Dienogest
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| Systematic (IUPAC) name | |
| 17-hydroxy-3-oxo-19-nor-17α-pregna-4,9-diene-21-nitrile | |
| Clinical data | |
| AHFS/Drugs.com | International Drug Names |
| Pregnancy cat. | ? |
| Legal status | ? |
| Routes | Oral |
| Pharmacokinetic data | |
| Bioavailability | 90%[1] |
| Protein binding | 90%[2] |
| Metabolism | Hepatic[3] |
| Half-life | 6-12 hours[4] |
| Excretion | Renal |
| Identifiers | |
| CAS number | 65928-58-7  |
| ATC code | G03DB08 G03FA15 (combination with estrogen) |
| PubChem | CID 68861 |
| UNII | 46M3EV8HHE  |
| KEGG | D03799 |
| ChEMBL | CHEMBL1201864 |
| Chemical data | |
| Formula | C20H25NO2 |
| Mol. mass | 311.42 g/mol[1] |
| Physical data | |
| Density | 1.2 g/cm³ |
| Boiling point | 549 °C (1020 °F) |
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Dienogest is an orally active synthetic progesterone (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] 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.
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[edit] History
Dienogest was synthesised in 1979 in Jena, Germany under the leadership of Prof. Kurt Ponsold, was initially referred to as STS 557.[6][7] It was found that its potency was 10 times that of levonorgestrel.[8] The first product on the market to contain dienogest as a contraceptive pill Valette in 1995 made by Jenapharm.[9] It has been little used outside of Germany.[10]
[edit] Indications
[edit] 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.[11] The minimum dose required to inhibit ovulation has been found to be approximately 1 mg.[12]
[edit] Endometriosis
Dienogest is also approved in the European Union for the treatment of endometriosis.[13][14] It has been shown to be equally effective as leuprorelin,[15] which is a second line medication against endometriosis.
[edit] Pharmacodynamics
[edit] Progestational activity
Dienogest has moderate affinity for the progesterone receptor in human uterus tissue, in vitro, about 10% that of progesterone.[16]
[edit] Inhibition of ovulation
The minimum effective dose of oral dienogest required to inhibit ovulation is 1 mg/day.[17] 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.[17]
[edit] 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.[18] It produces no androgenic side effects and has little effect on metabolic and lipid haemostatic parameters.[19]
[edit] References
- ^ a b c d e Foster RH, Wilde MI (1998). "Dienogest". Drugs 56 (5): 825–33; discussion 834–5. doi:10.2165/00003495-199856050-00007. PMID 9829156.
- ^ de Lignieres B, Dennerstein L, Backstrom T (1995). = MImg&_imagekey = B6T9F-3YCM173-D-1&_cdi = 5113&_user = 308069&_orig = search&_coverDate = 04%2F30%2F1995&_sk = 999789996&view = c&wchp = dGLbVtb-zSkzV&md5 = 661a69b659e2a9afde59f153d419f848&ie = /sdarticle.pdf "Influence of route of administration on progesterone metabolism". Maturitas 21 (3): 251–7. doi:10.1016/0378-5122(94)00882-8. PMID 7616875. http://www.sciencedirect.com/science?_ob = MImg&_imagekey = B6T9F-3YCM173-D-1&_cdi = 5113&_user = 308069&_orig = search&_coverDate = 04%2F30%2F1995&_sk = 999789996&view = c&wchp = dGLbVtb-zSkzV&md5 = 661a69b659e2a9afde59f153d419f848&ie = /sdarticle.pdf.
- ^ a b Stanczyk FZ (2003). = MImg&_imagekey = B6TC9-49W20RK-1-1H&_cdi = 5165&_user = 308069&_orig = search&_coverDate = 11%2F30%2F2003&_sk = 999319989&view = c&wchp = dGLbVtz-zSkWW&md5 = 7d8739b4182a2f943f6463f2b434653d&ie = /sdarticle.pdf "All progestins are not created equal". Steroids 68 (10–13): 879–90. doi:10.1016/j.steroids.2003.08.003. PMID 14667980. http://www.sciencedirect.com/science?_ob = MImg&_imagekey = B6TC9-49W20RK-1-1H&_cdi = 5165&_user = 308069&_orig = search&_coverDate = 11%2F30%2F2003&_sk = 999319989&view = c&wchp = dGLbVtz-zSkWW&md5 = 7d8739b4182a2f943f6463f2b434653d&ie = /sdarticle.pdf.
- ^ Sitruk-Ware R (2004). = MImg&_imagekey = B6T9F-4BY3WYN-7-8&_cdi = 5113&_user = 308069&_orig = search&_coverDate = 04%2F15%2F2004&_sk = 999529995&view = c&wchp = dGLzVzz-zSkzk&md5 = 8fcb633206527789f56a3c28d3956c06&ie = /sdarticle.pdf "Pharmacological profile of progestins". Maturitas 47 (4): 277–83. doi:10.1016/j.maturitas.2004.01.001. PMID 15063480. http://www.sciencedirect.com/science?_ob = MImg&_imagekey = B6T9F-4BY3WYN-7-8&_cdi = 5113&_user = 308069&_orig = search&_coverDate = 04%2F15%2F2004&_sk = 999529995&view = c&wchp = dGLzVzz-zSkzk&md5 = 8fcb633206527789f56a3c28d3956c06&ie = /sdarticle.pdf.
- ^ 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. http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T1J-3Y6GTW1-5-F&_cdi=4892&_user=308069&_orig=search&_coverDate=12%2F10%2F1999&_sk=996139998&view=c&wchp=dGLbVtz-zSkzV&md5=d3bd9b067f0732c4087f0ed6f78ef7cb&ie=/sdarticle.pdf.
- ^ 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.
- ^ 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. http://linkinghub.elsevier.com/retrieve/pii/S0039-128X(99)00028-8.
- ^ 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. http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T5P-4BWV44D-7-1&_cdi=5008&_user=308069&_orig=search&_coverDate=01%2F31%2F1980&_sk=999789998&view=c&wchp=dGLbVtb-zSkzk&md5=ce10dd4f44f22ea913e52651be02fe5b&ie=/sdarticle.pdf.
- ^ http://www.jenapharm.de/unternehmen/ueber-uns/geschichte/1965-1995/
- ^ Kuhl H (1998). "Dienogest. A Viewpoint by Herbert Kuhl". Drugs 56 (5): 834.
- ^ 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. http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T6K-4K48058-D-7&_cdi=5033&_user=308069&_orig=search&_coverDate=06%2F30%2F2006&_sk=999149993&view=c&wchp=dGLbVtz-zSkWA&md5=09a9c18943af939b02ba9d76b2edb79b&ie=/sdarticle.pdf.
- ^ 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. http://www.ingentaconnect.com/content/adis/cdi/1999/00000018/00000004/art00003.
- ^ "Dienogest for the treatment of endometriosis" (PDF). London New Drugs Group. http://www.nelm.nhs.uk/en/Download/?file=MDs3NTMyMTA7L3VwbG9hZC9EaWVub2dlc3RfU2VwdF8xMC5wZGY_.pdf. Retrieved 2010-12-07.
- ^ "Visanne" (in German). Netdoctor.de. http://www.netdoktor.de/Medikamente/Visanne-r-100012124.html.
- ^ 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.
- ^ 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.
- ^ a b 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.
- ^ 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. pp. 632. ISBN 978-0131869011. http://www.pearsoned.co.uk/Bookshop/detail.asp?item=100000000107920.
- ^ 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. http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T5P-45FD507-5-9&_cdi=5008&_user=308069&_orig=search&_coverDate=03%2F31%2F2002&_sk=999349996&view=c&wchp=dGLbVzW-zSkWb&md5=6a7fa2b0616afba9866f9c0dd1b11b48&ie=/sdarticle.pdf.
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