Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Etonogestrel: Difference between pages

{{Short description|Chemical compound}}

| Verifiedfields = verified

| Watchedfields = verified

| verifiedrevid = 461098012

| IUPAC_name = (8''S'',9''S'',10''R'',13''S'',14''S'',17''R'')-13-Ethyl-17-ethynyl-17-hydroxy-11-methylidene-2,6,7,8,9,10,12,14,15,16-decahydro-1''H''-cyclopenta[''a'']phenanthren-3-one

| image = Etonogestrel.svg

| width = 225

| image2 = Etonogestrel molecule ball.png

| width2 = 235

| tradename = Circlet, Implanon, Nexplanon, others

| Drugs.com = {{drugs.com|ppa|etonogestrel}}

| pregnancy_AU = B3

| pregnancy_category =

| routes_of_administration = [[Subcutaneous implant]], [[vaginal ring]]

| class = [[Progestogen (medication)|Progestogen]]; [[Progestin]]

| ATC_prefix = G03

| ATC_suffix = AC08

| ATC_supplemental =

| legal_CA = Rx-only

| legal_CA_comment = <ref>{{cite web|url=https://pdf.hres.ca/dpd_pm/00060728.PDF|title=NEXPLANON : Etonogestrel extended release subdermal implant|website=Pdf.hres.ca|access-date=2022-06-08|archive-date=2022-06-10|archive-url=https://web.archive.org/web/20220610025026/https://pdf.hres.ca/dpd_pm/00060728.PDF|url-status=live}}</ref>

| legal_EU = Rx-only

| legal_EU_comment = <ref>{{cite web|url=https://www.ema.europa.eu/documents/psusa/etonogestrel-list-nationally-authorised-medicinal-products-psusa/00001331/202109_en.pdf|title=List of nationally authorised medicinal products : Active substance: etonogestrel : Procedure no.: PSUSA/00001331/202109|website=Ema.europa.eu|access-date=2022-06-08|archive-date=2022-06-10|archive-url=https://web.archive.org/web/20220610025027/https://www.ema.europa.eu/en/documents/psusa/etonogestrel-list-nationally-authorised-medicinal-products-psusa/00001331/202109_en.pdf|url-status=live}}</ref>

| bioavailability = Implant: 100%<ref name="NexplanonLabel" /><br />Vaginal ring: 100%<ref name="NuvaRingLabel" />

| protein_bound = ≥98% (66% to [[human serum albumin|albumin]], 32% to {{abbrlink|SHBG|sex hormone-binding globulin}})<ref name="NexplanonLabel" />

| metabolism = [[Liver]] ([[CYP3A4]])<ref name="NexplanonLabel" /><ref name="NuvaRingLabel" />

| elimination_half-life = 21–38 hours<ref name="RunnebaumRabe2012" /><ref name="Mosby2001">{{cite book|title=Mosby's GenRx: A Comprehensive Reference for Generic and Brand Prescription Drugs|url=https://books.google.com/books?id=QxsobYYgm8oC|year=2001|publisher=Mosby|isbn=978-0-323-00629-3|page=687|quote=The elimination half-life for 3-keto-desogestrel is approximately 38 ± 20 hours at steady state.}}</ref><ref name="NexplanonLabel" /><ref name="NuvaRingLabel" />

| excretion = [[Urine]] (major), [[feces]] (minor)<ref name="NexplanonLabel" /><ref name="NuvaRingLabel" />

| IUPHAR_ligand = 7590

| KEGG_Ref = {{keggcite|correct|kegg}}

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| synonyms = ORG-3236; SCH-900702 (with {{abbrlink|EE|ethinylestradiol}}); 3-Ketodesogestrel; 3-Oxodesogestrel; 11-Methylenelevonorgestrel;<ref name="Ryan1999">{{cite book| vauthors = Ryan KJ |title=Kistner's Gynecology and Women's Health|url=https://books.google.com/books?id=i8xsAAAAMAAJ|year=1999|publisher=Mosby|isbn=978-0-323-00201-1|page=300}}</ref> 11-Methylene-17α-ethynyl-18-methyl-19-nortestosterone; 11-Methylene-17α-ethynyl-18-methylestr-4-en-17β-ol-3-one

| C=22 | H=28 | O=2

| SMILES = CC[C@]12CC(=C)[C@H]3[C@H]([C@@H]1CC[C@]2(C#C)O)CCC4=CC(=O)CC[C@H]34

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

{{Infobox Birth control

|name = Etonogestrel birth control implant

|image = Implanon 03.jpg

|width =

|caption = Implanon

|bc_type = Hormonal<br />Progestin-only implant

|synonyms = Etonogestrel contraceptive implant

|tradename = Implanon, Nexplanon, others

| Drugs.com = {{Drugs.com|pro|implanon}}

|date_first_use = 1998 {{IDN}}

|rate_type = Failure

|perfect_failure% = 0.05

|perfect_failure_ref =<ref name=Trus2011>{{cite book| vauthors = Trussell J |year=2011|chapter=Contraceptive efficacy| veditors = Hatcher RA, Trussell J, Nelson AL, Cates 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=779–863|chapter-url=http://www.contraceptivetechnology.org/wp-content/uploads/2013/09/CTFailureTable.pdf|url-status=live|archive-url=https://web.archive.org/web/20131112130150/http://www.contraceptivetechnology.org/wp-content/uploads/2013/09/CTFailureTable.pdf|archive-date=2013-11-12}}</ref>

|typical_failure% = 0.05

|typical_failure_ref =<ref name=Trus2011/>

|duration_effect = 3 to 5 years<ref name=Ham2016>{{cite book | vauthors = Hamilton RJ |title=Tarascon Pocket Pharmacopoeia 2016 Deluxe Lab-Coat Edition |date=2016 |publisher=Jones & Bartlett Publishers |isbn=9781284095289 |page=392 |url=https://books.google.com/books?id=YISkDAAAQBAJ&pg=PA392 |access-date=2021-02-18 |archive-date=2022-06-10 |archive-url=https://web.archive.org/web/20220610025027/https://books.google.com/books?id=YISkDAAAQBAJ&pg=PA392 |url-status=live }}</ref><ref>{{cite book | vauthors = Melville C |title=Sexual and Reproductive Health at a Glance |date=2015 |publisher=John Wiley & Sons |isbn=9781118460757 |page=21 |url=https://books.google.com/books?id=5r6SCgAAQBAJ&pg=PA21 |access-date=2021-02-18 |archive-date=2022-06-10 |archive-url=https://web.archive.org/web/20220610025030/https://books.google.com/books?id=5r6SCgAAQBAJ&pg=PA21 |url-status=live }}</ref>

|reversibility = Yes

|user_reminders = Requires removal after the 3–5 years<ref name=Lot2016/>

|clinic_interval =

|STD_protection_YesNo = No

|periods_advantage = Minimizes pain. In 33% no periods.

|benefits = Long-term contraception.

|periods_disadvantage = May cause irregular or prolonged bleeding

|weight_gain_loss = May cause weight gain

|risks =

|medical_notes =

}}

<!-- Definition and medical uses -->

'''Etonogestrel''' is a medication which is used as a means of [[hormonal contraceptive|birth control]] for women.<ref name="NexplanonLabel">{{cite web | title=Nexplanon- etonogestrel implant | website=DailyMed | date=18 November 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b03a3917-9a65-45c2-bbbb-871da858ef34 | access-date=25 September 2020 | archive-date=10 June 2022 | archive-url=https://web.archive.org/web/20220610025028/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b03a3917-9a65-45c2-bbbb-871da858ef34 | url-status=live }}</ref><ref name="NuvaRingLabel">{{cite web | title=NuvaRing- etonogestrel and ethinyl estradiol insert, extended release | website=DailyMed | date=24 January 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=017343fb-86c4-45ab-9c47-52cc5b9f3a02 | access-date=25 September 2020 | archive-date=8 August 2020 | archive-url=https://web.archive.org/web/20200808131025/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=017343fb-86c4-45ab-9c47-52cc5b9f3a02 | url-status=live }}</ref><ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA420|date=January 2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=420|access-date=2018-02-21|archive-date=2020-01-03|archive-url=https://web.archive.org/web/20200103203534/https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA420|url-status=live}}</ref><ref name="LemkeWilliams2012">{{cite book| vauthors = Lemke TL, Williams DA |title=Foye's Principles of Medicinal Chemistry|url=https://books.google.com/books?id=Sd6ot9ul-bUC&pg=PA1409|date=24 January 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-60913-345-0|pages=1409–|access-date=11 October 2016|archive-date=9 May 2022|archive-url=https://web.archive.org/web/20220509140017/https://books.google.com/books?id=Sd6ot9ul-bUC&pg=PA1409|url-status=live}}</ref> It is available as an implant placed under the skin of the upper arm under the brand names '''Nexplanon''' and '''Implanon.''' It is a [[progestin]] that is also used in combination with [[ethinylestradiol]], an [[estrogen (medication)|estrogen]], as a [[contraceptive vaginal ring|vaginal ring]] under the brand names ''NuvaRing'' and ''Circlet''.<ref name="Drugs.com" /> Etonogestrel is effective as a means of birth control and lasts at least three or four years with some data showing effectiveness for five years.<ref name=Ham2016/><ref name=Lot2016/> Following removal, [[fertility]] quickly returns.<ref name="WHO2015Use">{{cite book | vauthors = ((World Health Organization)) | year = 2015 | title = The selection and use of essential medicines. Twentieth report of the WHO Expert Committee 2015 (including 19th WHO Model List of Essential Medicines and 5th WHO Model List of Essential Medicines for Children) | publisher = World Health Organization | location = Geneva | author-link = World Health Organization | hdl = 10665/189763 | id = WHO technical report series;994 | hdl-access=free | isbn = 9789241209946 | issn = 0512-3054 | pages=332–36 }}</ref>

<!-- Side effects and mechanism -->

[[Side effect]]s of etonogestrel include [[menstrual irregularities]], [[breast tenderness]], [[mood (psychology)|mood]] changes, [[acne]], headaches, [[vaginitis]], and others.<ref name="NexplanonLabel" /> Etonogestrel is a [[progestin]], or a synthetic [[progestogen (medication)|progestogen]], and hence is an [[agonist]] of the [[progesterone receptor]], the [[biological target]] of progestogens like [[progesterone]].<ref name="pmid16112947i" /> It works by stopping [[ovulation]], thickening the [[mucus]] around the opening of the [[cervix]], and altering the lining of the [[uterus]].<ref name=Pat2010/> It has very weak [[androgen]]ic and [[glucocorticoid]] activity and no other important [[hormonal agent|hormonal]] activity.<ref name="pmid16112947i" />

<!-- History, society and culture -->

Etonogestrel was patented in 1972 and introduced for medical use in 1998.<ref name="CarcioANP-BC2014" /><ref name="Mayeaux2012" /><ref name=Fis2006>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=480 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA480 |language=en |access-date=2020-06-06 |archive-date=2022-05-09 |archive-url=https://web.archive.org/web/20220509140022/https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA480 |url-status=live }}</ref> It became available in the United States in 2006.<ref name="CarcioANP-BC2014" /><ref name="Mayeaux2012" /> Etonogestrel implants are approved in more than 90 countries and used by about three million women globally as of 2010.<ref name=Pat2010>{{cite book| veditors = Pattman R, Sankar N, Elawad B, Handy P, Price DA |title=Oxford Handbook of Genitourinary Medicine, HIV, and Sexual Health|date=2010|publisher=OUP Oxford|isbn=9780199571666|page=368|url=https://books.google.com/books?id=wuZIChOf3A8C&pg=PA368|url-status=live|archive-url=https://web.archive.org/web/20170924000754/https://books.google.com/books?id=wuZIChOf3A8C&pg=PA368|archive-date=2017-09-24}}</ref><ref name=Sen2008>{{cite book| vauthors = Senanayake P, Potts M |title=Atlas of Contraception, Second Edition|date=2008|publisher=CRC Press|isbn=9780203347324|page=53|edition= 2|url=https://books.google.com/books?id=7dDKBQAAQBAJ&pg=PA53|url-status=live|archive-url=https://web.archive.org/web/20170924000754/https://books.google.com/books?id=7dDKBQAAQBAJ&pg=PA53|archive-date=2017-09-24}}</ref>

A closely related and more widely known and used progestin, [[desogestrel]], is a [[prodrug]] of etonogestrel in the body.<ref name="pmid16112947i" />

==Medical uses==

Etonogestrel is used in hormonal contraception in form of the etonogestrel contraceptive implant<ref name="NexplanonLabel" /> and the [[contraceptive vaginal ring]] (brand names NuvaRing, Circlet), the latter in combination with [[ethinylestradiol]].<ref name="NuvaRingLabel" />

Etonogestrel birth control implants are a type of [[long-acting reversible contraception]], which has been shown to be one of the most effective form of birth control.<ref name=Winner2012>{{cite journal | vauthors = Winner B, Peipert JF, Zhao Q, Buckel C, Madden T, Allsworth JE, Secura GM | title = Effectiveness of long-acting reversible contraception | journal = The New England Journal of Medicine | volume = 366 | issue = 21 | pages = 1998–2007 | date = May 2012 | pmid = 22621627 | doi = 10.1056/nejmoa1110855 | s2cid = 16812353 | url = https://digitalcommons.wustl.edu/cgi/viewcontent.cgi?article=3776&context=open_access_pubs | access-date = 2021-02-18 | archive-date = 2020-06-11 | archive-url = https://web.archive.org/web/20200611191851/https://digitalcommons.wustl.edu/cgi/viewcontent.cgi?article=3776&context=open_access_pubs | url-status = live | doi-access = free }}</ref> The failure rate of the implants is 0.05% for both perfect use and typical use because the method requires no user action after placement.<ref name=Guttmacher>{{cite web |author=Guttmacher |title=Contraceptive Use in the United States |year=2012 |url=https://www.guttmacher.org/fact-sheet/contraceptive-use-united-states |url-status=live |archive-url=https://web.archive.org/web/20161211050342/https://www.guttmacher.org/fact-sheet/contraceptive-use-united-states |archive-date=2016-12-11 }}</ref> Studies of one type, which include over 2,467 women-years of exposure, found no pregnancies.<ref name="Ray2007">{{cite book | vauthors = Raymond EG |year=2011|chapter=Contraceptive Implants| veditors = Hatcher RA, Nelson TJ, Guest F, Kowal D |title=Contraceptive technology|edition= 19th revised|location=New York|publisher=Ardent Media|pages=144–156}}</ref><ref name="Funk2005">{{cite journal | vauthors = Funk S, Miller MM, Mishell DR, Archer DF, Poindexter A, Schmidt J, Zampaglione E | title = Safety and efficacy of Implanon, a single-rod implantable contraceptive containing etonogestrel | journal = Contraception | volume = 71 | issue = 5 | pages = 319–26 | date = May 2005 | pmid = 15854630 | doi = 10.1016/j.contraception.2004.11.007 }}</ref><ref name="Flores2005">{{cite journal | vauthors = Flores JB, Balderas ML, Bonilla MC, Vázquez-Estrada L | title = Clinical experience and acceptability of the etonogestrel subdermal contraceptive implant | journal = International Journal of Gynaecology and Obstetrics | volume = 90 | issue = 3 | pages = 228–33 | date = September 2005 | pmid = 16043175 | doi = 10.1016/j.ijgo.2005.06.007 | s2cid = 2747597 }}</ref>

Other studies have found some failures with this method, some attributed to failures of the method itself and others to improper placement, drug interactions, or conception prior to method insertion.<ref name=Harr1993>{{cite journal | vauthors = Harrison-Woolrych M, Hill R | title = Unintended pregnancies with the etonogestrel implant (Implanon): a case series from postmarketing experience in Australia | journal = Contraception | volume = 71 | issue = 4 | pages = 306–8 | date = April 2005 | pmid = 15792651 | doi = 10.1016/j.contraception.2004.10.005 }}</ref>

In comparison, tubal sterilization has a failure rate of 0.5% and IUDs have a failure rate of 0.2–0.8%.<ref name=Guttmacher /> A single implant is approved for three years with data showing effectiveness for five years.<ref name=Rob2018>{{Cite book|title=Contraceptive technology|others=Hatcher, Robert A. (Robert Anthony), 1937-|isbn=978-1732055605|edition= 21st |location=New York, NY|pages=Chapter 4, specifically pages 129–134|oclc=1048947218| vauthors = Hatcher RA |date = September 2018}}</ref><ref name=Lot2016>{{cite book | vauthors = Lotke PS |title=Contraception, An Issue of Obstetrics and Gynecology Clinics, E-Book |date=2016 |publisher=Elsevier Health Sciences |isbn=9780323402590 |page=634 |url=https://books.google.com/books?id=gtqZCwAAQBAJ&pg=PA634 |language=en |access-date=2021-02-18 |archive-date=2022-05-09 |archive-url=https://web.archive.org/web/20220509140016/https://books.google.com/books?id=gtqZCwAAQBAJ&pg=PA634 |url-status=live }}</ref>

==Contraindications==

{{See also|Progestin#Contraindications}}

Women should not use implants if they:<ref>{{Cite web|url=https://www.cdc.gov/reproductivehealth/contraception/mmwr/mec/appendixc_tableC1.html#mec_personal|title=US CDC Medical Eligibility Criteria for Contraceptive Use|date=2016|access-date=2021-02-18|archive-date=2019-06-21|archive-url=https://web.archive.org/web/20190621055843/https://www.cdc.gov/reproductivehealth/contraception/mmwr/mec/appendixc_tableC1.html#mec_personal|url-status=live}}</ref>

* are, or think they are, pregnant

* are allergic to etonogestrel

* have vaginal bleeding that has not been explained

* have some forms of severe liver disease.

Women should not use combined hormone contraceptives (CHC) if they have migraines with auras.<ref>{{cite journal | vauthors = Nappi RE, Merki-Feld GS, Terreno E, Pellegrinelli A, Viana M | title = Hormonal contraception in women with migraine: is progestogen-only contraception a better choice? | journal = The Journal of Headache and Pain | volume = 14 | issue = 1 | pages = 66 | date = August 2013 | pmid = 24456509 | pmc = 3735427 | doi = 10.1186/1129-2377-14-66 | doi-access = free }}</ref>

A full list of contraindications can be found in the WHO ''Medical Eligibility Criteria for Contraceptive Use 2015'' and the CDC ''United States Medical Eligibility Criteria for Contraceptive Use 2016''.

==Side effects==

{{See also|Desogestrel#Side effects|Progestin#Side effects}}

'''Irregular bleeding and spotting''': Many women will experience some type of irregular, unpredictable, prolonged, frequent, or infrequent bleeding.<ref name=Adams2009 /> Some women also experience [[amenorrhea]]. For some women, prolonged bleeding will decline after the first three months of use. However, other women may experience this bleeding pattern through all five years of use. While these patterns are not dangerous, they are the most common reason that women give for discontinuing the use of the implant. After removal, bleeding patterns return to previous patterns in most women.<ref name=Ray2007 /><ref name=Funk2005 /><ref name=Flores2005 />

'''Insertion complications''': Some minor side effects such as bruising, skin irritation, or pain around the insertion site are common.<ref name=Ray2007 /> However, there are some rare complications that can occur, such as infection or expulsion.<ref name=Ray2007 /><ref name=Smith2002>{{cite journal | vauthors = Smith A, Reuter S | title = An assessment of the use of Implanon in three community services | journal = The Journal of Family Planning and Reproductive Health Care | volume = 28 | issue = 4 | pages = 193–6 | date = October 2002 | pmid = 12419059 | doi = 10.1783/147118902101196540 | doi-access = free }}</ref> In some cases, a serious complication occurs when the provider fails to insert, and the rod is left in the inserter. An Australian study reported 84 pregnancies as a result of such failure.<ref name=Harr1993 />

'''Migration''': Although very rare, the rod can sometimes move slightly within the arm. This can make removal more difficult. It is possible that insertion in the same site as a previous implant increases the likelihood of migration.<ref name=Smith2002 /> Rods can be located only through high-frequency ultrasound or magnetic resonance imaging (MRI).<ref name=Ray2007 /> It can be located using traditional X-ray or CT-scan because of the inclusion of barium sulphate. There have been rare reports of implants having reached the lung via the pulmonary artery.<ref>{{cite web |url=https://www.gov.uk/drug-safety-update/nexplanon-etonogestrel-contraceptive-implants-reports-of-device-in-vasculature-and-lung |title=Nexplanon (etonogestrel) contraceptive implants: Reports of device in vasculature and lung |access-date=2016-07-31 |url-status=live |archive-url=https://web.archive.org/web/20160918043948/https://www.gov.uk/drug-safety-update/nexplanon-etonogestrel-contraceptive-implants-reports-of-device-in-vasculature-and-lung |archive-date=2016-09-18 }}</ref> Correct subdermal insertion over the triceps muscle reduces the risk of these events.

'''Possible weight gain''': Some women may experience slight weight gain when using the implant.<ref name=Ray2007 /> However, current studies are not conclusive because they do not compare the weight of women using implants with a control group of women not using the implant. The average increase in body weight in studies was less than 5 pounds (2,25&nbsp;kg) over 2 years.<ref name=Funk2005 />

'''Ovarian cysts''': A small portion of women using implants and other contraceptive implants develop ovarian cysts.<ref name=Ray2007 /> Usually these cysts will disappear without treatment.<ref name=Brache2002>{{cite journal | vauthors = Brache V, Faundes A, Alvarez F, Cochon L | title = Nonmenstrual adverse events during use of implantable contraceptives for women: data from clinical trials | journal = Contraception | volume = 65 | issue = 1 | pages = 63–74 | date = January 2002 | pmid = 11861056 | doi = 10.1016/s0010-7824(01)00289-x }}</ref>

'''Pregnancy''': it is recommended that implants be removed if a pregnancy does occur. However, there is no evidence to suggest that the implant has a negative effect on pregnancy or a developing fetus.<ref name=Ray2007 />

'''Acne''': Acne has been self-reported to be a side effect, and is listed as a side effect by the FDA. However, a study of users found that a majority of users with acne before their insertion reported that their acne had decreased, and only 16% of those who did not have acne before insertion developed acne.<ref name=Funk2005 />

'''Other possible symptoms''': Other symptoms that have been reported in trials of implants include headache, [[emotional lability]], depression, abdominal pain, loss of libido, and vaginal dryness.<ref name=Ray2007 /> However, there have been no studies that conclusively determine that these symptoms are caused by the implant.<ref name=Funk2005 /><ref name=Flores2005 />

==Overdose==

{{See also|Progestin#Overdose}}

No serious side effects are expected when overdosing contraceptives in general.<ref name="AC">{{cite book|title=Austria-Codex| veditors = Haberfeld H |at=Implanon NXT 68&nbsp;mg Implantat zur subkutanen Anwendung|publisher=Österreichischer Apothekerverlag|location=Vienna|year=2020|language=German}}</ref>

==Interactions==

{{See also|Progestin#Interactions}}

[[Efavirenz]], an [[Enzyme inducer|inducer]] of the liver enzyme [[CYP3A4]], appears to decrease etonogestrel levels<ref>{{cite journal | vauthors = Vieira CS, Bahamondes MV, de Souza RM, Brito MB, Rocha Prandini TR, Amaral E, Bahamondes L, Duarte G, Quintana SM, Scaranari C, Ferriani RA | display-authors = 6 | title = Effect of antiretroviral therapy including lopinavir/ritonavir or efavirenz on etonogestrel-releasing implant pharmacokinetics in HIV-positive women | journal = Journal of Acquired Immune Deficiency Syndromes | volume = 66 | issue = 4 | pages = 378–385 | date = August 2014 | pmid = 24798768 | doi = 10.1097/QAI.0000000000000189 | s2cid = 19545105 | doi-access = free }}</ref> and increase rates of undesired pregnancy among implant users.

Similar effects are expected for other CYP3A4 inducers, but it is not known whether these are clinically relevant. The opposite is true of CYP3A4 inhibitors such as [[ketoconazole]], [[itraconazole]] and [[clarithromycin]]: they might increase etonogestrel concentrations in the body.<ref name="AC" />

==Device description==

[[File:Implanon 04.jpg|thumb|upright=1.4|A removed rod]]

Nexplanon/Implanon consists of a single rod made of ethylene vinylacetate copolymer that is 4&nbsp;cm long and 2&nbsp;mm in diameter.<ref name=Adams2009>{{cite journal | vauthors = Adams K, Beal MW | title = Implanon: a review of the literature with recommendations for clinical management | journal = Journal of Midwifery & Women's Health | volume = 54 | issue = 2 | pages = 142–9 | year = 2009 | pmid = 19249660 | doi = 10.1016/j.jmwh.2008.09.004 | doi-access = free }}</ref> It is similar to a matchstick in size. The rod contains 68&nbsp;mg of etonogestrel (sometimes called 3-keto-destrogestrel), a type of progestin.<ref name=Ray2007 /> Peak serum etonogestrel concentrations have been found to reach 781–894&nbsp;pg/mL in the first few weeks, gradually decreasing to 192–261&nbsp;pg/mL after one year, 154–194&nbsp;pg/mL after two years, and 156–177&nbsp;pg/mL after three years, maintaining ovulation suppression and contraceptive efficacy.<ref name=fda_label>{{cite web | url=http://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?id=9311&type=display | title=Implanon label | publisher=FDA | format=PDF | date=2010-10-26 | access-date=2010-10-26 | url-status=live | archive-url=https://web.archive.org/web/20100310181824/http://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?id=9311&type=display | archive-date=2010-03-10 }}</ref> Serum levels maintain relatively stable through 36 months, which implies that the method may be effective for longer than three years.<ref name=Maka1998>{{cite journal | vauthors = Mäkäräinen L, van Beek A, Tuomivaara L, Asplund B, Coelingh Bennink H | title = Ovarian function during the use of a single contraceptive implant: Implanon compared with Norplant | journal = Fertility and Sterility | volume = 69 | issue = 4 | pages = 714–21 | date = April 1998 | pmid = 9548163 | doi = 10.1016/s0015-0282(98)00015-6 | doi-access = free }}</ref>

Although not formally approved by the manufacturer for more than three years, studies have shown it remains a highly effective contraceptive for five years.<ref name=Rob2018/>

It is a type of [[progestogen-only contraception]].

===Insertion and removal===

[[File:Implanon implantation.webm|thumb|upright=1.4|Implantation of Implanon]]

An experienced clinician must perform the insertion of implants to ensure proper insertion and minimize the risk of nerve damage or misplacement, which could result in pregnancy.<ref>{{cite journal | vauthors = Wechselberger G, Wolfram D, Pülzl P, Soelder E, Schoeller T | title = Nerve injury caused by removal of an implantable hormonal contraceptive | journal = American Journal of Obstetrics and Gynecology | volume = 195 | issue = 1 | pages = 323–6 | date = July 2006 | pmid = 16813761 | doi = 10.1016/j.ajog.2005.09.016 }}</ref> Before insertion, the arm is washed with a cleaning solution and a local anesthetic is applied to the upper arm around the insertion area.<ref name=Ray2007 /> A needle-like applicator is used to insert the rod under the skin into the subdermal tissue on the inner side of the arm posterior to the groove between the biceps and triceps muscles.<ref>{{Cite web|title=Nexplanon Prescribing Information|url=https://www.merck.com/product/usa/pi_circulars/n/nexplanon/nexplanon_pi.pdf|access-date=18 August 2020|archive-date=13 August 2020|archive-url=https://web.archive.org/web/20200813040523/https://www.merck.com/product/usa/pi_circulars/n/nexplanon/nexplanon_pi.pdf|url-status=live}}</ref> The average time for insertion is 0.5 to 1 minute.<ref name="Funk2005"/><ref name="Flores2005"/> A bandage should be kept on the insertion site for 24 hours afterwards. Bruising and mild discomfort are common after insertion.<ref name=Ray2007 /> Serious insertion site complications such as infection can occur very rarely, in less than 1% of patients. If a woman receives an implant outside the first five days of her period, she should wait to have sex or use a backup method of contraception (such as a [[condom]], [[female condom]], [[diaphragm (contraceptive)|diaphragm]], sponge, or [[emergency contraception]]) for the following week after insertion to prevent pregnancy. However, if the implant is inserted during the first five days of a woman's period, she is protected for that cycle and beyond.<ref name="bedsider.org">Bedsider (2010). "Implant." Retrieved from http://bedsider.org/methods/implant#how_to_tab {{webarchive|url=https://web.archive.org/web/20130728205925/http://bedsider.org/methods/implant |date=2013-07-28 }} on March 17, 2011.</ref>

[[File:Removal Implanon.webm|thumb|upright=1.4|Removal of Implanon]]

Implants can be removed at any time if pregnancy is desired. The rod must also be removed by an experienced clinician. At removal, a local anesthetic is again used around the implant area at the distal end.<ref name=Ray2007 /> If the provider cannot feel the implant, imaging tests may be necessary to locate the rod before it can be removed. A small incision is made in the skin over the end of the implant site. In some cases, a fibrous sheath may have formed around the implant, in which case the sheath must be incised.<ref name=Ray2007 /> The implant is removed using forceps. The removal procedure lasts, on average, 3 to 3.5 minutes.<ref name=Funk2005 /><ref name=Flores2005 />

===Fertility after removal===

Within a week of removal, the hormones from the device leave the body and etonogestrel is undetectable in most users.<ref name=Ray2007 /> Most women will begin to ovulate within six weeks of removal.<ref name=Maka1998 /><ref name=Davies1993>{{cite journal | vauthors = Davies GC, Feng LX, Newton JR, Van Beek A, Coelingh-Bennink HJ | title = Release characteristics, ovarian activity and menstrual bleeding pattern with a single contraceptive implant releasing 3-ketodesogestrel | journal = Contraception | volume = 47 | issue = 3 | pages = 251–61 | date = March 1993 | pmid = 8462316 | doi = 10.1016/0010-7824(93)90042-6 }}</ref>

Fertility levels will return to what they were before implant insertion.<ref name="WHO2015Use"/>

===Differences===

Nexplanon and Implanon NXT are essentially identical to Implanon except Nexplanon and Implanon NXT have 15&nbsp;mg of [[barium sulfate#Radiocontrast agent|barium sulphate]] added to the core, so it is detectable by x-ray.<ref name=Mansour2010>{{cite journal | vauthors = Mansour D | title = Nexplanon: what Implanon did next | journal = The Journal of Family Planning and Reproductive Health Care | volume = 36 | issue = 4 | pages = 187–9 | date = October 2010 | pmid = 21067632 | doi = 10.1783/147118910793048629 | doi-access = free }}</ref><ref name=Rob2018/> Nexplanon and Implanon NXT also has a pre-loaded applicator for easier insertion.<ref name=Reuters2011Jan05>{{cite news | vauthors = Ormsby A |title=Contraceptive alert after women fall pregnant |url=https://www.reuters.com/article/britain-contraceptive-idUSLDE7040T320110105 |access-date=10 May 2011 |newspaper=[[Reuters]] |date=5 Jan 2011 |archive-url=https://web.archive.org/web/20120522054008/http://www.reuters.com/article/2011/01/05/britain-contraceptive-idUSLDE7040T320110105 |archive-date=22 May 2012 |url-status=live }}</ref>

==Pharmacology==

The mechanism of action of [[Progestogen-only contraception|progestin-only contraceptives]] depends on the progestin activity and dose.<ref name=glasier>{{cite book | vauthors = Glasier A |author-link=Anna Glasier | veditors = DeGroot LJ, Jameson JL |title=Endocrinology |edition=5th |year=2006 |publisher=Elsevier Saunders |location=Philadelphia |isbn=978-0-7216-0376-6 |pages=[https://archive.org/details/endocrinology0003unse/page/3000 3000–1] |chapter=Contraception |chapter-url=https://archive.org/details/endocrinology0003unse/page/3000 }}</ref> Intermediate dose progestin-only contraceptives like Nexplanon or Implanon allow some follicular development but inhibit ovulation in almost all cycles as the primary mechanism of action. Ovulation was not observed in studies of Implanon in the first two years of use and only rarely in the third year with no pregnancies. A secondary mechanism of action is the progestogenic increase in cervical mucus viscosity which inhibits sperm penetration.<ref name="implanon spc">{{cite web |author=Organon |date=April 2006 |title=Implanon SPC (Summary of Product Characteristics) |url=http://emc.medicines.org.uk/emc/assets/c/html/displaydoc.asp?documentid=5382 |access-date=2007-04-15 |author-link=Organon International |url-status=dead |archive-url=https://web.archive.org/web/20070930185412/http://emc.medicines.org.uk/emc/assets/c/html/displaydoc.asp?documentid=5382 |archive-date=2007-09-30 }}</ref> Hormonal contraceptives also have effects on the endometrium that theoretically could affect implantation, however no scientific evidence indicates that prevention of implantation actually results from their use.<ref>{{cite journal | vauthors = Rivera R, Yacobson I, Grimes D | title = The mechanism of action of hormonal contraceptives and intrauterine contraceptive devices | journal = American Journal of Obstetrics and Gynecology | volume = 181 | issue = 5 Pt 1 | pages = 1263–9 | date = November 1999 | pmid = 10561657 | doi = 10.1016/S0002-9378(99)70120-1 }}</ref>

===Pharmacodynamics===

Etonogestrel is a [[progestogen (medication)|progestogen]], or an [[agonist]] of the [[progesterone receptor]].<ref name="pmid16112947i">{{cite journal | vauthors = Kuhl H | title = Pharmacology of estrogens and progestogens: influence of different routes of administration | journal = Climacteric | volume = 8 | issue = Suppl 1 | pages = 3–63 | year = 2005 | pmid = 16112947 | doi = 10.1080/13697130500148875 | s2cid = 24616324 | url = http://hormonebalance.org/images/documents/Kuhl%2005%20%20Pharm%20Estro%20Progest%20Climacteric_1313155660.pdf | access-date = 2018-02-21 | archive-date = 2016-08-22 | archive-url = https://web.archive.org/web/20160822055012/http://hormonebalance.org/images/documents/Kuhl%2005%20%20Pharm%20Estro%20Progest%20Climacteric_1313155660.pdf | url-status = live }}</ref> It is less [[androgenic]] than [[levonorgestrel]] and [[norethisterone]],<ref name="Danby2015">{{cite book| vauthors = Danby FW |title=Acne: Causes and Practical Management|url=https://books.google.com/books?id=Z1yFBQAAQBAJ&pg=PA77|date=27 January 2015|publisher=John Wiley & Sons|isbn=978-1-118-23277-4|pages=77–|access-date=11 October 2016|archive-date=9 May 2022|archive-url=https://web.archive.org/web/20220509140017/https://books.google.com/books?id=Z1yFBQAAQBAJ&pg=PA77|url-status=live}}</ref><ref name="Golan2008">{{cite book| vauthors = Golan DE |title=Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy|url=https://books.google.com/books?id=az8uSDkB0mgC&pg=PA521|year=2008|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-8355-2|pages=521–|access-date=2016-10-11|archive-date=2022-05-09|archive-url=https://web.archive.org/web/20220509140015/https://books.google.com/books?id=az8uSDkB0mgC&pg=PA521|url-status=live}}</ref> and it does not cause a decrease in [[sex hormone-binding globulin]] levels.<ref name="SperoffDarney2010">{{cite book| vauthors = Speroff L, Darney PD |title=A Clinical Guide for Contraception|url=https://books.google.com/books?id=f5XJtYkiJ0YC&pg=PT365|date=22 November 2010|publisher=Lippincott Williams & Wilkins|isbn=978-1-60831-610-6|pages=365–|access-date=11 October 2016|archive-date=9 May 2022|archive-url=https://web.archive.org/web/20220509140022/https://books.google.com/books?id=f5XJtYkiJ0YC&pg=PT365|url-status=live}}</ref> However, it is still associated with [[acne]] in up to 13.5% of patients when used as an implant, though this side effect only accounts for 1.3% of premature removals of the implant.<ref name="LentzLobo2012">{{cite book| vauthors = Lentz GM, Lobo RA, Gershenson DM, Katz VL |title=Comprehensive Gynecology|url=https://books.google.com/books?id=X5KT_w6Nye8C&pg=PA256|date=21 February 2012|publisher=Elsevier Health Sciences|isbn=978-0-323-09131-2|pages=256–|access-date=11 October 2016|archive-date=9 May 2022|archive-url=https://web.archive.org/web/20220509140022/https://books.google.com/books?id=X5KT_w6Nye8C&pg=PA256|url-status=live}}</ref> In addition to its progestogenic and weak androgenic activity, etonogestrel binds to the [[glucocorticoid receptor]] with about 14% of the [[affinity (pharmacology)|affinity]] of [[dexamethasone]] (relative to 1% for levonorgestrel) and has very weak [[glucocorticoid]] activity.<ref name="pmid16112947i" /> Etonogestrel has no other hormonal activity (e.g., [[estrogen (medication)|estrogen]]ic, [[antimineralocorticoid]]).<ref name="pmid16112947i" /> Some [[5α-reductase inhibitor|inhibition of 5α-reductase]] and hepatic [[cytochrome P450]] enzymes has been observed with etonogestrel ''[[in vitro]]'', similarly to other [[19-nortestosterone]] progestins.<ref name="pmid16112947i" />

{| class="wikitable mw-collapsible mw-collapsed" style="text-align:left; margin-left:auto; margin-right:auto; border:none;"

|+ class="nowrap" | Relative affinities (%) of etonogestrel and metabolites

|-

! Compound || {{abbrlink|PR|Progesterone receptor}} || {{abbrlink|AR|Androgen receptor}} || {{abbrlink|ER|Estrogen receptor}} || {{abbrlink|GR|Glucocorticoid receptor}} || {{abbrlink|MR|Mineralocorticoid receptor}} || {{abbrlink|SHBG|Sex hormone-binding globulin}} || {{abbrlink|CBG|Corticosteroid binding globulin}}

|-

| Etonogestrel || 150 || 20 || 0 || 14 || 0 || 15 || 0

|-

| 5α-Dihydroetonogestrel || 9 || 17 || 0 || ? || ? || ? || ?

|- class="sortbottom"

| colspan="8" style="width: 1px; background-color:#eaecf0; text-align: center;" | '''Sources:''' Values are percentages (%). Reference [[ligand (biochemistry)|ligand]]s (100%) were [[promegestone|prome-gestone]] for the {{abbrlink|PR|progesterone receptor}}, [[metribolone]] for the {{abbrlink|AR|androgen receptor}}, [[estradiol (medication)|{{abbr|E2|estradiol}}]] for the {{abbrlink|ER|estrogen receptor}}, {{abbrlink|DEXA|dexamethasone}} for the {{abbrlink|GR|glucocorticoid receptor}}, [[aldosterone]] for the {{abbrlink|MR|mineralocorticoid receptor}}, {{abbrlink|DHT|dihydrotestosterone}} for {{abbrlink|SHBG|sex hormone-binding globulin}}, and [[hydrocortisone|cortisol]] for {{abbrlink|CBG|Corticosteroid-binding globulin}}. '''Sources:''' <ref name="pmid2170822">{{cite journal |vauthors=Kuhl H |title=Pharmacokinetics of oestrogens and progestogens |journal=Maturitas |volume=12 |issue=3 |pages=171–97 |year=1990 |pmid=2170822 |doi=10.1016/0378-5122(90)90003-o }}</ref><ref name="pmid16112947i" />

|}

{{Glucocorticoid activity of selected steroids in vitro}}

===Pharmacokinetics===

The [[bioavailability]] of etonogestrel when given as a [[subcutaneous implant]] or as a [[vaginal ring]] is 100%.<ref name="NexplanonLabel" /><ref name="NuvaRingLabel" /> [[Steady-state (pharmacokinetics)|Steady-state]] levels of etonogestrel are achieved within one week upon insertion as an implant or vaginal ring.<ref name="NexplanonLabel" /><ref name="NuvaRingLabel" /> The mean [[volume of distribution]] of etonogestrel is 201&nbsp;L.<ref name="NexplanonLabel" /> The [[plasma protein binding]] of the medication is at least 98%, with 66% bound to [[human serum albumin|albumin]] and 32% bound to [[sex hormone-binding globulin]].<ref name="NexplanonLabel" /><ref name="NuvaRingLabel" /> Etonogestrel is [[metabolism|metabolized]] in the [[liver]] by [[CYP3A4]].<ref name="NexplanonLabel" /><ref name="NuvaRingLabel" /> The [[biological activity]] of its [[metabolite]]s is unknown.<ref name="NexplanonLabel" /><ref name="NuvaRingLabel" /> The [[elimination half-life]] of etonogestrel is about 25 to 29&nbsp;hours.<ref name="NexplanonLabel" /><ref name="NuvaRingLabel" /> Following removal of an etonogestrel-containing implant, levels of the medication were below the limits of assay detection by one week.<ref name="NexplanonLabel" /> The major portion of etonogestrel is [[elimination (pharmacology)|eliminated]] in [[urine]] and a minor portion is eliminated in [[feces]].<ref name="NexplanonLabel" /><ref name="NuvaRingLabel" />

==Chemistry==

{{See also|List of progestogens}}

Etonogestrel, also known as 11-methylene-17α-ethynyl-18-methyl-19-nortestosterone or as 11-methylene-17α-ethynyl-18-methylestr-4-en-17β-ol-3-one, is a synthetic [[estrane]] steroid and a [[chemical derivative|derivative]] of [[testosterone]].<ref name="IndexNominum2000" /><ref name="Drugs.com" /> It is more specifically a derivative of [[norethisterone]] (17α-ethynyl-19-nortestosterone) and is a member of the [[gonane]] (18-methylestrane) subgroup of the [[19-nortestosterone]] family of progestins.<ref name="BruckerKing2015">{{cite book| vauthors = Brucker MC, King TL |title=Pharmacology for Women's Health|url=https://books.google.com/books?id=AniUCgAAQBAJ&pg=PA368|date=8 September 2015|publisher=Jones & Bartlett Publishers|isbn=978-1-284-05748-5|pages=368–|access-date=3 August 2017|archive-date=26 April 2022|archive-url=https://web.archive.org/web/20220426054107/https://books.google.com/books?id=AniUCgAAQBAJ&pg=PA368|url-status=live}}</ref><ref name="Shoupe2007">{{cite book| vauthors = Shoupe D |title=The Handbook of Contraception: A Guide for Practical Management|url=https://books.google.com/books?id=sczb0Tk_2IwC&pg=PA16|date=7 November 2007|publisher=Springer Science & Business Media|isbn=978-1-59745-150-5|pages=16–|access-date=3 August 2017|archive-date=9 May 2022|archive-url=https://web.archive.org/web/20220509140021/https://books.google.com/books?id=sczb0Tk_2IwC&pg=PA16|url-status=live}}</ref> Etonogestrel is the C3 [[ketone]] derivative of [[desogestrel]] and the C11 [[methylene group|methylene]] derivative of [[levonorgestrel]] and is also known as 3-ketodesogestrel and as 11-methylenelevonorgestrel.<ref name="Ryan1999" />

==History==

The possibility of the subdermal contraceptive implant began when silicone was discovered in the 1940s and found to be bio-compatible with the human body.<ref name=Lapido2005>{{cite journal | vauthors = Ladipo OA, Akinso SA | title = Contraceptive implants | journal = African Journal of Reproductive Health | volume = 9 | issue = 1 | pages = 16–23 | date = April 2005 | pmid = 16104651 | doi = 10.2307/3583156 | jstor = 3583156 }}</ref>

In 1964, Folkman and Long published the first study demonstrating that such a rod could be used to deliver drugs.<ref name=Folk1964>{{cite journal | vauthors = Folkman J, Long DM | title = The use of silicone rubber as a carrier for prolonged drug therapy | journal = The Journal of Surgical Research | volume = 4 | issue = 3 | pages = 139–42 | date = March 1964 | pmid = 14130164 | doi = 10.1016/s0022-4804(64)80040-8 }}</ref>

In 1966 Dziuk and Cook published a study that looked at release rates and suggested that the rods could be well suited for contraception.<ref name=Dziuk1966>{{cite journal | vauthors = Dziuk PJ, Cook B | title = Passage of steroids through silicone rubber | journal = Endocrinology | volume = 78 | issue = 1 | pages = 208–11 | date = January 1966 | pmid = 5948426 | doi = 10.1210/endo-78-1-208 }}</ref> After a study that used implants with progestogens for contraception, the Population Council developed and patented [[Norplant]] and [[Jadelle]].<ref name=ARHP2008>{{cite web |author=Association of Reproductive Health Professionals |title=The Single-Rod Contraceptive Implant |date=July 2008 |url=http://www.arhp.org/publications-and-resources/clinical-proceedings/Single-Rod/History |url-status=live |archive-url=https://web.archive.org/web/20180320161733/http://www.arhp.org/publications-and-resources/clinical-proceedings/Single-Rod/History |archive-date=2018-03-20 }}</ref> Norplant has six rods and is considered a first-generation implant. Jadelle (Norplant II), a two-rod implant, and other single rod implants that followed, were developed because of complications resulting from Norplant's six-rod system. The Jadelle system contains two silicone rods mixed with levonorgestrel. In 1990 De Nijs patented a co-axial extrusion technique of ethylene vinylacetate copolymers and 3-keto-desogestrel (etonogestrel) for the preparation of long-acting contraceptive devices, such as Implanon, Nexplanon and Nuvaring.<ref>{{cite patent |country= US |number= 4957119 | status = granted |title= Contraceptive Implant|pubdate= |gdate= 18 September 1990 |fdate= 5 August 1988 |pridate= |inventor= De Nijs H |assign1= Akzo NV |assign2= |class= |url=}}</ref> The single rods were less visible under the skin and used etonogestrel as opposed to levonorgestrel in the hopes that it would reduce side effects.<ref name=Lapido2005 />

[[Desogestrel]] (3-deketoetonogestrel), a [[prodrug]] of etonogestrel, was introduced for medical use in 1981.<ref name="RunnebaumRabe2012">{{cite book| vauthors = Runnebaum BC, Rabe T, Kiesel L |title=Female Contraception: Update and Trends|url=https://books.google.com/books?id=LtT6CAAAQBAJ&pg=PA156|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-73790-9|pages=156–163}}</ref><ref name="Holtsclaw2007">{{cite book| vauthors = Holtsclaw JA |title=Progress Towards the Total Synthesis of Desogestrel and the Development of a New Chiral Dihydroimidazol-2-ylidene Ligand|url=https://books.google.com/books?id=-lUeAQAAMAAJ|year=2007|publisher=University of Michigan.|page=25|quote=In 1981, desogestrel was marketed as a new low dose oral contraceptive under the trade names Marvelon and Desogen.32}}</ref>

Norplant was used internationally beginning in 1983 and was marketed in the United States and the United Kingdom in 1993. There were many complications associated with Norplant removal in the United States and it was taken off the market in 2002. Although Jadelle was approved by the FDA, it has never been marketed in the United States, but it is widely used in Africa and Asia.<ref name=ARHP2008 />

Etonogestrel itself was first introduced as Implanon in Indonesia in 1998,<ref name="CarcioANP-BC2014">{{cite book| vauthors = Carcio H, Secor RM |title=Advanced Health Assessment of Women, Third Edition: Clinical Skills and Procedures|url=https://books.google.com/books?id=P1uFBQAAQBAJ&pg=PA411|date=10 October 2014|publisher=Springer Publishing Company|isbn=978-0-8261-2308-4|pages=411–|access-date=11 October 2016|archive-date=9 May 2022|archive-url=https://web.archive.org/web/20220509140019/https://books.google.com/books?id=P1uFBQAAQBAJ&pg=PA411|url-status=live}}</ref><ref name="Mayeaux2012">{{cite book| vauthors = Mayeaux EJ |title=The Essential Guide to Primary Care Procedures|url=https://books.google.com/books?id=d-wNb7eyonMC&pg=PA589|date=28 March 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-4511-5286-9|pages=589–|access-date=11 October 2016|archive-date=9 May 2022|archive-url=https://web.archive.org/web/20220509140021/https://books.google.com/books?id=d-wNb7eyonMC&pg=PA589|url-status=live}}</ref> was marketed in the United Kingdom shortly thereafter,<ref name="GlasierWinikoff1999">{{cite book| vauthors = Glasier A, Winikoff B |title= Contraception|url=https://books.google.com/books?id=QYPiaMbHVCsC|date=December 1999|publisher=Health Press|isbn=978-1-899541-18-8|page=41|access-date=2016-10-11|archive-date=2022-05-09|archive-url=https://web.archive.org/web/20220509140019/https://books.google.com/books?id=QYPiaMbHVCsC|url-status=live}}</ref> and approved for use in the United States in 2006.<ref name="CarcioANP-BC2014" /><ref name="Mayeaux2012" /> Nexplanon was developed to eliminate the problem of non-insertion and localization of Implanon by changing the inserter device and making the rod radiopaque.<ref name=Mansour2010 /> As of January 2012, Implanon is no longer being marketed and Nexplanon is the only available single-rod implant.

==Society and culture==

===Generic names===

''Etonogestrel'' is the [[generic term|generic name]] of the drug and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}, and {{abbrlink|BAN|British Approved Name}}.<ref name="IndexNominum2000" /><ref name="Drugs.com">{{Cite web | url=https://www.drugs.com/international/etonogestrel.html | title=Etonogestrel | website=Drugs.com | access-date=2017-08-03 | archive-date=2017-08-03 | archive-url=https://web.archive.org/web/20170803172845/https://www.drugs.com/international/etonogestrel.html | url-status=live }}</ref> It is also known by its developmental code name ''ORG-3236''.<ref name="IndexNominum2000" /><ref name="Drugs.com" />

===Brand names===

Etonogestrel is marketed under the brand names Circlet, Implanon, Nexplanon, and NuvaRing.<ref name="IndexNominum2000" /><ref name="Drugs.com"/>

===Availability===

Etonogestrel is available widely throughout the world, including in the United States, Canada, the United Kingdom, Ireland, elsewhere throughout Europe, South Africa, Latin America, [[South Asia|South]], [[East Asia|East]], and Southeast Asia, and elsewhere in the world.<ref name="Drugs.com" />

==Research==

An etonogestrel-releasing [[intrauterine device]] was under development for use as a form of birth control for women but development was discontinued in 2015.<ref name="AdisInsight-IUD">{{Cite web | url=http://adisinsight.springer.com/drugs/800032917 | title=Etonogestrel-releasing intrauterine system - Merck & Co. | website=Adisinsight.springer.com | access-date=2018-02-21 | archive-date=2022-06-10 | archive-url=https://web.archive.org/web/20220610025032/https://adisinsight.springer.com/drugs/800032917 | url-status=live }}</ref>

Etonogestrel has been studied for use as a potential [[male contraceptive]].<ref name="pmid20933120">{{cite journal | vauthors = Nieschlag E | title = Clinical trials in male hormonal contraception | journal = Contraception | volume = 82 | issue = 5 | pages = 457–70 | year = 2010 | pmid = 20933120 | doi = 10.1016/j.contraception.2010.03.020 | url = http://www.kup.at/kup/pdf/10172.pdf | access-date = 2020-09-05 | 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>

==See also==

* [[Ethinylestradiol/etonogestrel]]

==References==

{{Reflist}}

==Further reading==

{{refbegin|30em}}

* {{cite journal | vauthors = Bennink HJ | title = The pharmacokinetics and pharmacodynamics of Implanon, a single-rod etonogestrel contraceptive implant | journal = Eur J Contracept Reprod Health Care | volume = 5 | issue = Suppl 2 | pages = 12–20 | date = September 2000 | doi = 10.1080/14730782.2000.12288981 | pmid = 11246602 | s2cid = 67921250 }}

* {{cite journal | vauthors = Varma R, Mascarenhas L | title = Endometrial effects of etonogestrel (Implanon) contraceptive implant | journal = Curr. Opin. Obstet. Gynecol. | volume = 13 | issue = 3 | pages = 335–41 | date = June 2001 | pmid = 11396660 | doi = 10.1097/00001703-200106000-00015| s2cid = 45520124 }}

* {{cite journal | title = Etonogestrel implant (Implanon) for contraception | journal = Drug Ther Bull | volume = 39 | issue = 8 | pages = 57–9 | date = August 2001 | pmid = 11526801 }}

* {{cite journal | vauthors = Gaffield ME, Curtis KM, Mohllajee AP, Peterson HB | title = Medical eligibility criteria for new contraceptive methods: combined hormonal patch, combined hormonal vaginal ring and the etonogestrel implant | journal = Contraception | volume = 73 | issue = 2 | pages = 134–44 | date = February 2006 | pmid = 16413844 | doi = 10.1016/j.contraception.2005.08.002 }}

* {{cite journal | vauthors = Wagner MS, Arias RD, Nucatola DL | title = The combined etonogestrel/ethinyl estradiol contraceptive vaginal ring | journal = Expert Opin Pharmacother | volume = 8 | issue = 11 | pages = 1769–77 | date = August 2007 | pmid = 17685892 | doi = 10.1517/14656566.8.11.1769 | s2cid = 42412888 }}

* {{cite journal | vauthors = Mansour D, Bahamondes L, Critchley H, Darney P, Fraser IS | title = The management of unacceptable bleeding patterns in etonogestrel-releasing contraceptive implant users | journal = Contraception | volume = 83 | issue = 3 | pages = 202–10 | date = March 2011 | pmid = 21310280 | doi = 10.1016/j.contraception.2010.08.001 }}

* {{cite journal | vauthors = | title = In brief: etonogestrel (nexplanon) contraceptive implant | journal = The Medical Letter on Drugs and Therapeutics | volume = 54 | issue = 1383 | pages = 12 | date = February 2012 | pmid = 22354222 }}

* {{cite journal | vauthors = Stuebe AM, Bryant AG, Lewis R, Muddana A | title = Association of Etonogestrel-Releasing Contraceptive Implant with Reduced Weight Gain in an Exclusively Breastfed Infant: Report and Literature Review | journal = Breastfeed Med | volume = 11 | issue = 4| pages = 203–6 | date = May 2016 | pmid = 27032034 | pmc = 4860664 | doi = 10.1089/bfm.2016.0017 }}

* {{cite journal | vauthors = López-Picado A, Lapuente O, Lete I | title = Efficacy and side-effects profile of the ethinylestradiol and etonogestrel contraceptive vaginal ring: a systematic review and meta-analysis | journal = Eur J Contracept Reprod Health Care | volume = 22 | issue = 2 | pages = 131–146 | date = April 2017 | pmid = 28256919 | doi = 10.1080/13625187.2017.1287351 | s2cid = 24447820 }}

{{refend}}

==External links==

* [http://adisinsight.springer.com/drugs/800011815 Etonogestrel implant - AdisInsight]

* [http://adisinsight.springer.com/drugs/800012602 Ethinylestradiol/etonogestrel vaginal ring - AdisInsight]

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