Ormeloxifeneのソースを表示

{{Short description|Chemical compound}}
{{Use dmy dates|date=July 2020}}
{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 461741567
| IUPAC_name = 1-[2-[4-[(3''S'',4''S'')-7-methoxy-2,2-dimethyl-3-phenyl-chroman-4-yl]phenoxy]ethyl]pyrrolidine
| image = Ormeloxifene structure.svg
| width = 225px

<!--Clinical data-->
| tradename = Centron, Novex-DS, Saheli, Sevista, Chhaya
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category =
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S8 -->
| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->
| legal_US = Not FDA approved
| legal_status = Rx-only in India
| routes_of_administration = [[Oral administration|By mouth]]
| class = [[Selective estrogen receptor modulator]]

<!--Pharmacokinetic data-->
| bioavailability =
| protein_bound =
| metabolism =
| elimination_half-life = 7 days
| excretion =

<!--Identifiers-->
| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 31477-60-8
| ATC_prefix = G03
| ATC_suffix = XC04
| PubChem = 154413
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 32935
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 44AXY5VE90
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D08301
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 301327
| synonyms = Centchroman

<!--Chemical data-->
| C=30 | H=35 | N=1 | O=3
| SMILES = CC1([C@@H]([C@H](c2ccc(cc2O1)OC)c3ccc(cc3)OCCN4CCCC4)c5ccccc5)C
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 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+/m0/s1
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = XZEUAXYWNKYKPL-URLMMPGGSA-N
}}
{{Infobox Birth control
| image =
| width =
| caption =
| bc_type = Antiestrogen
| date_first_use = 1991
| rate_type = Failure
| perfect_failure% = 2
| typical_failure% = 9
| duration_effect = One week
| reversibility = Immediate
| user_reminders = Taken twice weekly for first 13 weeks
| clinic_interval = Annually
| STD_protection_YesNo = No
| benefits = Non hormonal
| breastfeeding_YesNo = Yes<ref>{{cite journal | vauthors = Gupta RC, Paliwal JK, Nityanand S, Asthana OP, Lal J | title = Centchroman: a new non-steroidal oral contraceptive in human milk | journal = Contraception | volume = 52 | issue = 5 | pages = 301–305 | date = November 1995 | pmid = 8585887 | doi = 10.1016/0010-7824(95)00214-U }}</ref>
| periods = May disrupt
| weight_gain_loss = No proven effect
| risks = [[Delayed menstruation]]
| medical_notes = Only approved as a contraceptive in India
}}

'''Ormeloxifene''', also known as '''centchroman''', is one of the [[selective estrogen receptor modulator]]s,<ref name="pmid18675966">{{cite journal | vauthors = Makker A, Tandon I, Goel MM, Singh M, Singh MM | title = 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 | journal = Fertility and Sterility | volume = 91 | issue = 6 | pages = 2298–2307 | date = June 2009 | pmid = 18675966 | doi = 10.1016/j.fertnstert.2008.04.018 | doi-access = free }}</ref> or SERMs, a class of medication which acts on the [[estrogen receptor]]. It is best known as a [[nonsteroidal]] [[oral contraceptive]] which is taken once per week.  In India, ormeloxifene has been available as [[birth control]] since the early 1990s, and it was marketed there under the trade name '''Saheli''',<ref>{{cite web |url=http://www.hindlatex.com/TipsnGuidesdetails.aspx?valid=1&category=0&id=170&type=25 |title=HLL - Product Overview |archive-url=https://web.archive.org/web/20181101091837/http://www.hindlatex.com/TipsnGuidesdetails.aspx?valid=1&category=0&id=170&type=25 |archive-date=1 November 2018 |url-status=dead }}</ref> currently available free-of-cost for the women in India as '''Chhaya (Centchroman)'''.<ref name="humdo.nhp.gov.in">{{Cite web|url=https://humdo.nhp.gov.in/choice_for_planning/chhaya/|access-date=2020-06-29 |title=Chhaya | work = Centre for Health Informatics (CHI) of the National Health Portal (NHP), by the Ministry of Health and Family Welfare (MoHFW) | publisher = Government of India |archive-date=11 May 2021|archive-url=https://web.archive.org/web/20210511165301/https://humdo.nhp.gov.in/choice_for_planning/chhaya/ |url-status=dead}}</ref><ref>{{Cite web|date=2018-07-10|title=Contraception and women's empowerment: Here's how safe, reliable contraceptives are freeing women to earn|url=https://www.hindustantimes.com/india-news/contraception-and-women-s-empowerment-here-s-how-safe-reliable-contraceptives-are-freeing-women-to-earn/story-Ykx9JXI5xUjxaoPzcuuHuJ.html|access-date=2020-06-29|website=Hindustan Times|language=en}}</ref>

Ormeloxifene has also been licensed under the trade names '''Ormalin''', '''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]].<ref name=Review10>{{cite journal | vauthors = Lal J | title = Clinical pharmacokinetics and interaction of centchroman--a mini review | journal = Contraception | volume = 81 | issue = 4 | pages = 275–280 | date = April 2010 | pmid = 20227542 | doi = 10.1016/j.contraception.2009.11.007 }}</ref>

===Birth control===
Ormeloxifene may be used as a weekly oral contraceptive.<ref name=Review10/> The weekly schedule is an advantage for women who prefer an oral contraceptive, but find it difficult or impractical to adhere to a daily schedule required by other oral contraceptives.{{cn|date=January 2025}}

For the first twelve weeks of use, it is advised to take the ormeloxifene pill twice per week.<ref name=Review10/> From the thirteenth week on, it is taken once per week.<ref name=Review10/><ref>{{cite web | url=http://www.reproline.jhu.edu/english/1fp/1advances/old/1centch/ceorvw.htm | title=Home &#124; ReproLinePlus }}</ref>
The consensus is that backup protection in the first month is a cautious but sensible choice. A standard dose is 30&nbsp;mg weekly, but 60&nbsp;mg loading doses can reduce pregnancy rates by 38%.<ref name="pmid11257249">{{cite journal | vauthors = Lal J, Nitynand S, Asthana OP, Nagaraja NV, Gupta RC | title = Optimization of contraceptive dosage regimen of Centchroman | journal = Contraception | volume = 63 | issue = 1 | pages = 47–51 | date = January 2001 | pmid = 11257249 | doi = 10.1016/S0010-7824(00)00189-X }}</ref>

It has a failure rate of about 1-2% with ideal use which is slightly less effective than found for [[combined oral contraceptive pill]]s.<ref name="Singh_2001"/>

===Other indications===
* Ormeloxifene has also been tested in experimental setting as a treatment for [[menorrhagia]].<ref name="pmid19751337">{{cite journal | vauthors = Kriplani A, Kulshrestha V, Agarwal N | title = Efficacy and safety of ormeloxifene in management of menorrhagia: a pilot study | journal = The Journal of Obstetrics and Gynaecology Research | volume = 35 | issue = 4 | pages = 746–752 | date = August 2009 | pmid = 19751337 | doi = 10.1111/j.1447-0756.2008.00987.x | s2cid = 39172838 }}</ref>
* use in treatment of [[mastalgia]] and [[fibroadenoma]] has also been described.<ref name="pmid17431715">{{cite journal | vauthors = Dhar A, Srivastava A | title = Role of centchroman in regression of mastalgia and fibroadenoma | journal = World Journal of Surgery | volume = 31 | issue = 6 | pages = 1178–1184 | date = June 2007 | pmid = 17431715 | doi = 10.1007/s00268-007-9040-4 | s2cid = 22828570 }}</ref>

==Side effects==
There are concerns that ormeloxifene may cause [[delayed menstruation]].<ref>{{cite journal | vauthors = Shelly W, Draper MW, Krishnan V, Wong M, Jaffe RB | title = Selective estrogen receptor modulators: an update on recent clinical findings | journal = Obstetrical & Gynecological Survey | volume = 63 | issue = 3 | pages = 163–181 | date = March 2008 | pmid = 18279543 | doi = 10.1097/OGX.0b013e31816400d7 | s2cid = 23585991 }}</ref>

==Pharmacology==
Ormeloxifene is a [[selective estrogen receptor modulator]] (SERM). In some parts of the body, its action is [[estrogen]]ic (e.g., [[bone]]s), in other parts of the body, its action is [[antiestrogen]]ic (e.g., [[uterus]], [[breast]]s).<ref name="cdri.res.in">{{Cite web|title=CSIR-CDRI {{!}} Home|url=https://cdri.res.in/Centchroman.aspx|access-date=2020-06-29|website=cdri.res.in}}</ref><ref>{{cite conference | vauthors = Kumar GR, Rituraj K, Hemant BK, Singh MM | title = In-vitro anti-cancer breast activity of ormeloxifene is mediated via induction of apoptosis and autophagy. | conference = 37th annual conference of the endocrine society of India | date = November 2007 | volume = 30 | page = 35 }}</ref><ref name="pmid18279897">{{cite journal | vauthors = Nigam M, Ranjan V, Srivastava S, Sharma R, Balapure AK | title = Centchroman induces G0/G1 arrest and caspase-dependent apoptosis involving mitochondrial membrane depolarization in MCF-7 and MDA MB-231 human breast cancer cells | journal = Life Sciences | volume = 82 | issue = 11–12 | pages = 577–590 | date = March 2008 | pmid = 18279897 | doi = 10.1016/j.lfs.2007.11.028 }}</ref> 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,<ref name="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 tube]]s more quickly than is normal.<ref name="Singh_2001"/> Presumably, this combination of effects creates an environment such that if fertilization occurs, implantation will not be possible.<ref name="Singh_2001">{{cite journal | vauthors = Singh MM | title = Centchroman, a selective estrogen receptor modulator, as a contraceptive and for the management of hormone-related clinical disorders | journal = Medicinal Research Reviews | volume = 21 | issue = 4 | pages = 302–347 | date = July 2001 | pmid = 11410933 | doi = 10.1002/med.1011 | s2cid = 37474826 }}</ref>

==History==
Ormeloxifene was first discovered by [[Central Drug Research Institute|Central Drug Research Institute (CDRI)]] in [[Lucknow]], India.<ref name="cdri.res.in" /><ref>{{Cite web | url = http://www.cdri.res.in/Centchroman.aspx | title = Centchroman | publisher = CSIR-CDRI | access-date = 25 September 2018 | archive-url = https://web.archive.org/web/20190214191222/http://www.cdri.res.in/Centchroman.aspx | archive-date = 14 February 2019 | url-status = dead }}</ref> Ormeloxifene was marketed in [[Delhi]] in July 1991 and in [[India]] in 1992, under the brand names ''Saheli'' and ''Choice-7''.<ref name="Singh_2001" /><ref name="pmid20227542">{{cite journal | vauthors = Lal J | title = Clinical pharmacokinetics and interaction of centchroman--a mini review | journal = Contraception | volume = 81 | issue = 4 | pages = 275–280 | date = April 2010 | pmid = 20227542 | doi = 10.1016/j.contraception.2009.11.007 }}</ref>

Since 2018, Centchroman is provided free-of-cost to the women in India by the government under the brand name ''Chhaya''.<ref name="humdo.nhp.gov.in" /><ref name="Patrika News_2018">{{Cite web |date=22 May 2018 |title=परिवार नियोजन विधियों में छाया से अधिक अंतरा में बढ़ी महिलाओं की दिलचस्पी, जानिये इनके बारे में |url=https://www.patrika.com/lalitpur-news/know-about-antara-and-chhaya-tablet-for-pregnancy-2837077/ |access-date=2020-06-29 |website=Patrika News |language=hindi}}</ref><ref name="Bhatia_2018">{{Cite web |date=7 April 2018 |title=antara chhaya: Two months after launch, Antara, Chhaya contraceptives get good response from locals |url=https://timesofindia.indiatimes.com/city/meerut/two-months-after-launch-antara-chhaya-contraceptives-get-good-response-from-locals/articleshow/63633454.cms |access-date=2020-06-29 |website=The Times of India |language=en |vauthors=Bhatia I}}</ref><ref name="Shelar_2018">{{Cite news |date=2018-01-12 |title=BMC rolls out new contraceptive pill |language=en-IN |work=The Hindu |url=https://www.thehindu.com/news/cities/mumbai/bmc-rolls-out-new-contraceptive-pill/article22424017.ece |access-date=2020-06-29 |issn=0971-751X |vauthors=Shelar J}}</ref>

==Society and culture==

===Marketing===
As of 2009, ormeloxifene was legally available only in India.<ref>{{cite book| vauthors = Tribhuwan RD, Patil BD |title=Body image : human reproduction and birth control : a tribal perspective|year=2009|publisher=Discovery Pub. House|location=New Delhi|isbn=978-81-8356-388-8|pages=20|url=https://books.google.com/books?id=VYYoDoJTwIkC&pg=PA20}}</ref>

Ormeloxifene has been tested and licensed as a form of birth control, as well as a treatment for dysfunctional uterine bleeding.{{cn|date=January 2025}}
* 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 [[HLL Lifecare|Hindustan Latex Ltd.]], which now manufactures ormeloxifene as birth control under the trade names '''[[HLL Lifecare|Saheli]]''', '''Novex''', and '''Novex-DS'''.
* Torrent Pharmaceuticals has resumed manufacture of ormeloxifene under the trade name '''Sevista''', as a treatment for dysfunctional uterine bleeding.

== See also ==
* [[Levormeloxifene]]

== References ==
{{reflist}}

== Further reading ==
{{refbegin}}
* {{cite journal | vauthors = Ray S, Grover PK, Kamboj VP, Setty BS, Kar AB, Anand N | title = Antifertility agents. 12. Structure-activity relationship of 3,4-diphenylchromenes and -chromans | journal = Journal of Medicinal Chemistry | volume = 19 | issue = 2 | pages = 276–279 | date = February 1976 | pmid = 1249807 | doi = 10.1021/jm00224a014 }}
{{refend}}

== External links ==
* [https://www.nlm.nih.gov/cgi/mesh/2006/MB_cgi?mode=&term=Centchroman&field=entry United States National Library of Medicine] ''Centchroman'' entry in the [[Medical Subject Headings]] (MeSH) database
* [http://www.reproline.jhu.edu/english/1fp/1advances/old/1centch/ceorvw.htm Reproductive Health Online], a [[Johns Hopkins University]] affiliate providing information on Centchroman
* [http://www.cdriindia.org/Centchroman.htm Central Drug Research Institute] {{Webarchive|url=https://web.archive.org/web/20160805031658/http://www.cdriindia.org/centchroman.htm |date=5 August 2016 }}, Lucknow, [[India]]: a government-funded laboratory, conducting [[R&D]] on Centchroman as birth control.
* [https://web.archive.org/web/20190816151550/https://mohfw.nic.in/ Ministry of Health and Family Welfare] - Indian government site; information about availability of Saheli.

{{Estrogens and antiestrogens}}
{{Birth control methods}}
{{Other sex hormones and modulators of the genital system}}
{{Estrogen receptor modulators}}

[[Category:Chromanes]]
[[Category:Drugs acting on the genito-urinary system]]
[[Category:Hormonal contraception]]
[[Category:Phenol ethers]]
[[Category:1-Pyrrolidinyl compounds]]
[[Category:Selective estrogen receptor modulators]]