# Promegestone

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> Markdown URL: https://mediated.wiki/source/Promegestone.md
> Source: https://en.wikipedia.org/wiki/Promegestone
> Source revision: 1329009901
> License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/)

{{Short description|Chemical compound}}
{{Distinguish|Progesterone (medication)}}
{{Drugbox
| IUPAC_name = (8''S'',13''S'',14''S'',17''S'')-13,17-dimethyl-17-propionyl-1,2,6,7,8,11,12,13,14,15,16,17-dodecahydro-3''H''-cyclopenta[''a'']phenanthren-3-one
| image = Promegestone.svg
| image_class = skin-invert-image
| width = 200px

<!--Clinical data-->
| tradename = Surgestone
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category = 
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C -->
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_status = 
| routes_of_administration = [By mouth](/source/Oral_administration)<ref name="pmid16112947" />
| class = [Progestogen](/source/Progestogen_(medication)); [Progestin](/source/Progestin)

<!--Pharmacokinetic data-->
| bioavailability = 
| protein_bound = To [albumin](/source/human_serum_albumin)<ref name="pmid16112947" />
| metabolism = [Liver](/source/Liver) ([hydroxylation](/source/hydroxylation))<ref name="pmid16112947" /><ref name="Kuhl2011" />
| metabolites = • [Trimegestone](/source/Trimegestone)
| elimination_half-life = Promegestone: ?<br />Trimegestone: 13.8–15.6&nbsp;hours<ref name="pmid16112947" /><ref name="pmid17616854" />
| excretion =

<!--Identifiers-->
| CAS_number = 34184-77-5
| ATC_prefix = G03
| ATC_suffix = DB07
| PubChem = 36709
| DrugBank = 
| ChemSpiderID = 33716
| UNII = 9XE0V2SQYX
| ChEBI = 73390
| ChEMBL = 196003
| KEGG = D08431
| synonyms = PMG; R-5020; RU-5020; 17α,21-Dimethyl-δ<sup>9</sup>-19-norprogesterone; 17α,21-Dimethyl-19-norpregna-4,9-diene-3,20-dione

<!--Chemical data-->
| C=22 | H=30 | O=2 
| SMILES = CCC(=O)[C@]1(CC[C@@H]2[C@@]1(CCC3=C4CCC(=O)C=C4CC[C@@H]23)C)C
| StdInChI = 1S/C22H30O2/c1-4-20(24)22(3)12-10-19-18-7-5-14-13-15(23)6-8-16(14)17(18)9-11-21(19,22)2/h13,18-19H,4-12H2,1-3H3/t18-,19+,21+,22-/m1/s1
| StdInChIKey = QFFCYTLOTYIJMR-XMGTWHOFSA-N
}}
<!-- Definition and medical uses -->
'''Promegestone''', sold under the brand name '''Surgestone''', is a [progestin](/source/progestin) medication which is used in [menopausal hormone therapy](/source/menopausal_hormone_therapy) and in the treatment of [gynecological disorder](/source/gynecological_disorder)s.<ref name="pmid6366037">{{cite journal | vauthors = Raynaud JP, Ojasoo T | title = [Promegestone, a new progestin] | language = fr | journal = Journal de Gynécologie, Obstétrique et Biologie de la Reproduction | volume = 12 | issue = 7 | pages = 697–710 | date = 1983 | pmid = 6366037 }}</ref><ref name="pmid16112947" /><ref name="Cain1984">{{cite book| vauthors = Allen RC | chapter = To Market – 1983 | veditors = Baily DM |title=Annual Reports in Medicinal Chemistry | volume = 19 |chapter-url=https://books.google.com/books?id=oX-IT5QykwwC&pg=PA323|date=11 September 1984|publisher=Academic Press|isbn=978-0-08-058363-1|pages=323–}}</ref><ref name="Drugs.com">{{cite web|url=https://www.drugs.com/international/promegestone.html|title = List of Progestins}}</ref> It is taken [by mouth](/source/oral_administration).<ref name="pmid16112947" />

<!-- Side effects and mechanism -->
[Side effect](/source/Side_effect)s of promegestone include [menstrual irregularities](/source/menstrual_irregularities) among others.<ref name="TulunayOrme2012">{{cite book| vauthors = Tulunay FC, Orme M |title=European Collaboration: Towards Drug {{sic|Develo|pement|nolink=y}} and Rational Drug Therapy: Proceedings of the Sixth Congress of the European Association for Clinical Pharmacology and Therapeutics Istanbul, June 24–28, 2003|url=https://books.google.com/books?id=Yk_xCAAAQBAJ&pg=PA107|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-55454-4|pages=107–|quote=Investigation of the Pharmacokinetics and Metabolism of Promegestone in Healthy Female Volunteers Following Single Oral Administration of 1 mg Promegestone I Gualano V., 1Geneteau A., I Chassard D., I Fordham P., 2Schatz B. I Aster-Cephac, 3/5, Rue Eugene Millon, 75015 Paris, France 2Laboratoire Aventis, 46 Quai De La Rapee, F-75601 Paris Cedex 12, France. A single 1 mg oral dose of promegestone (Surgestonee, 2x0.5 mg) was given to 12 healthy premenopausal women. The aims were to determine the concentrations of promegestone and its metabolites and their pharmacokinet-ic parameters. Blood and urine samples were followed until 96 hours post dose. To avoid any interference with natural hormones, promegestone was given between day 7 and 10 of the menstrual cycle. Clinical safety and tolerability were good. Most of the minor adverse events observed were estimated possibly linked to the study drug (menstrual disorders) because classically related to progestins therapy. In addition, no clinically relevant biological modifications were observed. There was a stereoselective metabolism of promegestone in favor of the 21S hydroxy-promegestone, the main circulating compound in plasma (AUC ratio 5/R of about 21). Levels of 21S hydroxy-promegestone are about twice greater than that of unchanged promegestone. The plasma levels of the second metabolite, i.e. 21 R hydroxy-promegestone are far below these of either promegestone and 21S hydroxy-promegestone. Promegestone, 215 hydroxy- and 21R hydroxy-promegestone are not excreted in urine. About 3% of the dose was recov-ered in urine as sulfo and/or glucuro-conjugate 21S hydroxy-promegestone and about 1% of the dose as sulfo and/or glucuro conjugate 21R hydroxy-promegestone.}}</ref> Promegestone is a progestin, or a [synthetic](/source/synthetic_compound) [progestogen](/source/progestogen_(medication)), and hence is an [agonist](/source/agonist) of the [progesterone receptor](/source/progesterone_receptor), the [biological target](/source/biological_target) of progestogens like [progesterone](/source/progesterone).<ref name="pmid16112947" /> It has weak [antiandrogen](/source/antiandrogen)ic, [glucocorticoid](/source/glucocorticoid), and [antimineralocorticoid](/source/antimineralocorticoid) activity and no other important [hormonal](/source/hormonal_agent) activity.<ref name="pmid16112947" /><ref name="pmid14667983" /><ref name="pmid17616854" /> The medication is largely a [prodrug](/source/prodrug) of [trimegestone](/source/trimegestone).<ref name="TulunayOrme2012" /><ref name="pmid16112947" />

<!-- History, society, and culture -->
Promegestone was first described in 1973 and was introduced for medical use in [France](/source/France) in 1983.<ref name="Elks2014" /><ref name="pmid4353432" /><ref name="Publishing2013" /> It has only been marketed in a few countries, including France, [Portugal](/source/Portugal), [Tunisia](/source/Tunisia), and [Argentina](/source/Argentina).<ref name="Drugs.com" /><ref name="IndexNominum2000" /> In addition to its use as a medication, promegestone has been widely used in [scientific research](/source/scientific_research) as a [radioligand](/source/radioligand) of the progesterone receptor.<ref name="pmid6366037" /><ref name="RaynaudOjasoo1981">{{cite book| vauthors = Raynaud JP, Ojasoo T, Vaché V |title=Reproductive Processes and Contraception|chapter=Stable and Specific Tracers|series=Biochemical Endocrinology |year=1981|pages=163–179|publisher=Springer |doi=10.1007/978-1-4684-3824-6_7|isbn=978-1-4684-3826-0}}</ref>

==Medical uses==
Promegestone is used in [menopausal hormone therapy](/source/menopausal_hormone_therapy) and in the treatment of [gynecological condition](/source/gynecological_condition)s caused by [luteal insufficiency](/source/luteal_insufficiency), including [premenopausal](/source/premenopausal) disorders, [dysmenorrhea](/source/dysmenorrhea) and other [menstrual disorder](/source/menstrual_disorder)s, and [premenstrual syndrome](/source/premenstrual_syndrome).<ref name="pmid16112947" /><ref name="Cain1984" /> It has also been used to treat [benign](/source/benign_tumor) [breast disorder](/source/breast_disorder)s such as [mastalgia](/source/mastalgia) (breast pain).<ref name="pmid1563574">{{cite journal | vauthors = Uzan S, Denis C, Pomi V, Varin C | title = Double-blind trial of promegestone (R 5020) and lynestrenol in the treatment of benign breast disease | journal = European Journal of Obstetrics, Gynecology, and Reproductive Biology | volume = 43 | issue = 3 | pages = 219–227 | date = February 1992 | pmid = 1563574 | doi = 10.1016/0028-2243(92)90177-z | doi-access = free }}</ref> Promegestone tablets have a contraceptive effect and are used as a form of [progestogen-only birth control](/source/progestogen-only_birth_control), although it is not specifically licensed as such.<ref name="pmid23078975">{{cite journal | vauthors = Gourdy P, Bachelot A, Catteau-Jonard S, Chabbert-Buffet N, Christin-Maître S, Conard J, Fredenrich A, Gompel A, Lamiche-Lorenzini F, Moreau C, Plu-Bureau G, Vambergue A, Vergès B, Kerlan V | display-authors = 6 | title = Hormonal contraception in women at risk of vascular and metabolic disorders: guidelines of the French Society of Endocrinology | journal = Annales d'Endocrinologie | volume = 73 | issue = 5 | pages = 469–487 | date = November 2012 | pmid = 23078975 | doi = 10.1016/j.ando.2012.09.001 }}</ref>

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

[Side effect](/source/Side_effect)s of promegestone include [menstrual irregularities](/source/menstrual_irregularities) among others.<ref name="TulunayOrme2012" /> It has no [androgen](/source/androgen)ic side effects.<ref name="pmid6366037" /><ref name="Cain1984" />

==Pharmacology==
===Pharmacodynamics===
[[File:Trimegestone.svg|thumb|right|225px|class=skin-invert-image|[Trimegestone](/source/Trimegestone) (21(''S'')-hydroxyl-promegestone), the major [active metabolite](/source/active_metabolite) of promegestone.]]

Promegestone is a [progestogen](/source/progestogen_(medication)), or an [agonist](/source/agonist) of the [progesterone receptor](/source/progesterone_receptor).<ref name="pmid16112947">{{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 | s2cid = 24616324 | url = http://hormonebalance.org/images/documents/Kuhl%2005%20%20Pharm%20Estro%20Progest%20Climacteric_1313155660.pdf }}</ref><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 = https://www.kup.at/kup/pdf/10168.pdf}}</ref> It has about 200% of the [affinity](/source/affinity_(pharmacology)) of [progesterone](/source/progesterone_(medication)) for the PR.<ref name="pmid16112947" /><ref name="Kuhl2011" /> The [endometrial transformation](/source/endometrial_transformation) dosage of promegestone is 10&nbsp;mg per cycle and its [ovulation](/source/ovulation)-inhibiting dosage is 0.5&nbsp;mg/day.<ref name="pmid16112947" /><ref name="Kuhl2011" /> Promegestone has weak [glucocorticoid](/source/glucocorticoid) activity in addition to its progestogenic activity.<ref name="pmid16112947" /><ref name="Kuhl2011" /> Conversely, it has no [androgen](/source/androgen)ic, [estrogen](/source/estrogen_(medication))ic, [mineralocorticoid](/source/mineralocorticoid), or other [hormonal](/source/hormonal_agent) activity.<ref name="pmid16112947" /><ref name="Kuhl2011" /><ref name="Cain1984" /> It appears to possess [antiandrogen](/source/antiandrogen)ic activity.<ref name="RaynaudOjasoo1981" /> Its major [metabolite](/source/metabolite) [trimegestone](/source/trimegestone) has weak [antimineralocorticoid](/source/antimineralocorticoid) and [antiandrogen](/source/antiandrogen)ic activity.<ref name="pmid14667983">{{cite journal | vauthors = Winneker RC, Bitran D, Zhang Z | title = The preclinical biology of a new potent and selective progestin: trimegestone | journal = Steroids | volume = 68 | issue = 10–13 | pages = 915–920 | date = November 2003 | pmid = 14667983 | doi = 10.1016/s0039-128x(03)00142-9 | s2cid = 24893971 }}</ref><ref name="pmid17616854">{{cite journal | vauthors = Sitruk-Ware R, Bossemeyer R, Bouchard P | title = Preclinical and clinical properties of trimegestone: a potent and selective progestin | journal = Gynecological Endocrinology | volume = 23 | issue = 6 | pages = 310–319 | date = June 2007 | pmid = 17616854 | doi = 10.1080/09513590701267727 | s2cid = 39422122 }}</ref> In addition, promegestone has been found to possess some [neurosteroid](/source/neurosteroid) activity by acting as a [non-competitive antagonist](/source/Receptor_antagonist) of the [nicotinic acetylcholine receptor](/source/nicotinic_acetylcholine_receptor), similarly to progesterone.<ref name="pmid9927618">{{cite journal | vauthors = Blanton MP, Xie Y, Dangott LJ, Cohen JB | title = The steroid promegestone is a noncompetitive antagonist of the Torpedo nicotinic acetylcholine receptor that interacts with the lipid-protein interface | journal = Molecular Pharmacology | volume = 55 | issue = 2 | pages = 269–278 | date = February 1999 | pmid = 9927618 | doi = 10.1124/mol.55.2.269 | s2cid = 491327 }}</ref>

===Pharmacokinetics===
Following [oral administration](/source/oral_administration), [peak serum levels](/source/Cmax_(pharmacology)) of promegestone are reached after 1 to 2&nbsp;hours.<ref name="pmid16112947" /><ref name="Kuhl2011" /> The medication is mainly [bound](/source/plasma_protein_binding) to [albumin](/source/serum_albumin); it does not bind to [sex hormone-binding globulin](/source/sex_hormone-binding_globulin), and binds only weakly to [corticosteroid-binding globulin](/source/corticosteroid-binding_globulin).<ref name="pmid16112947" /><ref name="Kuhl2011" /><ref name="pmid858781">{{cite journal | vauthors = Chan DW, Slaunwhite WR | title = The binding of a synthetic progestin, R5020 to transcortin and serum albumin | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 44 | issue = 5 | pages = 983–985 | date = May 1977 | pmid = 858781 | doi = 10.1210/jcem-44-5-983 }}</ref> The [metabolism](/source/metabolism) of promegestone is mainly via [hydroxylation](/source/hydroxylation) at the C21 position and at other positions.<ref name="pmid16112947" /><ref name="Kuhl2011" /> Progesterone is similarly hydroxylated at the C21 position, into [11-deoxycorticosterone](/source/11-deoxycorticosterone) (21-hydroxyprogesterone).<ref name="Litwack2012" /> However, the C9(10) [double bond](/source/double_bond) of promegestone greatly limits the A-ring [reduction](/source/redox) that progesterone undergoes, resulting in 21-hydroxylation being the main route of metabolism for promegestone.<ref name="Litwack2012">{{cite book| vauthors = Litwack G |title=Biochemical Actions of Hormones|url=https://books.google.com/books?id=tX9GwWPsMbQC&pg=PA314|date=2 December 2012|publisher=Elsevier|isbn=978-0-323-15344-7|pages=314–}}</ref> The medication is [stereoselectively](/source/stereoselectivity) metabolized into [trimegestone](/source/trimegestone), the 21(''S'')-hydroxy [metabolite](/source/metabolite), which is the main compound found in [plasma](/source/blood_plasma); it circulates at levels approximately twice those of promegestone itself.<ref name="TulunayOrme2012" /> In addition, trimegestone has more than three-fold higher affinity for the PR than does promegestone.<ref name="pmid16112947" /> As such, promegestone is largely a [prodrug](/source/prodrug) of trimegestone.<ref name="TulunayOrme2012" /><ref name="Carp2015">{{cite book| vauthors = Carp HJ |title=Progestogens in Obstetrics and Gynecology|url=https://books.google.com/books?id=Ik8SCAAAQBAJ&pg=PA34|date=9 April 2015|publisher=Springer|isbn=978-3-319-14385-9|pages=34–}}</ref> A second metabolite, 21(''R'')-hydroxypromegestone, circulates at far lower concentrations ({{abbrlink|AUC|area-under-the-curve levels}} ratio for the (''S'')- and (''R'')-[isomer](/source/isomer)s of about 21).<ref name="TulunayOrme2012" /> The [elimination half-life](/source/elimination_half-life) of trimegestone is 13.8 to 15.6&nbsp;hours.<ref name="pmid16112947" /><ref name="pmid17616854" /> Promegestone, trimegestone, and 21(''R'')-hydroxypromegestone are not [excreted](/source/excretion) in [urine](/source/urine), while 3% of a dose is recovered as the [glucuronide](/source/glucuronide) and/or [sulfate](/source/sulfate) [conjugate](/source/conjugate_(biochemistry)) of trimegestone and 1% of a dose is recovered as the glucuronide and/or sulfate conjugate of 21(''R'')-hydroxypromegestone.<ref name="TulunayOrme2012" />

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

Promegestone, also known as 17α,21-dimethyl-δ<sup>9</sup>-19-norprogesterone or as 17α,21-dimethyl-19-norpregna-4,9-diene-3,20-dione, is a [synthetic](/source/synthetic_compound) [norpregnane](/source/norpregnane) [steroid](/source/steroid) and a [derivative](/source/chemical_derivative) of [progesterone](/source/progesterone_(medication)).<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=PA1026|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=1026–}}</ref><ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA883|date=January 2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=883–}}</ref><ref name="Publishing2013">{{cite book|author=William Andrew Publishing|title=Pharmaceutical Manufacturing Encyclopedia, 3rd Edition|url=https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA2935-IA448|date=22 October 2013|publisher=Elsevier|isbn=978-0-8155-1856-3|pages=2935–36}}</ref><ref name="pmid16112947" /> It is specifically a combined derivative of [17α-methylprogesterone](/source/17%CE%B1-methylprogesterone) and [19-norprogesterone](/source/19-norprogesterone), or of [17α-methyl-19-norprogesterone](/source/17%CE%B1-methyl-19-norprogesterone).<ref name="Elks2014" /><ref name="Publishing2013" /><ref name="pmid16112947" /> Related derivatives of 17α-methyl-19-norprogesterone include [demegestone](/source/demegestone) and [trimegestone](/source/trimegestone).<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="pmid16112947" />

==History==
Promegestone was first described in the literature in 1973 and was introduced for medical use in [France](/source/France) in 1983.<ref name="Elks2014" /><ref name="pmid4353432">{{cite journal | vauthors = Philibert D, Raynaud JP | title = Progesterone binding in the immature mouse and rat uterus | journal = Steroids | volume = 22 | issue = 1 | pages = 89–98 | date = July 1973 | pmid = 4353432 | doi = 10.1016/0039-128x(73)90073-1 }}</ref><ref name="Publishing2013" /><ref name="Cain1984" /> It was developed by [Roussel Uclaf](/source/Roussel_Uclaf) in France.<ref name="Cain1984" />

==Society and culture==

===Generic names===
''Promegestone'' is the [generic name](/source/generic_term) of the drug and its {{abbrlink|INN|International Nonproprietary Name}}, while ''promégestone'' is its {{abbrlink|DCF|Dénomination Commune Française}}.<ref name="Drugs.com" /><ref name="Elks2014" /><ref name="IndexNominum2000" /> It is also known by its developmental code name ''R-5020'' or ''RU-5020''.<ref name="Drugs.com" /><ref name="Elks2014" /><ref name="IndexNominum2000" />

===Brand names===
Promegestone is marketed exclusively under the brand name Surgestone.<ref name="Drugs.com" /><ref name="IndexNominum2000" />

===Availability===
Promegestone is or has been marketed in [France](/source/France), [Portugal](/source/Portugal), [Tunisia](/source/Tunisia), and [Argentina](/source/Argentina).<ref name="Drugs.com" /><ref name="IndexNominum2000" />

== References ==
{{Reflist}}

== Further reading ==
{{refbegin}}
* {{cite journal | vauthors = Raynaud JP, Ojasoo T | title = [Promegestone, a new progestin] | language = fr | journal = Journal de Gynécologie, Obstétrique et Biologie de la Reproduction | volume = 12 | issue = 7 | pages = 697–710 | date = 1983 | pmid = 6366037 }}
* {{cite journal | vauthors = Brun G, Dargent D, Pontonnier G, Petrescou L | title = [Clinical use of promegestone, a progestational agent with high specificity for receptors] | language = fr | journal = Revue Française de Gynécologie et d'Obstétrique | volume = 79 | issue = 5 | pages = 423–426 | date = May 1984 | pmid = 6396815 }}
{{refend}}

{{Progestogens and antiprogestogens}}
{{Navboxes
| title = [Pharmacodynamics](/source/Pharmacodynamics)
| titlestyle = background:#ccccff
| list1 = 
{{Androgen receptor modulators}}
{{Glucocorticoid receptor modulators}}
{{Mineralocorticoid receptor modulators}}
{{Nicotinic acetylcholine receptor modulators}}
{{Progesterone receptor modulators}}
}}

Category:Antiandrogens
Category:Antimineralocorticoids
Category:Conjugated dienes
Category:Diketones
Category:Glucocorticoids
Category:Nicotinic antagonists
Category:Norpregnanes
Category:Sex hormone esters and conjugates
Category:Progestogens
Category:Enones

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Adapted from the Wikipedia article [Promegestone](https://en.wikipedia.org/wiki/Promegestone) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Promegestone?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.