Diethylstilbestrol: a public health disaster

A multi-use artificial hormone, Diethylstilbestrol was controversial from its discovery, with the inventor of the drug warning of possible side effects. Its impact on users, and their children, is still felt today.

Diethylstilbestrol (DES) was one of the first artificial female hormones to be synthesised in the laboratory. During its use from 1941 until the mid-1980s it was prescribed primarily to pregnant women to prevent miscarriages and a host of other pregnancy-related conditions. It was also used to treat breast and prostate cancer, control gynaecological bleeding, stunt abnormal height in girls, as hormone-replacement therapy, and as a post-coital contraceptive. On top of all these uses it was also widely used by livestock farmers (cattle, sheep and poultry) as a growth stimulant in feed.

In 1938 a team at Oxford University made up of researchers working under Sir Edward Charles Dobbs and Robert Robertson synthesised stilbestrol, which would go on to be called diethylstilbestrol (DES). In 1941 the US Food and Drug Administration (FDA) approved its use and by 1950 the drug was being prescribed to prevent miscarriage and as a method of birth control. Dobbs opposed its use in birth control and alerted doctors to the possibly carcinogenic nature of DES.

In action

DES enters cells in the female reproductive tract, mammary glands and sections of the brain, including the hypothalamus and the pituitary gland, binding to oestrogen receptors. In combination with progestin, DES suppresses the hypothalamic-pituitary system, decreasing the secretion of gonadotropin-releasing hormone (GnRH), causing chemical castration in men.

Renowned cryptographer Alan Turing, said by some to be the inventor of modern computing, chose a year-long course of DES as an alternative to prison for a conviction related to being in a homosexual relationship in 1952. (He was famously portrayed in the 2014 film The Imitation Game.)

By 1971 the link between mothers taking DES during pregnancy and instances of clear cell adenocarcinoma in the cervix and vagina of their female children became strong enough for the FDA to tell doctors to stop recommending the drug during pregnancy. Throughout the 1970s, in both recommended use, and ‘off label’, DES was used as an emergency contraceptive, but by 1975 this practice had been disendorsed by the FDA. As the 1970s ended, DES was recommended to treat fewer conditions; finally, 1985 was the end of DES use in the treatment of prostate cancer. In that same year, DES was labelled a carcinogen by the FDA.

It’s estimated that approximately 10 million women took DES during pregnancy, exposing millions more of their children to the risks of cancer and other complications. Tens of millions more people were exposed across the world to possible side effects from the meat they ate, when DES was a feed additive.

Use in Australia

DES was prescribed for a time in Australia, with an estimated 10,000 women exposed in-utero.

References

1. Abboud, Alexis, “Diethylstilbestrol (DES) in the US”. Embryo Project Encyclopedia. March 23 2015. At: http://embryo.asu.edu/handle/10776/8305
2. Reed CE, Fenton SE. Exposure to diethylstilboestrol during sensitive life stages: a legacy of heritable health effects. Birth Defects Research C Embryo Today. 2013; 99(2): 134–146. At: https://www.ncbi.nlm.nih.gov/pubmed/23897597
3. Diethylstilbestrol. DrugBank. At https://www.drugbank.ca/drugs/DB00255
4. Schwarcz J. Mathematician Alan Turing a Great Mind of the 20th Century. McGill Office for Science and Society. At https://www.mcgill.ca/oss/article/controversial-science-history-news/mathematician-alan-turing-great-mind-20th-century
5. Diethylstilboestrol (DES). Cancer Australia. At https://canceraustralia.gov.au/node/4003