Cyclofenil

Last updated
Cyclofenil
Cyclofenil.svg
Clinical data
Trade names Sexovid, others
Other namesCyclophenil; F-6066; H-3452; ICI-48213; bis(p-Acetoxyphenyl)-cyclohexylidenemethane
AHFS/Drugs.com International Drug Names
Routes of
administration 		By mouth
Drug class Selective estrogen receptor modulator; Progonadotropin
ATC code
Pharmacokinetic data
Elimination half-life 18–29 hours [1] [2]
Identifiers
  • [4-[(4-Acetoxyphenyl)-cyclohexylidene-methyl]phenyl] acetate
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.018.264 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C23H24O4
Molar mass 364.441 g·mol−1
3D model (JSmol)
  • O=C(Oc3ccc(C(/c1ccc(OC(=O)C)cc1)=C2\CCCCC2)cc3)C

Cyclofenil, sold under the brand name Sexovid among others, is a selective estrogen receptor modulator (SERM) medication which is used as a gonadotropin stimulant or ovulation inducer and in menopausal hormone therapy in women. [3] [4] [5] [6] It is mostly no longer available. [6] The medication is taken by mouth. [7] [8] [9]

Contents

Side effects of cyclofenil include liver toxicity among others. [10] It is a selective estrogen receptor modulator (SERM) and hence is a mixed agonist–antagonist of the estrogen receptor (ER), the biological target of estrogens like estradiol. [8] It has antiestrogenic effects on the hypothalamic–pituitary–gonadal axis and hence can increase sex hormone production and stimulate ovulation. [8] [11]

Cyclofenil was introduced for medical use in 1970. [12] It has been mostly discontinued, but remains available in a few countries, including Brazil, Italy, and Japan. [6] [13] [3] It has been used as a doping agent by male athletes. [8]

Medical use

Cyclofenil is used to treat menstrual disturbances and anovulatory infertility caused by insufficiency of the hypothalamic–pituitary–gonadal axis in women. [3] It has also been used to treat menopausal symptoms. [3] The medication is generally used at a dosage of 400 to 600 mg per day. [3] [8] [9]

Available forms

Cyclofenil has been available in the form of 100, 200, and 400 mg oral tablets. [8]

Non-medical use

Cyclofenil has been used by male athletes to increase testosterone levels. [8] It is not effective for this purpose in women. [8]

Contraindications

Cyclofenil is contraindicated during pregnancy and in those with severe liver disease and unexplained uterine bleeding. [14]

Side effects

Cyclofenil is associated with a relatively high incidence of hepatotoxicity. [10] Biochemical signs of undesirable liver changes have been observed in 35% or more of individuals and 1% of individuals experience overt hepatitis. [10]

Pharmacology

Pharmacodynamics

Cyclofenil is a SERM, or a mixed agonist and antagonist of the estrogen receptors (ERs). [8] It is described as a relatively weak/mild SERM. [8] The medication is generally less effective than other SERMs. [15] The medication is an "impeded estrogen" and is thought to work as a progonadotropin by blocking the actions of estrogens in the pituitary gland and hypothalamus, thereby disinhibiting release of the gonadotropins luteinizing hormone and follicle-stimulating hormone. [11] In men, cyclofenil can increase testosterone levels due its progonadotropic effects. [8]

Pharmacokinetics

In terms of distribution, cyclofenil acts both centrally and peripherally. [15] The elimination half-life of cyclofenil after a single 200 mg dose is 18 to 29 hours. [1] [2]

Chemistry

Cyclofenil is a nonsteroidal SERM and is closely related structurally to triphenylethylene SERMs like clomifene and tamoxifen. [9] It has been referred to as a diphenylethylene derivative, differing from triphenylethylenes only by the replacement of one of the phenyl rings with a cyclohexane ring. [16] [11]

History

Cyclofenil was first introduced for medical use in 1970 under the brand name Ondogyne in France. [12] Subsequently, it was introduced throughout the world under a variety of other brand names, including its most well-known brand name Sexovid. [12]

Society and culture

Generic names

Cyclofenil is the English generic name of the drug and its INN Tooltip International Nonproprietary Name, USAN Tooltip United States Adopted Name, and BAN Tooltip British Approved Name. [4] [5] [6]

Brand names

Cyclofenil has been marketed under a variety of brand names including Ciclifen, Fertodur, Gyneuro, Klofenil, Menoferil, Menopax, Neoclym, Oginex, Ondonid, Ondogyne, Rehibin, Sexadieno, Sexovar, and Sexovid. [17] [12] [13]

Availability

Cyclofenil remains available today only in Brazil, Italy, and Japan. [6] [13] [3] In the past, it has also been available in France, Germany, Mexico, Sweden, Switzerland, Turkey, and the United Kingdom. [5] [12] [13] [3]

Regulation

Cyclofenil is included on the World Anti-Doping Agency list of illegal doping agents in sport. [18] [19]

Research

Cyclofenil was investigated as a possible treatment for scleroderma in the 1980s, but was found to be ineffective. [20] Later study of its efficacy in treating Raynaud's phenomenon in people with scleroderma also found no significant benefit. [21]

Related Research Articles

<span class="mw-page-title-main">Clomifene</span> Infertility treatment for women

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<span class="mw-page-title-main">Selective estrogen receptor modulator</span> Drugs acting on the estrogen receptor

Selective estrogen receptor modulators (SERMs), also known as estrogen receptor agonist/antagonists (ERAAs), are a class of drugs that act on the estrogen receptor (ER). A characteristic that distinguishes these substances from pure ER agonists and antagonists is that their action is different in various tissues, thereby granting the possibility to selectively inhibit or stimulate estrogen-like action in various tissues.

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<span class="mw-page-title-main">Estropipate</span> Estrogen medication

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<span class="mw-page-title-main">Chlorotrianisene</span> Chemical compound

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<span class="mw-page-title-main">Zuclomifene</span> Chemical compound

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<span class="mw-page-title-main">Afimoxifene</span> Chemical compound

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<span class="mw-page-title-main">Nafoxidine</span> Chemical compound

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<span class="mw-page-title-main">Moxestrol</span> Chemical compound

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<span class="mw-page-title-main">Conjugated estrogens</span> Estrogen medication

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<span class="mw-page-title-main">Triphenylethylene</span> Chemical compound

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References

  1. 1 2 Vaclav Insler; Bruno Lunenfeld (January 1993). Infertility: Male and Female. Churchill Livingstone. p. 458. ISBN   978-0-443-04514-1.
  2. 1 2 Josef Blankstein; Shlomo Mashiach; Bruno Lunenfeld (1 July 1986). Ovulation Induction and in Vitro Fertilization. Year Book Medical Publishers. p. 113. ISBN   978-0-8151-0871-9.
  3. 1 2 3 4 5 6 7 Sweetman, Sean C., ed. (2009). "Sex hormones and their modulators". Martindale: The Complete Drug Reference (36th ed.). London: Pharmaceutical Press. p. 2088. ISBN   978-0-85369-840-1.
  4. 1 2 J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 329–. ISBN   978-1-4757-2085-3.
  5. 1 2 3 Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 284–. ISBN   978-3-88763-075-1.
  6. 1 2 3 4 5 "List of 7 Menopausal Disorders Medications Compared".
  7. ↑ G. Seyffart (6 December 2012). Drug Dosage in Renal Insufficiency. Springer Science & Business Media. pp. 166–. ISBN   978-94-011-3804-8.
  8. 1 2 3 4 5 6 7 8 9 10 11 Ashraf Mozayani; Lionel Raymon (15 October 2003). Handbook of Drug Interactions: A Clinical and Forensic Guide. Springer Science & Business Media. pp. 555–. ISBN   978-1-59259-654-6.
  9. 1 2 3 Godwin I. Meniru; Peter R. Brinsden; Ian L. Craft (31 July 1997). A Handbook of Intrauterine Insemination. Cambridge University Press. pp. 58–59, 207. ISBN   978-0-521-58676-4.
  10. 1 2 3 Ross Cameron; George Feuer; Felix de la Iglesia (6 December 2012). Drug-Induced Hepatotoxicity. Springer Science & Business Media. pp. 565–. ISBN   978-3-642-61013-4.
  11. 1 2 3 Solomon Zuckerman; Barbara J. Weir (22 October 2013). Physiology. Elsevier Science. pp. 209–. ISBN   978-1-4832-5975-8.
  12. 1 2 3 4 5 William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. Elsevier. pp. 1162–. ISBN   978-0-8155-1856-3.
  13. 1 2 3 4 "IBM Watson Health Products". IBM Watson Health Products. Retrieved 2021-11-01.
  14. ↑ Mutschler; Hartmut Derendorf (1995). Drug Actions: Basic Principles and Therapeutic Aspects. CRC Press. pp. 294–. ISBN   978-0-8493-7774-7.
  15. 1 2 E.P.W. Tatford (6 December 2012). Problems in Gynaecology. Springer Science & Business Media. pp. 105–106. ISBN   978-94-009-4125-0.
  16. ↑ J. Horsky; J. Presl (6 December 2012). Ovarian Function and its Disorders: Diagnosis and Therapy. Springer Science & Business Media. pp. 92–. ISBN   978-94-009-8195-9.
  17. ↑ Martin Negwer; Hans-Georg Scharnow (2001). Organic-chemical drugs and their synonyms: (an international survey). Wiley-VCH. p. 2397. ISBN   978-3-527-30247-5.
  18. ↑ David R. Mottram; Neil Chester (13 November 2014). Drugs in Sport. Routledge. pp. 117–. ISBN   978-1-134-70800-0.
  19. ↑ Ed The Emtree Editorial Team (1 January 2004). Doping Search Guide 2004: Over 10,000 Substance Names in Reference to the 2004 WADA (World Anti-Doping Agency) List of Prohibited Substances and Methods. Elsevier. p. 82. ISBN   978-0-444-51752-4.
  20. ↑ Torres MA, Furst DE (February 1990). "Treatment of generalized systemic sclerosis". Rheum Dis Clin North Am. 16 (1): 217–41. doi:10.1016/S0889-857X(21)01050-4. PMID   2406809.
  21. ↑ Pope J, Fenlon D, Thompson A, et al. (2000). Pope J (ed.). "Cyclofenil for Raynaud's phenomenon in progressive systemic sclerosis". Cochrane Database Syst Rev . 1998 (2): CD000955. doi:10.1002/14651858.CD000955. PMC   7032887 . PMID   10796397.
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