Tibolone

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Tibolone
Tibolone Structural Formulae V.1.svg
Systematic (IUPAC) name
17-Hydroxy-7α-methyl-19-nor-17α-pregn-5(10)-en-20-yn-3-one
Clinical data
AHFS/Drugs.com International Drug Names
  • ADEC Category D
oral
Identifiers
5630-53-5 N
G03CX01
PubChem CID 444008
ChemSpider 392038 YesY
UNII FF9X0205V2 YesY
KEGG D01639 YesY
ChEBI CHEBI:32223 YesY
ChEMBL CHEMBL1558898 N
Synonyms 7α-Methylnoretynodrel;
Org OD 14
(7α,17β)-17-ethynyl-17-hydroxy-7-methylestr-5(10)-en-3-one
Chemical data
Formula C21H28O2
312.446 g/mol
 N (what is this?)  (verify)

Tibolone (INN, USAN, BAN) (brand name Livial, Tibofem) is a synthetic steroid drug with estrogenic, progestogenic, and weak androgenic actions which was introduced in 1988 and is used widely in Europe, Asia, Australasia, and, with the exception of the United States (where it is not available), the rest of the world.[1][2][3][4] It is used mainly for treatment of endometriosis,[5] as well as hormone replacement therapy in post-menopausal women. Tibolone has similar or greater efficacy compared to older hormone replacement drugs, but shares a similar side effect profile.[6][7][8] It has also been investigated as a possible treatment for female sexual dysfunction.[9]

Pharmacology[edit]

Tibolone possesses a complex pharmacology.[10] Its two major active metabolites, 3α-hydroxytibolone and 3β-hydroxytibolone, act as potent, fully-activating agonists of the estrogen receptor (ER), with a high preference for ERα.[10][11][12] Tibolone and its metabolite Δ4-tibolone act as agonists of the progesterone and androgen receptors,[11] while 3α-hydroxytibolone and 3β-hydroxytibolone, conversely, act as antagonists of these receptors.[10] Lastly, tibolone, 3α-hydroxytibolone, and 3β-hydroxytibolone act as antagonists of the glucocorticoid and mineralocorticoid receptors, with preference for the mineralocorticoid receptor.[10]

Tibolone has tissue-selective estrogenic effects, with desirable effects in bone, the brain, and the vagina, and lack of undesirable action in the endometrium and breasts.[12] Its tissue selectivity is the result of metabolism, enzyme modulation (e.g., of estrogen sulfatase and estrogen sulfotransferase), and receptor modulation that vary in different target tissues, and differs mechanistically from that of selective estrogen receptor modulators (SERMs) such as tamoxifen, which produce their tissue-selectivity via means of modulation of the ER.[11][12] As such, to distinguish it from SERMs, tibolone has been described as a "selective tissue estrogenic activity regulator" (STEAR),[12] and also as a "selective estrogen enzyme modulator" (SEEM).[13]

Adverse effects[edit]

A report in September 2009 from Health and Human Services' Agency for Healthcare Research and Quality suggests that tamoxifen, raloxifene, and tibolone used to treat breast cancer significantly reduce invasive breast cancer in midlife and older women, but also increase the risk of adverse side effects.[14]

See also[edit]

References[edit]

  1. ^ C.R. Ganellin; David J. Triggle (21 November 1996). Dictionary of Pharmacological Agents. CRC Press. pp. 1974–. ISBN 978-0-412-46630-4. 
  2. ^ I.K. Morton; Judith M. Hall (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 275–. ISBN 978-94-011-4439-1. 
  3. ^ Sheldon J. Segal Population Council; Division of Human Reproduction Luigi Mastroianni Jr. Professor, Department of Obstetrics and Gynecology University of Pennsylvania School of Medicine (4 October 2003). Hormone Use in Menopause and Male Andropause : A Choice for Women and Men: A Choice for Women and Men. Oxford University Press, USA. pp. 73–. ISBN 978-0-19-803620-3. 
  4. ^ Irwin Goldstein; Cindy M. Meston; Susan Davis; Abdulmaged Traish (17 November 2005). Women's Sexual Function and Dysfunction: Study, Diagnosis and Treatment. CRC Press. pp. 556–. ISBN 978-1-84214-263-9. 
  5. ^ Al Kadri H, Hassan S, Al-Fozan HM, Hajeer A (2009). Al Kadri, Hanan, ed. "Hormone therapy for endometriosis and surgical menopause". Cochrane Database of Systematic Reviews (Online) (1): CD005997. doi:10.1002/14651858.CD005997.pub2. PMID 19160262. 
  6. ^ Lazovic G, Radivojevic U, Marinkovic J (April 2008). "Tibolone: the way to beat many a postmenopausal ailments". Expert Opinion on Pharmacotherapy 9 (6): 1039–47. doi:10.1517/14656566.9.6.1039. PMID 18377345. 
  7. ^ Garefalakis M, Hickey M (2008). "Role of androgens, progestins and tibolone in the treatment of menopausal symptoms: a review of the clinical evidence". Clinical Interventions in Aging 3 (1): 1–8. PMC 2544356. PMID 18488873. 
  8. ^ Vavilis D, Zafrakas M, Goulis DG, Pantazis K, Agorastos T, Bontis JN (2009). "Hormone therapy for postmenopausal breast cancer survivors: a survey among obstetrician-gynaecologists". European Journal of Gynaecological Oncology 30 (1): 82–4. PMID 19317264. 
  9. ^ Ziaei, S; Moghasemi, M; Faghihzadeh, S (2010). "Comparative effects of conventional hormone replacement therapy and tibolone on climacteric symptoms and sexual dysfunction in postmenopausal women". Climacteric : the journal of the International Menopause Society 13 (2): 147–56. doi:10.1080/13697130903009195. PMID 19731119. 
  10. ^ a b c d Escande A, Servant N, Rabenoelina F, Auzou G, Kloosterboer H, Cavaillès V, Balaguer P, Maudelonde T (August 2009). "Regulation of activities of steroid hormone receptors by tibolone and its primary metabolites". The Journal of Steroid Biochemistry and Molecular Biology 116 (1–2): 8–14. doi:10.1016/j.jsbmb.2009.03.008. PMID 19464167. 
  11. ^ a b c Tommaso Falcone; William W. Hurd (22 May 2013). Clinical Reproductive Medicine and Surgery: A Practical Guide. Springer Science & Business Media. pp. 152–. ISBN 978-1-4614-6837-0. 
  12. ^ a b c d Hermann P.G. Schneider; Frederick Naftolin (22 September 2004). Climacteric Medicine - Where Do We Go?: Proceedings of the 4th Workshop of the International Menopause Society. CRC Press. pp. 126–. ISBN 978-0-203-02496-6. 
  13. ^ Tekoa King; Mary C. Brucker (25 October 2010). Pharmacology for Women's Health. Jones & Bartlett Learning. pp. 371–. ISBN 978-0-7637-5329-0. 
  14. ^ "Medications Effective in Reducing Risk of Breast Cancer But Increase Risk of Adverse Effects, New Report Says". U.S. Department of Health & Human Services - Agency for Healthcare Research and Quality. September 2009. Retrieved 2 June 2014.