Dienogest

Dienogest

File:Dienogest.svg
Systematic (IUPAC) name
[(17β)-17-Hydroxy-3-oxoestra-4,9-dien-17-yl]acetonitrile
Clinical data
Trade names	Visanne
AHFS/Drugs.com	International Drug Names
Pregnancy category	AU: B3
Legal status	AU: S4 (Prescription only)
Routes of administration	Oral
Pharmacokinetic data
Bioavailability	90%
Protein binding	90%
Metabolism	Hepatic (CYP3A4-mediated)
Biological half-life	6-12 hours
Excretion	Renal
Identifiers
CAS Number	65928-58-7 Y
ATC code	G03DB08 (WHO) G03AB08 G03FA15 (combinations with estrogen)
PubChem	CID: 68861
IUPHAR/BPS	7654
ChemSpider	62093 N
UNII	46M3EV8HHE N
KEGG	D03799 Y
ChEBI	CHEBI:70708 N
ChEMBL	CHEMBL1201864 N
Synonyms	17-hydroxy-3-oxo-19-nor-17α-pregna-4,9-diene-21-nitrile 17α-cyanomethyl-17β-hydroxy-estra-4,9(10)-dien-3-one
Chemical data
Formula	C20H25NO2
Molecular mass	311.42 g/mol
Physical data
Density	1.2 g/cm3
Boiling point	549 °C (1,020 °F)
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Dienogest is an orally-active semisynthetic, steroidal progestogen (or progestin). 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. Dienogest given in isolation is available for the treatment of endometriosis under the trade name Visanne.

History

Dienogest was synthesised in 1979 in Jena, Germany under the leadership of Prof. Kurt Ponsold, was initially referred to as STS 557. It was found that its potency was 10 times that of levonorgestrel. The first product on the market to contain dienogest as a contraceptive pill Valette in 1995 made by Jenapharm. It has been little used outside of Germany.

Indications

Contraception

Dienogest is used primarily as a contraceptive in combination with ethinylestradiol. It is given as a tablet containing 2 mg of dienogest and 30 μg of ethinylestradiol. Dienogest is also available in a quadriphasic oral contraceptive pill combined with estradiol valerate, marketed as Natazia in the United States and Qlaira in some European countries and Russia. This formulation is also approved for the treatment of heavy menstrual bleeding.

The minimum dose required to inhibit ovulation has been found to be approximately 1 mg.

Endometriosis

Dienogest is also approved in the European Union for the treatment of endometriosis. It has been shown to be equally effective as leuprorelin, which is a second line medication against endometriosis.

Pharmacodynamics

Progestational activity

Dienogest has moderate affinity for the progesterone receptor in human uterus tissue, in vitro, about 10% that of progesterone.

Inhibition of ovulation

The minimum effective dose of oral dienogest required to inhibit ovulation is 1 mg/day. The inhibition of ovulation by dienogest occurs mainly via peripheral action as opposed to central action on gonadotrophin secretion. Oral treatment of dienogest 2 mg/day in cyclical women reduced serum progesterone levels to anovulatory levels, however serum levels of lutenising hormone and follicle-stimulating hormone are not significantly altered.

Adverse effects

Adverse effects associated with dienogest are the same as those expected of a progestogen. These include weight gain, increased blood pressure, breast tenderness and nausea. It produces no androgenic side effects and has little effect on metabolic and lipid haemostatic parameters.