Hearing to pregnancy drug tragedy , often Thalidomide comes to our mind but there is one more drug to this list that is
Diethylstilbesterol(DES):
Q. What actually this drug is ?
DES is a synthetic non steroidal estrogen, that was approved in the 1940s for mainly use in post menopausal women for Hormonal Replacement therapy as well as for suppressing milk production after birth in women.
This drug was approved in the era when there were no proper regulations, any drug was approved based on whether it is showing immediate toxicity or not , no efficacy and no such proper trials.
Q. How it reached to pregnant women?
At that time there was a article published stating that the cause of miscarriage could be low levels of estrogen and more such improper claims spread, that somewhere made the doctors to prescribe this drug “off label” to pregnant women to reduce the chance of miscarriage and pre-mature birth.
Q. How this drug became a tragedy ?
Between 1966-69 Dr. Arthur Herbst, a gynecologist at Massachusetts General Hospital in Boston, encountered seven young women (aged 15 to 22) diagnosed with clear-cell adenocarcinoma (CCA).He found it very strange because this cancer usually develops in older women after menopause mainly and this cancer of vagina and cervix was appearing in teenager girls.
Dr. Herbst and his colleague, pathologist Dr. Robert Scully started looking into these cases and it is mentioned one of the mother casually said that is there any chance that this cancer developed in her daughter because of a pill that she used 20 years ago during her pregnancy , and that was DES
With this hint , Dr Herbst and his colleague started researching and did a case control study (going through past data of those patients and their mother ,retrospectively with a control group )and found the common thread , 7 out of 8 patients with cancer , their mother took DES during her pregnancy.
With this study, around 1971 it was banned by FDA for use in pregnancy and later in 2000 it was completely banned for human use and removed from market.
Although DES is now used in animals but very precise dosing such as Dogs but banned in use for cattles and other so that it doesn’t reach humans through any means.
Q. how this DES is causing cancer ?
There are various mechanism by which it it carcinogenic , mainly it is a strong binder of estrogen receptor even more than that of natural estrogen , it causes a imbalance in fetus own hormonal environment. Cells are not able to migrate to their location like glandular cells of the uterus remain stuck in vagina that is called vaginal adenosis. This abnormal tissue can become cancerous in future.
Also shown to cause epigenetic changes in DNA that can lead to cancer and various other mechanism of its effect on the fetus.
This incident of DES shows that sometimes “off label use” can be so dangerous. Pregnant women are the vulnerable population, they are usually excluded from the Clinical trials of the drug.
There should be very CAUTIOUS use of drugs during pregnancy, keeping in mind its ability to cross placenta, teratogenicity, long term effects on the mother as well as the developing baby.
A question for the readers 
:
Why the cancer developed after puberty , after teenage in the girls, why it took so long to appear , this is called Transplacental Carcinogenesis
MBH/PS