Dienogest

Dienogest
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
  • AU: Prescription Only (S4)
Oral
Pharmacokinetic data
Bioavailability 90%[1]
Protein binding 90%[2]
Metabolism Hepatic (CYP3A4-mediated)[3]
Half-life 6-12 hours[4]
Excretion Renal
Identifiers
65928-58-7 Yes
G03DB08
G03AB08 G03FA15 (combinations with estrogen)
PubChem CID 68861
ChemSpider 62093 
UNII 46M3EV8HHE 
KEGG D03799 Yes
ChEBI CHEBI:70708 
ChEMBL CHEMBL1201864 
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
311.42 g/mol[1]
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).[5] 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.[1][6] It is a non-ethinylated progestin which is structurally related to testosterone.[3] 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.[7][8] It was found that its potency was 10 times that of levonorgestrel.[9] The first product on the market to contain dienogest as a contraceptive pill Valette in 1995 made by Jenapharm.[10] It has been little used outside of Germany.[11]

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.[12] 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.[13]

Endometriosis

Dienogest is also approved in the European Union for the treatment of endometriosis.[14][15] It has been shown to be equally effective as leuprorelin,[16] 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.[17]

Inhibition of ovulation

The minimum effective dose of oral dienogest required to inhibit ovulation is 1 mg/day.[18] The inhibition of ovulation by dienogest occurs mainly via peripheral action as opposed to central action on gonadotrophin secretion.[1] 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.[18]

Adverse effects

Adverse effects associated with dienogest are the same as those expected of a progestogen.[1] These include weight gain, increased blood pressure, breast tenderness and nausea.[19] It produces no androgenic side effects and has little effect on metabolic and lipid haemostatic parameters.[20]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 Foster RH, Wilde MI (1998). "Dienogest". Drugs 56 (5): 825–33; discussion 834–5. doi:10.2165/00003495-199856050-00007. PMID 9829156.
  2. ↑ de Lignieres B, Dennerstein L, Backstrom T (1995). "Influence of route of administration on progesterone metabolism". Maturitas 21 (3): 251–7. doi:10.1016/0378-5122(94)00882-8. PMID 7616875.
  3. ↑ 3.0 3.1 Stanczyk FZ (2003). "All progestins are not created equal". Steroids 68 (10–13): 879–90. doi:10.1016/j.steroids.2003.08.003. PMID 14667980.
  4. ↑ Sitruk-Ware R (2004). "Pharmacological profile of progestins". Maturitas 47 (4): 277–83. doi:10.1016/j.maturitas.2004.01.001. PMID 15063480.
  5. ↑ Nakamura M, Katsuki Y, Shibutani Y, Oikawa T (1999). "Dienogest, a synthetic steroid, suppresses both embryonic and tumor-cell-induced angiogenesis". European Journal of Pharmacology 386 (1): 33–40. doi:10.1016/S0014-2999(99)00765-7. PMID 10611461.
  6. ↑ Raudrant D, Rabe T (2003). "Progestogens with antiandrogenic properties". Drugs 63 (5): 463–92. doi:10.2165/00003495-200363050-00003. PMID 12600226.
  7. ↑ Menzenbach B, Hübner M, K. Ponsold (1984). "Untersuchungen zur Bromierung/Dehydrobromierung von 17-Cyanmethyl-17-hydroxy-östr-5(10)-en-3-on". Journal für Praktische Chemie 326 (6): 893–898. doi:10.1002/prac.19843260606.
  8. ↑ Kaufmann G, Dautzenberg H, Henkel H et al. (August 1999). "Nitrile hydratase from Rhodococcus erythropolis: metabolization of steroidal compounds with a nitrile group". Steroids 64 (8): 535–40. doi:10.1016/S0039-128X(99)00028-8. PMID 10493599.
  9. ↑ Oettel M, Kurischko A (1980). "STS 557, a new orally active progestin with antiprogestational and contragestational properties in rabbits". Contraception 21 (1): 61–9. doi:10.1016/0010-7824(80)90140-7. PMID 7357870.
  10. ↑ http://www.jenapharm.de/unternehmen/ueber-uns/geschichte/1965-1995/
  11. ↑ Kuhl H (1998). "Dienogest. A Viewpoint by Herbert Kuhl". Drugs 56 (5): 834. doi:10.2165/00003495-199856050-00008.
  12. ↑ Wiegratz I, Mittmann K, Dietrich H, Zimmermann T, Kuhl H (2006). "Fertility after discontinuation of treatment with an oral contraceptive containing 30 microg of ethinyl estradiol and 2 mg of dienogest". Fertil. Steril. 85 (6): 1812–9. doi:10.1016/j.fertnstert.2005.11.052. PMID 16759929.
  13. ↑ Moore C, Carol W, Gräser T, Mellinger U, Walter F (1999). "Influence of Dienogest on Ovulation in Young Fertile Women". Clinical Drug Investigation 18 (4): 271–278. doi:10.2165/00044011-199918040-00003.
  14. ↑ "Dienogest for the treatment of endometriosis" (PDF). London New Drugs Group. Retrieved 2010-12-07.
  15. ↑ "Visanne" (in German). Netdoctor.de.
  16. ↑ Strowitzki, T; Marr, J; Gerlinger, C; Faustmann, T; Seitz, C (2010). "Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial". Human reproduction (Oxford, England) 25 (3): 633–41. doi:10.1093/humrep/dep469. PMID 20089522.
  17. ↑ Oettel M, Bervoas-Martin S, Elger W, Golbs S, Hobe G, Kaufmann G, Mathieu M, Moore C, Schneider B, Puri C, Ritter P, Reddersen G, Schon R, Strauch G, Zimmermann H (1995). "A 19-norprogestin without 17α-ethinyl group II: Dienogest from a pharmacokinetic point of view". Drugs of Today 31 (7): 499–516.
  18. ↑ 18.0 18.1 Oettel M, Carol W, Elger W, Kaufmann G, Moore C, Romer W, Klinger G, Schneider B, Schroder J, Sobek L, Walter F, Zimmermann H (1995). "A 19-norprogestin without 17α-ethinyl group II: Dienogest from a pharmacodynamic point of view". Drugs of Today 31 (7): 517–536.
  19. ↑ Galbraith, Alan; Shane Bullock; Elizabeth Manias; Barry Hunt; Ann Richards (2007). Fundamentals of Pharmacology: An Applied Approach for Nursing and Health. United Kingdom: Pearson Education LTD. p. 632. ISBN 978-0-13-186901-1.
  20. ↑ Wiegratz I, Lee JH, Kutschera E, Bauer HH, von Hayn C, Moore C, Mellinger U, Winkler UH, Gross W, Kuhl H (2002). "Effect of dienogest-containing oral contraceptives on lipid metabolism". Contraception 65 (3): 223–9. doi:10.1016/S0010-7824(01)00310-9. PMID 11929644.