Certain pesticides, industrial by-products and other compounds can interact with the same receptor molecules inside the body that estrogen can. Because estrogen is a hormone that powerfully influences cell growth, development and other processes, some researchers have wondered whether "estrogen mimics" in the environment might subtly overdose living things with excesses of hormonelike signals.

This question has prompted some very charged reactions from certain environmentalists, who see a serious health threat, and from a number of scientists who question the data on which that assessment is based. The following respondents take a fairly conservative approach; for a more cautionary reaction to this question, see "Can Environmental Estrogens Cause Breast Cancer?" by Devra Lee Davis and H. Leon Bradlow in Scientific American, Vol. 273, No. 4; October 1995.

Mary S. Wolff of the Mount Sinai Environmental Health Sciences Center in New York City replies:

"It is helpful to define what constitutes conclusive research. Sufficient evidence for human health effects of a compound requires a consensus of independent epidemiological studies and compatibility of those studies with experimental findings (that is, biological plausibility). Positive proof demands even more exact parallels with laboratory data. Consider the example of lung cancer and cigarette smoking, where there is a very strong correlation, and look how long it has taken this association to be universally accepted. And there are still some skeptics! Therefore, it may take many years to obtain 'conclusive' evidence that environmental hormone mimics cause health effects, including cancer.

"In this relatively new area of research, the existing studies find somewhat weaker associations than those between smoking and lung cancer. In addition, the question of the risks from environmental estrogen mimics is a very difficult one, because the biological, epidemiological and exposure issues involved are all extremely complex. Thankfully, many of the most powerful endocrine-acting agents (such as DDE and TCDD) have been regulated, diminishing their threat as current environmental contaminants, at least in the U.S.

"The most compelling evidence of the risks of endocrine-disruptive effects of environmental pollutants comes from animal data. Birds exposed to DDT produced thinned eggshells, leading to reproductive failure; fish in polluted rivers have been observed to undergo anomalous development. Rodents studied in controlled laboratory experiments show a range of detrimental effects. These effects include gender alteration, neurological dysfunction, neuroendocrine modification and myriad reproductive alterations, such as changes in the onset of puberty, cyclicity of females, sexual behavior, fecundity and so on. Hormones--including estrogen, androgen and progestagens--have also been linked to these responses. As estrogen mimics, many environmental contaminants should have similar potential to cause adverse health effects.

"There are indeed analogous human health effects associated with environmental exposures, although not all the data are yet 'conclusive.' Examples include shortened duration of lactation (associated with exposure to DDT); modification of puberty (TCDD); male reproductive dysfunction (DBCP, Kepone and lead); breast cancer (organochlorines); and impaired neurological development (PCBs). At present, these reports provide limited evidence for human health effects from agents that can be termed estrogen mimics or endocrine disrupters. The search has just begun, but this emerging area of research promises to contribute considerably to our knowledge and may ultimately lead to possible prevention of conditions."

William J. Waddell is a professor and chairman of the department of pharmacology and toxicology at the University of Louisville Health Sciences Center. He offers the following survey:

"Increases in cancers of the testis, breast and prostate have been noted recently, and these increases have often been attributed to a ubiquitous exposure to endocrine-modulating substances. In an effort to either prove or refute these associations, I have reviewed worldwide morbidities of (and mortalities from) certain hormonally responsive organs. I selected cancers of the breast, ovary, uterus, cervix, prostate and testis for comparison and analysis of trends in incidence and mortality. I also looked at the incidences of cryptorchidism and hypospadias, birth defects that are representative of possible effects from in utero exposure to excessive estrogens. Sperm counts and endometriosis are other possible indicators of environmental estrogen effects.

"Wide geographical and ethnic differences--sometimes orders of magnitude--exist in the incidences of breast, cervical, uterine, ovarian, prostate and testicular cancer worldwide. The incidences of breast, prostate and testicular cancer have been increasing. Cervical cancer is decreasing, and uterine and ovarian are fairly stable. The incidence of uterine cancer in the U.S. increased temporarily in the 1970s, coinciding with the use of unopposed estrogen as therapy for menopausal symptoms. There is no evident increase in uterine cancer that would correlate with the recent increase in breast cancer. Estrogens are known to inhibit the proliferation of prostatic carcinoma cells, so one would expect that environmental estrogens would actually have a protective effect against cancer of the prostate.

"An increase in both breast and prostate cancer is not consistent with an effect from an environmental estrogen. The increase in the incidences of breast and prostate cancer appear to be, at least in part and perhaps entirely, the result of increased diagnosis. The increase in the incidence of testicular cancer appears to be real, but at present there is no convincing explanation for this rise. The data are inconsistent with exposure to PCBs and DDT, because increases in testicular cancer began in cohorts before the use of PCBs and DDT. The increases in breast and prostate cancer, on the other hand, are occurring after concentrations of these organochlorine compounds declined markedly in body tissues.

"Geographical differences in sperm counts are so large that the currently available statistics do not permit a conclusion that there has been a worldwide decline in semen quality. The data on endometriosis, cryptorchidism and hypospadias are not of sufficient quality and detail to make any strong inferences regarding exposure to an environmental estrogen.

"In summary, the epidemiological data on cancers of hormonally responsive tissues, sperm counts, endometriosis, cryptorchidism and hypospadias when taken together do not provide evidence, at least at the present, for an effect of exposure to an environmental estrogen; the data are actually contradictory to the notion that exposure to environmental organochlorine compounds has had an effect on these conditions."