Diethylstilbestrol (DES) is an artificially created hormone first synthesized in the late 1930s. Doctors widely prescribed DES first to pregnant women to prevent miscarriages, and later as an emergency contraceptive pill and to treat breast cancer. However, in 1971, physicians showed a link between DES and vaginal cancer during puberty in the children of women who had taken DES while pregnant. Consequently, the US Food and Drug Administration (FDA) banned its use during pregnancy. In the late 2000s, several studies showed that the grandchildren of women who had consumed DES also suffered medical issues. By the early decades of the twenty-first century, roughly ten million people in the US had been exposed to DES, and three generations of individuals had suffered medical issues due to DES exposure. Researchers class DES as an endocrine disruptor, which affects the form and function of the hormone (endocrine) system.

Published in 1971, Adenocarcinoma of the Vagina: Association of Maternal Stilbestrol Therapy with Tumor Appearance in Young Women, by Arthurs L. Herbst and colleagues, was the first piece of literature connecting maternal use of the drug diethylstilbestrol (DES), also called stilbestrol, with the development of a rare and severe form of vaginal cancer in young women. Diethylstilbestrol was later classified as an endocrine disruptor, a substance that disrupts the hormonal function of the body in those exposed to it during development or later in life. After Herbst and his team established the connection between DES and the occurrence of breast cancer, cervical cancer, infertility, and reproductive abnormalities, the US federal government banned use the drug for pregnant women. The article was published in the New England Journal of Medicine.

Sindell v. Abbott Laboratories was a 1980 California case that established the doctrine of market share liability for personal injury cases. For such liability, when a drug causes personal injury and the manufacturer of the drug cannot be identified, each producer is responsible for paying the settlement in proportion to the percentage of the market they supplied. Judith Sindell and Maureen Rogers brought the case against the producers of diethylstilbestrol (DES), which their mothers had taken during pregnancy to prevent miscarriage and other complications. Sindell and Rogers alleged that their mothers' ingestions of DES during pregnancy later caused Sindell and Rogers to develop cancers at the onset of puberty, but they could not identify the specific manufacturer of the drug. The market share liability ruling in Sindell allowed millions of DES-affected individuals to seek restitution for reproductive cancers caused by prenatal exposure to DES.

Edward Charles Dodds researched the function and effects of natural and artificial hormones on the endocrine system in England during the twentieth century. Though he first worked with hormones such as insulin, Dodds focused on the effects of estrogen in the body and how to replicate those effects with artificial substances. In 1938, along with chemist Robert Robinson, Dodds synthesized the first synthetic estrogen called diethylstilbestrol. Despite the wide use of diethylstilbestrol to treat a variety of hormonal problems like miscarriages during pregnancy and menopause, Dodds argued against the use of synthetic substances in the human body due to their unknown effects. Just before Dodds's death, his hypotheses were confirmed when researchers showed that people exposed to diethylstilbestrol often developed cancer. Dodds was one of the first researchers to investigate the endocrine or hormone system in humans, and his research led to the creation of other synthetic hormones used in contraceptive pills and hormone replacements.

In 1948, Olive Watkins Smith published 'Diethylstilbestrol in the Prevention and Treatment of Complications of Pregnancy' in the American Journal of Obstetrics and Gynecology. In 632 women treated with diethylstilbestrol, Smith demonstrated that the drug stimulated the production of progesterone, a hormone that regulates the uterine condition during pregnancy. On the basis of her article, and several follow up articles authored by Smith and her husband, George Van Siclen Smith, physicians around the world began prescribing DES to women at risk for pregnancy complications like miscarriage and premature delivery. However, in 1953, researchers at found that DES did not prevent pregnancy complications. In 1970, researchers linked fetal exposure to DES to rare and severe cancers later in life. Researchers labeled DES as an endocrine disruptor, a substance that disrupts the hormone system of the body across multiple generations.

Estrogen plays a key role in the regulation of gene transcription. This is accomplished by its ability to act as a ligand and to bind to specific estrogen receptor (ER) molecules, such as ERα and ERβ, which act as nuclear transcription factors. There are three major nuclear estrogen receptor protein domains: the estrogen binding domain, the protein interaction domain, and the DNA binding domain. The domain responsible for the regulation of transcription is the DNA binding domain, which binds to DNA sequences called estrogen-responsive elements (EREs), found in enhancer regions of specific genes. By the binding of estrogen or an estrogen mimic to these enhancers, the target genes become activated and the proteins produced are involved in numerous cellular processes. With an estrogen mimic or xenoestrogen, such as diethylstilbestrol (DES), the negative regulation of certain genes during embryonic development can be devastating to the developing anatomy, especially the reproductive system.

Developmental Effects of Endocrine-Disrupting Chemicals in Wildlife and Humans, was published in 1993 in Environmental Health Perspectives. In the article, the authors present an account of two decades' worth of scientific research that describes the effects of certain pollutants on the health of wildlife, domestic animals, and humans, particularly when exposure takes place during embryonic growth. The term endocrine disruptor was coined in the article to describe the chemical pollutants that target the development and function of the endocrine system. Since its publication, Developmental Effects has increased research interest in endocrine disruption and has raised awareness among the general public, the scientific community, and government organizations about the effects that some chemicals may have on development and reproduction.

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