Drug Review: DES – The Scandal Continues

Diethylstilboestrol (DES), the synthetic estrogen, caused re-productive deformities and reproductive cancer among a generation of children born to millions of American women who took the drug to prevent mis-carriage in the middle of the last century.

And now, a large study following the fate of the ‘DES daughters’, as they became known, has dropped a new bombshell on the long-discredited drug. Women exposed to the drug while in the womb face two to three times the risk of breast cancer as those not exposed to hormones prenatally (Cancer Epidemiol Biomarkers Prev, 2006; 15: 1509–14).

This new disclosure is particularly unsettling as it identifies the age with the highest risk as the over 50s. Most of the DES daughters, exposed to the drug in the 1950s and 1960s, are now in their 40s or 50s.

At least 100,000 women in the UK were exposed to the drug while in the womb.

Between 1938 and 1971, up to 10 million American women took DES, believing it to be a safe and effective way to prevent miscarriage. It was only in the 1970s that studies revealed that the drug was a time bomb. The mothers themselves were at risk of developing breast cancer, while their daughters who’d been exposed to the drugs in utero were at high risk of developing a rare cancer of the cervix or womb. Even ‘DES sons’ had a risk of developing genital abnormalities and non-cancerous growths on their testes.

Although the risk of the DES daughters developing clear cell carci-noma is now undisputed, researchers suspected that exposure to DES in the womb also predisposed the women to breast cancer once they’d reached maturity. DES daughters appeared to have a higher incidence of breast cancer, but no one knew the extent of the risk.

Since the 1970s, researchers at Slone Epidemiology Center at Boston University have been attempting to work out the risk of exposure. They compared the incidence of breast cancer among women exposed to DES while in the womb with a comparable group of women who were not exposed to the hormone prenatally.

They recruited 4817 mostly white women, mostly born in the 1950s, who had been exposed to DES in utero and compared them with 2073 women born around the same time, but who had not been exposed to the drug. All of the women were sent questionnaires about their health. Any breast cancers that developed were confirmed by pathology reports. The researchers also controlled for other risk factors for breast cancer.

When the results were tallied, the researchers discovered 102 cases of breast cancer, 76 of which occurred in DES-exposed women and 26 among women not exposed. Those who’d been exposed to DES had a 91 per cent greater risk of breast cancer after age 40 as those unexposed, while women over 50 had a threefold greater risk.

Julie Palmer, a professor of epidem-iology at Boston University’s School of Public Health, who led the study, believes that the extra dose of hormone to which these women were exposed stimulated the development of more breast stem cells than usual, and that this increased number of such cells increases breast-cancer risk.

DES is not an oestrogen or even a steroidal compound. Nevertheless, in 1938, it was discovered that this chemical had all the hallmarks of an oestrogen. Because its molecules lock into the same cell receptors as does oestrogen, the body is duped into thinking that this activity has been stimulated by its own stores of natural oestrogen (Grant E. Sexual Chemistry: Understanding Our Hormones, The Pill and HRT. London: Cedar Press, 1994). It was produced by drug giant Eli Lilly and a number of smaller drug firms, although Lilly discontinued manu-facturing the drug several years ago.

The DES saga represents one of the most shameful episodes in modern medicine. Indeed, the effect of thalidomide, which produced a generation of deformed, limbless children, pales in comparison. Many mothers-to-be never even knew they were taking a drug. At the time, some medical centers, such as the University of Chicago Medical Center, carried out clinical trials of the drug on pregnant women without obtaining their consent (Mendelsohn RS. Male Practice: How Doctors Manipulate Women. Chicago, IL: Contemporary Books, 1981). In the Chicago study, women given DES were led to believe they were taking a vitamin supplement.

Furthermore, although the evidence published in 1953 clearly showed the drug to be ineffective in preventing miscarriage, doctors continued to pres-cribe the drug anyway for more than 20 years.

The DES daughters not only risk cancer of the cervix, but also deformiies of the reproductive system. Many were born with a T-shaped uter-us, and others are infertile or suffer from pregnancy complications such as premature birth or ectopic pregnancies.

Even more worrying, animal research has discovered that the drug’s effects can persist across several generations. Even the granddaughters of mice given the drug are affected.

Since 1972, the US Centers for Disease Control and Prevention (CDC) has maintained a registry of DES sons and daughters in an attempt to track down all the young people exposed to this drug of the risks. In the UK, a national registry has yet to be created.

In 1989, the Supreme Court upheld one of the most sweeping product-liability rulings ever seen in America. Numerous women have had successful lawsuits; for instance, in 1994, a jury awarded $42.3million to 11 women who sued for compensation.

States such as Michigan have relaxed their requirements for proving liability. Women who received the drug as fetuses do not have to name the manufacturers of the drug that was given their mother. Other states have imposed a statute of limitations.

Lynne McTaggart