NationMaster - Encyclopedia: Diethylstilbestrol

Diethylstilbestrol (DES) is a drug, a synthetic nonsteroidal estrogen that was first synthesized in 1938. In 1971 it was found to be a teratogen when given to pregnant women. The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. ... In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body 1. ... Pharmacology (in Greek: pharmacon (Ï†Î¬ÏÎ¼Î±ÎºÎ¿Î½) meaning drug, and logos (Î»ÏŒÎ³Î¿Ï‚) meaning science) is the study of how substances interact with living organisms to produce a change in function. ... Estriol. ... Teratogenesis is a medical term from the Greek, literally meaning monster making. ...

Synthesis

DES was first synthesized in early 1938 by Leon Goldberg, then a graduate student of Sir Robert Robinson at the Dyson Perrins Laboratory at the University of Oxford, based on a formulation of Wilfrid Lawson at the Courtand Institute of Biochemistry, led by Sir Edward Charles Dodds at Middlesex Hospital Medical School of the University College London of the University of London, and a report of its synthesis was published in Nature on February 5, 1938.^[1]^[2]^[3] Sir Robert Robinson (1886 - 1975). ... The Dyson Perrins Laboratory was the main centre for research into organic chemistry of Oxford University from its foundation in 1916 with an endowment from Charles Dyson Perrins, the Worcester Sauce legatee, to its retirement in 2003. ... The University of Oxford, located in the city of Oxford, England, is the oldest university in the English-speaking world. ... The Cruciform (Medical School) viewed from the college portico. ... University College London, commonly known as UCL, is one of the colleges that make up the University of London. ... The University of London is a university based primarily in London. ... First title page, November 4, 1869 Nature is one of the oldest and most reputable scientific journals, first published on 4 November 1869. ...

Clinical use

DES (in tablets up to 5 mg) was approved by the FDA on September 19, 1941 for 4 indications: gonorrheal vaginitis, atrophic vaginitis, menopausal symptoms, and postpartum lactation suppression.^[3] The United States Food and Drug Administration is the government agency responsible for regulating food, dietary supplements, drugs, cosmetics, medical devices, biologics and blood products in the United States. ... Gonorrhoea (USA spelling: gonorrhea, slang term the clap) is among the most common curable sexually transmitted diseases in the world caused by the Gram-negative bacterium called Neisseria gonorrhoeae. ... Vaginitis is an infection of the vagina usually caused by a fungus. ... Atrophic vaginitis (also known as vaginal atrophy) is an inflammation of the vagina due to thinning and shrinking tissues and decreased lubrication of the vaginal walls. ... Menopause (also known as the Change of life or climacteric) is a stage of the human female reproductive cycle that occurs as the ovaries stop producing estrogen, causing the reproductive system to gradually shut down. ... Wean redirects here: see #Weaning. ...

It was first prescribed by physicians to prevent miscarriages (in women who had had previous miscarriages) in the 1940s as an off-label use. On July 1, 1947, the FDA approved the first supplemental new drug application (by Squibb) adding prevention of miscarriage as an indication and approved 25 mg (and later 100 mg) tablets of DES for this indication, and approved applications of several other pharmaceutical companies in the second half of 1947.^[4] The recommended regimen started at 5 mg per day in the 7th and 8th week of pregnancy (from first day of last menstrual period), increasing every other week by 5 mg per day through the 14th week, then increasing every week by 5 mg per day from 25 mg per day in the 15th week to 125 mg per day in the 35th week of pregnancy.^[5] DES was originally considered effective and safe for both the pregnant woman and the developing baby. A double-blind study of pregnant women (unselected for history of miscarriage) was not published until six years after DES received FDA approval for prevention of miscarriage.^[6] Even though it found that pregnant women given DES had just as many miscarriages and premature deliveries as the control group, DES continued to be aggressively marketed and routinely prescribed (though in decreasing frequency—sales peaked in 1953 and by the late 1960s six of seven leading textbooks of obstetrics said DES was ineffective at preventing miscarriage).^[4]^[7] Miscarriage or spontaneous abortion is the natural or accidental termination of a pregnancy at a stage where the embryo or the fetus is incapable of surviving, generally defined at a gestation of prior to 20 weeks. ... Off-label use is the practice of prescribing drugs for a purpose outside the scope of the drugs approved label, most often concerning the drugs indication. ... The New Drug Application (NDA) is the vehicle through which drug sponsors formally propose that the FDA approve a new pharmaceutical for sale and marketing in the U.S. The goals of the NDA are to provide enough information to permit FDA reviewer to reach the following: Is the drug... Bristol-Myers Squibb (NYSE: BMY), colloquially referred to as BMS, is a pharmaceutical corporation, formed by a 1989 merger between pharmaceutical companies Bristol-Myers Company, founded in 1887 by William McLaren Bristol and John Ripley Myers in Clinton, NY (both were graduates of Hamilton College), and Squibb Corporation. ... A pregnant woman near the end of her term Pregnancy is the carrying of one or more embryos or fetuses by female mammals, including humans, inside their bodies. ... Double-blind describes an especially stringent way of conducting an experiment, usually on living, conscious, human subjects. ...

In the United States, an estimated 5-10 million persons were exposed to DES during 1941-1971, including women who were prescribed DES while pregnant and the female and male children born of these pregnancies.

Associated health problems

On April 15, 1971, the New England Journal of Medicine published a report by three physicians at Massachusetts General Hospital on the association of DES therapy started during the first trimester of pregnancy by mothers of 7 of 8 girls and young women ages 14 to 22 diagnosed with adenocarcinoma of the vagina.^[8] The New England Journal of Medicine (NEJM) is a peer-reviewed medical journal published by the Massachusetts Medical Society with the highest impact factor for a general medical journal. ... Massachusetts General Hospital (often abbreviated to Mass General or just MGH) is a teaching hospital of Harvard Medical School and biomedical research facility in Boston, Massachusetts. ...

In November 1971, the FDA issued a Drug Bulletin advising physicians to stop prescribing DES to pregnant women because it was linked to a rare vaginal cancer in female offspring, and on November 10, 1971 ordered that prevention of miscarriage be removed from Indications and pregancy be added to Contraindications in the physician prescribing information for DES.^[9] On February 5, 1975, the FDA ordered 25 mg and 100 mg tablets of DES withdrawn, effective February 18, 1975.^[10] DES was, however, never banned and continued to be prescribed in the U.S. and other countries well beyond 1971 (until 1978 in most European countries and as late as 1994 in some third world countries).^{[citation needed]} Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these cells to invade other tissues, either by direct growth into adjacent tissue through invasion or by implantation into distant sites by metastasis. ...

More than 30 years of research have confirmed that DES is a teratogen, an agent that can cause malformations of an embryo or fetus. However, not all exposed persons will experience the following DES-related health problems.

First generation

Second generation

Researchers are still following the health of persons exposed to DES to determine whether other health problems occur as they grow older. In medicine, carcinoma is any cancer that arises from epithelial cells. ... The vagina, (from Latin, literally sheath or scabbard ) is the tubular tract leading from the uterus to the exterior of the body in female placental mammals and marsupials, or to the cloaca in female birds, monotremes, and some reptiles. ... Schematic frontal view of female anatomy The cervix (from Latin neck) is the lower, narrow portion of the uterus where it joins with the top end of the vagina. ... Infertility is the inability to naturally conceive a child or to carry a pregnancy to full term. ...

Third generation

Current research also looks at DES Third Generation. Third Generation refers to the offspring of DES Sons and Daughters. There is not yet much information available, because the Third Generation is not old enough to fully manifest possible physiological effects of inherited DES exposure.

Third generation injuries are associated with preterm labor or deliveries resulting in premature birth and cerebral palsy, blindess or other neurological deficits or death of a child. One DES Daughter had a child who, at the age of four years, had such a severe case of cerebral palsy that the child was unable to turn himself over; the cerebral palsy was linked to the DES exposure of the mother.

Another study (J Pediatr Hematol Oncol 2003; 25:635-636.) found DES to be transgenerational, meaning that the maternal grandmother had taken DES while pregnant but the mother did not experience any health associated with the DES exposure. This was realized when a rare tumor was discovered on a 15 year old girl.

DES for canines

DES has been very successful in treating female canine incontinence stemming from poor sphincter control. It is still available from compounding pharmacies, and at the low (1mg) dose, does not have the carcinogenic properties that were so problematic in humans. It is generally administered once a day for five days and then once every 4 to 7 days as needed.

References

^ Dodds EC, Goldberg L, Lawson W, Robinson R (1938). "Estrogenic activity of certain synthetic compounds". Nature 141 (3562): 247-8.
^ Dodds EC (1957). Biochemical contributions to endocrinology; experiments in hormonal research. Stanford: Stanford University Press.
^ ^a ^b Meyers, Robert (1983). D.E.S., the bitter pill. New York: Seaview/Putnam. ISBN 0-399-31008-8.
^ ^a ^b Dutton, Diana B. (1988). Worse than the disease: pitfalls of medical progress. Cambridge: Cambridge University Press. ISBN 0-521-34023-3.
^ (1961) Physicians' desk reference to pharmaceutical specialties and biologicals, 15th ed., Oradell NJ: Medical Economics.
^ Dieckmann WJ, Davis ME, Rynkiewicz LM, Pottinger RE (1953). "Does the administration of diethylstilbestrol during pregnancy have therapeutic value?". Am J Obstet Gynecol 66 (5): 1062-81. PMID 13104505.
^ Apfel, Roberta J.; Fisher Susan M. (1984). To do no harm: DES and the dilemmas of modern medicine. New Haven: Yale University Press. ISBN 0-300-03192-0.
^ Herbst AL, Ulfelder H, Poskanzer DC (1971). "Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women". N Engl J Med 284 (15): 878-81. PMID 5549830.
^ FDA (1971). "Certain estrogens for oral or parenteral use. Drugs for human use; drug efficacy study implementation". Fed Regist 36 (217): 21537-8.
^ FDA (1975). "Certain estrogens for oral use. Notice of withdrawal of approval of new drug applications". Fed Regist 40 (25): 5384.

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