Gestrinone: Difference between revisions

{{Short description|Chemical compound}}

| Watchedfields = changed

| verifiedrevid = 447568158

| IUPAC_name = (8''S'',13''S'',14''S'',17''R'')-13-ethyl-17-ethynyl-17-hydroxy-1,2,6,7,8,14,15,16-octahydrocyclopenta[''a'']phenanthren-3-one

| width = 225px

| tradename = Dimetriose, Dimetrose, Nemestran, others

| legal_BR = C5

| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-15 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2023-04-04}}</ref>

| legal_status =

| routes_of_administration = [[Oral administration|By mouth]], [[vaginal administration|vaginal]]<ref name="ThomasRock2012" />

| class = [[Progestogen (medication)|Progestogen]]; [[Progestin]]; [[Antiprogestogen]]; [[Androgen]]; [[Anabolic steroid]]; [[Steroidogenesis inhibitor]]; [[Antiestrogen]]

| bioavailability =

| protein_bound = To [[human serum albumin|albumin]]<ref name="ThomasRock2012" />

| metabolism = [[Liver]] ([[hydroxylation]])<ref name="ThomasRock2012" />

| metabolites =

| elimination_half-life = 27.3 hours<ref name="ThomasRock2012" />

| excretion = [[Urine]] and [[bile]]<ref name="ThomasRock2012" />

| CAS_number_Ref = {{cascite|correct|??}}

| DrugBank = DB11619

| ChEBI = 89642

| ChEMBL = 1868702

| synonyms = Ethylnorgestrienone; A-46745; R2323; R-2323; RU-2323; 17α-Ethynyl-18-methyl-δ^9,11-19-nortestosterone; 17α-Ethynyl-18-methylestra-4,9,11-trien-17β-ol-3-one; 13β-Ethyl-18,19-dinor-17α-pregna-4,9,11-trien-20-yn-17β-ol-3-one

| SMILES = O=C4\C=C3/C(=C2/C=C\[C@]1([C@@H](CC[C@]1(C#C)O)[C@@H]2CC3)CC)CC4

<!-- Definition and medical uses -->

'''Gestrinone''', sold under the brand names '''Dimetrose''' and '''Nemestran''' among others, is a medication which is used in the treatment of [[endometriosis]].<ref name="pmid2406749">{{cite journal | vauthors = Coutinho EM | title = Therapeutic experience with gestrinone | journal = Prog. Clin. Biol. Res. | volume = 323 | pages = 233–40 | date = 1990 | pmid = 2406749 }}</ref><ref name="MortonHall1999" /> It has also been used to treat other conditions such as [[uterine fibroids]] and [[menorrhagia|heavy menstrual bleeding]] and has been investigated as a method of [[birth control]].<ref name="pmid15589885" /><ref name="pmid14717620" /><ref name="ThomasRock2012" /> Gestrinone is used alone and is not formulated in combination with other medications.<ref name="Drugs.com" /> It is taken [[oral administration|by mouth]] or [[vaginal administration|in through the vagina]].<ref name="ThomasRock2012" /><ref name="Carp2015" />

<!-- Side effects and mechanism -->

[[Side effect]]s of gestrinone include [[menstrual abnormalities]], [[estrogen deficiency]], and [[symptom]]s of [[virilization|masculinization]] like [[acne]], [[seborrhea]], [[breast hypoplasia|breast shrinkage]], [[hirsutism|increased hair growth]], and [[scalp hair loss]], among others.<ref name="ThomasRock2012" /><ref name="Carp2015" /><ref name="DesaiPatel2012" /><ref name="BlackwellOlive2012" /> Gestrinone has a complex [[mechanism of action]], and is characterized as a mixed [[progestogen (medication)|progestogen]] and [[antiprogestogen]], a weak [[androgen]] and [[anabolic steroid]], a weak [[antigonadotropin]], a weak [[steroidogenesis inhibitor]], and a functional [[antiestrogen]].<ref name="Berek2007"/><ref name="ThomasRock2012">{{cite book| vauthors = Thomas EJ, Rock J |title=Modern Approaches to Endometriosis|url=https://books.google.com/books?id=AFP1CAAAQBAJ&pg=PA228|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-3864-2|pages=228, 232, 234}}</ref><ref name="FRCOG2015">{{cite book| vauthors = Carp HJ |title=Progestogens in Obstetrics and Gynecology|url=https://books.google.com/books?id=Ik8SCAAAQBAJ&pg=PA141|date=9 April 2015|publisher=Springer|isbn=978-3-319-14385-9|pages=141–}}</ref><ref name="BromhamBooker1995">{{cite journal | vauthors = Bromham DR, Booker MW, Rose GL, Wardle PG, Newton JR | title = A multicentre comparative study of gestrinone and danazol in the treatment of endometriosis | journal = Journal of Obstetrics and Gynaecology | volume = 15 | issue = 3 | year = 1995 | pages = 188–194 | issn = 0144-3615 | doi = 10.3109/01443619509015498}}</ref>

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

Gestrinone was introduced for medical use in 1986.<ref name="AcademicPress1988" /> It has been used extensively in [[Europe]] but appears to remains marketed only in a few countries throughout the world.<ref name="BlackwellOlive2012" /><ref name="Index Nominum2000" /><ref name="Drugs.com" /> The medication is not available in the [[United States]].<ref name="LedgerSchlaff2014" /> Due to its [[anabolic]] effects, the use of gestrinone in competition has been banned by the [[International Olympic Committee]].<ref>{{cite web|date=May 2000 |url=http://sport-dc.com/medcom/CANADA-LIST.pdf |title=Helping athletes compete drug-free |pages=34 |publisher=Canadian Centre for Ethics in Sport |access-date=2006-06-01 |archive-url=https://web.archive.org/web/20060517045357/http://sport-dc.com/medcom/CANADA-LIST.pdf |archive-date=2006-05-17 |url-status=dead }}</ref>

{{TOC limit|3}}

==Medical uses==

Gestrinone is approved for and used in the treatment of [[endometriosis]]. It is described as similar in action and effect to [[danazol]], which is also used in the treatment of endometriosis, but is reported to have fewer androgenic [[side effect]]s in comparison.<ref name="ShawLuesley2010">{{cite book | vauthors = Shaw RW, Luesley D, Monga AK |title=Gynaecology: Expert Consult: Online and Print|url=https://books.google.com/books?id=Ylqqk9-5zUsC&pg=PT2175|date=1 October 2010|publisher=Elsevier Health Sciences|isbn=978-0-7020-4838-8|pages=2175–}}</ref><ref name="Gupta2011">{{cite book| vauthors = Gupta S |title=A Comprehensive Textbook of Obstetrics and Gynecology|url=https://books.google.com/books?id=5GiDegG69E0C&pg=PT171|date=14 March 2011|publisher=JP Medical Ltd|isbn=978-93-5025-112-6|pages=171–}}</ref> Gestrinone has also been used to shrink [[uterine fibroid]]s and to reduce [[menorrhagia]].<ref name="pmid15589885">{{cite journal | vauthors = La Marca A, Giulini S, Vito G, Orvieto R, Volpe A, Jasonni VM | title = Gestrinone in the treatment of uterine leiomyomata: effects on uterine blood supply | journal = Fertility and Sterility | volume = 82 | issue = 6 | pages = 1694–1696 | date = December 2004 | pmid = 15589885 | doi = 10.1016/j.fertnstert.2004.08.004 | doi-access = free }}<!--| access-date = 2006-06-01 --></ref><ref name="pmid14717620">{{cite journal | vauthors = Roy SN, Bhattacharya S | title = Benefits and risks of pharmacological agents used for the treatment of menorrhagia | journal = Drug Safety | volume = 27 | issue = 2 | pages = 75–90 | year = 2004 | pmid = 14717620 | doi = 10.2165/00002018-200427020-00001 | s2cid = 33841299 }}<!--| access-date = 2006-06-01 --></ref>

Due to its [[antigonadotropic]] effects and ability to inhibit [[ovulation]], gestrinone has been studied as a method of [[hormonal birth control]] in women.<ref name="ThomasRock2012" /> Large studies across thousands of [[menstrual cycle]]s have found it to be effective in preventing [[pregnancy]].<ref name="ThomasRock2012" /> However, although effective, the pregnancy rate in the largest study conducted was 4.6 per 100 woman-years, which is too high of a failure rate for the medication to be recommended as a safe method of birth control.<ref name="ThomasRock2012" /> The medication has also been investigated as an [[emergency contraception|emergency post-coital contraceptive]].<ref>{{cite web|date=October 2006 |url=http://www.cecinfo.org/files/ecupdate-9610.rtf |title=Emergency Contraception Update |format=RTF |pages=5 |publisher=International Consortium for Emergency Contraception |access-date=2006-06-01 |archive-url=https://web.archive.org/web/20060620192932/http://www.cecinfo.org/files/ecupdate-9610.rtf |archive-date=2006-06-20 |url-status=usurped }}</ref>

==Contraindications==

The medication is [[contraindication|contraindicated]] in [[pregnancy]], during [[lactation]], and in patients with severe cardiac, [[chronic kidney disease]] or liver disease. It is also contraindicated in patients who experienced metabolic and/or vascular disorders during previous estrogen or progestogen therapy, or who are allergic to the medication. The medication is contraindicated in children.

==Side effects==

{{See also|Anabolic steroid#Adverse effects}}

The main side effects of gestrinone are [[androgen]]ic and [[antiestrogen]]ic in nature.<ref name="ThomasRock2012" /><ref name="BlackwellOlive2012" /> In one study of 2.5&nbsp;mg oral gestrinone twice per week in women, it caused [[seborrhea]] in 71%, [[acne]] in 65%, [[breast hypoplasia]] in 29%, [[hirsutism]] in 9%, and [[scalp hair loss]] in 9%.<ref name="ThomasRock2012" /> In another study, the rate of androgenic side effects was similarly 50%.<ref name="ThomasRock2012" /> Other androgenic side effects that have been reported include [[oily skin]] and [[greasy hair|hair]], [[weight gain]], [[voice deepening]], and [[clitoral enlargement]], the latter two of which as well as hirsutism may be irreversible.<ref name="Carp2015">{{cite book| vauthors = Carp HJ |title=Progestogens in Obstetrics and Gynecology|url=https://books.google.com/books?id=Ik8SCAAAQBAJ&pg=PA141|date=9 April 2015|publisher=Springer|isbn=978-3-319-14385-9|pages=141–|quote=Side effects [of gestrinone] are due to the androgenic and anti-estrogenic effects including, voice changes, hirsutism, and clittoral enlargement.}}</ref><ref name="DesaiPatel2012">{{cite book| vauthors = Desai P, Patel P |title=Current Practice in Obstetrics and Gynecology Endometriosis|url=https://books.google.com/books?id=Y-twBST-240C&pg=PT111|date=15 May 2012|publisher=JP Medical Ltd|isbn=978-93-5025-808-8|pages=111–|quote=The clinical side effects are dose dependent and similar but less intense than those caused by danazol.12 They include nausea, muscle cramps, and androgenic effects such as weight gain, acne, seborrhea, oily hair/skin, and irreversible voice changes.}}</ref><ref name="BlackwellOlive2012">{{cite book| vauthors = Blackwell RE, Olive DL |title=Chronic Pelvic Pain: Evaluation and Management|url=https://books.google.com/books?id=pJwxBQAAQBAJ&pg=PP107|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4612-1752-7|pages=106–107|quote=Side-effects [of gestrinone] include androgenic and antiestrogenic sequelae. Although most side-effects are mild and transient, several, such as voice changes, hirsutism, and clitoral hypertrophy, are potentially irreversible.}}</ref>

Gestrinone also inhibits [[gonadotropin]] [[secretion]] and causes [[amenorrhea]] or [[oligomenorrhea]] in a high percentage of women.<ref name="ThomasRock2012" /> Similarly, circulating [[estradiol]] levels have been found to be reduced by 50%, which may result in [[estrogen deficiency]] and associated [[symptom]]s.<ref name="BlackwellOlive2012" /> Studies of 2.5&nbsp;mg oral gestrinone twice per week have found a rate of amenorrhea of 50 to 58%, while a study of 5&nbsp;mg oral gestrinone per day found a rate of amenorrhea of 100%.<ref name="ThomasRock2012" />

It has been found that vaginal gestrinone shows fewer androgenic side effects and [[weight gain]] than oral gestrinone with equivalent effectiveness in endometriosis.<ref name="ThomasRock2012" /> Gestrinone appears to show similar effectiveness to [[danazol]] in the treatment of endometriosis but with fewer side effects, in particular androgenic side effects.<ref name="ThomasRock2012" /><ref name="ShawLuesley2010" /><ref name="Gupta2011" />

==Pharmacology==

===Pharmacodynamics===

The [[mechanism of action]] of gestrinone is complex and multifaceted.<ref name="ThomasRock2012" /><ref name="ShawLuesley2010" /> It shows high [[affinity (pharmacology)|affinity]] for the [[progesterone receptor]] (PR), as well as lower affinity for the [[androgen receptor]] (AR).<ref name="ThomasRock2012" /><ref name="ShawLuesley2010" /> The medication has mixed [[progestogen (medication)|progestogen]]ic and [[antiprogestogen]]ic activity – that is, it is a [[partial agonist]] of the PR or a [[selective progesterone receptor modulator]] (SPRM) – and is a weak [[agonist]] of the AR, or an [[anabolic–androgenic steroid]] (AAS).<ref name="Berek2007" /><ref name="ThomasRock2012" /><ref name="FRCOG2015" /><ref name="BromhamBooker1995" /> Similarly to danazol, gestrinone acts as a weak [[antigonadotropin]] via activation of the PR and AR in the [[pituitary gland]] and suppresses the mid-cycle surge of [[luteinizing hormone]] (LH) and [[follicle-stimulating hormone]] (FSH) during the [[menstrual cycle]] without affecting basal levels of these hormones.<ref name="ThomasRock2012" /><ref name="ShawLuesley2010" /> It also inhibits [[ovarian]] [[steroidogenesis]] and, via activation of the AR in the [[liver]], decreases circulating levels of [[sex hormone-binding globulin]] (SHBG), thereby resulting in increased levels of free [[testosterone]].<ref name="ThomasRock2012" /><ref name="ShawLuesley2010" /><ref name="ArakawaMitsuma1989">{{cite journal | vauthors = Arakawa S, Mitsuma M, Iyo M, Ohkawa R, Kambegawa A, Okinaga S, Arai K | title = Inhibition of rat ovarian 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), 17 alpha-hydroxylase and 17,20 lyase by progestins and danazol | journal = Endocrinologia Japonica | volume = 36 | issue = 3 | pages = 387–394 | date = June 1989 | pmid = 2583058 | doi = 10.1507/endocrj1954.36.387 | doi-access = free }}</ref> In addition to the PR and AR, gestrinone has been found to bind to the [[estrogen receptor]] (ER) with relatively "avid" affinity.<ref name="pmid3490730">{{cite journal | vauthors = Tamaya T, Fujimoto J, Watanabe Y, Arahori K, Okada H | title = Gestrinone (R2323) binding to steroid receptors in human uterine endometrial cytosol | journal = Acta Obstetricia et Gynecologica Scandinavica | volume = 65 | issue = 5 | pages = 439–441 | year = 1986 | pmid = 3490730 | doi = 10.3109/00016348609157380 | s2cid = 9229704 }}</ref> The medication has functional antiestrogenic activity in the [[endometrium]].<ref name="Berek2007" /><ref name="ThomasRock2012" /><ref name="FRCOG2015" /><ref name="BromhamBooker1995" /> Unlike danazol, gestrinone does not appear to bind to SHBG or [[corticosteroid-binding globulin]] (CBG).<ref name="pmid3490730" />

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

|+ class="nowrap" | Relative affinities (%) of gestrinone and related steroids

|-

! 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}}

|-

| [[Norethisterone]] || 155–156 || 43–45 || <0.1 || 2.7–2.8 || 0.2 || ? || ?

|-

| [[Norgestrienone]] || 63–65 || 70 || <0.1 || 11 || 1.8 || ? || ?

|-

| [[Levonorgestrel]] || 170 || 84–87 || <0.1 || 14 || 0.6–0.9 || ? || ?

|-

| Gestrinone || 75–76 || 83–85 || <0.1, 3–10 || 77 || 3.2 || ? || ?

|- class="sortbottom"

| colspan="8" style="width: 1px; background-color:#eaecf0; text-align: center;" | '''Notes:''' Values are percentages (%). Reference [[ligand (biochemistry)|ligand]]s (100%) were [[progesterone (medication)|progesterone]] for the {{abbrlink|PR|progesterone receptor}}, [[testosterone (medication)|testosterone]] 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="pmid7382482">{{cite journal | vauthors = Delettré J, Mornon JP, Lepicard G, Ojasoo T, Raynaud JP | title = Steroid flexibility and receptor specificity | journal = J. Steroid Biochem. | volume = 13 | issue = 1 | pages = 45–59 | date = January 1980 | pmid = 7382482 | doi = 10.1016/0022-4731(80)90112-0 }}</ref><ref name="pmid7421203">{{cite journal | vauthors = Raynaud JP, Bouton MM, Moguilewsky M, Ojasoo T, Philibert D, Beck G, Labrie F, Mornon JP | title = Steroid hormone receptors and pharmacology | journal = J. Steroid Biochem. | volume = 12 | pages = 143–57 | date = January 1980 | pmid = 7421203 | doi = 10.1016/0022-4731(80)90264-2 }}</ref><ref name="pmid8136304">{{cite journal | vauthors = Ojasoo T, Raynaud JP, Doé JC | title = Affiliations among steroid receptors as revealed by multivariate analysis of steroid binding data | journal = J. Steroid Biochem. Mol. Biol. | volume = 48 | issue = 1 | pages = 31–46 | date = January 1994 | pmid = 8136304 | doi = 10.1016/0960-0760(94)90248-8 | s2cid = 21336380 }}</ref><ref name="RaynaudOjasoo1979">{{Cite book| vauthors = Raynaud JP, Ojasoo T, Bouton MM, Philibert D |title=Drug Design|chapter=Chapter 4 - Receptor Binding as a Tool in the Development of New Bioactive Steroids |series=Medicinal Chemistry: A Series of Monographs |year=1979|volume=11 |pages=169–214|publisher=Academic Press |doi=10.1016/B978-0-12-060308-4.50010-X|chapter-url=https://books.google.com/books?id=bhAlBQAAQBAJ&pg=PA169|isbn=9780120603084}}</ref>

|}

===Pharmacokinetics===

Gestrinone is [[plasma protein binding|bound]] to [[human serum albumin|albumin]] in the circulation.<ref name="ThomasRock2012" /> It is [[metabolism|metabolized]] in the [[liver]] mainly by [[hydroxylation]].<ref name="ThomasRock2012" /> Four hydroxylated [[active metabolite]]s with reduced activity relative to gestrinone have been found to be formed.<ref name="ThomasRock2012" /> The [[elimination half-life]] of gestrinone is 27.3&nbsp;hours.<ref name="ThomasRock2012" /> The medication is [[excretion|excreted]] in [[urine]] and [[bile]].<ref name="ThomasRock2012" />

==Chemistry==

{{See also|List of progestogens|List of androgens/anabolic steroids}}

Gestrinone, also known as 17α-ethynyl-18-methyl-19-nor-δ^9,11-testosterone, as well as 17α-ethynyl-18-methylestra-4,9,11-trien-17β-ol-3-one or as 13β-ethyl-18,19-dinor-17α-pregna-4,9,11-trien-20-yn-17β-ol-3-one, is a [[synthetic compound|synthetic]] [[estrane]] [[steroid]] and a [[chemical derivative|derivative]] of [[testosterone]].<ref name="Elks2014" /><ref name="Index Nominum2000" /> 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="CarrellPeterson2010">{{cite book| vauthors = Carrell DT, Peterson CM |title=Reproductive Endocrinology and Infertility: Integrating Modern Clinical and Laboratory Practice|url=https://books.google.com/books?id=lcBEheiufVcC&pg=PA200|date=23 March 2010|publisher=Springer Science & Business Media|isbn=978-1-4419-1436-1|pages=200–}}</ref><ref name="Berek2007">{{cite book| vauthors = Berek JS |title=Berek & Novak's Gynecology|url=https://books.google.com/books?id=P3erI0J8tEQC&pg=PA1167|year=2007|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-6805-4|pages=1167–}}</ref><ref name="BlandIII2009">{{cite book| vauthors = Bland KI, Copeland III EM |title=The Breast: Comprehensive Management of Benign and Malignant Diseases|url=https://books.google.com/books?id=1u4x_iGiHNEC&pg=PA93|date=9 September 2009|publisher=Elsevier Health Sciences|isbn=978-1-4377-1121-9|pages=93–}}</ref><ref name="Lachelin2013">{{cite book| vauthors = Lachelin GC |title=Introduction to Clinical Reproductive Endocrinology|url=https://books.google.com/books?id=RaHpAgAAQBAJ&pg=PA109|date=11 September 2013|publisher=Elsevier Science|isbn=978-1-4831-9380-9|pages=109–}}</ref> Gestrinone is the C18 [[methyl group|methyl]] derivative of [[norgestrienone]] (17α-ethynyl-19-nor-δ^9,11-testosterone) and the δ^9,11 [[structural analog|analogue]] of [[levonorgestrel]] (17α-ethynyl-18-methyl-19-nortestosterone) and is also known as ethylnorgestrienone due to the fact that it is the C13β [[ethyl group|ethyl]] variant of norgestrienone.<ref name="BlackwellOlive2012" /><ref name="GomelBrill2010">{{cite book| vauthors = Gomel V, Brill A |title=Reconstructive and Reproductive Surgery in Gynecology|url=https://books.google.com/books?id=C4TOBQAAQBAJ&pg=PA90|date=27 September 2010|publisher=CRC Press|isbn=978-1-84184-757-3|pages=90–}}</ref> It is also the C17α [[ethynyl group|ethynyl]] and C18 methyl derivative of the AAS [[trenbolone]].<ref name="ThiemeHemmersbach2009">{{cite book| vauthors = Thieme E, Hemmersbach P |title=Doping in Sports|url=https://books.google.com/books?id=R-hIC-caIn8C&pg=PA160|date=18 December 2009|publisher=Springer Science & Business Media|isbn=978-3-540-79088-4|pages=160–162}}</ref><ref name="Litwack2012">{{cite book| vauthors = Litwack G |title=Biochemical Actions of Hormones|url=https://books.google.com/books?id=tX9GwWPsMbQC&pg=PA321|date=2 December 2012|publisher=Elsevier|isbn=978-0-323-15344-7|pages=321–}}</ref>

The androgenic properties of gestrinone are more exploited in its derivative [[tetrahydrogestrinone]] (THG; 17α-ethyl-18-methyl-δ^9,11-19-nortestosterone), a [[designer steroid]] which is far more potent as both an AAS and progestogen in comparison.<ref name="DeathMcGrath2004">{{cite journal | vauthors = Death AK, McGrath KC, Kazlauskas R, Handelsman DJ | title = Tetrahydrogestrinone is a potent androgen and progestin | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 89 | issue = 5 | pages = 2498–2500 | date = May 2004 | pmid = 15126583 | doi = 10.1210/jc.2004-0033 | doi-access = free }}</ref> THG was banned by the [[Food and Drug Administration]] (FDA) in 2003.<ref name="Hollinger2007">{{cite book| vauthors = Hollinger MA |title=Introduction to Pharmacology, Third Edition|url=https://books.google.com/books?id=qfrLBQAAQBAJ&pg=PA235|date=19 October 2007|publisher=CRC Press|isbn=978-1-4200-4742-4|pages=235–}}</ref>

==History==

Gestrinone was introduced for medical use in 1986.<ref name="AcademicPress1988">{{cite book | vauthors = Ong HH, Allen RC | chapter = To Market – 1987 | veditors = Allen RC |title=Annual Reports in Medicinal Chemistry|chapter-url=https://books.google.com/books?id=Plq6RpLymIcC&pg=PA387|date=1 November 1988|publisher=Academic Press|isbn=978-0-08-058367-9|pages=387–}}</ref>

==Society and culture==

===Generic names===

''Gestrinone'' 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}}, 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=PA595|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=595–}}</ref><ref name="Index Nominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA488|date=January 2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=488, 1288}}</ref><ref name="MortonHall1999">{{cite book | vauthors = Morton IK, Hall JM |title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=mqaOMOtk61IC&pg=PA132|date=31 October 1999|publisher=Springer Science & Business Media|isbn=978-0-7514-0499-9|pages=132–}}</ref><ref name="Drugs.com">{{cite web | url=https://www.drugs.com/international/gestrinone.html | title=Gestrinone}}</ref> It is also known by its developmental code names ''A-46745'' and ''R-2323'' (or ''RU-2323'').<ref name="Elks2014" /><ref name="Index Nominum2000" /><ref name="MortonHall1999" /><ref name="Drugs.com" />

===Brand names===

Gestrinone is or has been marketed under the brand names Dimetriose, Dimetrose, Dinone, Gestrin, and Nemestran.<ref name="Elks2014" /><ref name="Index Nominum2000" /><ref name="Drugs.com" />

===Availability===

Gestrinone is or has been marketed in [[Europe]], [[Australia]], [[Latin America]], and [[Southeast Asia]],<ref name="Index Nominum2000" /><ref name="Drugs.com" /> though notably not in the [[United States]].<ref name="LedgerSchlaff2014">{{cite book| vauthors = Ledger W, Schlaff WD, Vancaillie TG |title=Chronic Pelvic Pain|url=https://books.google.com/books?id=ON-VBQAAQBAJ&pg=PA57|date=11 December 2014|publisher=Cambridge University Press|isbn=978-1-316-21414-5|pages=57–}}</ref>

==Further reading==

{{refbegin}}

* {{cite journal | vauthors = Coutinho E, Gonçalves MT, Azadian-Boulanger G, Silva AR | title = Endometriosis therapy with gestrinone by oral, vaginal or parenteral administration | journal = Contrib Gynecol Obstet | volume = 16 | pages = 227–35 | date = 1987 | pmid = 3691096 | doi = 10.1159/000414891 | series = Contributions to Gynecology and Obstetrics | isbn = 978-3-8055-4627-0 }}

* {{cite journal | vauthors = Coutinho EM | title = Therapeutic experience with gestrinone | journal = Prog. Clin. Biol. Res. | volume = 323 | pages = 233–40 | date = 1990 | pmid = 2406749 }}

{{refend}}

{{Androgens and antiandrogens}}

{{Progestogens and antiprogestogens}}

{{Androgen receptor modulators}}

{{Progesterone receptor modulators}}

{{Other sex hormones and modulators of the genital system}}

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[[Category:Progestogens]]