Endocrine disruption of estrogen action and female reproductive tract cancers

Endocrine disrupting chemicals (EDC) are ubiquitous and persistent compounds that have the capacity to interfere with normal endocrine homeostasis. The female reproductive tract is exquisitely sensitive to the action of sex steroids and estrogens play a key role in normal reproductive function. Malignancies of the female reproductive tract are the fourth most common cancer in women with endometrial cancer accounting for most cases. Established risk factors for development of endometrial cancer include high body mass index, exposure to estrogens or synthetic compounds such as tamoxifen. Studies in cell and animal models have provided evidence that many EDC can bind estrogen receptors and highlighted early life exposure as a window of risk for adverse life-long effects on the reproductive system. In women the most robust evidence for a link between early life exposure to EDC and adverse reproductive health has come from studies on women who were exposed in utero to diethylstilbestrol (DES). Demonstration that EDC can alter expression of members of the HOX gene cluster highlights one pathway that might be vulnerable to their actions. In summary, evidence for a direct link between EDC exposure and cancers of the reproductive system is currently incomplete. It will be challenging to attribute causality to any single EDC when exposure and development of malignancy may be separated by many years and influenced by lifestyle factors such as diet (a source of phytoestrogens) and adiposity. This review considers some of the evidence to date.