Ormeloxifene

Ormeloxifene File:Ormeloxifene structure.png Systematic (IUPAC) name 1-[2-[4-[(3S,4R)-7-methoxy-2,2- dimethyl-3-phenyl-chroman-4-yl] phenoxy] ethyl] pyrrolidine Clinical data Routes of administration Oral Pharmacokinetic data Biological half-life 7 days Identifiers CAS Number 78994-24-8 ATC code none PubChem CID 154413 Chemical data Formula C30H35NO3 Molar mass 457.604 g/mol[[]]

Ormeloxifene Background Birth control type Anti-estrogen First use 1991 Failure rates (first year) Perfect use 2% Typical use 9% Usage Duration effect One week Reversibility Immediate User reminders Taken twice weekly for first 13 weeks Clinic review Annually Advantages and disadvantages STD protection No Periods May disrupt Weight No proven effect Medical notes Only approved as a contraceptive in India

Ormeloxifene (also known as Centchroman) is one of the selective estrogen receptor modulators, or SERMs, a class of medication which acts on the estrogen receptor. It is best known as a non-hormonal, non-steroidal oral contraceptive which is taken once per week. In India, ormeloxifene has been available as birth control since the early 1990s, and it is currently marketed there under the trade name Saheli. Ormeloxifene has also been licensed under the trade namesNovex-DS, Centron and Sevista.

Method of action

Ormeloxifene is a SERM, or selective estrogen receptor modulator. In some parts of the body, its action is estrogenic (e.g, bones), in other parts of the body, its action is anti-estrogenic (e.g., uterus, breasts. It causes an asynchrony in the menstrual cycle between ovulation and the development of the uterine lining, although its exact mode of action is not well defined. In clinical trials, it caused ovulation to occur later than it normally would in some women (Singh 2001), but did not affect ovulation in the majority of women, while causing the lining of the uterus to build more slowly. It speeds the transport of any fertilized egg through the fallopian tubes more quickly than is normal (Singh 2001). Presumably, this combination of effects creates an environment such that if fertilization occurs, implantation will not be possible.

Usage

Ormeloxifene may be used as a contraceptive or as a treatment for dysfunctional uterine bleeding.

As birth control

Ormeloxifene may be used as a weekly oral contraceptive. This is touted as a major advantage by its developer and its manufacturer. Hormonal birth control pills should be taken at approximately the same time each day. In the case of progestogen only pills other than Cerazette that do not consistently inhibit ovulation, a delay of as little as three hours can increase the risk of pregnancy because of the limited duration of their effect on the cervical mucus. Ormeloxifene's weekly schedule is an advantage for women who prefer an oral contraceptive, but find it difficult or impractical to adhere to a daily schedule.

For the first sixteen weeks of use, it is advised to take the ormeloxifene pill twice per week. From the thirteenth week on, it is taken once per week. The consensus is that backup protection in the first month is a cautious but sensible choice. A standard dose is 30mg weekly, but 60mg loading doses can reduce pregnancy rates by 38%.

Other

Ormeloxifene has also been proposed as a treatment for menorrhagia.

Use in treatment of mastalgia and fibroadenoma has also been described.

Effectiveness

One Phase III multicenter trial of ormeloxifene 30 mg weekly by 898 women for an average of 15 months found a method failure Pearl Index of 2.84.

A second Phase III multicenter trial of ormeloxifene 30 mg twice-a-week for 3 months followed by 30 mg weekly by 376 women for an average of 10.5 months found a method failure Pearl Index of 1.83 and a 12-month life-table method failure pregnancy rate of 1.63% ±0.74%.

The overall actual use (method failure plus user failure) Pearl Index was 9 in both Phase III multicenter trials of ormeloxifene — an order of magnitude less effective than found in Phase III multicenter trials of combined oral contraceptive pills.

Manufacture and marketing

Ormeloxifene has been tested and licensed as a form of birth control, as well as a treatment for dysfunctional uterine bleeding. It was first manufactured by Torrent Pharmaceuticals, and marketed as birth control under the trade name Centron. Centron was discontinued. A new license for ormeloxifene was issued to Hindustan Latex Ltd., which now manufactures ormeloxifene as birth control under the trade name Saheli. Torrent Pharmaceuticals has resumed manufacture of ormeloxifene under the trade name Sevista, as a treatment for dysfunctional uterine bleeding.

Synthesis

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Ray, Suprabhat; Grover, Payara K.; Kamboj, Ved P.; Setty, B. S.; Kar, Amiya B.; Anand, Nitya (1976). "Antifertility agents. 12. Structure-activity relation of 3,4-diphenylchromenes and -chromans". Journal of Medicinal Chemistry. 19 (2): 276. doi:10.1021/jm00224a014. PMID 1249807. 

See also

• Hormonal contraception
• Selective estrogen receptor modulator
• Reproductive health

External links

• United States National Library of Medicine Ormeloxifene entry in the Medical Subject Headings (MeSH) database
• United States National Library of Medicine Centchroman entry in the Medical Subject Headings (MeSH) database
• Reproductive Health Online, a Johns Hopkins University affiliate providing information on Centchroman
• Saheli manufacturer's website - Product details
• Saheli manufacturer's website - Clinical studies
• Central Drug Research Institute, Lucknow, India: a government-funded laboratory, conducting R&D on Centchroman as birth control.
• Ministry of Health and Family Welfare - Indian government site; information about availability of Saheli.

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