View source for Desogestrel

{{Short description|Medication}}
{{Use dmy dates|date=August 2021}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| Watchedfields = changed
| verifiedrevid = 460778212
| image = Desogestrel.svg
| width = 200
| alt = 
| image2 = Desogestrel molecule ball.png
| width2 = 250
| alt2 = 
| caption =

<!-- Clinical data -->
| pronounce = 
| tradename = Cerazette, Lovima, Hana, others
| Drugs.com = {{drugs.com|mtm|ethinyl-estradiol-and-desogestrel}}
| MedlinePlus = a601050
| licence_EU = <!-- EMA uses INN (or special INN_EMA) -->
| DailyMedID = Desogestrel
| licence_US = <!-- FDA may use generic or brand name (generic name preferred) -->
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_AU_comment = 
| pregnancy_category= 
| routes_of_administration = [[Oral administration|By mouth]]<ref name="pmid8616978" />
| class = [[Progestogen (medication)|Progestogen]]
| ATC_prefix = G03
| ATC_suffix = AC09
| ATC_supplemental =

<!-- 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 = /&nbsp;P<ref name="Marvelon SmPC">{{cite web | title=Marvelon Tablets - Summary of Product Characteristics (SmPC) | website=(emc) | date=11 March 2021 | url=https://www.medicines.org.uk/emc/product/1359/smpc | access-date=9 July 2021 | archive-date=10 July 2021 | archive-url=https://web.archive.org/web/20210710045255/https://www.medicines.org.uk/emc/product/1359/smpc | url-status=live }}</ref><ref name="Mercilon SmPC">{{cite web | title=Mercilon Tablets - Summary of Product Characteristics (SmPC) | website=(emc) | date=11 March 2021 | url=https://www.medicines.org.uk/emc/product/1360/smpc | access-date=9 July 2021 | archive-date=10 July 2021 | archive-url=https://web.archive.org/web/20210710043751/https://www.medicines.org.uk/emc/product/1360/smpc | url-status=live }}</ref><ref name="Cerazette SmPC">{{cite web | title=Cerazette 75 microgram film-coated tablet - Summary of Product Characteristics (SmPC) | website=(emc) | date=20 November 2020 | url=https://www.medicines.org.uk/emc/product/1698/smpc | access-date=9 July 2021 | archive-date=10 July 2021 | archive-url=https://web.archive.org/web/20210710045257/https://www.medicines.org.uk/emc/product/1698/smpc | url-status=live }}</ref><ref name="Hana SmPC" /><ref name="Lovima SmPC">{{cite web | title=Lovima 75 microgram film-coated tablets - Summary of Product Characteristics (SmPC) | website=(emc) | date=9 July 2021 | url=https://www.medicines.org.uk/emc/product/12736/smpc | access-date=6 July 2022 | archive-date=6 July 2022 | archive-url=https://web.archive.org/web/20220706052608/https://www.medicines.org.uk/emc/product/12736/smpc | url-status=live }}</ref>
| legal_US = Rx-only
| legal_US_comment = <ref>{{cite web | title=Apri 28 Day- desogestrel and ethinyl estradiol kit | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a9e08f9b-9862-4c2c-8302-53dc82d85126 | access-date=9 July 2021 | archive-date=10 July 2021 | archive-url=https://web.archive.org/web/20210710043751/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a9e08f9b-9862-4c2c-8302-53dc82d85126 | url-status=live }}</ref><ref>{{cite web | title=Mircette- desogestrel/ethinyl estradiol and ethinyl estradiol kit | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a39bb616-9e84-4142-8450-824f88528906 | access-date=9 July 2021 | archive-date=10 July 2021 | archive-url=https://web.archive.org/web/20210710043752/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a39bb616-9e84-4142-8450-824f88528906 | url-status=live }}</ref><ref>{{cite web | title=Kariva- desogestrel/ethinyl estradiol and ethinyl estradiol kit | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7b11e11f-6977-4109-b9bd-a066e5d1278a | access-date=9 July 2021 | archive-date=10 July 2021 | archive-url=https://web.archive.org/web/20210710043753/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7b11e11f-6977-4109-b9bd-a066e5d1278a | url-status=live }}</ref><ref>{{cite web | title=Velivet Triphasic Regimen- desogestrel and ethinyl estradiol kit | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a3ce5125-62ba-4983-93f0-91f254271605 | access-date=9 July 2021 | archive-date=10 July 2021 | archive-url=https://web.archive.org/web/20210710043751/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a3ce5125-62ba-4983-93f0-91f254271605 | url-status=live }}</ref>
| legal_EU = 
| legal_EU_comment = 
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment = 
| legal_status = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->
| bioavailability = 76% (range 40–100%)<ref name="pmid8447355" /><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>
| protein_bound = Desogestrel: 99%:<ref name="RunnebaumRabe2012" /><br />• [[Human serum albumin|Albumin]]: 99%<br />Etonogestrel: 95–98%:<ref name="pmid8616978" /><ref name="pmid8808163" /><br />• Albumin: 65–66%<br />• {{abbrlink|SHBG|sex hormone-binding globulin}}: 30–32%<br />• Free: 2–5%
| metabolism = [[Liver]], [[intestine]]s ([[5α-reductase|5α-]] and [[5β-reductase]], [[cytochrome P450]] [[enzyme]]s, others)<ref name="pmid8808163" />
| metabolites = • [[Etonogestrel]]<ref name="pmid8808163" /><ref name="pmid8616978" /><ref name="pmid8447355" /><br />• Others<ref name="RunnebaumRabe2012" /><ref name="pmid8808163" /><ref name="pmid8447355" />
| onset = 
| elimination_half-life = Desogestrel: 1.5 hours<ref name="RunnebaumRabe2012" /><br />Etonogestrel: 21–38 hrs<ref name="RunnebaumRabe2012" /><ref name="Mosby2001" />
| duration_of_action = 
| excretion = [[Urine]]: 50%<ref name="RunnebaumRabe2012" /><br />[[Feces]]: 35%<ref name="RunnebaumRabe2012" />

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 54024-22-5
| CAS_supplemental = 
| PubChem = 40973
| IUPHAR_ligand = 7065
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00304
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 37400
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 81K9V7M3A3
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D02367
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 4453
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1533
| NIAID_ChemDB = 
| PDB_ligand = 
| synonyms = DSG; ORG-2969; 3-Deketo-11-methylene-17α-ethynyl-18-methyl-19-nortestosterone; 11-Methylene-17α-ethynyl-18-methylestr-4-en-17β-ol

<!-- Chemical and physical data -->
| IUPAC_name = (8''S'',9''S'',10''R'',13''S'',14''S'',17''R'')-13-ethyl-17-ethynyl-11-methylidene-1,2,3,6,7,8,9,10,12,14,15,16-dodecahydrocyclopenta[''a'']phenanthren-17-ol
| C=22 | H=30 | O=1
| SMILES = CC[C@]12CC(=C)[C@H]3[C@H]([C@@H]1CC[C@]2(C#C)O)CCC4=CCCC[C@H]34
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C22H30O/c1-4-21-14-15(3)20-17-9-7-6-8-16(17)10-11-18(20)19(21)12-13-22(21,23)5-2/h2,8,17-20,23H,3-4,6-7,9-14H2,1H3/t17-,18-,19-,20+,21-,22-/m0/s1
| StdInChI_comment = 
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = RPLCPCMSCLEKRS-BPIQYHPVSA-N
| density = 
| density_notes = 
| melting_point = 109
| melting_high = 110
| melting_notes = 
| boiling_point = 
| boiling_notes = 
| solubility = 
| sol_units = 
| specific_rotation = 
}}

<!-- Definition and medical uses -->
'''Desogestrel''' is a [[progestin]] medication which is used in [[birth control pill]]s.<ref name="pmid8616978">{{cite journal | vauthors = Stone SC | title = Desogestrel | journal = Clinical Obstetrics and Gynecology | volume = 38 | issue = 4 | pages = 821–828 | date = December 1995 | pmid = 8616978 | doi = 10.1097/00003081-199538040-00017 }}</ref><ref name="pmid8808163">{{cite journal | vauthors = Kuhl H | title = Comparative pharmacology of newer progestogens | journal = Drugs | volume = 51 | issue = 2 | pages = 188–215 | date = February 1996 | pmid = 8808163 | doi = 10.2165/00003495-199651020-00002 | s2cid = 1019532 }}</ref> It is also used in the treatment of [[menopause|menopausal]] [[symptom]]s in women.<ref name="pmid8616978" /> The medication is available and used alone or in combination with an [[estrogen (medication)|estrogen]].<ref name="pmid8616978" /><ref name="pmid8808163" /> It is taken [[oral administration|by mouth]].<ref name="pmid8616978" />

<!-- Side effects and mechanism -->
[[Side effect]]s of desogestrel include [[menstrual irregularities]], [[headache]]s, [[nausea]], [[breast tenderness]], [[mood (psychology)|mood]] changes, [[acne]], [[hirsutism|increased hair growth]], and others.<ref name="pmid8616978" /> Desogestrel is a progestin, or a [[synthetic compound|synthetic]] [[progestogen (medication)|progestogen]], and hence is an [[agonist]] of the [[progesterone receptor]], the [[biological target]] of progestogens like [[progesterone]].<ref name="pmid8616978" /><ref name="pmid8808163" /> It has very weak [[androgen]]ic and [[glucocorticoid]] activity and no other important [[hormonal agent|hormonal]] activity.<ref name="pmid8808163" /> The medication is a [[prodrug]] of [[etonogestrel]] (3-ketodesogestrel) in the body.<ref name="pmid8616978" /><ref name="pmid8808163" />

<!-- History, society and culture -->
Desogestrel was discovered in 1972 and was introduced for medical use in [[Europe]] in 1981.<ref name="Kuhl2011" /><ref name="RunnebaumRabe2012" /><ref name="Holtsclaw2007" /> It became available in the United States in 1992.<ref name="pmid8520092" /><ref name="KornsteinClayton2004" /><ref name="pmid8178905" /> Desogestrel is sometimes referred to as a "third-generation" progestin.<ref name="Carp2015">{{cite book| vauthors = Carp HJ |title=Progestogens in Obstetrics and Gynecology|url=https://books.google.com/books?id=Ik8SCAAAQBAJ&pg=PA112|date=9 April 2015|publisher=Springer|isbn=978-3-319-14385-9|pages=112, 136}}</ref> Like[[norethisterone]] and [[Norgestrel]], Desogestrel is widely available as a [[progestogen-only pill|progestogen-only "mini pill"]] for birth control.<ref name="pmid24226383">{{cite journal | vauthors = Grimes DA, Lopez LM, O'Brien PA, Raymond EG | title = Progestin-only pills for contraception | journal = The Cochrane Database of Systematic Reviews | issue = 11 | pages = CD007541 | date = November 2013 | pmid = 24226383 | doi = 10.1002/14651858.CD007541.pub3 }}</ref><ref name="pmid14759612">{{cite journal | vauthors = Hussain SF | title = Progestogen-only pills and high blood pressure: is there an association? A literature review | journal = Contraception | volume = 69 | issue = 2 | pages = 89–97 | date = February 2004 | pmid = 14759612 | doi = 10.1016/j.contraception.2003.09.002 }}</ref><ref>{{Cite web |title=Opill: Package Insert / Prescribing Information |url=https://www.drugs.com/pro/opill.html |access-date=2024-09-30 |website=Drugs.com |language=en}}</ref> Desogestrel is marketed widely throughout the world.<ref name="Drugs.com" /> It is available as a [[generic drug|generic medication]].<ref name="Drugs.com-Generic">{{Cite web | url=https://www.drugs.com/availability/generic-desogen.html | title=Generic Desogen Availability | access-date=6 January 2018 | archive-date=6 January 2018 | archive-url=https://web.archive.org/web/20180106231802/https://www.drugs.com/availability/generic-desogen.html | url-status=live }}</ref> In 2020, the version with [[ethinylestradiol]] was the 120th most commonly prescribed medication in the United States, with more than 5{{nbsp}}million prescriptions.<ref>{{cite web | title = The Top 300 of 2020 | url = https://clincalc.com/DrugStats/Top300Drugs.aspx | website = ClinCalc | access-date = 7 October 2022 }}</ref><ref>{{cite web | title = Desogestrel; Ethinyl Estradiol - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/DesogestrelEthinylEstradiol | access-date = 7 October 2022 }}</ref>
{{TOC limit}}

==Medical uses==
Desogestrel is a hormone blocker, [[progesterone]] receptors [[agonist]], and [[antiandrogen]]. It is used in conjunction with [[estrogen]]s and [[testosterone]]s. Medications containing desogestrel and estrogen are used to treat [[endometriosis]]<ref name="Carp2015" /><ref>{{Cite web |title=Cerazette (Desogestrel) |url=https://endometriosisnews.com/cerazette-desogestrel/ |access-date=2024-03-22 |website=Endometriosis News |language=en-US}}</ref> and as a component of [[menopausal hormone therapy]].<ref name="pmid8616978" /><ref>{{cite journal | vauthors = Saure A, Hirvonen E, Tikkanen MJ, Viinikka L, Ylikorkala O | title = A novel oestradiol--desogestrel preparation for hormone replacement therapy: effects on hormones, lipids, bone, climacteric symptoms and endometrium | journal = Maturitas | volume = 16 | issue = 1 | pages = 1–12 | date = January 1993 | pmid = 8429799 | doi = 10.1016/0378-5122(93)90128-5 }}</ref> While commonly used as a female contraceptive, desogestrel suppresses [[spermogenesis]] and has been shown to have potential as a male contraceptive.<ref>{{cite journal | vauthors = Hair WM, Kitteridge K, O'Connor DB, Wu FC | title = A novel male contraceptive pill-patch combination: oral desogestrel and transdermal testosterone in the suppression of spermatogenesis in normal men | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 86 | issue = 11 | pages = 5201–5209 | date = November 2001 | pmid = 11701677 | doi = 10.1210/jcem.86.11.8028 }}</ref><ref>{{cite journal | vauthors = Kinniburgh D, Zhu H, Cheng L, Kicman AT, Baird DT, Anderson RA | title = Oral desogestrel with testosterone pellets induces consistent suppression of spermatogenesis to azoospermia in both Caucasian and Chinese men | journal = Human Reproduction | location = Oxford, England | volume = 17 | issue = 6 | pages = 1490–1501 | date = June 2002 | pmid = 12042267 | doi = 10.1093/humrep/17.6.1490 }}</ref>

Desogestrel and [[norethisterone]] are the only progestins that are widely used as a progestogen-only "mini pill".<ref name="pmid24226383" /><ref name="pmid14759612" /> It is also the only newer-generation progestin with reduced androgenic activity that is used in such formulations.<ref name="pmid24226383" /><ref name="pmid14759612" />

===Available forms===
{{See also|Ethinylestradiol/desogestrel}}

Desogestrel is available alone in the form of 75&nbsp;μg oral tablets and at a dose of 150&nbsp;μg in combination with 20 or 30&nbsp;μg [[ethinylestradiol]] in oral tablets.<ref name="FreissmuthBöhm2012">{{cite book| vauthors = Freissmuth M, Böhm S |title=Pharmakologie und Toxikologie: Von den molekularen Grundlagen zur Pharmakotherapie|url=https://books.google.com/books?id=X8Ag6iow5RIC&pg=PA572|date=9 March 2012|publisher=Springer Science & Business Media|isbn=978-3-642-12353-5|pages=572–}}</ref> These formulations are all indicated specifically for contraceptive purposes.<ref name="FreissmuthBöhm2012" />

==Contraindications==
[[Contraindication]]s of desogestrel include:<ref name="Cerazette SmPC" />
* [[Allergy]] to desogestrel or any other ingredients
* Active [[thrombosis]] ([[deep vein thrombosis]] or [[pulmonary embolism]])
* [[Jaundice]] or severe [[liver disease]]
* [[Hormone-sensitive cancer]]s (e.g., [[breast cancer]])
* Unexplained [[vaginal bleeding]]

Desogestrel is not indicated for use in [[pregnancy]].<ref name="Cerazette SmPC" /> It is not contraindicated during [[lactation]] and [[breastfeeding]].<ref name="Drugs.com-2">{{Cite web | url=https://www.drugs.com/breastfeeding/desogestrel.html | title=Desogestrel use while Breastfeeding | access-date=7 January 2018 | archive-date=7 January 2018 | archive-url=https://web.archive.org/web/20180107175022/https://www.drugs.com/breastfeeding/desogestrel.html | url-status=live }}</ref>

==Side effects==
{{See also|Etonogestrel#Side effects|Progestin#Side effects}}

Common [[side effect]]s of desogestrel may include [[menstrual irregularities]], [[amenorrhea]], [[headache]]s, [[nausea]], [[breast tenderness]], and [[mood (psychology)|mood]] changes (e.g., [[depression (mood)|depression]]), as well as [[weight gain]], [[acne]], and [[hirsutism]].<ref name="pmid8616978" /><ref name="Cerazette SmPC" /> However, it has also been reported to not adversely affect weight.<ref name="pmid8520092" /> In addition, acne and hirsutism are negligible when combined with [[ethinylestradiol]], and this combination can actually be used to treat such symptoms.<ref name="pmid8616978" /> Desogestrel can also cause changes in total, {{abbrlink|LDL|low-density lipoprotein}}, and {{abbrlink|HDL|high-density lipoprotein}} [[cholesterol]].<ref name="pmid8616978" /> Uncommon side effects of desogestrel may include [[vaginal infection]], [[contact lens]] intolerance, [[vomiting]], [[alopecia|hair loss]], [[dysmenorrhea]], [[ovarian cyst]]s, and [[fatigue (medical)|fatigue]], while rare side effects include [[rash]], [[urticaria]], and [[erythema nodosum]].<ref name="Cerazette SmPC" /> [[Breast discharge]], [[ectopic pregnancies]], and aggravation of [[angioedema]] may also occur with desogestrel.<ref name="Cerazette SmPC" /> Serious side effects of combined oral contraceptives containing desogestrel may include [[venous thromboembolism]], [[arterial thromboembolism]], [[hormone-dependent tumor]]s (e.g., [[liver tumor]]s, [[breast cancer]]), and [[melasma]].<ref name="Cerazette SmPC" />

==Overdose==
No serious harmful effects have been reported with [[overdose]] of desogestrel.<ref name="Cerazette SmPC" /> Symptoms may include [[nausea]], [[vomiting]], and, in young girls, slight [[vaginal bleeding]].<ref name="Cerazette SmPC" /> In [[drug safety|safety]] studies, dosages of up to 750&nbsp;μg/day desogestrel in women showed no adverse effects on laboratory and various other parameters and produced no reported subjective side effects.<ref name="RunnebaumRabe2012" /> There is no [[antidote]] to desogestrel overdose and treatment should be based on symptoms.<ref name="Cerazette SmPC" />

== Interactions ==

[[Enzyme inducer|Inducer]]s of [[liver]] [[enzyme]]s can increase the [[metabolism]] of desogestrel and etonogestrel and reduce their circulating levels.<ref name="Cerazette SmPC" /> This may result in contraceptive failure.<ref name="Cerazette SmPC" /> Examples of liver enzyme inducers include [[barbiturate]]s (e.g., [[phenobarbital]]), [[bosentan]], [[carbamazepine]], [[efavirenz]], [[phenytoin]], [[primidone]], [[rifampicin]], and possibly also [[felbamate]], [[griseofulvin]], [[oxcarbazepine]], [[rifabutin]], [[St. John's Wort]], and [[topiramate]].<ref name="Cerazette SmPC" /> Many [[antiviral]]s for [[HIV/AIDS]] and [[hepatitis C virus|HCV]], such as [[boceprevir]], [[nelfinavir]], [[nevirapine]], [[ritonavir]], and [[telaprevir]], may increase or decrease levels of desogestrel and etonogestrel.<ref name="Cerazette SmPC" /> [[CYP3A4]] [[enzyme inhibitor|inhibitor]]s including strong inhibitors like [[clarithromycin]], [[itraconazole]], and [[ketoconazole]] and moderate inhibitors like [[diltiazem]], [[erythromycin]], and [[fluconazole]] may increase levels of desogestrel and etonogestrel.<ref name="Cerazette SmPC" /> Hormonal contraceptives may interfere with the metabolism of other drugs, resulting in increased levels (e.g., [[ciclosporine]]) or decreased levels (e.g., [[lamotrigine]]).<ref name="Cerazette SmPC" />

==Pharmacology==

===Pharmacodynamics===
[[File:Etonogestrel.svg|thumb|right|225px|[[Etonogestrel]] (3-ketodesogestrel), the [[active metabolite|active form]] of desogestrel.]]

Desogestrel is a [[prodrug]] of [[etonogestrel]] (3-ketodesogestrel), and, via this [[active metabolite]], it has [[progestogen (medication)|progestogen]]ic activity, [[antigonadotropic]] effects, very weak [[androgen]]ic activity, very weak [[glucocorticoid]] activity, and no other [[hormonal]] activity.<ref name="pmid16112947a" /><ref name="pmid8616978" /><ref name="pmid8808163" />

{| class="wikitable mw-collapsible mw-collapsed" style="text-align:left; margin-left:auto; margin-right:auto; border:none;"
|+ class="nowrap" | Relative affinities (%) of desogestrel 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}}
|-
| Desogestrel || 1 || 0 || 0 || 0 || 0 || 0 || 0
|-
| [[Etonogestrel]] ({{abbr|3-keto-DSG|3-ketodesogestrel}}) || 150 || 20 || 0 || 14 || 0 || 15 || 0
|-
| 3α-Hydroxydesogestrel || 5 || 0 || 0 || ? || ? || ? || ?
|-
| 3β-Hydroxydesogestrel || 13 || 3 || 2 || ? || ? || ? || ?
|-
| 5α-Dihydroetonogestrel || 9 || 17 || 0 || ? || ? || ? || ?
|-
| 3α-Hydroxy-5α-dihydroetonogestrel || 0 || 0 || 0 || ? || ? || ? || ?
|-
| 3β-Hydroxy-5α-dihydroetonogestrel || 1 || 0 || 1 || ? || ? || ? || ?
|- class="sortbottom"
| colspan="8" style="width: 1px; background-color:#eaecf0; text-align: center;" | '''Notes:''' Values are percentages (%). Reference [[ligand (biochemistry)|ligand]]s (100%) were [[promegestone]] 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 = 171–197 | date = September 1990 | pmid = 2170822 | doi = 10.1016/0378-5122(90)90003-o }}</ref><ref name="pmid16112947a" />
|}

====Progestogenic activity====
Desogestrel is a [[progestogen (medication)|progestogen]], or an [[agonist]] of the [[progesterone receptor]] (PR).<ref name="pmid8616978" /> It is an inactive [[prodrug]] of [[etonogestrel]] with essentially no [[affinity (pharmacology)|affinity]] for the PR itself (about 1% of that of [[promegestone]]).<ref name="pmid8616978" /><ref name="pmid8808163" /><ref name="LemkeWilliams2008">{{cite book| vauthors = Lemke TL, Williams DA |title=Foye's Principles of Medicinal Chemistry|url=https://books.google.com/books?id=R0W1ErpsQpkC&pg=PA1316|year=2008|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-6879-5|pages=1316–}}</ref> Hence, etonogestrel is exclusively responsible for the effects of desogestrel.<ref name="pmid8447355">{{cite journal | vauthors = McClamrock HD, Adashi EY | title = Pharmacokinetics of desogestrel | journal = American Journal of Obstetrics and Gynecology | volume = 168 | issue = 3 Pt 2 | pages = 1021–1028 | date = March 1993 | pmid = 8447355 | doi = 10.1016/0002-9378(93)90332-D }}</ref> Etonogestrel has about 150% of the affinity of promegestone and 300% of the affinity of [[progesterone (medication)|progesterone]] for the PR.<ref name="pmid8808163" /> Desogestrel (via etonogestrel) is a very [[potency (pharmacology)|potent]] progestogen and inhibits [[ovulation]] at very low doses, in the low [[microgram]] range.<ref name="pmid8616978" /> The effective minimum dosage for inhibition of ovulation is 60&nbsp;μg/day desogestrel (alone, not in combination with an estrogen).<ref name="pmid8616978" /><ref name="pmid8808163" /> However, some studies in combination with oral estradiol have suggested that higher doses may be necessary.<ref name="pmid30325245">{{cite journal | vauthors = Bastianelli C, Farris M, Rosato E, Brosens I, Benagiano G | title = Pharmacodynamics of combined estrogen-progestin oral contraceptives 3. Inhibition of ovulation | journal = Expert Review of Clinical Pharmacology | volume = 11 | issue = 11 | pages = 1085–1098 | date = November 2018 | pmid = 30325245 | doi = 10.1080/17512433.2018.1536544 | s2cid = 53246678 }}</ref> Desogestrel and etonogestrel are among the most potent progestogens available, along with [[gestodene]] and [[levonorgestrel]] (which have effective ovulation-inhibiting dosages 40&nbsp;μg/day and 60&nbsp;μg/day, respectively).<ref name="pmid16112947a">{{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 | date = August 2005 | pmid = 16112947 | doi = 10.1080/13697130500148875 | url = http://hormonebalance.org/images/documents/Kuhl%2005%20%20Pharm%20Estro%20Progest%20Climacteric_1313155660.pdf | access-date = 6 January 2018 | url-status = live | s2cid = 24616324 | archive-url = https://web.archive.org/web/20160822055012/http://hormonebalance.org/images/documents/Kuhl%2005%20%20Pharm%20Estro%20Progest%20Climacteric_1313155660.pdf | archive-date = 22 August 2016 }}</ref> Oral desogestrel is clinically on the order of 5,000&nbsp;times more potent than oral micronized progesterone (which has an effective ovulation-inhibiting dosage of more than 300&nbsp;mg/day) in humans.<ref name="pmid16112947a" />

Due to its progestogenic activity, desogestrel has potent functional [[antiestrogen]]ic effects in certain [[tissue (biology)|tissue]]s.<ref name="pmid8808163" /><ref name="pmid16112947a" /> It dose-dependently antagonizes the effects of [[ethinylestradiol]] on the [[vaginal epithelium]], [[Cervix#Cervical mucus|cervical mucus]], and [[endometrium]], with marked progestogenic effects occurring at a dosage of 60&nbsp;μg/day.<ref name="pmid8808163" /> There is a rise in [[body temperature]] in some women at 30&nbsp;μg/day and in all women at 60&nbsp;μg/day.<ref name="pmid8808163" /> Desogestrel also has [[antigonadotropic]] effects, which are similarly due to its progestogenic activity.<ref name="pmid8808163" /><ref name="pmid16112947a" /> The contraceptive effects of desogestrel in women are mediated not only by prevention of [[ovulation]] via its antigonadotropic effects but also by its marked progestogenic and antiestrogenic effects on cervical mucus and the endometrium.<ref name="pmid8808163" />

Aside from its progestogenic activity, desogestrel also has some [[off-target activity|off-target hormonal activity]] at other [[steroid hormone receptor]]s (see below).<ref name="RunnebaumRabe2012" /><ref name="pmid16112947a" /> However, these activities are relatively weak, and desogestrel is said to be one of the most [[binding selectivity|selective]] and pure progestogens used in oral contraceptives.<ref name="RunnebaumRabe2012" />

====Antigonadotropic effects====
Desogestrel has [[antigonadotropic]] effects via its progestogenic activity, similarly to other progestogens.<ref name="pmid8808163" /><ref name="pmid16112947a" /> It has been found to reduce testosterone levels by 15% in women at a dosage of 125&nbsp;μg/day.<ref name="pmid8808163" /> In addition, desogestrel has been extensively investigated as an antigonadotropin at dosages of 150 to 300&nbsp;μg/day in combination with [[testosterone (medication)|testosterone]] in [[male contraceptive]] regimens.<ref name="pmid8808163" /> One study found that 150&nbsp;μg/day and 300&nbsp;μg/day desogestrel alone in healthy young men suppressed [[luteinizing hormone]] (LH) levels by about 35% and 42%<!--39–45%-->, respectively; [[follicle-stimulating hormone]] (FSH) levels by about 47% and 55%, respectively; and [[testosterone]] levels by about 59% and 68%, respectively.<ref name="pmid9920070">{{cite journal | vauthors = Wu FC, Balasubramanian R, Mulders TM, Coelingh-Bennink HJ | title = Oral progestogen combined with testosterone as a potential male contraceptive: additive effects between desogestrel and testosterone enanthate in suppression of spermatogenesis, pituitary-testicular axis, and lipid metabolism | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 84 | issue = 1 | pages = 112–122 | date = January 1999 | pmid = 9920070 | doi = 10.1210/jcem.84.1.5412 | doi-access = free }}</ref> LH levels were suppressed maximally by desogestrel within 3&nbsp;days, whereas 14&nbsp;days were necessary for maximal suppression of FSH and testosterone levels.<ref name="pmid9920070" /> A previous study by the same authors found that increasing the dosage of desogestrel from 300&nbsp;μg/day to 450&nbsp;μg/day resulted in no further suppression of gonadotropin concentrations.<ref name="pmid9920070" /> The addition of a low dose of 50 or 100&nbsp;mg/week [[intramuscular injection|intramuscular]] [[testosterone enanthate]] after 3&nbsp;weeks increased testosterone levels and further suppressed LH and FSH levels, to the limits of assay detection (i.e., to undetectable or near-undetectable levels), in both the 150&nbsp;μg/day and 300&nbsp;μg/day desogestrel groups.<ref name="pmid9920070" /> Upon cessation of treatment, levels of LH, FSH, and testosterone all recovered to baseline values within 4&nbsp;weeks.<ref name="pmid9920070" />

====Androgenic activity====
Etonogestrel has about 20% of the affinity of [[metribolone]] and 50% of the affinity of levonorgestrel for the [[androgen receptor]] (AR) while desogestrel has no affinity for this receptor.<ref name="pmid8616978" /><ref name="pmid8808163" /> The [[5α-reductase|5α-reduced]] [[metabolite]] of etonogestrel, 5α-dihydroetonogestrel (3-keto-5α-dihydrodesogestrel), also has some affinity for the AR (about 17% of that of metribolone).<ref name="pmid8808163" /> Desogestrel (via etonogestrel) has very low [[androgen]]ic potency, about 1.9 to 7.4% of that of [[methyltestosterone]] in [[animal research|animal]] [[bioassay|assay]]s, and hence is considered to be a very weak [[androgen]].<ref name="pmid8616978" /><ref name="pmid8808163" /><ref name="LemkeWilliams2008" /> Although etonogestrel has about the same affinity for the AR as [[norethisterone]], due to the relatively increased progestogenic potency and decreased androgenic activity of etonogestrel, the drug has markedly higher selectivity for the PR over the AR than older [[19-nortestosterone]] progestins like [[norethisterone]] and [[levonorgestrel]].<ref name="RunnebaumRabe2012" /><ref name="pmid8520092">{{cite journal | vauthors = Kaplan B | title = Desogestrel, norgestimate, and gestodene: the newer progestins | journal = The Annals of Pharmacotherapy | volume = 29 | issue = 7–8 | pages = 736–742 | year = 1995 | pmid = 8520092 | doi = 10.1177/106002809502907-817 | s2cid = 45885232 }}</ref><ref name="pmid8447353">{{cite journal | vauthors = Collins D | title = Selectivity information on desogestrel | journal = American Journal of Obstetrics and Gynecology | volume = 168 | issue = 3 Pt 2 | pages = 1010–1016 | date = March 1993 | pmid = 8447353 | doi = 10.1016/0002-9378(93)90330-L }}</ref> Conversely, its selectivity for the PR over the AR is similar to other newer 19-nortestosterone progestins like [[gestodene]] and [[norgestimate]].<ref name="pmid8520092" /><ref name="pmid8447353" /> It has been estimated that 150&nbsp;μg/day desogestrel has less than one-sixth of the androgenic effect of 1&nbsp;mg/day norethisterone (these being common dosages of the drugs used in combined oral contraceptives).<ref name="pmid8447353" /> Clinical studies with norethisterone even at very high dosages (e.g., 10 to 60&nbsp;mg/day) have observed only mild androgenic effects in a minority of women including [[acne]], increased [[sebum]] production, [[hirsutism]], and slight [[virilization]] of female [[fetus]]es.<ref name="pmid14450719">{{cite journal | vauthors = Jacobson BD | title = Hazards of norethindrone therapy during pregnancy | journal = American Journal of Obstetrics and Gynecology | volume = 84 | issue = 7 | pages = 962–968 | date = October 1962 | pmid = 14450719 | doi = 10.1016/0002-9378(62)90075-3 }}</ref><ref name="pmid5843402">{{cite journal | vauthors = Pochi PE, Strauss JS | title = Lack of androgen effect on human sebaceous glands with low-dosage norethindrone | journal = American Journal of Obstetrics and Gynecology | volume = 93 | issue = 7 | pages = 1002–1004 | date = December 1965 | pmid = 5843402 | doi = 10.1016/0002-9378(65)90162-6 }}</ref><ref name="Curwen1962">{{cite journal| vauthors = Curwen S |title=Virilization with Norethisterone|journal=BMJ|volume=1|issue=5289|year=1962|pages=1415|issn=0959-8138|doi=10.1136/bmj.1.5289.1415-a|pmc=1958463}}</ref><ref name="pmid22154396">{{cite journal | vauthors = Kaser DJ, Missmer SA, Berry KF, Laufer MR | title = Use of norethindrone acetate alone for postoperative suppression of endometriosis symptoms | journal = Journal of Pediatric and Adolescent Gynecology | volume = 25 | issue = 2 | pages = 105–108 | date = April 2012 | pmid = 22154396 | doi = 10.1016/j.jpag.2011.09.013 }}</ref>

In accordance with its very weak androgenic activity, desogestrel has minimal effects on [[lipid metabolism]] and the [[blood lipids|blood]] [[lipid profile]], although there may still be some significant changes.<ref name="pmid8616978" /> Desogestrel also reduces [[sex hormone-binding globulin]] (SHBG) levels by 50% when given to women alone, but when combined with 30&nbsp;μg/day ethinylestradiol, which in contrast strongly activates SHBG production, there is a 200% increase in SHBG concentrations.<ref name="pmid8808163" /> Desogestrel may slightly reduce ethinylestradiol-induced increases in SHBG levels.<ref name="pmid8808163" /> However, at the dosages used in oral contraceptives and in combination with ethinylestradiol, which has potent functional [[antiandrogen]]ic effects mainly due to increased SHBG levels, the androgenic activity of desogestrel is said to be essentially without any clinical relevance.<ref name="pmid8808163" /> Indeed, combined oral contraceptives containing ethinylestradiol and desogestrel have been found to significantly decrease free concentrations of [[testosterone]] and to possess overall antiandrogenic effects, significantly reducing symptoms of acne and hirsutism in women with [[hyperandrogenism]].<ref name="pmid8616978" />

====Glucocorticoid activity====
Desogestrel has no affinity for the [[glucocorticoid receptor]], but etonogestrel has about 14% of the affinity of [[dexamethasone]] for this receptor.<ref name="pmid8808163" /><ref name="pmid16112947a" /><ref name="pmid11594150">{{cite journal | vauthors = Kuhl H | title = [New gestagens--advantages and disadvantages] | language = de | journal = Therapeutische Umschau. Revue Therapeutique | volume = 58 | issue = 9 | pages = 527–533 | date = September 2001 | pmid = 11594150 | doi = 10.1024/0040-5930.58.9.527 }}</ref> Hence, desogestrel and etonogestrel have weak [[glucocorticoid]] activity.<ref name="pmid8808163" /><ref name="pmid16112947a" /><ref name="pmid11594150" /> At typical clinical dosages, the glucocorticoid activity of desogestrel is said to be negligible or very weak and hence not clinically relevant.<ref name="pmid8808163" /><ref name="pmid16112947a" /><ref name="pmid11594150" /> However, it may nonetheless possibly influence [[cardiovascular|vascular]] function, with some upregulation of the [[thrombin receptor]] observed with etonogestrel in [[vascular]] [[smooth muscle]] [[cell (biology)|cell]]s ''[[in vitro]]''.<ref name="pmid8808163" /><ref name="pmid16112947a" /><ref name="pmid11594150" /> This could, in theory, increase [[procoagulation|coagulation]] and contribute to an increased risk of [[venous thromboembolism]] and [[atherosclerosis]].<ref name="pmid16112947a" /> The affinity of etonogestrel for the glucocorticoid receptor is a product of its C11 [[methylene group|methylene]] [[substituent|substitution]], as substitutions at the C11 position are a common feature of [[corticosteroid]]s and as levonorgestrel, which is etonogestrel without the C11 methylene group (17α-ethynyl-18-methyl-19-nortestosterone), has only 1% of the affinity of dexamethasone for the receptor and hence is considered to have negligible glucocorticoid activity.<ref name="pmid16112947a" />

{{Glucocorticoid activity of selected steroids in vitro}}

====Other activities====
Desogestrel and etonogestrel have no affinity for the [[estrogen receptor]], and hence have no [[estrogen (medication)|estrogen]]ic activity.<ref name="pmid8808163" /><ref name="pmid8616978" /><ref name="RunnebaumRabe2012" /> However, the metabolite 3β-hydroxydesogestrel has weak affinity for the estrogen receptor (about 2% of that of [[estradiol (medication)|estradiol]]), although the significance of this is uncertain.<ref name="pmid8808163" />

Desogestrel and etonogestrel have no affinity for the [[mineralocorticoid receptor]], and hence have no [[mineralocorticoid]] or [[antimineralocorticoid]] activity.<ref name="pmid8808163" /><ref name="pmid16112947a" />

Desogestrel and etonogestrel show some albeit weak [[enzyme inhibition|inhibition]] of [[5α-reductase]] (5.7% inhibition at 0.1&nbsp;μM, 34.9% inhibition at 1&nbsp;μM) and [[cytochrome P450]] [[enzyme]]s (e.g., [[CYP3A4]]) ({{abbrlink|IC<sub>50</sub>|half-maximal inhibitory concentration}} = 5&nbsp;μM) ''in vitro''.<ref name="pmid8808163" /><ref name="pmid16112947a" />

Desogestrel stimulates the [[cell proliferation|proliferation]] of [[MCF-7]] [[breast cancer]] [[cell (biology)|cell]]s ''[[in vitro]]'', an action that is independent of the classical PRs and is instead mediated via the [[progesterone receptor membrane component-1]] (PGRMC1).<ref name="pmid23758160">{{cite journal | vauthors = Neubauer H, Ma Q, Zhou J, Yu Q, Ruan X, Seeger H, Fehm T, Mueck AO | title = Possible role of PGRMC1 in breast cancer development | journal = Climacteric | volume = 16 | issue = 5 | pages = 509–513 | date = October 2013 | pmid = 23758160 | doi = 10.3109/13697137.2013.800038 | s2cid = 29808177 }}</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 | title = Progestogens and membrane-initiated effects on the proliferation of human breast cancer cells | journal = Climacteric | volume = 15 | issue = 5 | pages = 467–472 | date = October 2012 | pmid = 22335423 | doi = 10.3109/13697137.2011.648232 | s2cid = 11302554 }}</ref> Certain other progestins act similarly in this assay, whereas [[progesterone (medication)|progesterone]] 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 [[clinical trial|clinical studies]].<ref name="pmid31512725">{{cite journal | vauthors = Trabert B, Sherman ME, Kannan N, Stanczyk FZ | title = Progesterone and Breast Cancer | journal = Endocrine Reviews | volume = 41 | issue = 2 | pages = 320–344 | date = April 2020 | pmid = 31512725 | pmc = 7156851 | doi = 10.1210/endrev/bnz001 | doi-access = free }}</ref>

===Pharmacokinetics===
The [[bioavailability]] of desogestrel has been found to range from 40 to 100%, with an average of 76%.<ref name="pmid8808163" /><ref name="pmid8447355" /><ref name="pmid8842581" /> This significant [[interindividual variability]] is comparable to that with [[norethisterone]] and [[levonorgestrel]].<ref name="pmid8447355" /> [[Cmax (pharmacology)|Peak concentrations]] of etonogestrel occur about 1.5&nbsp;hours after a dose while concentrations of desogestrel are very low and have disappeared by 3&nbsp;hours after a dose.<ref name="pmid8808163" /> [[Steady-state level]]s of etonogestrel are achieved after about 8 to 10&nbsp;days of daily administration.<ref name="pmid8616978" /> Accumulation of etonogestrel is thought to be related to progressive [[enzyme inhibition|inhibition]] of [[5α-reductase]] and [[cytochrome P450]] [[monooxygenase]]s (e.g., [[CYP3A4]]).<ref name="pmid8808163" /> The [[plasma protein binding]] of desogestrel is 99% and it is bound exclusively to [[human serum albumin|albumin]].<ref name="RunnebaumRabe2012" /> Etonogestrel is bound 95 to 98% to [[plasma protein]]s.<ref name="pmid8616978" /><ref name="pmid8808163" /> It is bound about 65 to 66% to albumin and 30 to 32% to SHBG, with 2 to 5% free in the circulation.<ref name="pmid8616978" /><ref name="pmid8808163" /> While desogestrel is not bound to SHBG, etonogestrel has relatively high affinity for this [[plasma protein]] of 3 to 15% of that of [[dihydrotestosterone]], although this is considerably less than that of the related progestins levonorgestrel and [[gestodene]].<ref name="pmid8808163" /><ref name="pmid8447355" /> Neither desogestrel nor etonogestrel are bound by [[corticosteroid-binding globulin]].<ref name="pmid8808163" />

Desogestrel is a [[prodrug]] of [[etonogestrel]] (3-ketodesogestrel) and upon ingestion is rapidly and completely [[biotransformation|transformed]] into this [[metabolite]] in the [[intestine]]s and [[liver]].<ref name="pmid8808163" /><ref name="pmid8616978" /><ref name="pmid8447355" /> [[Hydroxylation]] of the C3 position of desogestrel catalyzed by [[cytochrome P450]]-dependent [[enzyme]]s, with 3α-hydroxydesogestrel and 3β-hydroxydesogetrel as [[metabolic intermediate|intermediate]]s, followed by [[oxidation]] of the C3 [[hydroxyl group]], is responsible for the transformation.<ref name="RunnebaumRabe2012" /><ref name="pmid8808163" /><ref name="pmid8447355" /> A small percentage of desogestrel is [[metabolism|metabolized]] into levonorgestrel, which involves the removal of the C11 [[methylene group]].<ref name="pmid8616978" /> Following further [[metabolism]] of etonogestrel, which occurs mainly by [[redox|reduction]] of the Δ<sup>4</sup>-3-keto group (by [[5α-reductase|5α-]] and [[5β-reductase]]s) and [[hydroxylation]] (by [[monooxygenase]]s), the major metabolite of desogestrel is 3α,5α-tetrahydroetonogestrel.<ref name="pmid8808163" /> Desogestrel has a very short [[terminal half-life]] of about 1.5&nbsp;hours while etonogestrel has a relatively long [[elimination half-life]] of about 21 to 38&nbsp;hours, reflecting the nature of desogestrel as a prodrug.<ref name="RunnebaumRabe2012" /><ref name="pmid8616978" /><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> Desogestrel and etonogestrel are [[elimination (pharmacology)|eliminated]] exclusively as metabolites 50% in [[urine]] and 35% in [[feces]].<ref name="RunnebaumRabe2012" /><ref name="pmid8447355" />

==Chemistry==
{{See also|List of progestogens}}

Desogestrel, also known as 3-deketo-11-methylene-17α-ethynyl-18-methyl-19-nortestosterone or as 11-methylene-17α-ethynyl-18-methylestr-4-en-17β-ol, is a [[synthetic compound|synthetic]] [[estrane]] [[steroid]] and a [[chemical derivative|derivative]] of [[testosterone]].<ref name="pmid8808163" /><ref name="Elks2014" /><ref name="IndexNominum2000" /> It is more specifically a derivative of [[norethisterone]] (17α-ethynyl-19-nortestosterone) and is a member of the [[gonane]] (13β-ethylgonane or 18-methylestrane) subgroup of the [[19-nortestosterone]] family of progestins.<ref name="pmid8808163" /><ref name="Tripathi2013">{{cite book| vauthors = Tripathi KD |title=Essentials of Medical Pharmacology|url=https://books.google.com/books?id=FfG8AQAAQBAJ&pg=PA316|date=30 September 2013|publisher=JP Medical Ltd|isbn=978-93-5025-937-5|pages=316–}}</ref><ref name="Lentz2012">{{cite book| vauthors = Lentz GM |title=Comprehensive Gynecology|url=https://books.google.com/books?id=OmpULog7A_QC&pg=PA223|year=2012|publisher=Elsevier Health Sciences|isbn=978-0-323-06986-1|pages=223–}}</ref> Desogestrel is the C3 [[ketone|deketo]] [[structural analog|analogue]] of [[etonogestrel]] and the C3 deketo and C11 [[methylene group|methylene]] analogue of [[levonorgestrel]].<ref name="pmid8808163" /><ref name="Skouby1997">{{cite book| vauthors = Skouby SO |title=Clinical Perspectives on a New Gestodene Oral Contraceptive Containing 20μg of Ethinylestradiol|url=https://books.google.com/books?id=IYj54F5zvM4C&pg=PA11|date=15 July 1997|publisher=CRC Press|isbn=978-1-85070-786-8|pages=11–}}</ref>

===Synthesis===
A [[chemical synthesis]] of desogestrel has been published.<ref name="VanDenBroek1975">{{Cite journal | vauthors = Van den Broek AJ, Van Bokhoven C, Hobbelen PM, Leemhuis J |doi=10.1002/recl.19750940203|title=11-Alkylidene steroids in the 19-nor series|journal=Recueil des Travaux Chimiques des Pays-Bas|volume=94|issue=2|pages=35–39|year=1975 }}</ref>

==History==
Desogestrel was synthesized in 1972 by [[Organon International]] in the [[Netherlands]] and was first described in the literature in 1975.<ref name="Kuhl2011">{{cite journal | vauthors = Kuhl H | title = Pharmacology of progestogens | journal = Journal für Reproduktionsmedizin und Endokrinologie-Journal of Reproductive Medicine and Endocrinology | volume = 8 | issue = Special Issue 1 | pages = 157–176 | year = 2011 | url = http://www.kup.at/kup/pdf/10168.pdf | quote = Desogestrel was synthesized in 1972 at Organon [...] | access-date = 21 March 2018 | archive-date = 11 October 2016 | archive-url = https://web.archive.org/web/20161011060809/http://www.kup.at/kup/pdf/10168.pdf | url-status = live }}</ref><ref name="Cullberg1975">{{cite journal | vauthors = Cullberg G | date = January 1975 | title = ORG-2969, a New Progestational Compound. | journal = Reproduccion | volume = 2 | issue = 3–4 | pages = 330 }}</ref><ref name="Visser1975">{{cite journal | vauthors = De Visser J, De Jager E, De Jongh HP, Van der Vies J, Zeelen F | date  = 1975 | title = Pharmacological profile of a new orally active progestational steroid: Org 2969. | journal = Acta Endocrinologica | volume = 80 | issue = 199 | pages = 405 }}</ref><ref name="Viinikka1975">{{cite journal | vauthors = Viinikka L, Ylikorkala O, Nummi S, Virkkunen P, Ranta T, Alapiessa U, Vihko R | date = 1975 | title = The inhibition of ovulation by a new and potent progestin: a clinical study. | journal = Acta Endocrinologica | volume = 80 | issue = 199 | pages = 303 }}</ref> It was developed following the discovery that C11 substitutions enhance the biological activity of norethisterone.<ref name="RunnebaumRabe2012" /> Desogestrel was introduced for medical use in 1981 under the brand names Marvelon and Desogen in the Netherlands.<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><ref name="pmid8808163" /> Along with [[gestodene]] and [[norgestimate]], it is sometimes referred to as a "third-generation" progestin based on the time of its introduction to the market.<ref name="Carp2015" /> It was the first of the three "third-generation" progestins to be introduced.<ref name="RunnebaumRabe2012" /> Although desogestrel was introduced in 1981 and was widely used in [[Europe]] from this time, it was not introduced in the United States until 1992.<ref name="pmid8520092" /><ref name="KornsteinClayton2004">{{cite book| vauthors  = Kornstein SG, Clayton AH |title=Women's Mental Health: A Comprehensive Textbook|url=https://books.google.com/books?id=TFQG52_dpocC&pg=PA114|date=15 December 2004|publisher=Guilford Press|isbn=978-1-59385-144-6|pages=114–}}</ref><ref name="pmid8178905">{{cite journal | vauthors = Archer DF | title = Clinical and metabolic features of desogestrel: a new oral contraceptive preparation | journal = American Journal of Obstetrics and Gynecology | volume = 170 | issue = 5 Pt 2 | pages = 1550–1555 | date = May 1994 | pmid = 8178905 | doi = 10.1016/S0002-9378(94)05018-0 }}</ref>

==Society and culture==

===Generic names===
''Desogestrel'' is the [[generic term|generic name]] of the drug and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}, {{abbrlink|BAN|British Approved Name}}, {{abbrlink|DCF|Dénomination Commune Française}}, {{abbrlink|DCIT|Denominazione Comune Italiana}}, and {{abbrlink|JAN|Japanese Accepted Name}}.<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=PA364|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=364–}}</ref><ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA305|year=2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=305–}}</ref><ref name="Drugs.com">{{Cite web | url=https://www.drugs.com/international/desogestrel.html | title=Desogestrel | access-date=3 August 2017 | archive-date=3 August 2017 | archive-url=https://web.archive.org/web/20170803173623/https://www.drugs.com/international/desogestrel.html | url-status=live }}</ref> While under development, it was known as ''ORG-2969''.<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="Drugs.com" />

===Brand names===
Desogestrel is marketed under a variety of brand names throughout the world including Alenvona, Apri, Azalia, Azurette, Bekyree, Caziant, Cerazette,<ref name="Cerazette SmPC" /> Cerelle, Cesia, Cyclessa, Cyred, Denise, Desogen, Desirett, Diamilla, Emoquette, Enskyce, Feanolla, Gedarel, Gracial, Hana,<ref name="Hana SmPC">{{cite web | title=Hana 75 microgram film coated tablets - Summary of Product Characteristics (SmPC) | website=(emc) | date=9 July 2021 | url=https://www.medicines.org.uk/emc/product/12735/smpc | access-date=9 July 2021 | archive-date=10 July 2021 | archive-url=https://web.archive.org/web/20210710043751/https://www.medicines.org.uk/emc/product/12735/smpc | url-status=live }}</ref> Isibloom, Juleber, Kalliga, Kariva, Laurina, Lovima, Marvelon,<ref name="Marvelon SmPC" /> Mercilon,<ref name="Mercilon SmPC" /> Mircette, Mirvala, Novynette, Ortho-Cept, Pimtrea, Reclipsen, Regulon, Simliya, Solia, Velivet, Viorele, and Volnea among others.<ref name="IndexNominum2000" /><ref name="Drugs.com" /><ref>{{cite web | title = Active substance: desogestrel |  work = List of nationally authorised medicinal products | date = 9 March 2017 | publisher = European Medicines Agency | url = https://www.ema.europa.eu/en/documents/psusa/desogestrel-list-nationally-authorised-medicinal-products-psusa/00000966/201607_en.pdf | archive-url = https://web.archive.org/web/20210710043750/https://www.ema.europa.eu/en/documents/psusa/desogestrel-list-nationally-authorised-medicinal-products-psusa/00000966/201607_en.pdf | archive-date=10 July 2021 }}</ref><ref>{{cite web | title = Active substance: desogestrel / ethinylestradiol | date = 13 May 2016 | work = List of nationally authorised medicinal products | publisher = European Medicines Agency  | url = https://www.ema.europa.eu/en/documents/psusa/desogestrel/ethinylestradiol-list-nationally-authorised-medicinal-products-psusa/00000967/201509_en.pdf | archive-url = https://web.archive.org/web/20210624201559/https://www.ema.europa.eu/en/documents/psusa/desogestrel/ethinylestradiol-list-nationally-authorised-medicinal-products-psusa/00000967/201509_en.pdf | archive-date=24 June 2021 }}</ref>

===Availability===
{{See also|List of progestogens available in the United States}}

Desogestrel is available widely throughout the world, including in the United States, Canada, the United Kingdom, Ireland, many other European countries, Australia, New Zealand, South Africa, Latin America, Asia, and elsewhere.<ref name="Drugs.com" /><ref name="Drugs@FDA">{{cite web | title = Drugs@FDA: FDA Approved Drug Products | publisher = United States Food and Drug Administration | access-date = 6 January 2018 | url = http://www.accessdata.fda.gov/scripts/cder/daf/ | archive-date = 16 November 2016 | archive-url = https://web.archive.org/web/20161116164727/http://www.accessdata.fda.gov/scripts/cder/daf/ | url-status = live }}</ref> In the United States, it is available only in combination with ethinylestradiol as a combined oral contraceptive; it is not available alone and is not approved for any other indications.<ref name="Drugs.com-2" /><ref name="Drugs@FDA" />

In the UK, in July 2021, some Desogestrel pills were made available to purchase over the counter,<ref>{{Cite web |date=2021-07-08 |title=Contraceptive 'mini pills' to be offered over the counter in UK |url=http://www.theguardian.com/society/2021/jul/08/contraceptive-pill-will-be-available-over-the-counter-for-the-first-time |access-date=2022-07-05 |website=the Guardian |language=en |archive-date=24 April 2022 |archive-url=https://web.archive.org/web/20220424062714/https://www.theguardian.com/society/2021/jul/08/contraceptive-pill-will-be-available-over-the-counter-for-the-first-time |url-status=live }}</ref> without requiring a prescription from a doctor beforehand. Pharmacists use a suitability questionnaire to determine if the medication is going to be suitable for the person, and if it is then they can purchase it from a pharmacy or online (all online purchases require the suitability questionnaire completed before the medication is sent to the customer).

===Controversy===
In February 2007, the consumer advocacy group [[Public Citizen]] released a petition requesting that the [[Food and Drug Administration]] ban oral contraceptives containing desogestrel in the United States, citing studies going as far back as 1995 that suggest the risk of dangerous [[thrombus|blood clots]] is doubled for women on such pills in comparison to other oral contraceptives.<ref name="PublicCitizen2007">Public Citizen's Health Research Group: [http://www.citizen.org/publications/release.cfm?ID=7503 Petition to the U.S. Food and Drug Administration to Ban Third Generation Oral Contraceptives Containing Desogestrel due to Increased Risk of Venous Thrombosis] {{Webarchive|url=https://web.archive.org/web/20160401120001/http://www.citizen.org/publications/release.cfm?ID=7503 |date=1 April 2016 }} HRG Publication #1799, 2007</ref> In 2009, Public Citizen released a list of recommendations that included numerous alternative, second-generation birth control pills that women could take in place of oral contraceptives containing desogestrel.<ref name="PublicCitizen2009">Public Citizen [http://www.worstpills.org/member/newsletter.cfm?n_id=670 Think Twice About Third-Generation Oral Contraceptives and YASMIN] {{Webarchive|url=https://web.archive.org/web/20200710123619/http://www.worstpills.org/member/newsletter.cfm?n_id=670 |date=10 July 2020 }} Worst Pills, Best Pills, December 2009</ref> Most of those second-generation medications have been on the market longer and have been shown to be as effective in preventing unwanted pregnancy, but with a lower risk of blood clots.<ref name="PublicCitizen2009" /> Medications cited specifically in the petition include Apri-28, Cyclessa, Desogen, Kariva, Mircette, Ortho-Cept, Reclipsen, Velivet, and some generic pills, all of which contain desogestrel in combination with ethinylestradiol.<ref name="PublicCitizen2007" /> Medications containing desogestrel as the only active ingredient (as opposed to being used in conjunction with ethinylestradiol, like in combined oral contraceptives) do not show an increased thrombosis risk and are therefore safer than second-generation birth-control pills in regards to thrombosis.<ref name="pmid22027398">{{cite journal | vauthors = Lidegaard Ø, Nielsen LH, Skovlund CW, Skjeldestad FE, Løkkegaard E | title = Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001-9 | journal = BMJ | volume = 343 | pages = d6423 | date = October 2011 | pmid = 22027398 | pmc = 3202015 | doi = 10.1136/bmj.d6423 | quote = Progestogen only products conferred no increased risk of venous thromboembolism, whether taken as low dose norethisterone pills, as desogestrel only pills, or in the form of hormone releasing intrauterine devices. }}</ref>

==Research==
Desogestrel has been studied extensively as an [[antigonadotropin]] for use in combination with [[testosterone (medication)|testosterone]] as a [[male contraceptive|hormonal contraceptive in men]].<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 = 7 July 2019 | url-status = live | archive-url = https://web.archive.org/web/20201205082822/https://www.kup.at/kup/pdf/10172.pdf | archive-date = 5 December 2020 }}</ref><ref name="pmid22419294">{{cite journal | vauthors = Grimes DA, Lopez LM, Gallo MF, Halpern V, Nanda K, Schulz KF | title = Steroid hormones for contraception in men | journal = The Cochrane Database of Systematic Reviews | issue = 3 | pages = CD004316 | date = March 2012 | pmid = 22419294 | doi = 10.1002/14651858.CD004316.pub4 }}</ref> Such combinations have been found to be effective in producing reversible [[azoospermia]] in most men and reversible azoospermia or severe [[oligozoospermia]] in almost all men.<ref name="pmid20933120" />

== References ==
{{Reflist}}

== Further reading ==
{{refbegin|30em}}
* {{cite journal | vauthors = Chez RA | title = Clinical aspects of three new progestogens: desogestrel, gestodene, and norgestimate | journal = American Journal of Obstetrics and Gynecology | volume = 160 | issue = 5 Pt 2 | pages = 1296–1300 | date = May 1989 | pmid = 2524163 | doi = 10.1016/S0002-9378(89)80016-X }}
* {{cite journal | vauthors = op ten Berg M | title = Desogestrel: using a selective progestogen in a combined oral contraceptive | journal = Advances in Contraception | volume = 7 | issue = 2–3 | pages = 241–250 | year = 1991 | pmid = 1835255 | doi = 10.1007/BF01849414 | s2cid = 74471093 }}
* {{cite journal | vauthors = Stone S | title = Clinical review of a monophasic oral contraceptive containing desogestrel and ethinyl estradiol | journal = International Journal of Fertility and Menopausal Studies | volume = 38 | issue = Suppl 3 | pages = 117–121 | year = 1993 | pmid = 8260969 }}
* {{cite journal | vauthors = Collins D | title = Selectivity information on desogestrel | journal = American Journal of Obstetrics and Gynecology | volume = 168 | issue = 3 Pt 2 | pages = 1010–1016 | date = March 1993 | pmid = 8447353 | doi = 10.1016/0002-9378(93)90330-L }}
* {{cite journal | vauthors = McClamrock HD, Adashi EY | title = Pharmacokinetics of desogestrel | journal = American Journal of Obstetrics and Gynecology | volume = 168 | issue = 3 Pt 2 | pages = 1021–1028 | date = March 1993 | pmid = 8447355 | doi = 10.1016/0002-9378(93)90332-D }}
* {{cite journal | vauthors = Kaunitz AM | title = Combined oral contraception with desogestrel/ethinyl estradiol: tolerability profile | journal = American Journal of Obstetrics and Gynecology | volume = 168 | issue = 3 Pt 2 | pages = 1028–1033 | date = March 1993 | pmid = 8447356 | doi = 10.1016/0002-9378(93)90333-E }}
* {{cite journal | vauthors = Archer DF | title = Clinical and metabolic features of desogestrel: a new oral contraceptive preparation | journal = American Journal of Obstetrics and Gynecology | volume = 170 | issue = 5 Pt 2 | pages = 1550–1555 | date = May 1994 | pmid = 8178905 | doi = 10.1016/S0002-9378(94)05018-0 }}
* {{cite journal | vauthors = Sobel NB | title = Progestins in preventive hormone therapy. Including pharmacology of the new progestins, desogestrel, norgestimate, and gestodene: are there advantages? | journal = Obstetrics and Gynecology Clinics of North America | volume = 21 | issue = 2 | pages = 299–319 | date = June 1994 | pmid = 7936546 | doi = 10.1016/S0889-8545(21)00630-6 }}
* {{cite journal | vauthors = Fotherby K | title = Twelve years of clinical experience with an oral contraceptive containing 30 micrograms ethinyloestradiol and 150 micrograms desogestrel | journal = Contraception | volume = 51 | issue = 1 | pages = 3–12 | date = January 1995 | pmid = 7750281 | doi = 10.1016/0010-7824(94)00010-T }}
* {{cite journal | vauthors = Kaplan B | title = Desogestrel, norgestimate, and gestodene: the newer progestins | journal = The Annals of Pharmacotherapy | volume = 29 | issue = 7–8 | pages = 736–742 | year = 1995 | pmid = 8520092 | doi = 10.1177/106002809502907-817 | s2cid = 45885232 }}
* {{cite journal | vauthors = Stone SC | title = Desogestrel | journal = Clinical Obstetrics and Gynecology | volume = 38 | issue = 4 | pages = 821–828 | date = December 1995 | pmid = 8616978 | doi = 10.1097/00003081-199538040-00017 }}
* {{cite journal | vauthors = Stanczyk FZ | title = Pharmacokinetics of the new progestogens and influence of gestodene and desogestrel on ethinylestradiol metabolism | journal = Contraception | volume = 55 | issue = 5 | pages = 273–282 | date = May 1997 | pmid = 9220223 | doi = 10.1016/S0010-7824(97)00030-9 }}
* {{cite journal | vauthors = Lammers P, Blumenthal PD, Huggins GR | title = Developments in contraception: a comprehensive review of Desogen (desogestrel and ethinyl estradiol) | journal = Contraception | volume = 57 | issue = 5 Suppl | pages = 1S–27S | date = May 1998 | pmid = 9673846 | doi = 10.1016/S0010-7824(98)00030-4 | doi-access = free }}
* {{cite journal | vauthors = Benagiano G, Primiero FM | title = Seventy-five microgram desogestrel minipill, a new perspective in estrogen-free contraception | journal = Annals of the New York Academy of Sciences | volume = 997 | issue = 1 | pages = 163–173 | date = November 2003 | pmid = 14644823 | doi = 10.1196/annals.1290.019 | s2cid = 25421859 | bibcode = 2003NYASA.997..163B }}
* {{cite journal | vauthors = Scala C, Leone Roberti Maggiore U, Remorgida V, Venturini PL, Ferrero S | title = Drug safety evaluation of desogestrel | journal = Expert Opinion on Drug Safety | volume = 12 | issue = 3 | pages = 433–444 | date = May 2013 | pmid = 23560561 | doi = 10.1517/14740338.2013.788147 | hdl-access = free | s2cid = 25923595 | hdl = 11567/576120 }}
* {{cite journal | vauthors = Grandi G, Cagnacci A, Volpe A | title = Pharmacokinetic evaluation of desogestrel as a female contraceptive | journal = Expert Opinion on Drug Metabolism & Toxicology | volume = 10 | issue = 1 | pages = 1–10 | date = January 2014 | pmid = 24102478 | doi = 10.1517/17425255.2013.844229 | s2cid = 275170 }}
{{refend}}

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