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Revision as of 11:50, 23 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,054 edits Saving copy of the {{drugbox}} taken from revid 461204583 of page Levonorgestrel for the Chem/Drugbox validation project (updated: 'DrugBank').		Latest revision as of 00:08, 14 January 2025 edit Arthurfragoso (talk | contribs)Extended confirmed users, Template editors4,591 edits dark mode fix
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			{{Short description|Hormonal medication used for birth control}}
	{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}}
			{{Distinguish|text= ]}}
	{{Drugbox
			{{Infobox drug
	| Verifiedfields = changed
	| Watchedfields = changed		| Watchedfields = changed
	| verifiedrevid = 376102204		| verifiedrevid = 462091161
	| IUPAC_name = 13-ethyl-17-ethynyl-17-hydroxy- 1,2,6,7,8,9,10,11,12,13,14,15,16, 17- tetradecahydrocyclopenta phenanthren-3-one
	| image = Levonorgestrel.svg		| image = Levonorgestrel.svg
			| image_class = skin-invert-image
	| image2 = Levonorgestrel3d.png
	| width2 = 200		| width = 225
			| image2 = Levonorgestrel molecule ball.png
			| width2 = 235
	<!--Clinical data-->		<!--Clinical data-->
	| tradename = Norplant		| tradename = Plan B, Julie, Mirena, Plan B One-Step, Liletta, others
			| Drugs.com = {{drugs.com|monograph|progestins-etonogestrel-levonorgestrel-norethindrone}}
	| MedlinePlus = a610021		| MedlinePlus = a610021
	| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->		| pregnancy_AU = B3
			| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Levonorgestrel Use During Pregnancy | website=Drugs.com | date=23 March 2020 | url=https://www.drugs.com/pregnancy/levonorgestrel.html | access-date=29 June 2020 | archive-date=2 July 2020 | archive-url=https://web.archive.org/web/20200702123750/https://www.drugs.com/pregnancy/levonorgestrel.html | url-status=live }}</ref>
	| pregnancy_US = <!-- A / B / C / D / X -->
	| pregnancy_category = X		| pregnancy_category = Contraindicated<ref name="Drugs.com pregnancy" />
			| routes_of_administration = ], ], ], ]
	| legal_AU = <!-- Unscheduled / S2 / S4 / S8 -->
			| class = ]; ]
	| legal_UK = <!-- GSL / P / POM / CD -->
			| ATC_prefix = G03
	| legal_US = <!-- OTC / Rx-only -->
	| legal_status =		| ATC_suffix = AC03
			| ATC_supplemental = {{ATC|G03|AD01}}
	| routes_of_administration = ]; insert (extended-release); oral
			<!-- Legal status -->
			| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->
			| legal_AU_comment =
			| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
			| legal_BR_comment =
			| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
			| legal_CA_comment =
			| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
			| legal_DE_comment =
			| legal_NZ = <!-- Class A, B, C -->
			| legal_NZ_comment =
			| legal_UK = POM
			| legal_UK_comment = <ref>{{cite web | title=Jaydess 13.5 mg intrauterine delivery system - Summary of Product Characteristics (SmPC) | website=(emc) | date=1 July 2022 | url=https://www.medicines.org.uk/emc/product/5297/smpc | access-date=1 July 2022 | archive-date=13 April 2021 | archive-url=https://web.archive.org/web/20210413020051/https://www.medicines.org.uk/emc/product/5297/smpc | url-status=live }}</ref>
			| legal_US = Rx-only
			| legal_US_comment = /&nbsp;OTC<ref name="Plan B One-Step FDA label">{{cite web | title=Plan B One-Step- levonorgestrel tablet | website=DailyMed | date=21 December 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6ce6b40e-14ac-47bd-a648-ddf9e452e559 | access-date=26 December 2022}}</ref>
			| legal_EU =
			| legal_EU_comment =
			| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
			| legal_UN_comment =
			| legal_status = Rx/OTC
	<!--Pharmacokinetic data-->		<!--Pharmacokinetic data-->
	| bioavailability = ~100%		| bioavailability = 95% (range 85–100%)<ref name="pmid16112947" /><ref name="pmid8842581" />
			| protein_bound = 98% (50% to ], 48% to {{abbrlink|SHBG|sex hormone-binding globulin}})<ref name="pmid16112947" />
	| protein_bound = 55%
			| metabolism = ] (], ], ])<ref name="pmid16112947" /><ref name="ShoupeHaseltine2012" />
	| metabolism = ] via ]
			| metabolites = • ]<ref name="pmid16112947" />
	| elimination_half-life = 36 ± 13 hours
			| elimination_half-life = 24–32 hours<ref name="pmid16112947" />
	| excretion = ]: 45%; ]:32%
			| excretion = ]: 20–67%<br />]: 21–34%<ref name="ShoupeHaseltine2012" />
	<!--Identifiers-->		<!--Identifiers-->
	| CASNo_Ref = {{cascite}}		| CAS_number_Ref = {{cascite|correct|CAS}}
	| CAS_number_Ref = {{cascite|correct|??}}
	| CAS_number = 797-63-7		| CAS_number = 797-63-7
	| ATC_prefix = G03
	| ATC_suffix = AC03
	| ATC_supplemental = {{ATC|G03|AD01}}
	| PubChem = 13109		| PubChem = 13109
			| IUPHAR_ligand = 2881
	| DrugBank_Ref = {{drugbankcite|correct|drugbank}}		| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
	| DrugBank = DB00367		| DrugBank = DB00367
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}		| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| ChemSpiderID = 12560		| ChemSpiderID = 12560
	| UNII_Ref = {{fdacite|changed|FDA}}		| UNII_Ref = {{fdacite|correct|FDA}}
	| UNII = 5W7SIA7YZW		| UNII = 5W7SIA7YZW
	| KEGG_Ref = {{keggcite|changed|kegg}}		| KEGG_Ref = {{keggcite|correct|kegg}}
	| KEGG = D00950		| KEGG = D00950
	| ChEBI_Ref = {{ebicite|changed|EBI}}		| ChEBI_Ref = {{ebicite|correct|EBI}}
	| ChEBI = 6443		| ChEBI = 6443
	| ChEMBL_Ref = {{ebicite|changed|EBI}}		| ChEMBL_Ref = {{ebicite|correct|EBI}}
	| ChEMBL = 1389		| ChEMBL = 1389
			| synonyms = LNG; LNG-EC; d-Norgestrel; d(–)-Norgestrel; <small>D</small>-Norgestrel; WY-5104; SH-90999; NSC-744007; 18-Methylnorethisterone; 17α-Ethynyl-18-methyl-19-nortestosterone; 17α-Ethynyl-18-methylestr-4-en-17β-ol-3-one; 13β-Ethyl-17α-hydroxy-18,19-dinorpregn-4-en-20-yn-3-one
	<!--Chemical data-->		<!--Chemical data-->
			| IUPAC_name = (8''R'',9''S'',10''R'',13''S'',14''S'',17''R'')-13-ethyl-17-ethynyl-17-hydroxy-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopentaphenanthren-3-one
	| C=21 | H=28 | O=2
			| C=21 | H=28 | O=2
	| molecular_weight = 312.446 g/mol
			<!-- | LogP =3.8 unk param -->
	| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
			| SMILES = CC12CC3(1CC2(C#C)O)CCC4=CC(=O)CC34
			| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChI = 1S/C21H28O2/c1-3-20-11-9-17-16-8-6-15(22)13-14(16)5-7-18(17)19(20)10-12-21(20,23)4-2/h2,13,16-19,23H,3,5-12H2,1H3/t16-,17+,18+,19-,20-,21-/m0/s1		| StdInChI = 1S/C21H28O2/c1-3-20-11-9-17-16-8-6-15(22)13-14(16)5-7-18(17)19(20)10-12-21(20,23)4-2/h2,13,16-19,23H,3,5-12H2,1H3/t16-,17+,18+,19-,20-,21-/m0/s1
	| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}		| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChIKey = WWYNJERNGUHSAO-XUDSTZEESA-N		| StdInChIKey = WWYNJERNGUHSAO-XUDSTZEESA-N
			| melting_point = 235
			| melting_high = 237
	}}		}}
			<!-- Definition and medical uses -->
			'''Levonorgestrel''' is a ] which is used in a number of ] methods.<ref name="Plan B One-Step FDA label" /><ref name=AHFS2015>{{cite web|title=Progestins (Etonogestrel, Levonorgestrel, Norethindrone)|url=https://www.drugs.com/monograph/progestins-etonogestrel-levonorgestrel-norethindrone.html|publisher=The American Society of Health-System Pharmacists|access-date=Aug 21, 2015|url-status=live|archive-url=https://web.archive.org/web/20150907223756/http://www.drugs.com/monograph/progestins-etonogestrel-levonorgestrel-norethindrone.html|archive-date=2015-09-07}}</ref> It is combined with an ] to make ]s.<ref>{{cite book|title=Postgraduate Gynecology.|date=2011|publisher=Jaypee Brothers Medical Pub|isbn=9789350250822|page=159|url=https://books.google.com/books?id=Kd7lNFPipaIC&pg=PT174|url-status=live|archive-url=https://web.archive.org/web/20150926022813/https://books.google.ca/books?id=Kd7lNFPipaIC&pg=PT174|archive-date=2015-09-26}}</ref> As an ], sold under the brand names '''Plan B One-Step''' and '''Julie''', among others, it is useful within 72 hours<!-- The reference clearly states 72 hours for Levonorgestrel. Also can be checked on various different medicine websites, including BNF, eMC, NICE guidelines, and various other reputable sources including the reference provided!! --> of unprotected ].<ref name="Plan B One-Step FDA label" /><ref name=AHFS2015/><ref>{{cite web | title = Levonorgestrel 1.5 mg Tablet Emergency Contraceptive: New Drug Application 21998, Supplement 5 | publisher = U.S. Food and Drug Administration | url = https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/021998Orig1s005SumR.pdf}}</ref> The more time that has passed since sex, the less effective the medication becomes, and it does not work after pregnancy (]) has occurred.<ref name=AHFS2015/> Levonorgestrel works by preventing ] or ] from occurring.<ref>{{Cite web |title=Now Is the Time to Change Label on Emergency Contraceptives |url=https://www.reliasmedia.com/articles/149425-now-is-the-time-to-change-label-on-emergency-contraceptives |access-date=2022-08-16 |website=Relias Media {{!}} Online Continuing Medical Education {{!}} Relias Media - Continuing Medical Education Publishing |language=en-US}}</ref> It decreases the chances of pregnancy by 57–93%.<ref name=Gem2010>{{cite journal | vauthors = Gemzell-Danielsson K | title = Mechanism of action of emergency contraception | journal = Contraception | volume = 82 | issue = 5 | pages = 404–409 | date = November 2010 | pmid = 20933113 | doi = 10.1016/j.contraception.2010.05.004 }}</ref> In an ] (IUD), such as '''Mirena''' among others, it is effective for the long-term prevention of ].<ref name=AHFS2015/> A ] is also available in some countries.<ref>{{cite book|title=Research on reproductive health at WHO: biennial report 2000-2001|date=2002|publisher=World health organization|location=Geneva|isbn=9789241562089|chapter-url=https://books.google.com/books?id=cvKaqyMOGjUC&pg=PT15|chapter=Chapter 1|url-status=live|archive-url=https://web.archive.org/web/20150926040930/https://books.google.ca/books?id=cvKaqyMOGjUC&pg=PT15|archive-date=2015-09-26}}</ref>
			<!-- Side effects and mechanism of action -->
			Common ]s include ], ], ]s, and ], ], or ].<ref name=AHFS2015/> When used as an emergency contraceptive, if pregnancy occurs, there is no evidence that its use ].<ref name=AHFS2015/> It is safe to use during ].<ref name=AHFS2015/> Birth control that contains levonorgestrel will not change the risk of ]s.<ref name=AHFS2015/> It is a ] and has effects similar to those of the hormone ].<ref name=AHFS2015/> It works primarily by preventing ] and closing off the ] to prevent the passage of ].<ref name=AHFS2015/>
			<!-- History, society, and culture -->
			Levonorgestrel was patented in 1960 and introduced for medical use together with ] in 1970.<ref name=Fis2006>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=479 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA479 |access-date=2020-08-05 |archive-date=2021-08-28 |archive-url=https://web.archive.org/web/20210828143151/https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA479 |url-status=live }}</ref><ref name=Roth2014/> It is on the ].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO }}</ref> It is available as a ].<ref name=Ric2014>{{cite book| vauthors = Hamilton RJ |title=Tarascon pocket pharmacopoeia : 2014 deluxe lab-pocket edition|date=2014|publisher=Jones & Bartlett Learning|location=Sudbury|isbn=9781284053999|pages=310–312|edition=15th|url=https://books.google.com/books?id=BwqEAgAAQBAJ&pg=PA310|url-status=live|archive-url=https://web.archive.org/web/20150926022049/https://books.google.ca/books?id=BwqEAgAAQBAJ&pg=PA310|archive-date=2015-09-26}}</ref> In the United States, levonorgestrel-containing emergency contraceptives are available ] (OTC) for all ages.<ref>{{cite press release |title=FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm358082.htm|access-date=2 February 2016|date=June 20, 2013|url-status=dead|archive-url=https://web.archive.org/web/20160114114254/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm358082.htm|archive-date=14 January 2016}}</ref> In 2020, it was the 323rd most commonly prescribed medication in the United States, with more than 800{{nbsp}}thousand prescriptions.<ref>{{cite web | title = Levonorgestrel - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Levonorgestrel | access-date = 7 October 2022 }}</ref>
			{{TOC limit}}
			==Medical uses==
			===Birth control===
			{{See also|Ethinylestradiol/levonorgestrel}}
			At low doses, levonorgestrel is used in ] and ] formulations of ]s, with available monophasic doses ranging from 100 to 250&nbsp;μg, and triphasic doses of 50&nbsp;μg, 75&nbsp;μg, and 125&nbsp;μg.<ref name="Drugs.com" /> It is combined with the estrogen ] in these formulations.<ref name="Drugs.com" />
			At very low daily dose of 30&nbsp;μg, levonorgestrel is used in some ] ].<ref name="Drugs.com" />
			Levonorgestrel is the active ingredient in a number of ] including Mirena and Skyla.<ref name="Drugs.com" /><ref name="pmid26732558" /> It is also the active ingredient in the ]s ] and ].<ref name="Drugs.com" /><ref name="pmid26732558" />
			One of the more common forms of contraception that contains only levonorgestrel is an IUD. One IUD, the Mirena, is a small hollow cylinder containing levonorgestrel and polydimethylsiloxane and covered with a release rate-controlling membrane.<ref name="Bao Q 2018">{{cite journal | vauthors = Bao Q, Gu B, Price CF, Zou Y, Wang Y, Kozak D, Choi S, Burgess DJ | title = Manufacturing and characterization of long-acting levonorgestrel intrauterine systems | journal = International Journal of Pharmaceutics | volume = 550 | issue = 1–2 | pages = 447–454 | date = October 2018 | pmid = 30195080 | doi = 10.1016/j.ijpharm.2018.09.004 | pmc = 6622171 }}</ref>
			===Emergency birth control===
			Levonorgestrel is used in ] (ECPs), both in a combined ] which includes estrogen, and as a levonorgestrel-only method. The levonorgestrel-only method uses levonorgestrel 1.5&nbsp;mg (as a single dose or as two 0.75&nbsp;mg doses 12 hours apart) taken within three days of unprotected sex. One study indicated that beginning as late as 120 hours (5 days) after intercourse could be effective.{{medical citation needed|date=January 2020}} However, taking more than one dose of emergency contraception does not increase the chance of pregnancy not happening. Planned Parenthood asserts "Taking the morning-after pill (also known as emergency contraception) multiple times doesn't change its effectiveness, and won't cause any long-term side effects."<ref>{{Cite web |title=How often can you take the morning-after pill? |url=https://www.plannedparenthood.org/learn/ask-experts/how-often-can-you-take-the-morning-after-pill |access-date=2022-06-18 |website=www.plannedparenthood.org |language=en |archive-date=2022-06-24 |archive-url=https://web.archive.org/web/20220624164100/https://www.plannedparenthood.org/learn/ask-experts/how-often-can-you-take-the-morning-after-pill |url-status=live }}</ref>
			The primary mechanism of action of levonorgestrel as a progestogen-only emergency contraceptive pill is, according to ] (FIGO), to prevent fertilization by inhibition of ] and thickening of cervical mucus.<ref name="Trussell 2011">{{cite book| vauthors = Trussell J, Schwarz EB | name-list-style = vanc |year=2011|chapter=Emergency contraception| veditors = Hatcher RA, Trussell J, Nelson AL, Cates Jr W, Kowal D, Policar MS |title=Contraceptive technology|edition=20th revised|location=New York|publisher=Ardent Media|isbn=978-1-59708-004-0|issn=0091-9721|oclc=781956734|pages=113–145 }} p. 121:<blockquote>Mechanism of action<br />Copper-releasing IUCs<br />When used as a regular or emergency method of contraception, copper-releasing IUCs act primarily to prevent fertilization. Emergency insertion of a copper IUC is significantly more effective than the use of ECPs, reducing the risk of pregnancy following unprotected intercourse by more than 99%.<sup>2,3</sup> This very high level of effectiveness implies that emergency insertion of a copper IUC must prevent some pregnancies after fertilization.<br />Emergency contraceptive pills<br />To make an informed choice, women must know that ECPs—like the birth control pill, patch, ring, shot, and implant,<sup>76</sup> and even like breastfeeding<sup>77</sup>—prevent pregnancy primarily by delaying or inhibiting ovulation and inhibiting fertilization, but may at times inhibit implantation of a fertilized egg in the endometrium. However, women should also be informed that the best available evidence indicates that ECPs prevent pregnancy by mechanisms that do not involve interference with post-fertilization events.<br />ECPs do not cause abortion<sup>78</sup> or harm an established pregnancy. Pregnancy begins with implantation according to medical authorities such as the US FDA, the National Institutes of Health<sup>79</sup> and the American College of Obstetricians and Gynecologists (ACOG).<sup>80</sup><br />''Ulipristal acetate (UPA).'' One study has demonstrated that UP can delay ovulation.<sup>81</sup>... Another study found that UPA altered the endometrium, but whether this change would inhibit implantation is unknown.<sup>82</sup><br />p. 122:<br />''Progestin-only emergency contraceptive pills.'' Early treatment with ECPs containing only the progestin levonorgestrel has been shown to impair the ovulatory process and luteal function.<sup>83–87</sup><br />p. 123:<br />''Combined emergency contraceptive pills.'' Several clinical studies have shown that combined ECPs containing ethinyl estradiol and levonorgestrel can inhibit or delay ovulation.<sup>107–110</sup></blockquote></ref><ref name="FSRH EC 2012">{{cite journal|author1=RCOG Faculty of Sexual|author2=Reproductive Healthcare|author3=Clinical Effectiveness Unit|date=January 2012|title=Clinical guidance: emergency contraception|journal=Clinical Guidance|location=London|publisher=Royal College of Obstetricians and Gynaecologists|issn=1755-103X|url=http://www.fsrh.org/pdfs/CEUguidanceEmergencyContraception11.pdf|access-date=2012-04-30|url-status=dead|archive-url=https://web.archive.org/web/20120526135043/http://www.fsrh.org/pdfs/CEUguidanceEmergencyContraception11.pdf|archive-date=2012-05-26}} p.3:<blockquote>How does EC work?<br />In 2002, a judicial review ruled that pregnancy begins at implantation, not fertilisation.<sup>8</sup> The possible mechanisms of action should be explained to the patient as some methods may not be acceptable, depending on individual beliefs about the onset of pregnancy and abortion.<br />Copper-bearing intrauterine device (Cu-IUD). Copper is toxic to the ovum and sperm and thus the copper-bearing intrauterine device (Cu-IUD) is effective immediately after insertion and works primarily by inhibiting fertilisation.<sup>9–11</sup> A systematic review on mechanisms of action of IUDs showed that both pre- and postfertilisation effects contribute to efficacy.<sup>11</sup> If fertilisation has already occurred, it is accepted that there is an anti-implantation effect,<sup>12,13</sup><br />Levonorgestrel (LNG). The precise mode of action of levonorgestrel (LNG) is incompletely understood but it is thought to work primarily by inhibition of ovulation.<sup>16,17</sup><br />Ulipristal acetate (UPA). UPA's primary mechanism of action is thought to be inhibition or delay of ovulation.<sup>2</sup></blockquote></ref><ref name="WHO 2010">{{cite web|author=UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP)|date=March 25, 2010|title=Fact sheet on the safety of levonorgestrel-alone emergency contraceptive pills (LNG ECPs)|location=Geneva|publisher=World Health Organization|url=http://whqlibdoc.who.int/hq/2010/WHO_RHR_HRP_10.06_eng.pdf|url-status=live|archive-url=https://web.archive.org/web/20120316134151/http://whqlibdoc.who.int/hq/2010/WHO_RHR_HRP_10.06_eng.pdf|archive-date=March 16, 2012}}<blockquote>Can LNG ECPs cause an abortion?<br />LNG ECPs do not interrupt an established pregnancy or harm a developing embryo.<sup>15</sup> The evidence available to date shows that LNG ECP use does not prevent a fertilized egg from attaching to the uterine lining. The primary mechanism of action is to stop or disrupt ovulation; LNG ECP use may also prevent the sperm and egg from meeting.<sup>16</sup></blockquote></ref><ref name="Speroff 2011">{{cite book| vauthors = Speroff L, Darney PD |year=2011|chapter=Special uses of oral contraception: emergency contraception, the progestin-only minipill|title=A clinical guide for contraception|edition=5th|location=Philadelphia|publisher=Lippincott Williams & Wilkins|pages=153–166|isbn=978-1-60831-610-6}} p. 155: <blockquote>Emergency postcoital contraception<br />Levonorgestrel<br />Mechanism and efficacy</blockquote></ref> FIGO has stated that: "review of the evidence suggests that LNG ECPs cannot prevent implantation of a fertilized egg. Language on implantation should not be included in LNG ECP product labeling."<ref name="Belluck 2012b">{{cite news| vauthors = Belluck P |date=June 6, 2012|title=No abortion role seen for morning-after pill|newspaper=The New York Times|page=A1|url=https://www.nytimes.com/2012/06/06/health/research/morning-after-pills-dont-block-implantation-science-suggests.html?pagewanted=all|url-status=live|archive-url=https://web.archive.org/web/20170227112421/http://www.nytimes.com/2012/06/06/health/research/morning-after-pills-dont-block-implantation-science-suggests.html?pagewanted=all|archive-date=February 27, 2017}}<br />{{cite news| vauthors = Belluck P |date=June 6, 2012|title=Drug's nickname may have aided politicization|newspaper=The New York Times |page=A14 |url= https://www.nytimes.com/2012/06/06/health/research/medications-nickname-may-have-helped-in-its-politcization.html}}</ref><ref name="FIGO 2011">{{cite web|author=] (FIGO) and International Consortium for Emergency Contraception (ICEC)|date=April 4, 2011|title=Mechanism of action: How do levonorgestrel-only emergency contraceptive pills (LNG ECPs) prevent pregnancy?|location=London|publisher=International Federation of Gynecology and Obstetrics|url=http://www.figo.org/sites/default/files/uploads/MOA_FINAL_2011_ENG.pdf|url-status=live|archive-url=https://web.archive.org/web/20141229024754/http://www.figo.org/sites/default/files/uploads/MOA_FINAL_2011_ENG.pdf|archive-date=December 29, 2014}}<blockquote>Levonorgestrel-only emergency contraceptive pills:<br />• Interfere with the process of ovulation;<br />• May possibly prevent the sperm and the egg from meeting.<br />Implications of the research:<br />• Inhibition or delay of ovulation is LNG ECPs principal and possibly only mechanism of action.<br />• Review of the evidence suggests that LNG-ECs cannot prevent implantation of a fertilized egg. Language on implantation should not be included in LNG ECP product labeling.<br />• The fact that LNG-ECs have no demonstrated effect on implantation explains why they are not 100% effective in preventing pregnancy and are less effective the later they are taken. Women should be given a clear message that LNG-ECs are more effective the sooner they are taken.<br />• LNG ECPs do not interrupt a pregnancy (by any definition of the beginning of pregnancy). However, LNG ECPs can prevent abortions by reducing unwanted pregnancies.</blockquote></ref> In November 2013, the ] (EMA) approved a change to the label saying it cannot prevent implantation of a fertilized egg.<ref name="Belluck 2013">{{cite news| vauthors = Belluck P |date=November 26, 2013|title=New birth control label counters lawsuit claim; European authorities found that a drug like Plan B One-Step cannot prevent fertilized eggs from implanting in the womb|newspaper=The New York Times|url=https://www.nytimes.com/2013/11/27/us/shift-on-birth-control-pill-may-affect-court-cases.html|access-date=March 5, 2014|url-status=live|archive-url=https://web.archive.org/web/20140304233807/http://www.nytimes.com/2013/11/27/us/shift-on-birth-control-pill-may-affect-court-cases.html|archive-date=March 4, 2014}}<br />{{cite web|author=HRA Pharma|author-link=HRA Pharma|date=November 2013|title=NorLevo 1.5 mg tablet Patient Information Leaflet (PIL)|location=Dublin|publisher=Irish Medicines Board|url=http://www.imb.ie/images/uploaded/swedocuments/2126041.PA1166_002_001.a60606c0-00f0-4866-bc34-91bdfd679b1e.000001PACKAGE%20LEAFLET%201.5.131128.pdf|access-date=March 5, 2014|quote=NorLevo works by stopping your ovaries from releasing an egg. It cannot stop a fertilized egg from attaching to the womb.|url-status=live|archive-url=https://web.archive.org/web/20140305170311/http://www.imb.ie/images/uploaded/swedocuments/2126041.PA1166_002_001.a60606c0-00f0-4866-bc34-91bdfd679b1e.000001PACKAGE%20LEAFLET%201.5.131128.pdf|archive-date=March 5, 2014}}<br />{{cite web|author=HRA Pharma|author-link=HRA Pharma|date=November 2013<!--|chapter=5.1 Pharmacodynamic properties-->|title=NorLevo 1.5 mg tablet Summary of Product Characteristics (SPC)|location=Dublin|publisher=Irish Pharmaceutical Healthcare Association|url=http://www.medicines.ie/medicine/11933/SPC/Norlevo+1.5mg+tablet/#PHARMACODYNAMIC_PROPS|access-date=March 5, 2014|archive-url=https://web.archive.org/web/20120615184048/http://www.medicines.ie/medicine/11933/SPC/Norlevo+1.5mg+tablet#PHARMACODYNAMIC_PROPS|archive-date=June 15, 2012|url-status=dead}}<br />{{cite news|author=European Medicines Agency|date=January 24, 2014|title=Review of emergency contraceptives started|location=London|publisher=European Medicines Agency|url=http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2014/01/news_detail_002010.jsp&mid=WC0b01ac058004d5c1|access-date=March 5, 2014|url-status=live|archive-url=https://web.archive.org/web/20140327002519/http://www.ema.europa.eu/ema/index.jsp?curl=pages%2Fnews_and_events%2Fnews%2F2014%2F01%2Fnews_detail_002010.jsp&mid=WC0b01ac058004d5c1|archive-date=March 27, 2014}}</ref>
			Other studies still find the evidence to be unclear.<ref>{{cite journal | vauthors = Mozzanega B, Cosmi E | s2cid = 6431709 | title = How do levonorgestrel-only emergency contraceptive pills prevent pregnancy? Some considerations | journal = Gynecological Endocrinology | volume = 27 | issue = 6 | pages = 439–42 | date = June 2011 | pmid = 20670097 | doi = 10.3109/09513590.2010.501885 | hdl = 11577/2476296 }}</ref> While it is unlikely that emergency contraception affects implantation it is impossible to completely exclude the possibility of post-fertilization effect.<ref>{{cite journal | vauthors = Leung VW, Levine M, Soon JA | title = Mechanisms of action of hormonal emergency contraceptives | journal = Pharmacotherapy | volume = 30 | issue = 2 | pages = 158–68 | date = February 2010 | pmid = 20099990 | doi = 10.1592/phco.30.2.158 | s2cid = 41337748 }}</ref>
			In November 2013, the EMA also approved a change to the label for ]'s ''NorLevo'' saying: "In clinical trials, contraceptive efficacy was reduced in women weighing 75 kg or more, and levonorgestrel was not effective in women who weighed more than 80 kg ."<ref name="Belluck 2013"/><ref name="Glasier 2011">{{cite journal | vauthors = Glasier A, Cameron ST, Blithe D, Scherrer B, Mathe H, Levy D, Gainer E, Ulmann A | title = Can we identify women at risk of pregnancy despite using emergency contraception? Data from randomized trials of ulipristal acetate and levonorgestrel | journal = Contraception | volume = 84 | issue = 4 | pages = 363–7 | date = October 2011 | pmid = 21920190 | doi = 10.1016/j.contraception.2011.02.009 }}</ref><ref name="Trussell 2014">{{cite web| vauthors = Trussell J, Raymond EG, Cleland K |date=February 2014|title=Emergency contraception: a last chance to prevent unintended pregnancy|location=Princeton|publisher=Office of Population Research at Princeton University, Association of Reproductive Health Professionals|url=http://ec.princeton.edu/questions/ec-review.pdf|access-date=April 9, 2014|url-status=dead|archive-url=https://web.archive.org/web/20100923040101/http://ec.princeton.edu/questions/ec-review.pdf|archive-date=September 23, 2010}}</ref> In November 2013 and January 2014, the FDA and the EMA said they were reviewing whether increased weight and ] (BMI) reduce the efficacy of emergency contraceptives.<ref name="Belluck 2013"/>
			An analysis of four WHO randomised clinical trials, published in January 2017, showed pregnancy rates of 1.25% (68/5428) in women with BMI under 25, 0.61% (7/1140) in women with BMI between 25 and 30, and 2.03% (6/295) in women with BMI over 30.<ref>{{cite journal | vauthors = Festin MP, Peregoudov A, Seuc A, Kiarie J, Temmerman M | title = Effect of BMI and body weight on pregnancy rates with LNG as emergency contraception: analysis of four WHO HRP studies | journal = Contraception | volume = 95 | issue = 1 | pages = 50–54 | date = January 2017 | pmid = 27527670 | pmc = 5357708 | doi = 10.1016/j.contraception.2016.08.001 }}</ref> These values yield an eight-fold reduction in efficacy for women with a BMI over 30 compared to women with a BMI under 25. However, emergency contraceptives remain effective regardless of BMI.
			===Hormone therapy===
			Levonorgestrel is used in combination with an ] in ].<ref name="Drugs.com" /><ref name="Kubíková2014" /> It is used under the brand name ''Klimonorm'' as a ] with ] and under the brand name ''Climara Pro'' as a ] with ].<ref name="Drugs.com" /><ref name="Kubíková2014" />
			===Available forms===
			As a type of emergency contraception, levonorgestrel is used after unprotected intercourse to reduce the risk of pregnancy.<ref name="Emergency Contraception - ACOG">{{Cite web|url=https://www.acog.org/Clinical-Guidance-and-Publications/Practice-Bulletins/Committee-on-Practice-Bulletins-Gynecology/Emergency-Contraception?IsMobileSet=false|title=Emergency Contraception - ACOG|website=www.acog.org|access-date=2019-06-01|archive-date=2019-10-09|archive-url=https://web.archive.org/web/20191009072551/https://www.acog.org/Clinical-Guidance-and-Publications/Practice-Bulletins/Committee-on-Practice-Bulletins-Gynecology/Emergency-Contraception?IsMobileSet=false|url-status=live}}</ref> However, it can serve different hormonal purposes in its different methods of delivery. It is available for use in a variety of forms:
			====By mouth====
			Levonorgestrel can be taken by mouth as a form of emergency birth control. The typical dosage is either 1.5&nbsp;mg taken once or 0.75&nbsp;mg taken 12–24 hours apart.<ref name=":0">{{cite journal | vauthors = Hansen LB, Saseen JJ, Teal SB | title = Levonorgestrel-only dosing strategies for emergency contraception | journal = Pharmacotherapy | volume = 27 | issue = 2 | pages = 278–84 | date = February 2007 | pmid = 17253917 | doi = 10.1592/phco.27.2.278 | s2cid = 24229915 }}</ref> The effectiveness in both methods is similar.<ref name=":0" /> The most widely used form of oral emergency contraception is the ], which contains a 1.5&nbsp;mg dosage of levonorgestrel.<ref name="Emergency Contraception - ACOG"/> Levonorgestrel-only emergency contraceptive pills are reported to have an 89% effectiveness rate if taken within the recommended 72 hours after sex.<ref name=":1">{{cite journal | vauthors = Shohel M, Rahman MM, Zaman A, Uddin MM, Al-Amin MM, Reza HM | title = A systematic review of effectiveness and safety of different regimens of levonorgestrel oral tablets for emergency contraception | journal = BMC Women's Health | volume = 14 | pages = 54 | date = April 2014 | pmid = 24708837 | pmc = 3977662 | doi = 10.1186/1472-6874-14-54 | doi-access = free }}</ref> The efficacy of the drug decreases by 50% for each 12-hour delay in taking the dose after the emergency contraceptive regimen has been started.<ref name=":1" />
			====Skin patch====
			{{See also|Estradiol/levonorgestrel}}
			] in the form of a skin patch is used under the brand name Climara Pro for ] in postmenstrual women, treating symptoms such as ]es or ].<ref name=":2">{{Cite web|url=https://www.mayoclinic.org/drugs-supplements/estradiol-and-levonorgestrel-transdermal-route/description/drg-20112971|title=Estradiol And Levonorgestrel (Transdermal Route) Description and Brand Names - Mayo Clinic|website=www.mayoclinic.org|access-date=2019-06-01|archive-date=2019-05-31|archive-url=https://web.archive.org/web/20190531172016/https://www.mayoclinic.org/drugs-supplements/estradiol-and-levonorgestrel-transdermal-route/description/drg-20112971|url-status=live}}</ref> The simultaneous delivery of a ] such as levonorgestrel is necessary for the protection of the ].<ref name=":3">{{Cite web|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021885lbl.pdf|title=Climara Pro® (Estradiol/Levonorgestrel Transdermal System)|website=Food and Drug Administration|access-date=2019-06-01|archive-date=2021-02-28|archive-url=https://web.archive.org/web/20210228161531/https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021885lbl.pdf|url-status=live}}</ref><ref>{{cite journal | vauthors = Mueck AO, Römer T | s2cid = 51886877 | title = Choice of progestogen for endometrial protection in combination with transdermal estradiol in menopausal women | journal = Hormone Molecular Biology and Clinical Investigation | volume = 37 | issue = 2 | date = July 2018 | pmid = 30063464 | doi = 10.1515/hmbci-2018-0033 | doi-access = free }}</ref>
			====Intrauterine device====
			The levonorgestrel intrauterine system (LNG-IUS) is a type of long-term birth control that releases the progestin into the uterine cavity.<ref name=Jeff2005>{{cite journal | vauthors = Jensen JT | s2cid = 43177026 | title = Contraceptive and therapeutic effects of the levonorgestrel intrauterine system: an overview | language = en-US | journal = Obstetrical & Gynecological Survey | volume = 60 | issue = 9 | pages = 604–12 | date = September 2005 | pmid = 16121115 | doi = 10.1097/01.ogx.0000175805.90122.af }}</ref><ref name="Bao Q 2018"/> Levonorgestrel is released at a constant, gradual rate of 0.02&nbsp;mg per day by the polydimethylsiloxane membrane of the device, which renders it effective for up to five years.<ref name=Jeff2005 /> Because it is inserted directly into the uterus, levonorgestrel is present in the endometrium in much higher concentrations that would result from a LNG-containing oral pill; the LNG-IUS delivers 391&nbsp;ng of levonorgestrel to the inner uterine region while a comparable oral contraceptive delivers only 1.35&nbsp;ng.<ref name=Jeff2005 /> This high level of levonorgestrel impedes the function of the endometrium, making it hostile for sperm transport, fertilization, and implantation of an ovum.<ref name=Jeff2005 />
			====Implant====
			]s of levonorgestrel have been marketed as ]s under the brand names Norplant and Jadelle and are available for use in some countries.<ref name="pmid18803473">{{cite journal | vauthors = Benagiano G, Gabelnick H, Farris M | title = Contraceptive devices: subcutaneous delivery systems | journal = Expert Review of Medical Devices | volume = 5 | issue = 5 | pages = 623–637 | date = September 2008 | pmid = 18803473 | doi = 10.1586/17434440.5.5.623 | s2cid = 207201811 }}</ref><ref name="Drugs.com" />
			==Contraindications==
			Known or suspected pregnancy is a ] of levonorgestrel as an emergency contraceptive.<ref name="PlanB_One-Step-Label" />
			==Side effects==
			{{See also|Progestin#Side effects}}
			After an intake of 1.5&nbsp;mg levonorgestrel in ]s, very common ]s (reported by 10% or more) included: ], ], ], ], ], ], ], ], ], ], and ]; common side effects (reported by 1% to 10%) included ], ], and ]; these side effects usually disappeared within 48&nbsp;hours.<ref>{{cite web|author=HRA Pharma|author-link=HRA Pharma|date=November 2013<!--|chapter=4.8 Undesireable effects-->|title=NorLevo 1.5 mg tablet Summary of Product Characteristics (SPC)|location=Dublin|publisher=Irish Pharmaceutical Healthcare Association|url=http://www.medicines.ie/medicine/11933/SPC/Norlevo+1.5mg+tablet/#UNDESIRABLE_EFFECTS|access-date=April 9, 2014|archive-url=https://web.archive.org/web/20120615184048/http://www.medicines.ie/medicine/11933/SPC/Norlevo+1.5mg+tablet#UNDESIRABLE_EFFECTS|archive-date=June 15, 2012|url-status=dead}}</ref><ref name="pmid24708811">{{cite journal | vauthors = Chen X, Wu X, Zhu H | title = Acute urticaria as a side effect of the Mirena® (levonorgestrel-releasing intrauterine system): a case report | journal = BMC Research Notes | volume = 7 | pages = 209 | date = April 2014 | pmid = 24708811 | pmc = 3992142 | doi = 10.1186/1756-0500-7-209 | doi-access = free }}</ref> However, the long term side effects common with oral contraceptives such as arterial disease are lower with levonorgestrel than in combination pills.{{medical citation needed|date=January 2020}}
			Levonorgestrel as a contraceptive ] is associated with a higher risk of ] than with non-use.<ref name="pmid31990981">{{cite journal | vauthors = Conz L, Mota BS, Bahamondes L, Teixeira Dória M, Françoise Mauricette Derchain S, Rieira R, Sarian LO | title = Levonorgestrel-releasing intrauterine system and breast cancer risk: A systematic review and meta-analysis | journal = Acta Obstet Gynecol Scand | volume = 99| issue = 8| pages = 970–982| date = January 2020 | pmid = 31990981 | doi = 10.1111/aogs.13817 | s2cid = 210946832 | doi-access = free }}</ref>
			==Overdose==
			] of levonorgestrel as an emergency contraceptive has not been described.<ref name="PlanB_One-Step-Label">{{cite web| title = Plan B One-Step (levonorgestrel) tablet, 1.5 mg, for oral use | date = July 2009 | work = Barr Pharmaceuticals, Inc.| publisher = U.S. Food and Drug Administration | url = https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021998lbl.pdf | archive-url = https://web.archive.org/web/20190417174924/https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021998lbl.pdf | archive-date=2019-04-17 }}</ref> ] and ] might be expected.<ref name="PlanB_One-Step-Label" />
			== Interactions ==
			If taken together with drugs that ] the ] ] ] ], levonorgestrel may be ] faster and may have lower effectiveness.<ref>{{cite web|author1=Medicines and Healthcare products Regulatory Agency|title=Levonorgestrel-containing emergency hormonal contraception: advice on interactions with hepatic enzyme inducers and contraceptive efficacy|url=https://www.gov.uk/drug-safety-update/levonorgestrel-containing-emergency-hormonal-contraception-advice-on-interactions-with-hepatic-enzyme-inducers-and-contraceptive-efficacy|website=GOV.UK|access-date=6 June 2017|archive-url=https://web.archive.org/web/20170121212031/https://www.gov.uk/drug-safety-update/levonorgestrel-containing-emergency-hormonal-contraception-advice-on-interactions-with-hepatic-enzyme-inducers-and-contraceptive-efficacy|archive-date=21 January 2017|language=en|date=15 September 2016|url-status=dead}}</ref>
			These include, but are not limited to barbiturates, bosentan, carbamazepine, felbamate, griseofulvin, oxcarbazepine, phenytoin, rifampin, St. John's wort and topiramate.{{medical citation needed|date=January 2020}}
			==Pharmacology==
			===Pharmacodynamics===
			Levonorgestrel is a ] with weak ]ic activity.<ref name="pmid16112947">{{cite journal |vauthors=Kuhl H |s2cid=24616324 |title=Pharmacology of estrogens and progestogens: influence of different routes of administration |journal=Climacteric |volume=8 |issue=Suppl 1 |pages=3–63 |date=August 2005 |pmid=16112947 |doi=10.1080/13697130500148875}}</ref> It has no other important ] activity, including no ]ic, ], or ] activity.<ref name="pmid16112947" /> The lack of significant ] or antimineralocorticoid activity with levonorgestrel is in spite of it having relatively high ] for the ], which is as much as 75% of that of ].<ref name="pmid16112947" />
			{{Relative affinities of levonorgestrel and metabolites}}
			====Progestogenic activity====
			Levonorgestrel is a ]; that is, an ] of the ] (PR), the main ] of the progestogen ] ].<ref name="pmid16112947" /> It has effects similar to those of the hormone ].<ref name=AHFS2015/> As a contraceptive, it works primarily by preventing ] and closing off the ] to prevent the passage of ].<ref name=AHFS2015/> The ] of levonorgestrel is 150 to 250{{nbsp}}μg/day or 2.5 to 6{{nbsp}}mg per cycle.<ref name="pmid16112947" /><ref name="pmid14670641">{{cite journal | vauthors = Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH | title = Classification and pharmacology of progestins | journal = Maturitas | volume = 46 | issue = Suppl 1 | pages = S7–S16 | date = December 2003 | pmid = 14670641 | doi = 10.1016/j.maturitas.2003.09.014 | url = }}</ref><ref name="KnörrKnörr-Gärtner2013">{{cite book| vauthors = Knörr K, Knörr-Gärtner H, Beller FK, Lauritzen C |title=Geburtshilfe und Gynäkologie: Physiologie und Pathologie der Reproduktion|url=https://books.google.com/books?id=tpmgBgAAQBAJ&pg=PA583|date=8 March 2013|publisher=Springer-Verlag|isbn=978-3-642-95583-9|pages=583–}}</ref><ref name="pmid2215269">{{cite journal | vauthors = Lauritzen C | title = Clinical use of oestrogens and progestogens | journal = Maturitas | volume = 12 | issue = 3 | pages = 199–214 | date = September 1990 | pmid = 2215269 | doi = 10.1016/0378-5122(90)90004-p | url = }}</ref>
			====Antigonadotropic effects====
			Due to its progestogenic activity, levonorgestrel has ] effects and is able to suppress the secretion of the ]s, ] and ], from the ].<ref name="pmid16112947" /> This in turn, results in suppression of ]al activity, including reduction of ] and ]al ] ] in both women and men.<ref name="pmid16112947" /><ref name="pmid20933120">{{cite journal |vauthors=Nieschlag E |title=Clinical trials in male hormonal contraception |journal=Contraception |volume=82 |issue=5 |pages=457–470 |date=November 2010 |pmid=20933120 |doi=10.1016/j.contraception.2010.03.020 |url=http://www.kup.at/kup/pdf/10172.pdf |access-date=2019-07-11 |archive-date=2020-12-05 |archive-url=https://web.archive.org/web/20201205082822/https://www.kup.at/kup/pdf/10172.pdf |url-status=live }}</ref> The ]-inhibiting dose of levonorgestrel in ] women is 50 to 60{{nbsp}}μg/day.<ref name="pmid16112947" /><ref name="pmid14670641" /><ref name="pmid22078182">{{cite journal | vauthors = Endrikat J, Gerlinger C, Richard S, Rosenbaum P, Düsterberg B | title = Ovulation inhibition doses of progestins: a systematic review of the available literature and of marketed preparations worldwide | journal = Contraception | volume = 84 | issue = 6 | pages = 549–57 | date = December 2011 | pmid = 22078182 | doi = 10.1016/j.contraception.2011.04.009 | url = }}</ref>
			In men, levonorgestrel causes marked suppression of circulating testosterone levels secondary to its antigonadotropic effects.<ref name="pmid12826683">{{cite journal | vauthors = Meriggiola MC, Farley TM, Mbizvo MT | title = A review of androgen-progestin regimens for male contraception | journal = Journal of Andrology | volume = 24 | issue = 4 | pages = 466–83 | date = 2003 | pmid = 12826683 | doi = 10.1002/j.1939-4640.2003.tb02695.x | quote = Based on animal studies and clinical studies in women, 19‐norderived progestins are known to be potent in terms of gonadotropin suppression (Couzinet et al, 1996). Among this class of steroidal compounds are norethisterone (NET), norethynodrel, and its dextrorotatory isomer LNG (ie, the biologically active form of this progestin). The progestins of this class are known to be potent suppressors of gonadotropin secretion, and when administered to men these compounds induced a profound suppression of sperm production (Frick, 1973). However, a decrease in libido and sexual potency was also reported, presumably due to the suppression of T production secondary to gonadotropin suppression (Kamischke et al, 2000b). Therefore, like other progestins available thus far, nor‐progestins should not be administered alone for male contraception because their residual androgenic activity is not sufficient to maintain androgen‐dependent physiological functions like libido or sexual potency (Kamischke et al, 2000a). | doi-access = free }}</ref> In healthy young men, levonorgestrel alone at a dose of 120 to 240&nbsp;μg/day orally for 2&nbsp;weeks suppressed testosterone levels from ~450&nbsp;ng/dL to ~248&nbsp;ng/dL (–45%).<ref name="pmid28189123">{{cite journal | vauthors = Zitzmann M, Rohayem J, Raidt J, Kliesch S, Kumar N, Sitruk-Ware R, Nieschlag E | title = Impact of various progestins with or without transdermal testosterone on gonadotropin levels for non-invasive hormonal male contraception: a randomized clinical trial | journal = Andrology | volume = 5 | issue = 3 | pages = 516–526 | date = May 2017 | pmid = 28189123 | doi = 10.1111/andr.12328 | s2cid = 41502711 | url = | doi-access = free }}</ref> Because of its effects on testosterone levels, and due to its androgenic activity being only weak and hence insufficient for purposes of androgen replacement in males, levonorgestrel has potent functional ]ic effects in men.<ref name="pmid12826683" /> Consequently, it can produce ]s like ] and ], among others.<ref name="pmid12826683" /> Levonorgestrel has been combined with an ] like ] or ] when it has been studied as a ].<ref name="pmid20933120" /><ref name="pmid12826683" />
			====Androgenic activity====
			Levonorgestrel is a weak agonist of the ] (AR), the main biological target of the ] sex hormone ].<ref name="pmid16112947" /> It is a weakly ]ic progestin and in women may cause androgenic ] changes and side effects such as decreased ] (SHBG) levels, decreased ] levels, ], and ].<ref name="pmid16112947" /><ref name="pmid7825629">{{cite journal | vauthors = Darney PD | title = The androgenicity of progestins | journal = The American Journal of Medicine | volume = 98 | issue = 1A | pages = 104S–110S | date = January 1995 | pmid = 7825629 | doi = 10.1016/s0002-9343(99)80067-9 }}</ref>
			In combination with a potent estrogen like ] however, all contraceptives containing androgenic progestins are negligibly androgenic in practice and in fact can be used to treat ]s like acne and ] in women.<ref name="pmid7825629" /> This is because ethinylestradiol causes a marked increase in SHBG levels and thereby decreases levels of free and hence bioactive testosterone, acting as a functional ].<ref name="pmid7825629" /> Nonetheless, contraceptives containing progestins that are less androgenic increase SHBG levels to a greater extent and may be more effective for such indications.<ref name="pmid7825629" /> Levonorgestrel is currently the most androgenic progestin that is used in contraceptives, and contraceptives containing levonorgestrel may be less effective for androgen-dependent conditions relative to those containing other progestins that are less androgenic.<ref name="KnausIsaacs2012">{{cite book| vauthors = Knaus JV, Isaacs JH |title=Office Gynecology: Advanced Management Concepts|url=https://books.google.com/books?id=dgnpBwAAQBAJ&pg=PA151|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4612-4340-3|pages=151–|url-status=live|archive-url=https://web.archive.org/web/20170908140504/https://books.google.com/books?id=dgnpBwAAQBAJ&pg=PA151|archive-date=8 September 2017}}</ref><ref name="GolanTashjian2011">{{cite book| vauthors = Golan DE, Tashjian AH, Armstrong EJ |title=Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy|url=https://books.google.com/books?id=WM7rvNUcrdsC&pg=PA516|date=15 December 2011|publisher=Lippincott Williams & Wilkins|isbn=978-1-60831-270-2|pages=516–|url-status=live|archive-url=https://web.archive.org/web/20170908140504/https://books.google.com/books?id=WM7rvNUcrdsC&pg=PA516|archive-date=8 September 2017}}</ref><ref name="BreastCancer1991">{{cite book|author=Committee on the Relationship Between Oral Contraceptives and BreastCancer|title=Oral Contraceptives and Breast Cancer|url=https://books.google.com/books?id=upYrAAAAYAAJ&pg=PA147|date=1 January 1991|publisher=National Academies|pages=147–|isbn=9780309044936|id=NAP:13774|url-status=live|archive-url=https://web.archive.org/web/20170908140504/https://books.google.com/books?id=upYrAAAAYAAJ&pg=PA147|archive-date=8 September 2017}}</ref>
			====Other activity====
			Levonorgestrel stimulates the ] of ] ] ]s '']'', an action that is independent of the classical PRs and is instead mediated via the ] (PGRMC1).<ref name="pmid23758160">{{cite journal | vauthors = Neubauer H, Ma Q, Zhou J, Yu Q, Ruan X, Seeger H, Fehm T, Mueck AO | s2cid = 29808177 | title = Possible role of PGRMC1 in breast cancer development | journal = Climacteric | volume = 16 | issue = 5 | pages = 509–13 | date = October 2013 | pmid = 23758160 | doi = 10.3109/13697137.2013.800038 }}</ref><ref name="pmid22335423">{{cite journal | vauthors = Ruan X, Neubauer H, Yang Y, Schneck H, Schultz S, Fehm T, Cahill MA, Seeger H, Mueck AO | s2cid = 11302554 | title = Progestogens and membrane-initiated effects on the proliferation of human breast cancer cells | journal = Climacteric | volume = 15 | issue = 5 | pages = 467–72 | date = October 2012 | pmid = 22335423 | doi = 10.3109/13697137.2011.648232 }}</ref> Certain other progestins act similarly in this assay, whereas ] acts neutrally.<ref name="pmid23758160" /><ref name="pmid22335423" /> It is unclear if these findings may explain the different risks of breast cancer observed with progesterone and progestins in ].<ref name="pmid31512725">{{cite journal | vauthors = Trabert B, Sherman ME, Kannan N, Stanczyk FZ | title = Progesterone and breast cancer | journal = Endocr. Rev. | volume = 41| issue = 2| pages = 320–344| date = September 2019 | pmid = 31512725 | doi = 10.1210/endrev/bnz001 | pmc = 7156851 | doi-access = free }}</ref>
			===Pharmacokinetics===
			The ] of levonorgestrel is approximately 95% (range 85 to 100%).<ref name="pmid16112947" /><ref name="pmid8842581">{{cite journal | vauthors = Fotherby K | title = Bioavailability of orally administered sex steroids used in oral contraception and hormone replacement therapy | journal = Contraception | volume = 54 | issue = 2 | pages = 59–69 | date = August 1996 | pmid = 8842581 | doi = 10.1016/0010-7824(96)00136-9 }}</ref> The ] of levonorgestrel is about 98%.<ref name="pmid16112947" /> It is bound 50% to ] and 48% to SHBG.<ref name="pmid16112947" /> Levonorgestrel is ] in the ], via ], ], and ] (specifically ] and ]).<ref name="pmid16112947" /><ref name="ShoupeHaseltine2012">{{cite book| vauthors = Shoupe D, Haseltine FP |title=Contraception |url= https://books.google.com/books?id=cpDhBwAAQBAJ&pg=PA22 |date=6 December 2012 |publisher=Springer Science & Business Media |isbn=978-1-4612-2730-4 |pages=22– |access-date=15 April 2018 |archive-date=28 August 2021 |archive-url= https://web.archive.org/web/20210828143221/https://books.google.com/books?id=cpDhBwAAQBAJ&pg=PA22 |url-status=live}}</ref> ] occurs primarily at the C2α and C16β positions, while reduction occurs in the A ring.<ref name="ShoupeHaseltine2012" /> ] is produced as an ] of levonorgestrel by ].<ref name="pmid16112947" /> The ] of levonorgestrel is 24 to 32&nbsp;hours, although values as short as 8&nbsp;hours and as great as 45&nbsp;hours have been reported.<ref name="pmid16112947" /><ref name="ShoupeHaseltine2012" /> About 20 to 67% of a single oral dose of levonorgestrel is ] in ] and 21 to 34% in ].<ref name="ShoupeHaseltine2012" />
			==Chemistry==
			{{See also|List of progestogens|List of androgens/anabolic steroids|Norgestrel}}
			Levonorgestrel, also known as 17α-ethynyl-18-methyl-19-nortestosterone or as 17α-ethynyl-18-methylestr-4-en-17β-ol-3-one, is a ] ] ] and a ] of ].<ref name="Elks2014">{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA887|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=887–|url-status=live|archive-url=https://web.archive.org/web/20170908140504/https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA887|archive-date=8 September 2017}}</ref><ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA605|year=2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=605–|url-status=live|archive-url=https://web.archive.org/web/20170908140504/https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA605|archive-date=2017-09-08}}</ref> It is the C13β or ] ] and ] form of ], the C13α or dextrorotatory isomer being inactive.<ref name="AlldredgeCorelli2012">{{cite book| vauthors = Alldredge BK, Corelli RL, Ernst ME |title=Koda-Kimble and Young's Applied Therapeutics: The Clinical Use of Drugs|url=https://books.google.com/books?id=qcVpuHngXK0C&pg=PA1072|date=1 February 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-60913-713-7|pages=1072–|url-status=live|archive-url=https://web.archive.org/web/20170908140504/https://books.google.com/books?id=qcVpuHngXK0C&pg=PA1072|archive-date=8 September 2017}}</ref><ref name="LaverySanfilippo2012">{{cite book| vauthors = Lavery JP, Sanfilippo JS |title=Pediatric and Adolescent Obstetrics and Gynecology|url=https://books.google.com/books?id=l9XTBwAAQBAJ&pg=PA248|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4612-5064-7|pages=248–|url-status=live|archive-url=https://web.archive.org/web/20170908140504/https://books.google.com/books?id=l9XTBwAAQBAJ&pg=PA248|archive-date=8 September 2017}}</ref> Levonorgestrel is more specifically a derivative of ] (17α-ethynyl-19-nortestosterone) and is the ] of the ] (18-methylestrane or 13β-ethylgonane) subgroup of the ] family of progestins.<ref name="OffermannsRosenthal2008">{{cite book| vauthors = Offermanns S, Rosenthal W |title=Encyclopedia of Molecular Pharmacology|url=https://books.google.com/books?id=iwwo5gx8aX8C&pg=PA390|date=14 August 2008|publisher=Springer Science & Business Media|isbn=978-3-540-38916-3|pages=390–|url-status=live|archive-url=https://web.archive.org/web/20170908140504/https://books.google.com/books?id=iwwo5gx8aX8C&pg=PA390|archive-date=8 September 2017}}</ref> Besides levonorgestrel itself, this group includes ], ], ], ], ], ], and ].<ref name="pmid24333799">{{cite journal | vauthors = Schindler AE | title = The "newer" progestogens and postmenopausal hormone therapy (HRT) | journal = J Steroid Biochem Mol Biol | volume = 142 | issue = | pages = 48–51 | date = July 2014 | pmid = 24333799 | doi = 10.1016/j.jsbmb.2013.12.003 | s2cid = 32126275 | url = }}</ref> ] and ] are C17β ]s of levonorgestrel.<ref name="GWU1987">{{cite book|title=Population Reports: Injectables and implants|url=https://books.google.com/books?id=zZhLAQAAIAAJ|year=1987|publisher=Department of Medical and Public Affairs, George Washington University.|quote=The Population Council also plans to test vaginal rings with two other progestins, ST-1435 and levonorgestrel acetate, alone and combined with ethinyl estradiol (168).|access-date=2018-04-15|archive-date=2021-04-20|archive-url=https://web.archive.org/web/20210420164649/https://books.google.com/books?id=zZhLAQAAIAAJ|url-status=live}}</ref><ref name="pmid6658872">{{cite journal | vauthors = Crabbé P, Archer S, Benagiano G, Diczfalusy E, Djerassi C, Fried J, Higuchi T | s2cid = 12896179 | title = Long-acting contraceptive agents: design of the WHO Chemical Synthesis Programme | journal = Steroids | volume = 41 | issue = 3 | pages = 243–53 | date = March 1983 | pmid = 6658872 | doi = 10.1016/0039-128X(83)90095-8 }}</ref> Levonorgestrel has a ] of 312.45&nbsp;g/mol and a ] (log ''P'') of 3.8.<ref name="PubChem">{{cite web | title=Levonorgestrel | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/13109 | access-date=18 August 2022}}</ref><ref name="DrugBank">{{cite web | title=Levonorgestrel: Uses, Interactions, Mechanism of Action | website=DrugBank Online | date=30 October 2013 | url=https://go.drugbank.com/drugs/DB00367 | access-date=18 August 2022}}</ref>
			==History==
			] (''rac''-13-ethyl-17α-ethynyl-19-nortestosterone), the ] containing levonorgestrel and ], was discovered by Hughes and colleagues at ] in 1963 via ] of ] (17α-ethynyl-19-nortestosterone).<ref name="Meikle1999">{{cite book| vauthors = Meikle AW |title=Hormone Replacement Therapy|url=https://books.google.com/books?id=ja2nBgAAQBAJ&pg=PA383|date=1 June 1999|publisher=Springer Science & Business Media|isbn=978-1-59259-700-0|pages=383–|quote=The gonanes share the structural modifications found in the estranes and also possess group at the position 13 and a keto group at position 3. Norgestrel was synthesized in 1963 and is a racemic mixture of dextro and levorotatory forms. The levorotatory form, levonorgestrel, provides the biological activity.|access-date=15 April 2018|archive-date=1 August 2020|archive-url=https://web.archive.org/web/20200801012058/https://books.google.com/books?id=ja2nBgAAQBAJ&pg=PA383|url-status=live}}</ref><ref name="SzejtliSzente2012">{{cite book|vauthors=Szejtli J, Szente L|title=Proceedings of the Eighth International Symposium on Cyclodextrins: Budapest, Hungary, March 31–April 2, 1996|url=https://books.google.com/books?id=hkbqCAAAQBAJ&pg=PA317|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-5448-2|pages=317–|quote= was discovered by Hughes et al. (1963).|access-date=15 April 2018|archive-date=28 August 2021|archive-url=https://web.archive.org/web/20210828143153/https://books.google.com/books?id=hkbqCAAAQBAJ&pg=PA317|url-status=live}}</ref><ref name="FilshieGuillebaud2013">{{cite book| vauthors = Filshie M, Guillebaud J |title=Contraception: Science and Practice|url=https://books.google.com/books?id=Ug3-BAAAQBAJ&pg=PA12|date=22 October 2013|publisher=Elsevier Science|isbn=978-1-4831-6366-6|pages=12–|quote=Norgestrel, developed by Wyeth and patented in 1964, was the first progestogen to be manufactured by total chemical synthesis. It was subsequently licensed to Schering AG, who separated the racemic mixture into an inactive structural isomer l-norgestrel and the active d-norgestrel -- more usually known as dextronorgestrel and levonorgestrel respectively, because of the optical isomerism that each displays.}}</ref><ref name="Marks2010">{{cite book| vauthors = Marks L |title=Sexual Chemistry: A History of the Contraceptive Pill|url=https://books.google.com/books?id=_i-s4biQs7MC&pg=PA76|year=2010|publisher=Yale University Press|isbn=978-0-300-16791-7|pages=73, 76|quote=In 1964 the pharmaceutical company Wyeth developed norgestrel, the first progestogen to be made from a total chemical synthesis. Subsequently licensed to Schering AG, norgestrel was used to develop levonorgestrel, another active progestogen later used for oral contraception.}}</ref> It was the first progestogen to be manufactured via ].<ref name="FilshieGuillebaud2013" /><ref name="Marks2010" /> Norgestrel was introduced for medical use as a ] with ] under the brand name ''Eugynon'' in ] in 1966 and under the brand name ''Ovral'' in the United States 1968, and as a ] under the brand name ''Ovrette'' in the United States in 1973.<ref name="Marks2010" /><ref name="Pohl2004" /><ref name="Ortiz-GómezSantesmases2016" /><ref name="ToneWatkins2007">{{cite book| vauthors = Tone A, Watkins ES |title=Medicating Modern America: Prescription Drugs in History|url=https://archive.org/details/isbn_9780814783016| url-access = registration |date=8 January 2007|publisher=NYU Press|isbn=978-0-8147-8300-9|pages=–119}}</ref> Following its discovery, norgestrel had been licensed by Wyeth to ], which separated the racemic mixture into its two ]s and identified levonorgestrel (13β-ethyl-17α-ethynyl-19-nortestosterone) as the active component of the mixture.<ref name="Roth2014" /><ref name="FilshieGuillebaud2013" /><ref name="Marks2010" /> Levonorgestrel was first studied in humans by 1970, and was introduced for medical use in Germany as a combined birth control pill with ethinylestradiol under the brand name ''Neogynon'' in August 1970.<ref name="Roth2014">{{cite book| vauthors = Roth K |title=Chemische Leckerbissen|url=https://books.google.com/books?id=FsKpBAAAQBAJ&pg=PA77|year=2014|publisher=John Wiley & Sons|isbn=978-3-527-33739-2|pages=77–|quote= and developed a biotechnological process for the preparation of the pure levorotatory enantiomer. This was the active ingredient levonorgestrel born. With the single-acting enantiomer, the dose and thus the liver burden could be halved again. The resulting Neogynon® contained 0.25 mg levonorgestrel and 0.05 mg ethinylestradiol and was introduced in 1970.]|access-date=2018-04-18|archive-date=2021-08-28|archive-url=https://web.archive.org/web/20210828143152/https://books.google.com/books?id=FsKpBAAAQBAJ&pg=PA77|url-status=live}}</ref><ref name="Pohl2004">{{cite book| vauthors = Pohl WG |title=Die wissenschaftliche Welt von gestern: die Preisträger des Ignaz L. Lieben-Preises 1865-1937 und des Richard Lieben-Preises 1912-1928 : ein Kapitel österreichischer Wissenschaftsgeschichte in Kurzbiografien|url=https://books.google.com/books?id=PtTuOXYBi3IC&pg=PA150|year=2004|publisher=Böhlau Verlag Wien|isbn=978-3-205-77303-0|pages=150–|quote=|access-date=2018-04-18|archive-date=2021-08-28|archive-url=https://web.archive.org/web/20210828143152/https://books.google.com/books?id=PtTuOXYBi3IC&pg=PA150|url-status=live}}</ref><ref name="Ortiz-GómezSantesmases2016">{{cite book| vauthors = Ortiz-Gómez T, Santesmases MJ |title=Gendered Drugs and Medicine: Historical and Socio-Cultural Perspectives|url=https://books.google.com/books?id=snUGDAAAQBAJ&pg=PT175|date=22 April 2016|publisher=Taylor & Francis|isbn=978-1-317-12981-3|pages=175–|quote=The 1966 marketing campaign for Schering's second contraceptive, Eugynon, (Schering AG Berline 1966, 11). In 1970 had already conducted an opinion poll among doctors in the run-up to the marketing campaign for the newly introduced Neogynon. |access-date=18 April 2018|archive-date=6 October 2021|archive-url=https://web.archive.org/web/20211006041600/https://books.google.com/books?id=SNuGDAAAQBAJ|url-status=live}}</ref><ref name="Albach1993">{{cite book| vauthors = Albach H |title=Culture and Technical Innovation: A Cross-Cultural Analysis and Policy Recommendations|url=https://books.google.com/books?id=jIi3AAAAIAAJ&q=neogynon|year=1993|publisher=Walter de Gruyter|isbn=978-3-11-013947-1|page=952|quote= After the OC market had risen sharply in 1968 and 1969, the launch of Neogynon / Schering and Stediril-d / Wyeth in August 1970 gave the market a fresh boost.]|access-date=August 5, 2020|archive-date=August 28, 2021|archive-url=https://web.archive.org/web/20210828143153/https://books.google.com/books?id=jIi3AAAAIAAJ&q=neogynon|url-status=live}}</ref><ref name="ApeloVeloso1970">{{cite journal| vauthors = Apelo R, Veloso I |title=Results of a controlled study employing d-norgestrel and ethinyl estradiol|journal=Contraception|volume=2|issue=6|year=1970|pages=391–400|issn=0010-7824|doi=10.1016/S0010-7824(70)80002-6 | quote = The results obtained in these series clinically confirmed the findings in animal work on the potency of d-norgestrel, i.e., that the biological activity of norgestrel resides largely in the d-enantlomer (5,6).}}</ref><ref name="BrosensVanAssche1971">{{cite journal | vauthors = Brosens I, Van Assche A, Wijnants P | title = Comparative clinical and morphological studies on 2 oral contraceptives which contain DL-norgestrel and D-norgestrel respectively. | year = 1971 | journal = Geburtshilfe und Frauenheilkunde | volume = 31 | issue = 3 | pages = 251–257 | url = https://www.popline.org/node/485953 | quote = Comparison of the effects of Eugynon and Neogynon (.05 mg ethinyl estradiol with .5 mg norgestrel or with .25 mg d-norgestrel, respectively) in 272 women is reported. The 2 preparations were comparable as regards effectiveness (100%), cycle control, and endometrial and cervical morphology. No clinical or biological complications occurred, and the incidence of minor side effects was very small. The d-norgestrel preparation (Neogynon) may be preferable for metabolic reasons because of its lower steroid dose. | access-date = 2018-04-15 | archive-date = 2018-04-15 | archive-url = https://web.archive.org/web/20180415190302/https://www.popline.org/node/485953 | url-status = live }}</ref> A more widely used formulation, containing lower doses of ethinylestradiol and levonorgestrel, was introduced under the brand name ''Microgynon'' by 1973.<ref name="Drugs.com" /><ref name="SchneiderSpona1974">{{cite journal| vauthors = Schneider W, Spona J, Matt K |title=Inhibition of ovulation by means of a combined preparation with reduced amounts of active substance|journal=Contraception|volume=9|issue=1|year=1974|pages=81–92|issn=0010-7824|doi=10.1016/0010-7824(74)90096-1}}</ref><ref name="pmid4614952">{{cite journal | vauthors = Brat T | title = Clinical trial with a new low oestrogen combined oral contraceptive | journal = Current Medical Research and Opinion | volume = 2 | issue = 8 | pages = 465–470 | date = 1974 | pmid = 4614952 | doi = 10.1185/03007997409115244 }}</ref> In addition to combined formulations, levonorgestrel was introduced as a progestogen-only pill under the brand names ''Microlut'' by 1972 and ''Microval'' by 1974.<ref name="Scharff1972">{{cite journal | vauthors = Scharff HJ | title = Clinical experience with Microlut. | journal = Medical News Schering | issue = 9 | date = 1972 | volume = 28 | pages = 2–9 | url = https://www.popline.org/node/488633 | archive-url = https://web.archive.org/web/20180415190319/https://www.popline.org/node/488633 | archive-date = 2018-04-15 }}</ref><ref name="pmid4817042">{{cite journal | vauthors = Lambotte R, Werbrouck-Navette J | title = | language = fr | journal = Revue Médicale de Liège | volume = 29 | issue = 6 | pages = 157–159 | date = March 1974 | pmid = 4817042 | url = https://www.popline.org/node/493200 | access-date = 2018-04-15 | url-status = live | archive-url = https://web.archive.org/web/20180415190418/https://www.popline.org/node/493200 | archive-date = 2018-04-15 }}</ref> Many other formulations and brand names of levonorgestrel-containing birth control pills have also been marketed.<ref name="Drugs.com" />
			Levonorgestrel, taken alone in a single high dose, was first evaluated as a form of ] in 1973.<ref name="KesserüLarrañaga1973">{{cite journal| vauthors = Kesserü E, Larrañaga A, Parada J |title=Postcoital contraception with D-norgestrel|journal=Contraception|volume=7|issue=5|year=1973|pages=367–379|issn=0010-7824|doi=10.1016/0010-7824(73)90139-X}}</ref> It was the second progestin to be evaluated for such purposes, following a study of ] in 1970.<ref name="KesserüLarrañaga1973" /><ref name="RubioBerman1970">{{cite journal| vauthors = Rubio B, Berman E, Larranaga A, Guiloff E |title=A new postcoital oral contraceptive|journal=Contraception|volume=1|issue=5|year=1970|pages=303–314|issn=0010-7824|doi=10.1016/0010-7824(70)90016-8}}</ref> In 1974, the ], which consisted of high doses of a combined birth control pill containing ethinylestradiol and norgestrel, was described as a method of emergency contraception by ] and colleagues, and saw widespread interest.<ref name="Balaji2009">{{cite book|author=Balaji|title=Textbook of Oral and Maxillofacial Surgery|url=https://books.google.com/books?id=xbp2B4fFL7wC&pg=RA1-PA569|date=19 November 2009|publisher=Elsevier India|isbn=978-81-312-0300-2|page=569|quote=There are two main methods involving oral emergency pills, commonly misleadingly described as the 'morning-after pill'. The first older method, developed in the mid-1970s, involves two high-dose combined pills containing oestrogen (50 ug ethinyloestradiol) and progesterone (0.25 mg levonorgestrel): the Yuzpe regime (Schering PC4 or Ovran). The second involves progesterone only (0.75 mg levonorgestrel), and therefore, has a lower incidence of side effects, in particular vomiting (6%).|access-date=15 April 2018|archive-date=28 August 2021|archive-url=https://web.archive.org/web/20210828143153/https://www.google.com/books/edition/Textbook_of_Oral_and_Maxillofacial_Surge/xbp2B4fFL7wC?hl=en&gbpv=1&pg=RA1-PA569&printsec=frontcover|url-status=live}}</ref><ref name="pmid4844513">{{cite journal | vauthors = Yuzpe AA, Thurlow HJ, Ramzy I, Leyshon JI | title = Post coital contraception--A pilot study | journal = The Journal of Reproductive Medicine | volume = 13 | issue = 2 | pages = 53–8 | date = August 1974 | pmid = 4844513 }}</ref> Levonorgestrel-only emergency contraception was introduced under the brand name ''Postinor'' by 1978.<ref name="Farkas1978">{{cite journal | vauthors = Farkas M | title = Post-coital contraception with Postinor, a preparation containing 0.75 mg d-norgestrel. | journal = Magyar Nöorvosok Lapja | date = 1978 | volume = 41 | pages = 474 | url = https://scholar.google.com/scholar?cluster=8190066278284376785 }}</ref> Ho and Kwan published the first study comparing levonorgestrel only and the Yuzpe regimen as methods of emergency contraception in 1993 and found that they had similar effectiveness but that levonorgestrel alone was better-tolerated.<ref name="ArtiniGenazzani2001">{{cite book | vauthors = Artini PG, Genazzani AR, Petraglia F | title = Advances in Gynecological Endocrinology | url = https://books.google.com/books?id=dknDdAonzlUC&pg=PA96 | date = 11 December 2001 | publisher = CRC Press | isbn = 978-1-84214-071-0 | pages = 96– | access-date = 15 April 2018 | archive-date = 28 August 2021 | archive-url = https://web.archive.org/web/20210828143313/https://books.google.com/books?id=dknDdAonzlUC&pg=PA96 | url-status = live }}</ref><ref name="pmid8473453">{{cite journal | vauthors = Ho PC, Kwan MS | title = A prospective randomized comparison of levonorgestrel with the Yuzpe regimen in post-coital contraception | journal = Human Reproduction | volume = 8 | issue = 3 | pages = 389–92 | date = March 1993 | pmid = 8473453 | doi = 10.1093/oxfordjournals.humrep.a138057 }}</ref> In relation to this, the Yuzpe regimen has largely been replaced as a method of emergency contraception by levonorgrestrel-only preparations.<ref name="King2013">{{cite book|author=King|title=Varney's Midwifery|url=https://books.google.com/books?id=dbaNAQAAQBAJ&pg=PA493|date=21 October 2013|publisher=Jones & Bartlett Publishers|isbn=978-1-284-02542-2|pages=493–|access-date=15 April 2018|archive-date=28 August 2021|archive-url=https://web.archive.org/web/20210828143335/https://books.google.com/books?id=dbaNAQAAQBAJ&pg=PA493|url-status=live}}</ref> Levonorgestrel-only emergency contraception was approved in the United States under the brand name ''Plan B'' in 1999, and has also been marketed widely elsewhere throughout the world under other brand names such as ''Levonelle'' and ''NorLevo'' in addition to ''Postinor''.<ref name="Drugs.com" /><ref name="Harrison-Woolrych2015">{{cite book| vauthors = Harrison-Woolrych M |title=Medicines For Women|url=https://books.google.com/books?id=A0ZvBgAAQBAJ&pg=PA205|date=28 January 2015|publisher=Springer|isbn=978-3-319-12406-3|pages=205–|access-date=15 April 2018|archive-date=28 August 2021|archive-url=https://web.archive.org/web/20210828143313/https://books.google.com/books?id=A0ZvBgAAQBAJ&pg=PA205|url-status=live}}</ref> In 2013, the ] approved ''Plan B One-Step'' for sale ] in the United States without a prescription or age restriction.<ref name="CBSNews2013">{{cite web |url=http://www.cbsnews.com/news/fda-approves-over-the-counter-sales-of-plan-b-one-step-for-all-ages/ |title=FDA approves over-the-counter sales of Plan B One-Step for all ages |website=] |date=20 June 2013 |access-date=2017-08-03 |url-status=live |archive-url=https://web.archive.org/web/20170803212130/http://www.cbsnews.com/news/fda-approves-over-the-counter-sales-of-plan-b-one-step-for-all-ages/ |archive-date=2017-08-03 }}</ref>
			Levonorgestrel has also been introduced for use as a ] under the brand names ''Mirena'' and ''Skyla'' among others, as a ] under the brand names ''Norplant'' and ''Jadelle'', as a ] with ] for ] under the brand name ''Klimonorm'', and as a ] with ] for menopausal hormone therapy under the brand name ''Climara Pro''.<ref name="Drugs.com" /><ref name="pmid26732558">{{cite journal | vauthors = Friend DR | title = Development of controlled release systems over the past 50 years in the area of contraception | journal = Journal of Controlled Release | volume = 240 | pages = 235–241 | date = October 2016 | pmid = 26732558 | doi = 10.1016/j.jconrel.2015.12.043 }}</ref><ref name="Kubíková2014">{{cite journal | author = Kubíková D | year = 2014 | title = | url = https://www.praktickelekarenstvi.cz/pdfs/lek/2014/02/05.pdf | journal = Praktické Lékárenství | volume = 10 | issue = 2| pages = 68–73 }}</ref> ] ]s of levonorgestrel such as ] and ] have been developed and studied as other forms of birth control such as long-acting ]s and ]s, but have not been marketed for medical use.<ref name="GWU1987"/><ref name="pmid6658872"/>
			==Society and culture==
			===Generic names===
			''Levonorgestrel'' is the ] of the drug and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}, {{abbrlink|USP|United States Pharmacopeia}}, {{abbrlink|BAN|British Approved Name}}, {{abbrlink|DCIT|Denominazione Comune Italiana}}, and {{abbrlink|JAN|Japanese Accepted Name}}, while ''lévonorgestrel'' is its {{abbrlink|DCF|Dénomination Commune Française}}.<ref name="Drugs.com">{{cite web |url=https://www.drugs.com/international/levonorgestrel.html |title=Levonorgestrel |access-date=2017-08-03 |url-status=live |archive-url=https://web.archive.org/web/20170803221748/https://www.drugs.com/international/levonorgestrel.html |archive-date=2017-08-03 }}</ref><ref name="Elks2014" /><ref name="IndexNominum2000" /> It is also known as ''d-norgestrel'', ''d(–)-norgestrel'', or ''<small>D</small>-norgestrel'', as well as by its developmental code names ''WY-5104'' (]) and ''SH-90999'' (]).<ref name="Drugs.com" /><ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="Scharff1972" />
			===Brand names===
			Levonorgestrel is marketed alone or in combination with an ] (specifically ], ], or ]) under a multitude of brand names throughout the world, including ''Alesse'', Altavera, Alysena, Amethia, Amethyst, Ashlyna, Aviane, Camrese, Chateal, ''Climara Pro'', ''Cycle 21'', Daysee, Emerres, Enpresse, Erlibelle, ''Escapelle'', Falmina, Introvale, Isteranda, ''Jadelle'', ''Jaydess'', Jolessa, ''Klimonorm'', Kurvelo, Kyleena, Lessina, ''Levlen'', Levodonna, ''Levonelle'', Levonest, Levosert, Levora, Liletta, ''Loette'', ''Logynon'', ''LoSeasonique'', Lutera, Lybrel, Marlissa, ''Microgynon'', ''Microlut'', ''Microvlar'', Min-Ovral, ''Miranova'', ''Mirena'', My Way, Myzilra, Next Choice, ''Nordette'', Norgeston, NorLevo, ''Norplant'', One Pill, Option 2, Orsythia, Ovima, Ovranette, ''Plan B'', ''Plan B One-Step'', Portia, ''Postinor'', ''Postinor-2'', Preventeza, Ramonna, '']'', Quartette, Quasense, ''Seasonale'', ''Seasonique'', ''Skyla'', Sronyx, Tri-Levlen, ''Trinordiol'', Triphasil, ''Triquilar'', ''Tri-Regol'', Trivora, and Upostelle, among many others.<ref name="Drugs.com" /><ref name="IndexNominum2000" /><ref name="Princeton2017">{{cite web | vauthors = Trussell J, Cleland K |date=2007-04-10 |title=Emergency Contraceptive Pills Worldwide |url=http://ec.princeton.edu/questions/dedicated.html |publisher=] |access-date=2007-05-28 |url-status=live |archive-url=https://web.archive.org/web/20070522214523/http://ec.princeton.edu/questions/dedicated.html |archive-date=2007-05-22 }}</ref> These formulations are used as emergency contraceptives, normal contraceptives, or in menopausal hormone therapy for the treatment of menopausal symptoms.{{medical citation needed|date=January 2020}}
			As an emergency contraceptive, levonorgestrel is often referred to colloquially as the "morning-after pill".<ref name="OatsAbraham2011">{{cite book| vauthors = Oats JJ, Abraham S |title=Llewellyn-Jones Fundamentals of Obstetrics and Gynaecology E-Book|url=https://books.google.com/books?id=oZjGAAAAQBAJ&pg=PA247|date=17 November 2011|publisher=Elsevier Health Sciences|isbn=978-0-7234-3719-2|pages=247–}}</ref><ref name="CarlsonEisenstat2004">{{cite book| vauthors = Carlson KJ, Eisenstat SA, Ziporyn TD |title=The New Harvard Guide to Women's Health|url=https://archive.org/details/newharvardguidet00carl| url-access = registration |year=2004|publisher=Harvard University Press|isbn=978-0-674-01282-0|pages=–}}</ref>
			===Availability===
			{{See also|List of progestogens available in the United States}}
			Levonorgestrel is very widely marketed throughout the world and is available in almost every country.<ref name="Drugs.com" /><ref name="IndexNominum2000" />
			===Accessibility===
			Levonorgestrel-containing emergency contraception is available ] in some countries, such as the United States.<ref name="CBSNews2013" /> On some college campuses, Plan B is available from vending machines.<ref>{{cite news |title=As some states seek to limit reproductive freedoms, BU opens 'Plan B' vending machine |url=https://www.bostonglobe.com/2022/03/27/metro/some-states-seek-limit-reproductive-freedoms-bu-opens-plan-b-vending-machine/ |author=Dugan Arnett |newspaper=] |date=March 27, 2022 |access-date=March 28, 2022 |archive-date=March 28, 2022 |archive-url=https://web.archive.org/web/20220328235410/https://www.bostonglobe.com/2022/03/27/metro/some-states-seek-limit-reproductive-freedoms-bu-opens-plan-b-vending-machine/ |url-status=live }}</ref>
			A policy update in 2015, required all pharmacies, clinics, and emergency departments run by ] (for Native Americans) to have Plan B One-Step in stock, to distribute it to any woman (or her representative) who asked for it without a prescription, age verification, registration or any other requirement, to provide orientation training to all staff regarding the medication, to provide unbiased and medically accurate information about emergency contraception, and to make someone available at all times to distribute the pill in case the primary staffer objected to providing it on religious or moral grounds.<ref>{{cite web | vauthors = Rankin K |url=http://www.colorlines.com/articles/policy-gives-native-women-equal-access-emergency-contraception |title=This Policy Gives Native Women Equal Access to Emergency Contraception |publisher=Colorlines |date= 2015-10-22|access-date=2015-10-24 |url-status=live |archive-url=https://web.archive.org/web/20151026014315/http://www.colorlines.com/articles/policy-gives-native-women-equal-access-emergency-contraception |archive-date=2015-10-26 }}</ref>
			==Research==
			Levonorgestrel has been studied in combination with ]s such as ] and ] as a ].<ref name="pmid20933120" /><ref name="pmid12826683" />
			==References==
			{{Reflist}}
			==External links==
			{{Commons-inline}}
			{{Progestogens and antiprogestogens}}
			{{Progesterone receptor modulators}}
			{{Androgen receptor modulators}}{{Birth control methods}}{{Portal bar|Medicine}}
			{{Authority control}}
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