Ethinylestradiol
Encyclopedia
Ethynylestradiol also ethynyl estradiol (EE), is a derivative
of estradiol
. Ethynyl estradiol is an orally bio-active estrogen
used in almost all modern formulations
of combined oral contraceptive pills. It is one of the most commonly used medication
s.
The same contraindication
s and precautions apply for EE as with other estrogen medications.
Estinyl was a preparation of EE alone that was used for the management of menopausal symptoms and female hypogonadism
.
EE is released into the environment as a xenoestrogen
from the urine
and feces
of people who take it as a medication.
analog of estradiol
, was synthesized
in 1938 by Hans Herloff Inhoffen and Walter Hohlweg at Schering AG
in Berlin
.
Ethinyl estradiol was approved by the FDA
in the U.S.
on June 25, 1943 and marketed by Schering
as Estinyl.
The FDA withdrew approval of Estinyl effective June 4, 2004 at the request of Schering, who had discontinued marketing Estinyl.
. Substitution at C17 of the estrane steroid with an ethinyl group proved to provide an estrogen that is much more resistant to degradation and paved the way for the development of oral contraceptives.
EE is absorbed in the small intestine and reaches a serum peak about 2 hours later. It undergoes extensive metabolism in the liver involving the cytochrome P450 3A4 isoenzyme. EE and its metabolites are excreted with the bile. Due to the effect of enterohepatic circulation
a second peak is seen several hours later. Individually, wide variations exist in the overall absorption process, and can be further modified by drugs (i.e. antibiotic
s) that affect the enterohepatic circulation or liver enzymes. In circulation EE is almost fully bound to plasma albumin
. It is metabolized by hydroxylation
of the aromatic ring and excreted in both feces and urine, in part as glucuronide
and sulfate
conjugate.
EE is hormonally effective by activating the estrogen receptor
and thus is an estrogen. It finds its most common use in the estrogen-progestin
combination preparations of oral contraceptives. Over time, formulations have decreased the EE dose from as high as 100 μg to as low as 10 μg in LoLoestrin Fe.
and sodium amide
.
Derivative (chemistry)
In chemistry, a derivative is a compound that is derived from a similar compound by some chemical or physical process. In the past it was also used to mean a compound that can be imagined to arise from another compound, if one atom is replaced with another atom or group of atoms, but modern...
of estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
. Ethynyl estradiol is an orally bio-active estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
used in almost all modern formulations
Oral contraceptive formulations
Oral contraceptives come in a variety of formulations. The main division is between combined oral contraceptive pills, containing both estrogen and synthetic progestogens , and progestogen only pills...
of combined oral contraceptive pills. It is one of the most commonly used medication
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
s.
The same contraindication
Contraindication
In medicine, a contraindication is a condition or factor that serves as a reason to withhold a certain medical treatment.Some contraindications are absolute, meaning that there are no reasonable circumstances for undertaking a course of action...
s and precautions apply for EE as with other estrogen medications.
Estinyl was a preparation of EE alone that was used for the management of menopausal symptoms and female hypogonadism
Hypogonadism
Hypogonadism is a medical term for decreased functional activity of the gonads. Low testosterone is caused by a decline or deficiency in gonadal production of testosterone in males...
.
EE is released into the environment as a xenoestrogen
Xenoestrogen
Xenoestrogens are a type of xenohormone that imitates estrogen. They are widely used industrial compounds such as PCB, BPA and Phthalates, that have estrogenic effects on a living organism even though they differ chemically from the naturally occurring estrogenic substances internally produced by...
from the urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
and feces
Feces
Feces, faeces, or fæces is a waste product from an animal's digestive tract expelled through the anus or cloaca during defecation.-Etymology:...
of people who take it as a medication.
History
The first orally active semisynthetic steroidal estrogen, ethinylestradiol (17α-ethynylestradiol), the 17α-ethynylEthynyl radical
The ethynyl radical, with chemical formula C2H, is an abundant interstellar polyatomic molecule that does not occur naturally on Earth. It was first observed by electron spin resonance isolated in a solid argon matrix at liquid helium temperatures in 1963 by Cochran and coworkers at the Johns...
analog of estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
, was synthesized
Chemical synthesis
In chemistry, chemical synthesis is purposeful execution of chemical reactions to get a product, or several products. This happens by physical and chemical manipulations usually involving one or more reactions...
in 1938 by Hans Herloff Inhoffen and Walter Hohlweg at Schering AG
Schering
Schering AG was a research-centered German pharmaceutical company. It was founded in 1851 by Ernst Christian Friedrich Schering and merged with Bayer's pharma sector in December 2006. The company's headquarters was in Berlin-Wedding, Germany...
in Berlin
Berlin
Berlin is the capital city of Germany and is one of the 16 states of Germany. With a population of 3.45 million people, Berlin is Germany's largest city. It is the second most populous city proper and the seventh most populous urban area in the European Union...
.
Ethinyl estradiol was approved by the FDA
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
in the U.S.
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
on June 25, 1943 and marketed by Schering
Schering-Plough
Schering-Plough Corporation was a United States-based pharmaceutical company. It was founded in 1851 by Ernst Christian Friedrich Schering as Schering AG in Germany. In 1971, the Schering Corporation merged with Plough to form Schering-Plough. On November 4, 2009 Merck & Co...
as Estinyl.
The FDA withdrew approval of Estinyl effective June 4, 2004 at the request of Schering, who had discontinued marketing Estinyl.
Pharmacology
While estradiol is readily absorbed when taken orally, it is also quickly inactivated by the liverLiver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
. Substitution at C17 of the estrane steroid with an ethinyl group proved to provide an estrogen that is much more resistant to degradation and paved the way for the development of oral contraceptives.
EE is absorbed in the small intestine and reaches a serum peak about 2 hours later. It undergoes extensive metabolism in the liver involving the cytochrome P450 3A4 isoenzyme. EE and its metabolites are excreted with the bile. Due to the effect of enterohepatic circulation
Enterohepatic circulation
Enterohepatic circulation refers to the circulation of biliary acids from the liver, where they are produced and secreted in the bile, to the small intestine, where it aids in digestion of fats and other substances, back to the liver....
a second peak is seen several hours later. Individually, wide variations exist in the overall absorption process, and can be further modified by drugs (i.e. antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
s) that affect the enterohepatic circulation or liver enzymes. In circulation EE is almost fully bound to plasma albumin
Human serum albumin
Human serum albumin is the most abundant protein in human blood plasma. It is produced in the liver. Albumin constitutes about half of the blood serum protein...
. It is metabolized by hydroxylation
Hydroxylation
Hydroxylation is a chemical process that introduces a hydroxyl group into an organic compound. In biochemistry, hydroxylation reactions are often facilitated by enzymes called hydroxylases. Hydroxylation is the first step in the oxidative degradation of organic compounds in air...
of the aromatic ring and excreted in both feces and urine, in part as glucuronide
Glucuronide
A glucuronide, also known as glucuronoside, is any substance produced by linking glucuronic acid to another substance via a glycosidic bond...
and sulfate
Sulfate
In inorganic chemistry, a sulfate is a salt of sulfuric acid.-Chemical properties:...
conjugate.
EE is hormonally effective by activating the estrogen receptor
Estrogen receptor
Estrogen receptor refers to a group of receptors that are activated by the hormone 17β-estradiol . Two types of estrogen receptor exist: ER, which is a member of the nuclear hormone family of intracellular receptors, and the estrogen G protein-coupled receptor GPR30 , which is a G protein-coupled...
and thus is an estrogen. It finds its most common use in the estrogen-progestin
Progestin
A progestin is a synthetic progestogen that has progestinic effects similar to progesterone. The two most common uses of progestins are for hormonal contraception , and to prevent endometrial hyperplasia from unopposed estrogen in hormone replacement therapy...
combination preparations of oral contraceptives. Over time, formulations have decreased the EE dose from as high as 100 μg to as low as 10 μg in LoLoestrin Fe.
Dosing
Depends on needs and age, see Consumer Information for more information.Chemistry
Ethinylestradiol is prepared from estron in one step by ethinylation with ethine, sodiumSodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
and sodium amide
Sodium amide
Sodium amide, commonly called sodamide, is the chemical compound with the formula NaNH2. This solid, which is dangerously reactive toward water, is white when pure, but commercial samples are typically gray due to the presence of small quantities of metallic iron from the manufacturing process...
.
See also
- Hormonal contraceptionHormonal contraceptionHormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The original hormonal method—the combined oral contraceptive...
- Oral contraceptive formulationsOral contraceptive formulationsOral contraceptives come in a variety of formulations. The main division is between combined oral contraceptive pills, containing both estrogen and synthetic progestogens , and progestogen only pills...
- DiethylstilbestrolDiethylstilbestrolDiethylstilbestrol is a synthetic nonsteroidal estrogen that was first synthesized in 1938. Human exposure to DES occurred through diverse sources, such as dietary ingestion from supplemented cattle feed and medical treatment for certain conditions, including breast and prostate cancers...
- Esterified Estrogens
- EstradiolEstradiolEstradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
- EstroneEstroneEstrone is an estrogenic hormone secreted by the ovary as well as adipose tissue.Estrone is one of several natural estrogens, which also include estriol and estradiol...
- EstropipateEstropipateEstropipate is a form of estrogen sold under the brand names Ogen and Ortho-Est. It is a salt of estrone sulfate and piperazine.-Uses:Estropipate is used to:* Alleviate symptoms of menopause as hormone replacement therapy...
- Antineoplastic
- Osteoporosis prophylactic
- Ovarian hormone therapy
- Systemic Estrogen
- Birth ControlBirth controlBirth control is an umbrella term for several techniques and methods used to prevent fertilization or to interrupt pregnancy at various stages. Birth control techniques and methods include contraception , contragestion and abortion...
External links
- http://www.drugs.com/sfx/ethinyl-estradiol-side-effects.html
- http://www.drugs.com/cons/ethinyl-estradiol.html