Cyclofenil
Chemical compound
From Wikipedia, the free encyclopedia
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]
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| Clinical data | |
|---|---|
| Trade names | Sexovid, others |
| Other names | Cyclophenil; 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 | |
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| CAS Number | |
| PubChem CID | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEMBL | |
| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.018.264 |
| Chemical and physical data | |
| Formula | C23H24O4 |
| Molar mass | 364.441 g·mol−1 |
| 3D model (JSmol) | |
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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
Society and culture
Generic names
Cyclofenil is the English generic name of the drug and its INN, USAN, and BAN.[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]