Our Stolen Futurea book by Theo Colborn, Dianne Dumanoski, and John Peterson Myers


  Research on the relative impacts of phytoestrogens and synthetic hormone disruptors.  

Newbold, RR, EP Banks, B Bullock, and WN Jefferson 2001. Uterine adenocarcinoma in mice treated neonatally with genistein. Cancer Research 61: 4325-4328.

Newbold et al. report that when neonatal mice are exposed to genistein—a phytoestrogen present in soy—later in life they develop uterine cancer of the same form caused by diethylstilbestrol (DES). The levels of genistein used in these experiments are comparable to those found in infant formula based on soy. More...

Miyakoda, H, M Tabata, S Onodera and K Takeda. 1999. Passage of bisphenol A into the fetus of the pregnant rat. Journal of Health Science 45(6):318-323.

Orally administered bisphenol A (10 ppm) appears immediately in materal blood and is transferred into the fetus. The concentration of BPA in the fetus peaked within one hour after administration, reaching 11 ppb. in fetal blood.

This paper suggests that BPA passes easily through the placental barrier, bypassing protections that limit the impact of native estradiol and phytoestrogens.

Arnold, SF, MK Robinson, A Notides, LJ Guillete, Jr. and JA McLachlan. 1996. A yeast estrogen screen for examining the relative exposures of cells to natural and xenoestrogens. . Environmental Health Perspectives 104(5):544-548
The somewhat forbidding title of this article may make one of its key results less than obvious. Arnold et al. show that certain xenoestrogens (a catch-all term for synthetic contaminants like DES, DDT, etc. which interfere with estrogen signalling) are less likely to be bound by blood serum than estrogens found naturally in the body. This is important because it sheds light on why apparently "weakly" estrogenic contaminants may nonetheless have important effects. The term "weakly estrogenic" comes from comparing the tightness with which the contaminant binds with the estrogen receptor. Natural estrogens bind very tightly. Contaminants less so, sometimes less by a factor of 1000x or more. This might be taken to indicate that they represent little risk.

What this paper points out is that binding affinity is only one of a series of factors that control risk. Blood serum contains binding proteins which, in effect, reduce the amount of natural estrogen that is freely available to enter cells and interact with estrogen receptors. Arnold et al.'s work shows that these blood serum proteins remove much more of the natural estrogen than of the contaminants. As they put it: "As shown in this study, the bioavailability of xenoestrogens in serum is apparently greater than that of estradiol" (one form of natural estrogen).

Arnold, SF, BM Collins, MK Robinson, LJ Guillette, Jr and JA McLachlan. 1996. Differential Interaction of Natural and Synthetic Estrogens with Extracellular Binding Proteins in a Yeast Estrogen Screen Steroids 61(11):642-646.
Arnold et al. used the yeast estrogen screen technique to evaluate interactions between extracellular binding proteins and ovarian estrogen, phytoestrogen and xenobiotic estrogens. The experiments involved yeast cells genetically engineered to indicate estrogen receptor activity when incubated in the presence of an estrogen. They report that the activities of human estradiol and two phytoestrogen--coumestrol and genestein--are reduced in the presence of three extracellular binding proteins found in human serum. The activities of three xenobiotic estrogens--DES, kepone and p,p'-DDT were only minimally reduced.

The research team thus found that the blood proteins do provide protection from the plant estrogens they tested but do not appear to protect against the man-made estrogens that were used in the experiment. Commenting on these specific results, the team noted that "phytoestrogens bind... with a higher affinity than synthetic estrogens suggesting that humans have evolved a mechanism to protect themselves from continuous exposure to phytoestrogens. On the other hand, the relative inability of synthetic estrogens to bind indicates a potential fundamental difference in the interaction of estrogens from diverse sources with these proteins."

Toppari, J, J Larsen, P Christiansen, A Giwercman, P Grandjean, LJ Guillette Jr., B Jegou, TK Jensen, P Jouannet, N Keiding, H Leffers, JA McLachlan, O Meyer, J Muller, E Rajpert-De Meyts, T Scheike, R Sharpe, J Sumpter, and NE Skakkebaek. 1996. Male Reproductive Health and Environmental Xenoestrogens. Environmental Health Perspectives 104(Suppl 4):741-803.
This paper is the result of a one-week workshop convened at the request of the Danish Environmental Protection Agency in Copenhagen in January 1995. Toppari et al. review the literature on changes in male reproductive health, on chemicals known to have estrogenic activity and on sources of human exposure.

On phytoestrogens, they comment: "Large amounts of phytoestrogens such as isoflavones can be ingested daily by humans, especially in a vegetarian diet. Antiestrogenic action of isoflavones was demonstrated in women who consumed a soy protein-enriched diet containing 45 mg isoflavones daily for 1 month....
A study of postmenopausal women in Australia suggested an estrogenic influence by phytoestrogens on the vaginal epithelium.
Many infants are fed with soy-based milk-substitute formulas rich in phytoestrogens. There are no data available about the possible endocrine effects in children, but it is presumed that the situation would be radically different from the adult because of the negligible endogenous production of estrogens in infancy (especially in male infants). Female rats exposed neonatally to phytoestrogens show an increased incidence of premature anovulatory syndrome in adult life. This syndrome is recognized as a classical consequence of inappropriate exposure to estrogens in neonatal life. Many phytoestrogens, such as lignans and isoflavonoids, are metabolized and excreted in urine similarly to endogenous estrogens. Thus, they may not bioaccumulate in the body."


Nagel, SC, FS vom Saal, KA Thayer, MG Dhar, M Boechler and WV Welshons. 1997. Relative binding affinity-serum modified access (RBA-SMA) assay predicts in vivo bioactivity of the xenoestrogens Bisphenol A and Octylphenol. Environmental Health Perspectives 105:70-76.

A common way to gauge the power of an endocrine disruptor is to carry out experiments in vitro that reveal the strength with which the compound binds to a hormone receptor. These studies, while useful to identify endocrine disruptors whose impacts are a result of direct interaction with the receptor (not all are), can be misleading because "binding affinity" is only one parameter of many that effects a contaminant's potency.

In this paper Nagel et al. combine several different types of information to predict the potency of bisphenol A and octylphenol. Bisphenol A turns out to be more powerful than predicted simply on the basis of binding affinity alone, while octylphenol is less powerful. Studies like this are important in understanding why simplistic arguments about the quantity of phytoestrogens in the diet are misleading.

This paper presents new data on the low level effects of bisphenol A, demonstrating that fetal exposure to environmentally-relevant doses of bisphenol A (parts per billion, in the range currently consumed by people), alters reproductive development in mice. More...





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