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The story of DES - A cautionary tale
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extracted from Women and the Crisis in Sex Hormones (Seaman and Seaman 1971)

1928 George and Olive Smith "started right in on the ovary" and worked on it for 50 years.
1938 Sir Charles Dodds synthesized DES - the first hormone product cheap to manufacture and effective taken by mouth.(In 1965 Sir Charles said "It is interesting to speculate about the difference in attitude toward new drugs thirty years ago and today. Within a few months of the first publication of the synthesis of stilbestrol,. the product was marketed throughout the world. No long term toxicity tests on animals such as dogs were done.....It is really surprising that we escaped major pharmacological disasters until a few years ago.")
1941 The Smiths conceived the idea of using stilbestrol to help pregnancy threatened by miscarriage (after observing the low hormone levels of those aborting). (George was now head of the Gynecology Dept at Harvard
1943 on Boston "study" of 632 DES treated pregnancies (no controls)  reported on to the Smiths by cooperative obstetricians. Pills were supplied by E. R. Squibb.
April 47 on New Boston study started  by the Smiths- 387 first time healthy mothers got DES, 550 did not (controls got no treatment whatsoever). Women with known illness were excluded. Mothers were not told they were part of an experiment and were told the pills were "vitamins". 
"The babies of the treated mothers gave evidence of being in a better maternal environment. The explanation appears to be that the drug stimulated better placental function and bigger and healthier babies...Although stilbestrol was expected to keep gestations normal... we did not anticipate that it could render normal gestation ‘more normal,' as it were."Am. J. of Obstetrics and Gynecology 58:994-1009 (1949) 
1948 By now the  Smiths were convinced that DES "could be" effective against threatened complications of pregnancy, including diabetes and threatened miscarriage." In addition the babies were said to be "unusually rugged; the placentas were grossly more healthy-looking". (Am. J. of Obstetrics and Gynecology Nov 1948)
1949 Dr Willard M. Allen of St Louis an authority on ovulation in rabbits was puzzled. He pointed out that in rabbits at least the addition of estrogen is very deleterious to the fetus, in the early stages it can prevent implantation, in later stages causes death of the fetus. (He was onto something - DES was later used as a "morning-after" pill.)
1950-52 Objections re lack of a placebo led to the Chicago and New Orleans studies 

New Orleans:
Almost half dropped out leaving 184 treated women, 198 controls receiving placebo. 
Results - more miscarriages and premature births with DES, bigger and healthier babies on placebo. (Am. J. of Obstetrics and Gynecology 65:592-601 (1953)) 

Chicago study: (Eli Lilly provided the pills, NIH provided the funds.) 
2162 mothers of all sorts were invited to take part in double blinded study. After dropouts 840 DES mothers, 806 controls were left. 

Results : twice as many DES mothers had miscarriages, they had more hypertension and smaller babies than mothers on placebo 

Conclusion - DES actually favours premature labour, as in rabbits. "The number of patients studied and the methods used showed that stilbestrol has no therapeutic value in pregnancy." (Am. J. of Obstetrics and Gynecology 66:1062-1081 (1953)) 

This was 15 years after Charles Dodds perfected the first oral estrogen, and 12 years after the Smiths started to treat pregnant women with it. Even worse, by 1940 DES had already been proved to be carcinogenic in mice  (Proceedings of the Society for Experimental Biology and Medicine 45:246-248 1940) and the Smiths knew it. George Smith remarked "but you can do anything to mice by giving them overdoses."

1966 A 15 yr old girl was diagnosed with clear cell carcinoma of the vagina - the first time at Massachusetts General Hospital in any woman under 25. Within 3 years 6 similar cases had turned up in the same hospital with women aged 15 to 22. These 7 cases were more than had been reported in all the world's medical literature. All had mothers who had taken DES in pregnancy. This was the first time that it had been shown that estrogen products can be cancer- promoting in humans. (Cancer 25:745 1970)
late 1960s Tentatively prescribed as a morning-after contraceptive
1970 After JAMA published a report claiming that of 1000 women who were prescribed the morning-after contraceptive in Ann Arbor, not one pregnancy resulted, Tablicaps, a NJ drug comany, merchandised DESma as "...the optimum contraceptive since it does not compromise the spontaneity of the sex act."

It was later discovered that there *were* pregnancies, some women were unable to finish the course of treatment due to vomiting, some were nauseated but kept the pills down - and still were pregnant. Those women who did not believe in abortion carried to term babies who had been exposed to several dozen higher levels of DES than had been associated with adenocarcinoma.

1971 A plea was sent out in NY State to stop prescribing DES to pregnant women, and the FDA were notified. In the 7 months it took for the FDA to act it was estimated that an additional 20,000 pregnancies were put at risk.. 

While the daughters of DES treated women were (and are) most at risk, the sons did not entirely escape. Changes in their genitalia were also found when they were looked for after such changes were first noted in *mice* (again)

1972 "Most university health services are giving the morning-after pill" (official at NIH)-

DES was proved carcinogenic in adult women as well as in foetuses, when unusual types of endometrial cancer, reminiscent of the adenocarcinomas of the vagina of DES daughters, developed in young women treated with DES for five years or longer.
may 1973 FDA mailed a drug bulletin to physicians stating that DES was effective in preventing pregnancy and was approved under restricted conditions. In September a similar press release was made. The Medical Letter (the Consumer Reports of prescription drugs) stated:" DES a nonsteroidal synthetic estrogen which has been in clinical use for many years has recently been approved as a "morning-after" contraceptive."
1974 Drug companies were becoming anxious about possible lawsuits in the future. Eli Lilly sent a letter to 230,000 US physicians and 55,000 pharmacists disclaiming postcoital contraception as a valid use for DES
1975 Belita Cowan testified at Senator Kennedy's hearings about a survey she had made of over 200 women in Ann Arbor who had taken DES as a morning after pill between 1968 and 1974. This revealed that it had been prescribed carelessly and casually:

45% had no breast or pelvic exam, 56% stated the doctor did not take a personal or family medical history, 29% had taken it at least twice within a year. 8 women got it for a friend or roommate, and only 26% were followed up to see if they were pregnant. 

57% were unaware that it did not have FDA approval and had never been proven efficacious. Many women were not told of the possibly cancerous effects on the foetus should they be already pregnant and not one woman had a pregnancy test either before or after the treatment.

DES had even been given to women for whom estrogens were contraindicated - they could not take birth control pills but were given the morning-after pill - and not told that it was estrogen. 6% were themselves DES daughters.

24% stated they did not finish the course of treatment due to being made so sick by it, and 65% said that had they been fully informed, they would not have taken it in the first place.



FDA denied approving the drug and stated that the press release etc had simply stated the conditions under which it would be marketed in the future.
1976 National Center for Disease Control presented further evidence that DES is not a reliable post coital contraceptive. Out of several hundred rape victims treated at Grady Memorial hospital, 5 became pregnant anyway - about the same proportion as among untreated women.
1977 Eli Lilly was a major supplier of DES to Tablicaps for use as post-coital contraceptive, the use it had denied 3 years earlier.


DES was used interchangeably with Premarin to treat menopause, and Premarin was sometimes used as a morning after pill.
1998 http://dailynews.yahoo.com/headlines/hl/story.html?s=v/nm/19981002/hl/des10_1.html
Friday October 2 5:40 PM EDT 

DES granddaughters may be at risk

NEW YORK, Oct 02 (Reuters) -- Like the daughters of women who took DESS (diethylstilbestrol) during pregnancy, the granddaughters of these women may also have an increased risk of reproductive tract cancers, according to researchers at the National Institute of Environmental Health Sciences (NIEHS), a division of the national Institutes of Health. 

DES, a synthetic estrogen, was used to treat women at risk for miscarriage for more than 20 years until 1971, when investigators began to find rare reproductive tract cancers in the young daughters of the treated women. 

Now, studies of mice indicate that the next generation of women, the granddaughters, may also have a higher risk for certain cancers, including cancer of the uterus.
<snip> 

"While the occurrence of reproductive tract tumors in DES lineage mice does not predict a similar outcome in DES-exposed humans, continued close surveillance of the prenatally DES-exposed (mice) and their offspring is warranted,'' the authors write.

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