Levonorgestrel
Encyclopedia
Levonorgestrel is a second generation synthetic progestogen used as an active ingredient in some hormonal contraceptives
.
active levorotatory enantiomer
of the racemic mixture norgestrel
. It is a gonane progestin
derived from 19-nortestosterone.
Its in vitro
relative binding affinities
at human steroid hormone receptor
s are: 323% that of progesterone
at the progesterone receptor
, 58% that of testosterone
at the androgen receptor
, 17% that of aldosterone
at the mineralocorticoid receptor
, 7.5% that of cortisol
at the glucocorticoid receptor
, and <0.02% that of estradiol
at the estrogen receptor
.
If taken concommitantly with drugs that induce the CYP3A4
cytochrome liver enzyme, the levonorgestrel will be metabolized faster and have lower efficacy.(Citation?) A larger dose is required to maintain the high level of efficacy expected of a birth control medication.
and triphasic
formulations of combined oral contraceptive pills, with available monophasic doses ranging from 100-250 µg, and triphasic doses of 50 µg/75 µg/125 µg.
At very low daily dose of 30 µg, levonorgestrel is used in some progestogen only pill
formulations.
which includes estrogen, and as a levonorgestrel-only method. The levonorgestrel-only method uses levonorgestrel 1500 μg (as a single dose or as two 750 μg doses 12 hours apart) taken within 3 days of unprotected sex, with one study indicating that beginning as late as 120 hours (5 days) after intercourse could be effective. There are many brand names of levonorgestrel-only ECPs, including: Escapelle, Plan B, Levonelle, NorLevo, Postinor-2, i-pill, "Next Choice" and 72-HOURS.
.
and Jadelle
.
It decreases total and free testosterone
, androstenedione
, dehydroepiandrosterone sulfate (DHEAS), dihydrotestosterone
(DHT) and sex hormone–binding globulin (SHBG), but has no effect on sexual function or markers of androgen bioactivity.
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...
.
Chemistry
Chemically, it is a hormonallySteroid hormone
A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens...
active levorotatory enantiomer
Enantiomer
In chemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are non-superposable , much as one's left and right hands are the same except for opposite orientation. It can be clearly understood if you try to place your hands one over the other without...
of the racemic mixture 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...
. It is a gonane 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...
derived from 19-nortestosterone.
Its in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
relative binding affinities
Ligand (biochemistry)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...
at human steroid hormone receptor
Steroid hormone receptor
Steroid hormone receptors are found on the plasma membrane, in the cytosol and also in the nucleus of target cells. They are generally intracellular receptors and initiate signal transduction for steroid hormones which lead to changes in gene expression over a time period of hours to days...
s are: 323% that of progesterone
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...
at the progesterone receptor
Progesterone receptor
The progesterone receptor also known as NR3C3 , is an intracellular steroid receptor that specifically binds progesterone...
, 58% that 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...
at the androgen receptor
Androgen receptor
The androgen receptor , also known as NR3C4 , is a type of nuclear receptor that is activated by binding of either of the androgenic hormones testosterone or dihydrotestosterone in the cytoplasm and then translocating into the nucleus...
, 17% that of aldosterone
Aldosterone
Aldosterone is a hormone that increases the reabsorption of sodium ions and water and the release of potassium in the collecting ducts and distal convoluted tubule of the kidneys' functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that...
at the mineralocorticoid receptor
Mineralocorticoid receptor
The mineralocorticoid receptor , also known as the aldosterone receptor or nuclear receptor subfamily 3, group C, member 2, is a protein that in humans is encoded by the NR3C2 gene that is located on chromosome 4q31.1-31.2.MR is a receptor with high affinity for mineralocorticoids...
, 7.5% that of cortisol
Cortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...
at the glucocorticoid receptor
Glucocorticoid receptor
The glucocorticoid receptor also known as NR3C1 is the receptor to which cortisol and other glucocorticoids bind....
, and <0.02% that 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...
at 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...
.
If taken concommitantly with drugs that induce the CYP3A4
CYP3A4
Cytochrome P450 3A4 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. CYP3A4 is involved in the oxidation of the largest range of substrates of all the CYPs. As a result, CYP3A4 is present in...
cytochrome liver enzyme, the levonorgestrel will be metabolized faster and have lower efficacy.(Citation?) A larger dose is required to maintain the high level of efficacy expected of a birth control medication.
Oral contraception
At low doses, levonorgestrel is used in monophasicOral 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...
and triphasic
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...
formulations of combined oral contraceptive pills, with available monophasic doses ranging from 100-250 µg, and triphasic doses of 50 µg/75 µg/125 µg.
At very low daily dose of 30 µg, levonorgestrel is used in some progestogen only pill
formulations.
Emergency contraception
Levonorgestrel is used in emergency contraceptive pills (ECPs), both in a combined Yuzpe regimenYuzpe regimen
The Yuzpe Regimen is a method of emergency contraception using a combination of estrogen and progestogen hormones and started within 72 hours of sexual intercourse. It has been superseded by a progestogen-only hormonal regimen.-History:...
which includes estrogen, and as a levonorgestrel-only method. The levonorgestrel-only method uses levonorgestrel 1500 μg (as a single dose or as two 750 μg doses 12 hours apart) taken within 3 days of unprotected sex, with one study indicating that beginning as late as 120 hours (5 days) after intercourse could be effective. There are many brand names of levonorgestrel-only ECPs, including: Escapelle, Plan B, Levonelle, NorLevo, Postinor-2, i-pill, "Next Choice" and 72-HOURS.
Intrauterine system
Levonorgestrel is the active ingredient in the Mirena intrauterine systemIntraUterine 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...
.
Contraceptive implants
Levonorgestrel is the active ingredient in NorplantNorplant
Norplant is a form of birth control developed by the Population Council that was first approved in 1983 in Finland, where it was manufactured by Leiras Oy Pharmaceuticals...
and Jadelle
Norplant
Norplant is a form of birth control developed by the Population Council that was first approved in 1983 in Finland, where it was manufactured by Leiras Oy Pharmaceuticals...
.
Side effects
Possible side effects of levonorgestrel include nausea, vomiting, stomach pain, dizziness, breast tenderness, tiredness and weakness, headache, menstrual changes, and diarrhea.It decreases total and free 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...
, androstenedione
Androstenedione
Androstenedione is a 19-carbon steroid hormone produced in the adrenal glands and the gonads as an intermediate step in the biochemical pathway that produces the androgen testosterone and the estrogens estrone and estradiol.-Synthesis:Androstenedione is the common precursor of male and female sex...
, dehydroepiandrosterone sulfate (DHEAS), dihydrotestosterone
Dihydrotestosterone
Dihydrotestosterone is an androgen or male sex hormone. The enzyme 5α-reductase synthesises DHT in the prostate, testes, hair follicles, and adrenal glands...
(DHT) and sex hormone–binding globulin (SHBG), but has no effect on sexual function or markers of androgen bioactivity.
External links
- Levonelle manufacturer's product information from ScheringScheringSchering 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...
- Monograph for levonorgestrel - Uk Medicines Information
- U.S. National Library of Medicine: Drug Information Portal - Levonorgestrel