Editing Emergency contraception (section)

==Mechanism of action==
The primary mechanism of action of progestogen-only emergency contraceptive pills is to prevent fertilization by inhibition of ovulation.<ref name="Trussell 2011"/><ref name="FSRH EC 2012"/><ref name="WHO 2010"/><ref name="Speroff 2011">{{cite book| vauthors = Speroff L, Darney P |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<br /> There is strong evidence that treatment with emergency contraception acts primarily by preventing or delaying ovulation and by preventing fertilization.<sup>22–26</sup> Studies have indicated that emergency contraception does not prevent implantation.<sup>27–29</sup> Experiments in monkeys and rats could detect no effect of a high dose of levonorgesterel administered postcoitally once fertilization had occurred.<sup>30,31</sup> The evidence indicates that a postfertilization effect does not contribute to the efficacy of emergency contraception.<sup>25,30–33</sup> Clinicians, pharmacists, and patients can be reassured that treatment with emergency contraception is not an abortifacient.<br />p. 157:<br />The use of progesterone receptor modulators for emergency contraception<br /> Mifepristone. In randomized trials, 10 mg mifepristone was as effective as 25, 50, or 600 mg. preventing about 80–85% of expected pregnancies (the same efficacy and side effects as with the levonorgestrel method), with a slight decrease in efficacy when treatment was delayed to 5 days after intercourse.<sup>16,52–54</sup><br />Ulipristal Acetate. Ulipristal acetate (ellaOne) has similar biologic effects as mifepristone and is approved for emergency contraception in Europe and is expected to become available in the U.S.in a single oral dose of 30 mg. Randomized trials demonstrated that ulipristal acetate is slightly more effective than the single 1.5 mg dose of levonorgestrel when used within 72 hours after sexual intercourse and even between 72 h and 120h.<sup>55,56</sup> ... Progesterone receptor modulators like ulipristal acetate and mifepristone suppress ovarian follicular growth and also delay endometrial maturation, manifested in a delay in menstruation after treatment. Ovulation can be temporarily postponed.<br />Other methods<br />Another method of emergency contraception is the insertion of a copper IUD, anytime during the preovulatory phase of the menstrual cycle and up to 5 days after ovulation. The failure rate (in a small number of studies) is very low, 0.1%.<sup>34,35</sup> This method definitely prevents implantation, but it is not suitable for women who are not candidates for intrauterine contraception, e.g., multiple sexual partners or a rape victim. The use of a copper IUD for emergency contraception is expensive, but not if it is retained as an ongoing method of contraception.}}</ref><ref name="Jensen">{{cite book| vauthors = Jensen JT, Mishell Jr DR |year=2012|chapter=Family planning: contraception, sterilization, and pregnancy termination| veditors = Lentz GM, Lobo RA, Gershenson DM, Katz VL |title=Comprehensive gynecology|edition  =6th|location=Philadelphia|publisher=Mosby Elsevier|isbn=978-0-323-06986-1|pages=215–272}} p. 257:{{blockquote|Emergency contraception<br />It is believed that the main mechanism of action of high-dose progestin emergency contraception is inhibition of ovulation, but other mechanisms may be involved... Taken together, these data are highly supportive of the concept that levonorgestrel emergency contraception has little or no effect on postovulation events but is highly effective when taken before ovulation. Levonorgestrel emergency contraception does not affect implantation and is not abortifacient.<br />Intrauterine insertion of a copper IUD within 5 to 10 days of midcycle coitus is a very effective method of preventing continuation of the pregnancy... The LNG-IUS should not be used for emergency contraception.<br />A study by the WHO reported that use of a single tablet of 10 mg of mifepristone was an effective emergency contraceptive with a pregnancy rate of 1.2%.<br />Ulipristal, also known as CDB-2914, has been studied as an emergency contraceptive pill... In 2009, European regulatory approval was granted for a 30-mg tablet of ulipristal (under the brand name of EllaOne) as an emergency contraceptive pill for use up to 5 days after unprotected intercourse. An application for approval in the United States is under review.}}</ref><ref name="Flatow 2012">{{cite web| vauthors = Flatow I |date=June 15, 2012|title=How the morning-after pill works (interview with Kristina Gemzell-Danielsson, MD, Professor and Chair, Division of Obstetrics and Gynecology, Karolinska Institute, Stockholm, Sweden)|work=Talk of the Nation Science Friday|location=New York|publisher=NPR|url=https://www.npr.org/2012/06/15/155110476/how-the-morning-after-pill-works}}</ref> The best available evidence is that they do not have any post-fertilization effects such as the prevention of [[implantation (human embryo)|implantation]].<ref name="Trussell 2011"/><ref name="FSRH EC 2012"/><ref name="WHO 2010"/><ref name="Speroff 2011"/><ref name="Jensen"/><ref name="Flatow 2012"/> The U.S. [[Food and Drug Administration|FDA]]-approved labels and European [[European Medicines Agency|EMA]]-approved labels (except for HRA Pharma's ''NorLevo'') levonorgestrel emergency contraceptive pills (based on labels for regular [[combined oral contraceptive pill|oral contraceptive pills]]) say they may cause [[endometrium|endometrial]] changes that discourage implantation.<ref name="Belluck 2012b">{{cite news|last1=Belluck|first1=Pam|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}}<br />{{cite news|last=Belluck|first=Pam|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>{{cite web|author=Bayer|date=March 22, 2010|title=Summary of Product Characteristics: Levonelle One Step 1500 mcg; 5.1 Pharmacodynamic properties|location=London|publisher=electronic Medicines Compendium (eMC), Datapharm|url=http://www.medicines.org.uk/EMC/medicine/15227/SPC/Levonelle+One+Step/#PHARMACODYNAMIC_PROPS|quote=The precise mode of action of Levonelle One Step is not known. At the recommended regimen, levonorgestrel is thought to work mainly by preventing ovulation and fertilisation if intercourse has taken place in the preovulatory phase when the likelihood of fertilisation is the highest. It may also cause endometrial changes that discourage implantation. Levonelle One Step is not effective once the process of implantation has begun.}}<br />{{cite web|author=HRA Pharma|author-link=HRA Pharma|date=July 19, 2011|title=Summary of Product Characteristics: NorLevo 1.5 mg; 5.1 Pharmacodynamic properties|location=Dublin|publisher=Irish Pharmaceutical Healthcare Association|url=http://www.medicines.ie/medicine/11933/SPC/Norlevo+1.5mg+tablet/#PHARMACODYNAMIC_PROPS|quote=The precise mode of action of Norlevo 1.5 mg is not known. At the used regimen, levonorgestrel is believed to suppress ovulation thus preventing fertilization if the intercourse has taken place in the preovulatory phase when the likelihood of fertilization is the highest. It could also prevent implantation. It is not effective once the process of implantation has begun.|access-date=August 21, 2012|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}}</ref><ref>{{cite web|author=Duramed Pharmaceuticals/Barr Pharmaceuticals (now Teva Women's Health)|date=July 9, 2010|title=Prescribing information: Plan B One-Step; 12.1 Mechanism of action|location=Silver Spring, Md.|publisher=FDA Center for Drug Evaluation and Research (CDER)|page=4|url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021998lbl.pdf|quote=Emergency contraceptive pills are not effective if a woman is already pregnant. Plan B One-Step is believed to act as an emergency contraceptive principally by preventing ovulation or fertilization (by altering tubal transport of sperm and/or ova). In addition, it may inhibit implantation (by altering the endometrium). It is not effective once the process of implantation has begun.}}</ref> Daily use of regular oral contraceptive pills can alter the endometrium (although this has not been proven to interfere with implantation), but the isolated use of a levonorgestrel emergency contraceptive pill does not have time to alter the endometrium.<ref name="Belluck 2012b"/>

In March 2011, the [[International Federation of Gynecology and Obstetrics]] (FIGO) issued a statement that: "review of the evidence suggests that LNG [levonorgestreol] ECPs cannot prevent implantation of a fertilized egg. Language on implantation should not be included in LNG ECP product labeling."<ref name="Belluck 2012b"/><ref name="FIGO 2011">{{cite web|author=[[International Federation of Gynecology and Obstetrics]] (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.cecinfo.org/icec-publications/mechanism-action-levonorgestrel-emergency-contraceptive-pills-lng-ecps-prevent-pregnancy/|access-date=June 17, 2018|archive-date=July 20, 2022|archive-url=https://web.archive.org/web/20220720001426/https://www.cecinfo.org/icec-publications/mechanism-action-levonorgestrel-emergency-contraceptive-pills-lng-ecps-prevent-pregnancy/|url-status=usurped}}{{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 the only mechanism of action.<br />• Review of the evidence suggests that LNG ECPs cannot prevent the implantation of a fertilized egg. Language on implantation should not be included in LNG ECP product labeling.<br />• The fact that LNG ECPs 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 ECPs 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.}}</ref> In June 2012, a ''[[The New York Times|New York Times]]'' editorial called on the FDA to remove from the label the unsupported suggestion that levonorgestrel emergency contraceptive pills inhibit implantation.<ref name="NYT 2012">{{cite news|author=editorial|date=June 9, 2012|title=How morning-after pills really work|newspaper=The New York Times|page=A20|url=https://www.nytimes.com/2012/06/09/opinion/how-morning-after-pills-really-work.html|quote=The F.D.A. now acknowledges that the emerging data suggest the morning-after pill, often called Plan B, does not inhibit implantation. It should remove that unsupported suggestion from the label.}}</ref> In November 2013, the [[European Medicines Agency]] (EMA) approved a change to the label for HRA Pharma's ''NorLevo'' saying it cannot prevent implantation of a fertilized egg.<ref name="Belluck 2014">{{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}}<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.}}<br />{{cite web|author=HRA Pharma|author-link=HRA Pharma|date=November 2013|title=NorLevo 1.5 mg tablet Summary of Product Characteristics: 5.1 Pharmacodynamic properties (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/20140305164336/http://www.medicines.ie/medicine/11933/SPC/Norlevo+1.5mg+tablet/#PHARMACODYNAMIC_PROPS|archive-date=March 5, 2014|url-status=dead}}<br />{{cite news|publisher=European Medicines Agency|date=January 24, 2014|title=Review of emergency contraceptives started|location=London|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|archive-date=March 27, 2014|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|url-status=dead}}</ref>

Progestogen-only emergency contraceptive does not appear to affect the function of the fallopian tubes or increase the rate of ectopic pregnancies.<ref name="Davidoff 2006"/>

The primary mechanism of action of [[selective progesterone receptor modulator|progesterone receptor modulator]] emergency contraceptive pills like low-dose and mid-dose [[mifepristone]] and [[ulipristal acetate]] is to prevent fertilization by inhibition or delay of ovulation.<ref name="Trussell 2011"/><ref name="FSRH EC 2012"/><ref name="Speroff 2011"/><ref name="Jensen"/><ref name="Flatow 2012"/> One clinical study found that post-ovulatory administration of ulipristal acetate altered the endometrium, but whether the changes would inhibit implantation is unknown.<ref name="Trussell 2011"/><ref name="Stratton 2010">{{cite journal | vauthors = Stratton P, Levens ED, Hartog B, Piquion J, Wei Q, Merino M, Nieman LK | title = Endometrial effects of a single early luteal dose of the selective progesterone receptor modulator CDB-2914 | journal = Fertility and Sterility | volume = 93 | issue = 6 | pages = 2035–2041 | date = April 2010 | pmid = 19200989 | pmc = 2911236 | doi = 10.1016/j.fertnstert.2008.12.057 }} Post-ovulatory early luteal phase administration of 10–100 mg of ulipristal acetate resulted in a statistically significant dose-dependent 0.6 ± 2.2 mm ''decrease'' in endometrial thickness from a baseline of 10.3 ± 2.3 mm to 9.7 ± 1.8 mm (vs. a 1.3 ± 2.3 mm ''increase'' in endometrial thickness from a baseline of 10.2 ± 3.2 mm to 11.5 ± 4.1 mm with placebo administration) which the authors hypothesized could hamper implantation.</ref> The European EMA-approved labels for ulipristal acetate emergency contraceptive pills do not mention an effect on implantation, but the U.S. FDA-approved label says: "alterations to the endometrium that may affect implantation may also contribute to efficacy."<ref name="Belluck 2012b"/><ref>{{cite web|author=HRA Pharma|author-link=HRA Pharma|date=March 15, 2012|title=Summary of Product Characteristics: ellaOne 30 mg; 5.1 Pharmacodynamic properties|location=London|publisher=European Medicines Agency|page=7|url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001027/WC500023670.pdf|quote=Ulipristal acetate is an orally-active synthetic selective progesterone receptor modulator which acts via high-affinity binding to the human progesterone receptor. The primary mechanism of action is inhibition or delay of ovulation. Pharmacodynamic data show that even when taken immediately before ovulation is scheduled to occur, ulipristal acetate is able to postpone follicular rupture in some women.|access-date=August 21, 2012|archive-date=May 3, 2012|archive-url=https://web.archive.org/web/20120503102312/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001027/WC500023670.pdf|url-status=dead}}</ref><ref>{{cite web|author=Watson Pharma (under license from [[HRA Pharma]])|date=May 2, 2012|title=Prescribing information: Ella; 12.1 Mechanism of action|location=Silver Spring, Md.|publisher=FDA Center for Drug Evaluation and Research (CDER)|pages=4–5|url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022474s002lbl.pdf|quote=When taken immediately before ovulation is to occur, ella postpones follicular rupture. The likely primary mechanism of action of ulipristal acetate for emergency contraception is therefore inhibition or delay of ovulation; however, alterations to the endometrium that may affect implantation may also contribute to efficacy... The pharmacodynamics of ulipristal acetate depends on the timing of administration in the menstrual cycle. Administration in the mid-follicular phase causes inhibition of folliculogenesis and reduction of estradiol concentration. Administration at the time of the luteinizing hormone peak delays follicular rupture by 5 to 9 days. Dosing in the early luteal phase does not significantly delay endometrial maturation but decreases endometrial thickness by 0.6 ± 2.2 mm (mean ± SD).}}</ref>

The primary mechanism of action of [[IUD with copper|copper-releasing intrauterine devices]] (IUDs) as emergency contraceptives is to prevent fertilization because of copper toxicity to [[Spermatozoon|sperm]] and [[ovum|ova]].<ref name="Trussell 2011"/><ref name="FSRH EC 2012"/> The very high effectiveness of copper-releasing IUDs as emergency contraceptives implies that they must also prevent some pregnancies by post-fertilization effects such as prevention of implantation.<ref name="Trussell 2011"/><ref name="FSRH EC 2012"/><ref name="Speroff 2011"/>