Progestin
Encyclopedia
Progesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
. The two most common uses of progestins are for hormonal contraception
Hormonal contraception
Hormonal 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...
(either alone or with an 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...
), and to prevent endometrial hyperplasia
Endometrial hyperplasia
Endometrial hyperplasia is a condition of excessive proliferation of the cells of the endometrium, or inner lining of the uterus.Most cases of endometrial hyperplasia result from high levels of estrogens, combined with insufficient levels of the progesterone-like hormones which ordinarily...
from unopposed estrogen in hormone replacement therapy
Hormone replacement therapy (menopause)
Hormone replacement therapy is a system of medical treatment for surgically menopausal, perimenopausal and to a lesser extent postmenopausal women...
. Progestins are also used to treat secondary amenorrhea, dysfunctional uterine bleeding
Dysfunctional uterine bleeding
Dysfunctional Uterine Bleeding is abnormal genital tract bleeding based in the uterus and found in the absence of demonstrable structural or organic pathology.usually due to hormonal disturbances....
and endometriosis
Endometriosis
Endometriosis is a gynecological medical condition in which cells from the lining of the uterus appear and flourish outside the uterine cavity, most commonly on the ovaries. The uterine cavity is lined by endometrial cells, which are under the influence of female hormones...
,
and as palliative
Palliative care
Palliative care is a specialized area of healthcare that focuses on relieving and preventing the suffering of patients...
treatment of endometrial cancer
Endometrial cancer
Endometrial cancer refers to several types of malignancies that arise from the endometrium, or lining, of the uterus. Endometrial cancers are the most common gynecologic cancers in the United States, with over 35,000 women diagnosed each year. The incidence is on a slow rise secondary to the...
, renal cell carcinoma
Renal cell carcinoma
Renal cell carcinoma is a kidney cancer that originates in the lining of the proximal convoluted tubule, the very small tubes in the kidney that filter the blood and remove waste products. RCC is the most common type of kidney cancer in adults, responsible for approximately 80% of cases...
, breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
, and prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
. High-dose megestrol acetate is used to treat anorexia
Anorexia (symptom)
Anorexia is the decreased sensation of appetite...
, cachexia
Cachexia
Cachexia or wasting syndrome is loss of weight, muscle atrophy, fatigue, weakness, and significant loss of appetite in someone who is not actively trying to lose weight...
, and AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
-related wasting
Wasting
In medicine, wasting refers to the process by which a debilitating disease causes muscle and fat tissue to "waste" away. Wasting is sometimes referred to as "acute malnutrition" because it is believed that episodes of wasting have a short duration, in contrast to stunting, which is regarded as...
.
Progesterone (or sometimes the progestin dydrogesterone
Dydrogesterone
Dydrogesterone is a progestogen hormone. The brand name is Duphaston and manufactured by Abbott .Dydrogesterone was first introduced to the market in 1961, and is currently approved in over 100 countries worldwide...
or 17α-hydroxyprogesterone caproate
17-Hydroxyprogesterone caproate
17α-Hydroxyprogesterone caproate is a synthetic steroid hormone that is similar to medroxyprogesterone acetate and megestrol acetate. It is an ester derivative of 17α-hydroxyprogesterone formed from caproic acid ....
) is used for luteal
Corpus luteum
The corpus luteum is a temporary endocrine structure in mammals, involved in production of relatively high levels of progesterone and moderate levels of estradiol and inhibin A...
support in IVF
In vitro fertilisation
In vitro fertilisation is a process by which egg cells are fertilised by sperm outside the body: in vitro. IVF is a major treatment in infertility when other methods of assisted reproductive technology have failed...
protocols, questionably for treatment of
recurrent pregnancy loss
Habitual abortion
Habitual abortion, recurrent miscarriage or recurrent pregnancy loss is the occurrence of three or more pregnancies that end in miscarriage of the fetus, usually before 20 weeks of gestation...
, and for prevention of preterm birth
Premature birth
In humans preterm birth refers to the birth of a baby of less than 37 weeks gestational age. The cause for preterm birth is in many situations elusive and unknown; many factors appear to be associated with the development of preterm birth, making the reduction of preterm birth a challenging...
in pregnant women with a history of at least one spontaneous preterm birth. They are also used in judicial chemical castration
Chemical castration
Chemical castration is the administration of medication designed to reduce libido and sexual activity, usually in the hope of preventing rapists, child molesters and other sex offenders from repeating their crimes...
of sex offenders as well as a treatment options for those suffering from paraphilia
Paraphilia
Paraphilia is a biomedical term used to describe sexual arousal to objects, situations, or individuals that are not part of normative stimulation and that may cause distress or serious problems for the paraphiliac or persons associated with him or her...
.
History
The recognition of progesterone's ability to suppress ovulationOvulation
Ovulation is the process in a female's menstrual cycle by which a mature ovarian follicle ruptures and discharges an ovum . Ovulation also occurs in the estrous cycle of other female mammals, which differs in many fundamental ways from the menstrual cycle...
during pregnancy spawned a search for a similar hormone that could bypass the problems associated with administering progesterone (low bioavailability when administered orally and local irritation and pain when continually administered parenterally) and, at the same time, serve the purpose of controlling ovulation. The many synthetic hormones that resulted are known as progestins.
The first orally active progestin, ethisterone
Ethisterone
Ethisterone is a progestogen hormone.The first orally active progestin, ethisterone , the 17α-ethynyl analog of testosterone, was synthesized in 1938 by Hans Herloff Inhoffen, Willy Logemann, Walter Hohlweg, and Arthur Serini at Schering AG in Berlin and marketed in Germany in 1939 as Proluton C...
(pregneninolone, 17α-ethynyltestosterone), the 17α-ethynyl
Ethynyl 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 testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
, 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, Willy Logemann, Walter Hohlweg and Arthur Serini 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...
, was marketed in Germany
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
in 1939 as Proluton C and 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...
in the U.S.
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
in 1945 as Pranone
A more potent orally active progestin, norethisterone
Norethisterone
Norethisterone is a molecule used in some combined oral contraceptive pills, progestogen only pills and is also available as a stand-alone drug...
(norethindrone, 19-nor-17α-ethynyltestosterone), the 19-nor
Nor-
In chemical nomenclature, nor is a prefix to name a structural analog that can be derived from a parent compound by the removal of one carbon atom along with the accompanying hydrogen. The nor-compound can be derived by demethylation or by removal of a methylenegroup, a CH group or a C atom...
analog of ethisterone, synthesized in 1951 by Carl Djerassi
Carl Djerassi
Carl Djerassi is an Austrian-American chemist, novelist, and playwright best known for his contribution to the development of the first oral contraceptive pill . Djerassi is emeritus professor of chemistry at Stanford University.He participated in the invention in 1951, together with Mexican Luis E...
, Luis Miramontes
Luis E. Miramontes
Luis Ernesto Miramontes Cárdenas , was a Mexican chemist known as the co-inventor of the progestin used in one of the first two oral contraceptives....
, and George Rosenkranz
George Rosenkranz
George Rosenkranz is a Mexican scientist in steroid research and a professional bridge player. He was born in Hungary, educated in Switzerland and lived in Mexico for 66 years...
at Syntex
Syntex
Laboratorios Syntex SA was a pharmaceutical company formed in Mexico City in 1944 by Russell Marker to manufacture therapeutic steroids from the Mexican yam....
in Mexico City
Mexico City
Mexico City is the Federal District , capital of Mexico and seat of the federal powers of the Mexican Union. It is a federal entity within Mexico which is not part of any one of the 31 Mexican states but belongs to the federation as a whole...
, was marketed by Parke-Davis
Parke-Davis
Parke-Davis is a subsidiary of the pharmaceutical company Pfizer. Although no longer an independent corporation, it was once America's oldest and largest drug maker, and played an important role in medical history.- History :...
in the U.S. in 1957 as Norlutin, and was used as the progestin in some of the first oral contraceptives (Ortho-Novum, Norinyl, etc.) in the early 1960s.
Norethynodrel
Norethynodrel
Norethynodrel was the progestin used in Enovid, the first oral contraceptive....
, an isomer
Isomer
In chemistry, isomers are compounds with the same molecular formula but different structural formulas. Isomers do not necessarily share similar properties, unless they also have the same functional groups. There are many different classes of isomers, like stereoisomers, enantiomers, geometrical...
of norethisterone, was synthesized in 1952 by Frank B. Colton
Frank B. Colton
Frank Benjamin Colton , American chemist who first synthesized norethynodrel, the progestin used in Enovid, the first oral contraceptive, at G. D. Searle & Company in Skokie, Illinois in 1952....
at Searle
G. D. Searle & Company
G.D. Searle & Company or just Searle was a company focusing on life sciences, specifically pharmaceuticals, agriculture, and animal health. It is now part of Pfizer.- History :...
in Skokie, Illinois
Skokie, Illinois
Skokie is a village in Cook County, Illinois, United States. Its name comes from a Native American word for "fire". A Chicago suburb, for many years Skokie promoted itself as "The World's Largest Village". Its population, per the 2000 census, was 63,348...
and used as the progestin in Enovid, marketed in the U.S. in 1957 and approved as the first oral contraceptive in 1960.
Examples
Some examples of progestins that have been used in hormonal contraceptives are norethynodrelNorethynodrel
Norethynodrel was the progestin used in Enovid, the first oral contraceptive....
(Enovid), norethindrone (many brand names, most notably Ortho-Novum and Ovcon) norgestimate
Norgestimate
Norgestimate is a molecule used in hormonal contraceptives.Norgestimate is a form of progesterone, which is a female hormone important for the regulation of ovulation and menstruation. Norgestimate is used with estradiol , to treat the symptoms of menopause....
(Ortho Tricyclen, Ortho-Cyclen), norgestrel
Norgestrel
Norgestrel is a progestin used in hormonal contraceptives. Norgestrel is a mixture of two stereoisomers, dextro-norgestrel and levo-norgestrel . Only levonorgestrel is biologically active...
, levonorgestrel
Levonorgestrel
Levonorgestrel is a second generation synthetic progestogen used as an active ingredient in some hormonal contraceptives.-Chemistry:...
(Alesse, Trivora-28, Plan B, Mirena
IntraUterine System
The IUD with progestogen, intrauterine system , or IntraUterine Contraceptive is a long-acting reversible hormonal contraceptive device that is placed in the uterus. An IUS has a hormone cylinder that releases a progestin called levonorgestrel...
), medroxyprogesterone
Medroxyprogesterone
Medroxyprogesterone is a pregnane that acts as a progestin. An acylated derivative, medroxyprogesterone 17-acetate is clinically used as a drug. Compared to MPA, MP is approximately 100 fold less potent as a progestin...
(Provera, Depo-Provera), desogestrel
Desogestrel
Desogestrel is a molecule used in hormonal contraceptives.-Benefits:Third-generation oral contraceptives are suitable for use in patients with diabetes or lipid disorders because they have minimal impact on blood glucose levels and the lipid profile...
, etonogestrel
Etonogestrel
Etonogestrel is a progestin used in hormonal contraceptives, most notably the subdermal implant Implanon and the contraceptive vaginal ring NuvaRing....
(Implanon
Implanon
Implanon, made by Organon International, is a single-rod long acting reversible hormonal contraceptive subdermal implant that is inserted just under the skin of a woman's upper arm. The 4 cm by 2 mm Implanon rod contains 68 milligrams of etonogestrel which is released over a three year...
), and drospirenone
Drospirenone
Drospirenone is an anti-androgenic synthetic progestin that is typically used in birth control. There have been concerns raised regarding its safety and is thus not recommended as a first line agent.- Medical uses :...
(Yasmin, Yasminelle, YAZ).
Sometimes progestins are classified by generation:
- First (estraneEstraneEstrane is a steroid derivative.Estrenes are estrane derivatives containing a double bond.-References:...
): norethindrone, norethynodrelNorethynodrelNorethynodrel was the progestin used in Enovid, the first oral contraceptive....
, norethindrone acetateNorethindrone acetateNorethisterone acetate or norethindrone acetate is a progestin used in contraception. It is the acetate ester of norethisterone....
, ethynodiol diacetateEthynodiol diacetateEthynodiol diacetate is a molecule used in hormonal contraceptives....
- Second (gonane): levonorgestrelLevonorgestrelLevonorgestrel is a second generation synthetic progestogen used as an active ingredient in some hormonal contraceptives.-Chemistry:...
, norethisteroneNorethisteroneNorethisterone is a molecule used in some combined oral contraceptive pills, progestogen only pills and is also available as a stand-alone drug...
, norgestrelNorgestrelNorgestrel is a progestin used in hormonal contraceptives. Norgestrel is a mixture of two stereoisomers, dextro-norgestrel and levo-norgestrel . Only levonorgestrel is biologically active...
- Third (gonaneGonaneGonane is a steroid nucleus. Gonane can exist as sixty-four isomers, the most common are known as 5α-gonane and 5β-gonane....
): desogestrelDesogestrelDesogestrel is a molecule used in hormonal contraceptives.-Benefits:Third-generation oral contraceptives are suitable for use in patients with diabetes or lipid disorders because they have minimal impact on blood glucose levels and the lipid profile...
, gestodeneGestodeneGestodene is a progestogen hormonal contraceptive. Products containing gestodene include:*Melodene-15, Mirelle, and Minesse which contain 15 mcg of ethinylestradiol and 60 mcg of gestodene;...
, norgestimateNorgestimateNorgestimate is a molecule used in hormonal contraceptives.Norgestimate is a form of progesterone, which is a female hormone important for the regulation of ovulation and menstruation. Norgestimate is used with estradiol , to treat the symptoms of menopause....
, drospirenoneDrospirenoneDrospirenone is an anti-androgenic synthetic progestin that is typically used in birth control. There have been concerns raised regarding its safety and is thus not recommended as a first line agent.- Medical uses :...
- Fourth: dienogestDienogestDienogest is an orally active synthetic progesterone . It is available for use as an oral contraceptive in combination with ethinylestradiol. It has antiandrogenic activity and as a result can improve androgenic symptoms. It is a non-ethinylated progestin which is structurally related to testosterone...
, drospirenoneDrospirenoneDrospirenone is an anti-androgenic synthetic progestin that is typically used in birth control. There have been concerns raised regarding its safety and is thus not recommended as a first line agent.- Medical uses :...
, nestorone, nomegestrol acetate and trimegestoneTrimegestoneTrimegestone is a progestogen.It has been described as fourth generation....
Tanaproget is a non-steroidal progestin.
Methods of progestin-based contraception
It has been found that the most effective method of hormonal contraception is with a combination of estrogenEstrogen
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...
and progestin. This can be done in a monophasic, biphasic, or triphasic manner. In the monophasic method, both an estrogen and a progestin are administered for 20 or 21 days and stopped for a 7- or 8-day period that includes the 5-day menstrual period. Sometimes, a 28-day regimen that includes 6 or 7 inert tablets is used. Newer biphasic and triphasic methods are now used to more closely simulate the normal menstrual cycle. Yet another method is to administer a small dose of progestin only (no estrogen) in order to decrease certain risks associated with administering estrogen, but a major side-effect is irregular bleeding usually observed during the first 18 months of such therapy.
Alternatively, it can be delivered by intra-muscular injection every several months.