Information about Diethylstilbestrol
Diethylstilbestrol (DES) is a drug, an orally active synthetic nonsteroidal estrogen that was first synthesized in 1938. In 1971 it was found to be a teratogen when given to pregnant women.
Unlike the orally active synthetic steroidal estrogen ethinyl estradiol (first synthesized in 1938 and patented by the German pharmaceutical company Schering), DES was first synthesized by English university research funded by the MRC who had a policy against patenting drugs discovered using public funds. Because DES was not patented, was inexpensive to synthesize from coal tar, and was produced by over 300 pharmaceutical companies, its price was kept low from the beginning by competition.
In 1941, Charles Huggins and Clarence Hodges at the University of Chicago found DES to be the first effective drug for treatment of metastatic prostate cancer.[4][5] Orchiectomy or DES or both were the standard initial treatment for symptomatic advanced prostate cancer for over forty years, until the (much more expensive) GnRH agonist leuprolide was found to have efficacy similar to DES with fewer side effects and was approved in 1985.[6]
From the 1940s until the late 1980s, DES was FDA-approved as estrogen-replacement therapy for estrogen deficiency states such as ovarian dysgenesis, premature ovarian failure, and post-oophorectomy.
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.[7] 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.[8] 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.[9] 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).[7][10]
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.
In 1960, DES was found to be more effective than androgens in the treatment of advanced breast cancer in postmenopausal women.[11] DES was the hormonal treatment of choice for advanced breast cancer in postmenopausal women for two decades, until the (much more expensive) selective estrogen receptor modulator tamoxifen was found to have efficacy similar to DES with fewer side effects and was approved at the end of 1977.[12]
In 1973, in an attempt to restrict off-label use of DES as a postcoital contraceptive (which had become prevalent at many university health services following publication of an influential study in 1971 in JAMA) to emergency situations such as rape, a FDA Drug Bulletin was sent to all U.S. physicians and pharmacists that said the FDA had approved, under restricted conditions, postcoital contraceptive use of DES.[13][14] In 1975, the FDA said it had not actually given (and never did give) approval to any manufacturer to market DES as a postcoital contraceptive, but would approve that indication for emergency situations such as rape or incest if a manufacturer provided patient labeling and special packaging as set out in a FDA final rule published in 1975.[15] To discourage off-label use of DES as a postcoital contraceptive, the FDA in 1975 removed DES 25 mg tablets from the market and ordered the labeling of lower doses (5 mg and lower) of DES still approved for other indications changed to state: "This drug product should not be used as a postcoital contraceptive" in block capital letters on the first line of the physician prescribing information package insert and in a prominent and conspicuous location of the container and carton label.[16][17] In the 1980s, off-label use of the Yuzpe regimen of certain regular combined oral contraceptive pills superseded off-label use of DES as a postcoital contraceptive.[18]
In 1978, the FDA removed postpartum lactation suppression to prevent breast engorgement from their approved indications for DES and other estrogens.[19]
In the 1990s, the only approved indications for DES were treatment of advanced prostate cancer and treatment of advanced breast cancer in postmenopausal women.
The last remaining U.S. manufacturer of DES, Eli Lilly, stopped making and marketing DES in 1997.
In November 1971, the FDA sent a FDA Drug Bulletin to all U.S. physicians advising them 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 pregnancy be added to Contraindications in the physician prescribing information for DES.[21] On February 5, 1975, the FDA ordered 25 mg and 100 mg tablets of DES withdrawn, effective February 18, 1975.[16] 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).
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.
Third generation injuries are associated with preterm labor or deliveries resulting in premature birth and cerebral palsy, blindness or other neurological deficits or death of a child.
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 problems associated with the DES exposure. This was realized when a rare tumor was discovered on a 15 year old girl.
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]Unlike the orally active synthetic steroidal estrogen ethinyl estradiol (first synthesized in 1938 and patented by the German pharmaceutical company Schering), DES was first synthesized by English university research funded by the MRC who had a policy against patenting drugs discovered using public funds. Because DES was not patented, was inexpensive to synthesize from coal tar, and was produced by over 300 pharmaceutical companies, its price was kept low from the beginning by competition.
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 to prevent breast engorgement.[3] The gonorrheal vaginitis indication was dropped when the antibiotic penicillin became available.In 1941, Charles Huggins and Clarence Hodges at the University of Chicago found DES to be the first effective drug for treatment of metastatic prostate cancer.[4][5] Orchiectomy or DES or both were the standard initial treatment for symptomatic advanced prostate cancer for over forty years, until the (much more expensive) GnRH agonist leuprolide was found to have efficacy similar to DES with fewer side effects and was approved in 1985.[6]
From the 1940s until the late 1980s, DES was FDA-approved as estrogen-replacement therapy for estrogen deficiency states such as ovarian dysgenesis, premature ovarian failure, and post-oophorectomy.
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.[7] 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.[8] 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.[9] 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).[7][10]
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.
In 1960, DES was found to be more effective than androgens in the treatment of advanced breast cancer in postmenopausal women.[11] DES was the hormonal treatment of choice for advanced breast cancer in postmenopausal women for two decades, until the (much more expensive) selective estrogen receptor modulator tamoxifen was found to have efficacy similar to DES with fewer side effects and was approved at the end of 1977.[12]
In 1973, in an attempt to restrict off-label use of DES as a postcoital contraceptive (which had become prevalent at many university health services following publication of an influential study in 1971 in JAMA) to emergency situations such as rape, a FDA Drug Bulletin was sent to all U.S. physicians and pharmacists that said the FDA had approved, under restricted conditions, postcoital contraceptive use of DES.[13][14] In 1975, the FDA said it had not actually given (and never did give) approval to any manufacturer to market DES as a postcoital contraceptive, but would approve that indication for emergency situations such as rape or incest if a manufacturer provided patient labeling and special packaging as set out in a FDA final rule published in 1975.[15] To discourage off-label use of DES as a postcoital contraceptive, the FDA in 1975 removed DES 25 mg tablets from the market and ordered the labeling of lower doses (5 mg and lower) of DES still approved for other indications changed to state: "This drug product should not be used as a postcoital contraceptive" in block capital letters on the first line of the physician prescribing information package insert and in a prominent and conspicuous location of the container and carton label.[16][17] In the 1980s, off-label use of the Yuzpe regimen of certain regular combined oral contraceptive pills superseded off-label use of DES as a postcoital contraceptive.[18]
In 1978, the FDA removed postpartum lactation suppression to prevent breast engorgement from their approved indications for DES and other estrogens.[19]
In the 1990s, the only approved indications for DES were treatment of advanced prostate cancer and treatment of advanced breast cancer in postmenopausal women.
The last remaining U.S. manufacturer of DES, Eli Lilly, stopped making and marketing DES in 1997.
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.[20]In November 1971, the FDA sent a FDA Drug Bulletin to all U.S. physicians advising them 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 pregnancy be added to Contraindications in the physician prescribing information for DES.[21] On February 5, 1975, the FDA ordered 25 mg and 100 mg tablets of DES withdrawn, effective February 18, 1975.[16] 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).
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
- Women prescribed DES while pregnant are at a modestly increased risk for breast cancer.
Second generation
- A new study shows DES daughters as having a 2.5 fold increase in breast cancer after age 40.
- Women exposed to DES before birth (in the womb), known as DES Daughters, are at an increased risk for clear cell adenocarcinoma (CCA) of the vagina and cervix, reproductive tract structural differences, pregnancy complications, infertility, and auto-immune disorders. Although DES Daughters appear to be at highest risk for clear cell cancer in their teens and early 20s, cases have been reported in DES Daughters in their 30s and 40s (Hatch, 1998).
- Men exposed to DES before birth (in the womb), known as DES Sons, are at an increased risk for non-cancerous epididymal cysts and auto-immune disorders. Diethylstilbestrol can also cause feminisation of the male foetus, as DES undergoes metabolic epoxidation, and the epoxide product has affinity towards the estrogen receptors. In some cases there are sons with only one testis or both abdominal. In 2002, a study indicated that maternal usage of DES resulted in a 20-fold increase in prevalence of hypospadias in their sons[22] although a followup study showed the risk, though present, to be much lesser. [23]
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, blindness or other neurological deficits or death of a child.
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 problems 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
1. ^ Dodds EC, Goldberg L, Lawson W, Robinson R (February 5, 1938). "Estrogenic activity of certain synthetic compounds". Nature 141 (3562): 247-8.
2. ^ Dodds EC (1957). Biochemical contributions to endocrinology; experiments in hormonal research. Stanford: Stanford University Press. OCLC 1483899.
3. ^ Meyers, Robert (1983). D.E.S., the bitter pill. New York: Seaview/Putnam. ISBN 0-399-31008-8.
4. ^ Huggins C, Hodges CV (1941). "Studies on prostatic cancer. I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate". Cancer Res 1 (4): 293-7.
5. ^ (Dec 15, 1943) "Prostate cancer yields to a drug". The New York Times: p. 29.
6. ^ The Leuprolide Study Group (1984). "Leuprolide versus diethylstilbestrol for metastatic prostate cancer". N Engl J Med 311 (20): 1281-6. PMID 6436700.
7. ^ Dutton, Diana B. (1988). Worse than the disease: pitfalls of medical progress. Cambridge: Cambridge University Press. ISBN 0-521-34023-3.
8. ^ (1961) Physicians' desk reference to pharmaceutical specialties and biologicals, 15th ed., Oradell NJ: Medical Economics.
9. ^ 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.
10. ^ 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.
11. ^ Council on Drugs (1960). "Androgens and estrogens in the treatment of disseminated mammary carcinoma: retrospective study of nine hundred forty-four patients". JAMA 172 (12): 1271-83.
12. ^ Ingle JN, Ahmann DL, Green SJ, Edmonson JH, Bisel HF, Kvols LK, Nichols WC, Creagan ET, Hahn RG, Rubin J, Frytak S (1984). "Randomized clinical trial of diethylstilbestrol versus tamoxifen in postmenopausal women with advanced breast cancer". N Engl J Med 304 (1): 16-21. PMID 7001242.
13. ^ Kuchera LK (1971). "Postcoital contraception with diethylstilbestrol". JAMA 218 (4): 562-3. PMID 5171004.
14. ^ FDA (May 1973). "Postcoital diethylstilbestrol". FDA Drug Bull.
15. ^ FDA (1975). "Diethylstilbestrol as posticoital oral contraceptive; patient labeling". Fed Regist 40 (25): 5451-5.
16. ^ FDA (1975). "Certain estrogens for oral use. Notice of withdrawal of approval of new drug applications". Fed Regist 40 (25): 5384.
17. ^ FDA (1975). "Estrogens for oral or parenteral use. Drugs for human use; drug efficacy study; amended notice". Fed Regist 40 (39): 8242.
18. ^ Hatcher, Robert A.; Stewart, Gary K., Stewart, Felicia; Guest, Felicia; Josephs, Nancy; Dale, Janet (1982). Contraceptive Technology 1982-1983. New York: Irvington Publishers, pp. 152-7. ISBN 0-829-00705-9.
19. ^ FDA (1978). "Estrogens for postpartum breast engorgement". Fed Regist 43 (206): 49564-7.
20. ^ 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.
21. ^ FDA (1971). "Certain estrogens for oral or parenteral use. Drugs for human use; drug efficacy study implementation". Fed Regist 36 (217): 21537-8.
22. ^ Klip, H.; J. Verloop et al. (March 2002). "Hypospadias in sons of women exposed to diethylstilbestrol in utero: a cohort study". The Lancet 359 (9312): 1081-1082. PMID 11943257. Retrieved on 2007-04-24.
23. ^ Brouwers, MM.; WF. Feitz et al. (March 2006). "Hypospadias: a transgenerational effect of diethylstilbestrol?". Hum. Reprod. 21 (3): 666-669. PMID 16293648. Retrieved on 2007-04-24.
2. ^ Dodds EC (1957). Biochemical contributions to endocrinology; experiments in hormonal research. Stanford: Stanford University Press. OCLC 1483899.
3. ^ Meyers, Robert (1983). D.E.S., the bitter pill. New York: Seaview/Putnam. ISBN 0-399-31008-8.
4. ^ Huggins C, Hodges CV (1941). "Studies on prostatic cancer. I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate". Cancer Res 1 (4): 293-7.
5. ^ (Dec 15, 1943) "Prostate cancer yields to a drug". The New York Times: p. 29.
6. ^ The Leuprolide Study Group (1984). "Leuprolide versus diethylstilbestrol for metastatic prostate cancer". N Engl J Med 311 (20): 1281-6. PMID 6436700.
7. ^ Dutton, Diana B. (1988). Worse than the disease: pitfalls of medical progress. Cambridge: Cambridge University Press. ISBN 0-521-34023-3.
8. ^ (1961) Physicians' desk reference to pharmaceutical specialties and biologicals, 15th ed., Oradell NJ: Medical Economics.
9. ^ 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.
10. ^ 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.
11. ^ Council on Drugs (1960). "Androgens and estrogens in the treatment of disseminated mammary carcinoma: retrospective study of nine hundred forty-four patients". JAMA 172 (12): 1271-83.
12. ^ Ingle JN, Ahmann DL, Green SJ, Edmonson JH, Bisel HF, Kvols LK, Nichols WC, Creagan ET, Hahn RG, Rubin J, Frytak S (1984). "Randomized clinical trial of diethylstilbestrol versus tamoxifen in postmenopausal women with advanced breast cancer". N Engl J Med 304 (1): 16-21. PMID 7001242.
13. ^ Kuchera LK (1971). "Postcoital contraception with diethylstilbestrol". JAMA 218 (4): 562-3. PMID 5171004.
14. ^ FDA (May 1973). "Postcoital diethylstilbestrol". FDA Drug Bull.
15. ^ FDA (1975). "Diethylstilbestrol as posticoital oral contraceptive; patient labeling". Fed Regist 40 (25): 5451-5.
16. ^ FDA (1975). "Certain estrogens for oral use. Notice of withdrawal of approval of new drug applications". Fed Regist 40 (25): 5384.
17. ^ FDA (1975). "Estrogens for oral or parenteral use. Drugs for human use; drug efficacy study; amended notice". Fed Regist 40 (39): 8242.
18. ^ Hatcher, Robert A.; Stewart, Gary K., Stewart, Felicia; Guest, Felicia; Josephs, Nancy; Dale, Janet (1982). Contraceptive Technology 1982-1983. New York: Irvington Publishers, pp. 152-7. ISBN 0-829-00705-9.
19. ^ FDA (1978). "Estrogens for postpartum breast engorgement". Fed Regist 43 (206): 49564-7.
20. ^ 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.
21. ^ FDA (1971). "Certain estrogens for oral or parenteral use. Drugs for human use; drug efficacy study implementation". Fed Regist 36 (217): 21537-8.
22. ^ Klip, H.; J. Verloop et al. (March 2002). "Hypospadias in sons of women exposed to diethylstilbestrol in utero: a cohort study". The Lancet 359 (9312): 1081-1082. PMID 11943257. Retrieved on 2007-04-24.
23. ^ Brouwers, MM.; WF. Feitz et al. (March 2006). "Hypospadias: a transgenerational effect of diethylstilbestrol?". Hum. Reprod. 21 (3): 666-669. PMID 16293648. Retrieved on 2007-04-24.
External links
- DES Action USA and DES Action Canada offer information and resources for DES-exposed persons
- DES Update from the U.S. Centers for Disease Control and Prevention
- DES Booklets from the U.S. National Institutes of Health (circa 1980)
- DES Follow-up Study longterm cohort study of DES-exposed persons (including the DES-AD Project)
- DES Cancer Network offers support for DES cancer victims and their families
- National Cancer Institutes's Cancer Information Service
- University of Chicago DES Registry of patients with CCA (clear cell adenocarcinoma) of the vagina and/or cervix.
Other Resources
Pharmacology is the study of how drugs interact with living organisms to produce a change in function.[1] If substances have medicinal properties, they are considered pharmaceuticals.
..... Click the link for more information.
..... Click the link for more information.
Estrogens (alternative spellings: oestrogens or œstrogens) are a group of steroid compounds, named for their importance in the estrous cycle, and functioning as the primary female sex hormone.
..... Click the link for more information.
..... Click the link for more information.
Teratology (from the Greek τέρᾰς (genitive τέρᾰτος), meaning monster, or marvel and
..... Click the link for more information.
..... Click the link for more information.
Robert Robinson
Born September 13, 1886
Chesterfield, England
Died January 8 1975 (aged 90)
Residence England
Nationality English
Field Chemistry
..... Click the link for more information.
Born September 13, 1886
Chesterfield, England
Died January 8 1975 (aged 90)
Residence England
Nationality English
Field Chemistry
..... Click the link for more information.
The Dyson Perrins Laboratory was the main centre for research into organic chemistry of Oxford University from its foundation in 1916 until its retirement as a laboratory in 2003.
..... Click the link for more information.
..... Click the link for more information.
University of Oxford (usually abbreviated as Oxon. for post-nominals, from "Oxoniensis"), located in the city of Oxford, England, is the oldest university in the English-speaking world.
..... Click the link for more information.
..... Click the link for more information.
Royal Free and University College Medical School (RFUCMS) is the medical school of University College London. It was formed in 1998 following a series of mergers between a number of existing medical schools: in 1987 the Middlesex Hospital Medical School (founded 1746) merged with
..... Click the link for more information.
..... Click the link for more information.
University College London, commonly known as UCL, is the oldest multi-faculty constituent college of the University of London, one of the two original founding colleges, and the first British University to be founded on a non-religious basis.
..... Click the link for more information.
..... Click the link for more information.
University of London is a university based primarily in London. It is the second-largest university in the United Kingdom (after the Open University), with 135,090 campus-based students and over 40,000 in the University of London External Programme.
..... Click the link for more information.
..... Click the link for more information.
Nature is a prominent scientific journal, first published on 4 November 1869. Although most scientific journals are now highly specialized, Nature is one of the few journals, along with other weekly journals such as Science and
..... Click the link for more information.
..... Click the link for more information.
Ethinylestradiol, also ethinyl estradiol (EE), is a synthetic derivative of estradiol. Ethinyl estradiol is orally bio-active and the estrogen in almost all modern formulations of combined oral contraceptive pills (the Pill). It is one of the most commonly used medications.
..... Click the link for more information.
..... Click the link for more information.
patent is a set of exclusive rights granted by a state to a patentee for a fixed period of time in exchange for a disclosure of an invention.
The procedure for granting patents, the requirements placed on the patentee and the extent of the exclusive rights vary widely
..... Click the link for more information.
The procedure for granting patents, the requirements placed on the patentee and the extent of the exclusive rights vary widely
..... Click the link for more information.
Schering AG was a research-centered pharmaceutical company founded in 1851 that merged with Bayer in December 2006. At that time the company employed more than 26,000 people in 140 subsidiaries all over the world. The company's headquarters are in Berlin-Wedding, Germany.
..... Click the link for more information.
..... Click the link for more information.
The Medical Research Council (MRC) is a UK organisation dedicated to "promot[ing] the balanced development of medical and related biological research in the UK".
..... Click the link for more information.
Organisation
..... Click the link for more information.
Coal tar is a brown or black liquid of high viscosity, which smells of naphthalene and aromatic hydrocarbons. Coal tar is among the by-products when coal is carbonized to make coke or gasified to make coal gas.
..... Click the link for more information.
..... Click the link for more information.
Food and Drug Administration (FDA) is an agency of the United States Department of Health and Human Services and is responsible the safety regulation of most types of foods, dietary supplements, drugs, vaccines, biological medical products, blood products, medical devices,
..... Click the link for more information.
..... Click the link for more information.
Gonorrhea
Classification & external resources
Neutrophils infected with N. gonorrheae show typical gram-negative diplococci (small red dots).
ICD-10 A54
ICD-9 098
..... Click the link for more information.
Classification & external resources
Neutrophils infected with N. gonorrheae show typical gram-negative diplococci (small red dots).
ICD-10 A54
ICD-9 098
“The clap” redirects here.
..... Click the link for more information.
Vaginitis
Classification & external resources
ICD-10 N 76.0 -N 76.1
ICD-9 616.1
DiseasesDB 14017
eMedicine .htm med/3369 med/2358 emerg/631 emerg/639
Vaginitis
..... Click the link for more information.
Classification & external resources
ICD-10 N 76.0 -N 76.1
ICD-9 616.1
DiseasesDB 14017
eMedicine .htm med/3369 med/2358 emerg/631 emerg/639
Vaginitis
..... Click the link for more information.
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. It is caused by a lack of estrogen.
..... Click the link for more information.
..... Click the link for more information.
The word menopause literally means the permanent physiological, or natural, cessation of menstrual cycles, from the Greek roots 'meno-' (month) and 'pausis' (a pause, a cessation).
..... Click the link for more information.
..... Click the link for more information.
Breastfeeding is the feeding of an infant or young child with milk from a woman's breasts. Babies have a sucking reflex that enables them to suck and milk.
With few exceptions, human breast milk is the best source of nourishment for human infants.
..... Click the link for more information.
With few exceptions, human breast milk is the best source of nourishment for human infants.
..... Click the link for more information.
antibiotic is a chemotherapeutic agent that inhibits or abolishes the growth of micro-organisms, such as bacteria, fungi, or protozoans. The term originally referred to any agent with biological activity against living organisms; however, "antibiotic" now is used to refer to
..... Click the link for more information.
..... Click the link for more information.
Penicillin (sometimes abbreviated PCN) is a group of beta-lactam antibiotics used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms.
..... Click the link for more information.
..... Click the link for more information.
Dr. Charles Brenton Huggins (September 22, 1901 – January 12, 1997) was a Canadian-born American physician and physiologist and cancer researcher at the University of Chicago specializing in prostate cancer.
..... Click the link for more information.
..... Click the link for more information.
The University of Chicago is a private university located principally in the Hyde Park neighborhood of Chicago. Founded in 1890 by the American Baptist Education Society and the oil magnate John D. Rockefeller, the University of Chicago held its first classes on October 1, 1892.
..... Click the link for more information.
..... Click the link for more information.
Prostate cancer
Classification & external resources
ICD-10 C 61.
ICD-9 185
OMIM 176807
DiseasesDB 10780
MedlinePlus 000380
eMedicine radio/574 Prostate cancer
..... Click the link for more information.
Classification & external resources
ICD-10 C 61.
ICD-9 185
OMIM 176807
DiseasesDB 10780
MedlinePlus 000380
eMedicine radio/574 Prostate cancer
..... Click the link for more information.
Castration (also referred as: gelding, neutering, orchiectomy, orchidectomy, and oophorectomy) is any action, surgical, chemical, or otherwise, by which a male loses the functions of the testes or a female loses the functions of the ovaries.
..... Click the link for more information.
..... Click the link for more information.
A gonadotropin-releasing hormone agonist (GnRH agonist) is a synthetic peptide modeled after the hypothalamic neurohormone GnRH that interacts with the gonadotropin-releasing hormone receptor to elicit its biologic response, the release of the pituitary hormones FSH and LH.
..... Click the link for more information.
..... Click the link for more information.
Leuprorelin (INN) or leuprolide acetate (USAN) is a gonadotropin-releasing hormone agonist (GnRH agonist).
..... Click the link for more information.
Mode of action
By causing constant stimulation of the pituitary GnRH receptors, it initially causes stimulation (flare), but thereafter decreases pituitary..... Click the link for more information.
Hormone replacement therapy (HRT) is a system of medical treatment for surgically menopausal, perimenopausal and postmenopausal women, based on the assumption that it may prevent discomfort and health problems caused by diminished circulating estrogen and progesterone hormones.
..... Click the link for more information.
..... Click the link for more information.
This article is copied from an article on Wikipedia.org - the free encyclopedia created and edited by online user community. The text was not checked or edited by anyone on our staff. Although the vast majority of the wikipedia encyclopedia articles provide accurate and timely information please do not assume the accuracy of any particular article. This article is distributed under the terms of GNU Free Documentation License.
Herod_Archelaus
