Cyclofenil Explained

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.^{[1] [2] [3]} It is mostly no longer available. The medication is taken by mouth.^{[4] [5]}

Side effects of cyclofenil include liver toxicity among others. 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. It has antiestrogenic effects on the hypothalamic–pituitary–gonadal axis and hence can increase sex hormone production and stimulate ovulation.

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

Medical use

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

Available forms

Cyclofenil has been available in the form of 100, 200, and 400 mg oral tablets.^[6]

Non-medical use

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

Contraindications

Cyclofenil is contraindicated during pregnancy and in those with severe liver disease and unexplained uterine bleeding.^[7]

Side effects

Cyclofenil is associated with a relatively high incidence of hepatotoxicity.^[8] Biochemical signs of undesirable liver changes have been observed in 35% or more of individuals and 1% of individuals experience overt hepatitis.

Pharmacology

Pharmacodynamics

Cyclofenil is a SERM, or a mixed agonist and antagonist of the estrogen receptors (ERs). It is described as a relatively weak/mild SERM. The medication is generally less effective than other SERMs. 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. In men, cyclofenil can increase testosterone levels due its progonadotropic effects.

Pharmacokinetics

In terms of distribution, cyclofenil acts both centrally and peripherally.^[9] The elimination half-life of cyclofenil after a single 200 mg dose is 18 to 29 hours.^{[10] [11]}

Chemistry

Cyclofenil is a nonsteroidal SERM and is closely related structurally to triphenylethylene SERMs like clomifene and tamoxifen. 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.^{[12] [13]}

History

Cyclofenil was first introduced for medical use in 1970 under the brand name Ondogyne in France.^[14] Subsequently, it was introduced throughout the world under a variety of other brand names, including its most well-known brand name Sexovid.

Society and culture

Generic names

Cyclofenil is the English generic name of the drug and its,, and .

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.^{[15] [16]}

Availability

Cyclofenil remains available today only in Brazil, Italy, and Japan. In the past, it has also been available in France, Germany, Mexico, Sweden, Switzerland, Turkey, and the United Kingdom.^[17]

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]

Notes and References

1. Book: Elks J . The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. 14 November 2014. Springer. 978-1-4757-2085-3. 329–.
2. Book: Index Nominum 2000: International Drug Directory. January 2000. Taylor & Francis. 978-3-88763-075-1. 284–.
3. Web site: List of 7 Menopausal Disorders Medications Compared . Drugs.com .
4. Book: Seyffart G . Cyclofenil . Drug Dosage in Renal Insufficiency. https://books.google.com/books?id=OavnCAAAQBAJ&pg=PA166. 6 December 2012. Springer Science & Business Media. 978-94-011-3804-8. 166–.
5. Book: Meniru GI, Craft IL . Ovarian stimulation for assisted reproduction technologies. Meniru GI, Brinsden PR, Craft IL . A Handbook of Intrauterine Insemination. https://books.google.com/books?id=UpNScYN8B2YC&pg=PA58 . 31 July 1997 . Cambridge University Press . 978-0-521-58676-4 . 58–59,207 .
6. Book: von Deutsch DA, Abukhalaf IK, Socci RR . Anabolic Doping Agents . Mozayani A, Raymon L . Handbook of Drug Interactions: A Clinical and Forensic Guide . https://books.google.com/books?id=dwMyBwAAQBAJ&pg=PA555 . 15 October 2003. Springer Science & Business Media. 978-1-59259-654-6. 555–.
7. Book: Mutschler E, Derendorf H, Schäfer-Korting M, Elrod K, Estes KS . Ovaries . Drug Actions: Basic Principles and Therapeutic Aspects. https://books.google.com/books?id=IvN4mZxraMkC&pg=PA294. 1995. CRC Press. 978-0-8493-7774-7. 294–.
8. Book: Zimmerman HJ, Ishak KG . Steroids and Other Hormones. Cameron R, Feuer G, de la Iglesia F . Drug-Induced Hepatotoxicity. https://books.google.com/books?id=xZf-CAAAQBAJ&pg=PA565. 6 December 2012. Springer Science & Business Media. 978-3-642-61013-4. 565–.
9. Book: Tatford EP . Excessive Vaginal Bleeding . Problems in Gynaecology. https://books.google.com/books?id=q0inBgAAQBAJ&pg=PA105. 6 December 2012. Springer Science & Business Media. 978-94-009-4125-0. 105–106.
10. Book: Insler V, Lunenfeld B . Infertility: Male and Female. January 1993. Churchill Livingstone. 978-0-443-04514-1. 458.
11. Book: Blankstein J, Mashiach S, Lunenfeld B . Ovulation Induction and in Vitro Fertilization. 1 July 1986. Year Book Medical Publishers. 978-0-8151-0871-9. 113.
12. Book: Horsky J . Oestrogens . Horsky J, Presl J . Ovarian Function and its Disorders: Diagnosis and Therapy. https://books.google.com/books?id=7IrpCAAAQBAJ&pg=PA92. 6 December 2012. Springer Science & Business Media. 978-94-009-8195-9. 92–.
13. Book: Bishop PM . Clinical Manifestations of Disorders of the Human Ovary. Zuckerman S, Weir BJ . Physiology. https://books.google.com/books?id=4R_FAgAAQBAJ&pg=PA209. 22 October 2013. Elsevier Science. 978-1-4832-5975-8. 209–.
14. Book: William Andrew Publishing. Pharmaceutical Manufacturing Encyclopedia . 3rd . 22 October 2013. Elsevier. 978-0-8155-1856-3. 1162–.
15. Book: Negwer M, Scharnow HG . Organic-chemical drugs and their synonyms: (an international survey). 2001. Wiley-VCH. 978-3-527-30247-5. 2397.
16. Web site: IBM Watson Health Products . IBM Watson Health Products . 2021-11-01.
17. Book: Sweetman SC . Sex hormones and their modulators . Martindale: The Complete Drug Reference . 36th . 2009 . Pharmaceutical Press . London. 978-0-85369-840-1. 2088.
18. Book: Chester N . Hormone and metabolic modulators . Mottram DR, Chester N . Drugs in Sport. https://books.google.com/books?id=ESFWBQAAQBAJ&pg=PA117. 13 November 2014. Routledge. 978-1-134-70800-0. 117–.
19. Book: Ed The Emtree Editorial Team. 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. 1 January 2004. Elsevier. 978-0-444-51752-4. 82.
20. Torres MA, Furst DE . Treatment of generalized systemic sclerosis . Rheum Dis Clin North Am . 16 . 1 . 217–41 . February 1990 . 10.1016/S0889-857X(21)01050-4 . 2406809.
21. Pope J, Fenlon D, Thompson A . Pope J . Cyclofenil for Raynaud's phenomenon in progressive systemic sclerosis . . 2 . CD000955 . 2000 . 1998 . 10796397 . 10.1002/14651858.CD000955. etal. 7032887 .