benefits, including protection from some hormone-related cancers. Estrogenic hormones are used with great success by millions of postmenopausal women as hormone-replacement therapy, and the antiestrogenic compound tamoxifen is used as the first line of defense for the treatment of women with breast cancer. Moreover, birth-control pills and several other hormonally active drugs are used for treating prostate cancer and other diseases. The dietary intake of natural estrogenic compounds in various foods and estrogenic drugs used in pharmaceuticals far outweighs exposure to trace dietary levels of xenoestrogens.
The sperm-count issue has been hotly debated and intensively investigated since the appearance of the 1992 paper. Reports from France, Belgium and Sweden also showed declining sperm counts from donors in local clinics over a period of 20 to 25 years. But other recent studies have shown that over the same period sperm counts in California, Minnesota, New York, Washington state, Finland and Toulouse, France, were unchanged.
Last summer, Per Emil Rasmussen of Denmark's Odense University Hospital presented a scientific paper which showed that from 1993 to 1995, the average sperm count at the Odense clinic was 144 million sperm per milliliter of semen--significantly higher than the 70 million per milliliter observed in Copenhagen (which formed part of the basis for the initial scare). Other recent studies demonstrate clearly that there are remarkable regional differences in sperm counts. Harry Fisch and his colleagues at New York's Columbia-Presbyterian Medical Center reported that average sperm counts in New York, Minneapolis and Los Angeles were 131.5 million, 100.8 million and 72.7 million per milliliter, respectively. These levels remained constant from 1970 to 1994.
The causes of these regional differences are unknown and require further study. But it is unlikely that they are related to environmental estrogens and related contaminants, since levels of these compounds in humans, wildlife and foods are similar in most regions, and some have been declining.
Two recent studies also cast doubt on the hypothesis that xenoestrogens are a cause of breast cancer. A 1994 study of 150 breast cancer patients and 150 control subjects in California reported that there were no significant differences in serum PCB and DDE levels in either group. And a study that appeared last month in the British Medical Journal reported that DDE levels in
265 postmenopausal women with breast cancer and 341 control subjects were not significantly different. Genetics, diet and a woman's lifetime exposure to estrogens are the major known risk factors for breast cancer; no causal association between environmental chemicals and the disease has been demonstrated.
Formally WithdrewWhat about the Tulane study published in Science that so concerned the press? Subsequent work in several other laboratories failed to produce any evidence of the effects the study had hypothesized. In the July 25, 1997, issue of Science, the Tulane scientists formally withdrew their original paper, acknowledging that they "have not been able to replicate our initial results."
There are still claims that xenoestrogens and other environmental compounds may affect the immune system and neurodevelopment in children; these are being investigated and no conclusions have been reached yet. However, it is clear that the best science now points to the conclusion that xenoestrogens and related compounds are less harmful than had been suggested. Which raises two questions: In light of the new findings, will Congress reconsider the laws it passed last year? And will newspapers and magazines pay as much attention to scientific news that isn't alarming?
Mr. Safe is a professor of toxicology at Texas A&M University.
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