Ormeloxifene

Ormeloxifene

Systematic (IUPAC) name
1-[2-[4-[(3S,4R)-7-methoxy-2,2- dimethyl-3-phenyl-chroman-4-yl] phenoxy] ethyl] pyrrolidine
Clinical data
Trade names	Centron, Novex-DS, Saheli, Sevista
Pregnancy cat.	?
Legal status	?
Routes	Oral
Pharmacokinetic data
Half-life	7 days
Identifiers
CAS number	78994-24-8 Y
ATC code	None
PubChem	CID 154413
ChemSpider	32935 Y
UNII	44AXY5VE90 N
KEGG	D08301 Y
ChEMBL	CHEMBL301327 Y
Synonyms	Centchroman
Chemical data
Formula	C30H35NO3
Mol. mass	457.604 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/C30H35NO3/c1-30(2)29(23-9-5-4-6-10-23)28(26-16-15-25(32-3)21-27(26)34-30)22-11-13-24(14-12-22)33-20-19-31-17-7-8-18-31/h4-6,9-16,21,28-29H,7-8,17-20H2,1-3H3/t28-,29+/m1/s1 Y Key:XZEUAXYWNKYKPL-WDYNHAJCSA-N Y
N(what is this?)  (verify)

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,^[1] 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.^[2] Ormeloxifene has also been licensed under the trade names Novex-DS, Centron and Sevista.

Medical uses

Ormeloxifene is primarily used as a contraceptive but may also be effective for dysfunctional uterine bleeding and advanced breast cancer.^[3]

As birth control

Ormeloxifene may be used as a weekly oral contraceptive.^[3] 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 twelve weeks of use, it is advised to take the ormeloxifene pill twice per week.^[3] From the thirteenth week on, it is taken once per week.^[3][4] 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%.^[5]

It has a failure rate of about 1-2% with ideal use which is slight less effective than found for combined oral contraceptive pills.^[6]

Other

Ormeloxifene has also been proposed as a treatment for menorrhagia.^[7]

Use in treatment of mastalgia and fibroadenoma has also been described.^[8]

Adverse effects

There are concerns that ormeloxifene may cause urinary incontinence or uterine prolapse.^[9]

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.^[10][11]) 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,^[6] 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.^[6] Presumably, this combination of effects creates an environment such that if fertilization occurs, implantation will not be possible.^[6]

Marketing

Ormeloxifene is only legally available in India as of 2009.^[12]

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

See also

• Hormonal contraception
• Levormeloxifene, a related SERM

References

1. ^ Makker, Annu; Tandon, Indu; Goel, Madhu Mati; Singh, Mastan; Singh, Man Mohan (2009). "Effect of ormeloxifene, a selective estrogen receptor modulator, on biomarkers of endometrial receptivity and pinopode development and its relation to fertility and infertility in Indian subjects". Fertility and Sterility 91 (6): 2298–307. doi:10.1016/j.fertnstert.2008.04.018. PMID 18675966. 
2. ^ >">"<< HLL - Product Overview >>". http://www.hindlatex.com/TipsnGuidesdetails.aspx?valid=1&category=0&id=170&type=25. 
3. ^ ^{a b c d} Lal, J (2010 Apr). "Clinical pharmacokinetics and interaction of centchroman--a mini review.". Contraception 81 (4): 275-80. PMID 20227542. 
4. ^ http://www.reproline.jhu.edu/english/1fp/1advances/old/1centch/ceorvw.htm
5. ^ Lal J, Nitynand S, Asthana OP, Nagaraja NV, Gupta RC (January 2001). "Optimization of contraceptive dosage regimen of Centchroman". Contraception 63 (1): 47–51. doi:10.1016/S0010-7824(00)00189-X. PMID 11257249. 
6. ^ ^{a b c d} Singh, M.M. (2001). "Centchroman, a selective estrogen receptor modulator, as a contraceptive and for the management of hormone-related clinical disorders". Medicinal Research Reviews 21 (4): 302–47. doi:10.1002/med.1011. PMID 11410933. 
7. ^ Kriplani A, Kulshrestha V, Agarwal N (August 2009). "Efficacy and safety of ormeloxifene in management of menorrhagia: a pilot study". J. Obstet. Gynaecol. Res. 35 (4): 746–52. doi:10.1111/j.1447-0756.2008.00987.x. PMID 19751337. 
8. ^ Dhar A, Srivastava A (June 2007). "Role of centchroman in regression of mastalgia and fibroadenoma". World J Surg 31 (6): 1178–84. doi:10.1007/s00268-007-9040-4. PMID 17431715. 
9. ^ Shelly, W; Draper, MW, Krishnan, V, Wong, M, Jaffe, RB (2008 Mar). "Selective estrogen receptor modulators: an update on recent clinical findings.". Obstetrical & gynecological survey 63 (3): 163-81. PMID 18279543. 
10. ^ Gara Rishi Kumar, Konwar Rituraj, Bid Hemant K and MM Singh. In-vitro anti-cancer breast activity of ormeloxifene is mediated via induction of apoptosis and autophagy. 37th annual conference of the endocrine society of India. 30 nov-2 dec, 2007. Abstract p35.
11. ^ Nigam, Manisha; Ranjan, Vishal; Srivastava, Swasti; Sharma, Ramesh; Balapure, Anil K. (2008). "Centchroman induces G0/G1 arrest and Caspase-dependent Apoptosis involving Mitochondrial Membrane Depolarization in MCF-7 and MDA MB-231 Human Breast Cancer Cells". Life Sciences 82 (11–12): 577–90. doi:10.1016/j.lfs.2007.11.028. PMID 18279897. 
12. ^ Patil, Robin D. Tribhuwan & Benazir D. (2009). Body image : human reproduction and birth control : a tribal perspective. New Delhi: Discovery Pub. House. pp. 20. ISBN 9788183563888. http://books.google.com/books?id=VYYoDoJTwIkC&pg=PA20. 

Further reading

• 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): 276–9. doi:10.1021/jm00224a014. PMID 1249807. 

External links

• 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
• 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.