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Revision as of 14:25, 10 August 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'ChEBI', 'StdInChI', 'StdInChIKey').← Previous edit		Latest revision as of 01:50, 4 January 2025 edit undoArthurfragoso (talk | contribs)Extended confirmed users2,076 edits dark mode fixes
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			{{Short description|Sex hormone}}
	{{drugbox | Verifiedfields = changed
			{{Use dmy dates|date=December 2023}}
	| Watchedfields = changed
			{{About|progesterone as a hormone|its use as a medication|progesterone (medication)}}
	| verifiedrevid = 395158861
			{{cs1 config|name-list-style=vanc}}
	| IUPAC_name = Pregn-4-ene-3,20-dione
			{{Chembox
	| image = Progesteron.svg
			<!-- Images -->| Name =
	| image2 = Progesterone-3D-vdW.png
			| ImageFile1 = Progesterone.svg
	| width=200 <!-- low res image -->
			| ImageClass1 = skin-invert
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| ChemSpiderID = 5773		| ImageSize1 = 225px
			| ImageAlt1 = The chemical structure of progesterone.
			| ImageFile2 = Progesterone-3D-balls.png
			| ImageSize2 = 225px
			| ImageAlt2 = A ball-and-stick model of progesterone.
			<!-- Names -->| IUPACName = Pregn-4-ene-3,20-dione<ref name="Adler-2012">{{cite book | vauthors = Adler N, Pfaff D, Goy RW | title = Handbook of Behavioral Neurobiology Volume 7 Reproduction | date = 6 December 2012 | publisher = Plenum Press | location = New York | isbn = 978-1-4684-4834-4 | page = 189 | edition = 1st | url = https://books.google.com/books?id=MoDrBwAAQBAJ&q=pregn-4-ene-3,20-dione;+abbreviated+as+P4&pg=PA189 | access-date = 4 July 2015 | archive-date = 14 January 2023 | archive-url = https://web.archive.org/web/20230114024946/https://books.google.com/books?id=MoDrBwAAQBAJ&q=pregn-4-ene-3,20-dione;+abbreviated+as+P4&pg=PA189 | url-status = live }}</ref><ref name="ChEBI-17026">{{cite web|title=progesterone (CHEBI:17026)|url=http://www.ebi.ac.uk/chebi/searchId.do;jsessionid=309FCC7D184C0AD58410071F3F163155?chebiId=17026&structureView=applet&viewTermLineage=|website=ChEBI|publisher=European Molecular Biology Laboratory-EBI|access-date=4 July 2015|archive-date=20 March 2016|archive-url=https://web.archive.org/web/20160320211423/http://www.ebi.ac.uk/chebi/searchId.do;jsessionid=309FCC7D184C0AD58410071F3F163155?chebiId=17026&structureView=applet&viewTermLineage=|url-status=live}}</ref>
			| SystematicName = (1''S'',3a''S'',3b''S'',9a''R'',9b''S'',11a''S'')-1-Acetyl-9a,11a-dimethyl-1,2,3,3a,3b,4,5,8,9,9a,9b,10,11,11a-tetradecahydro-7''H''-cyclopentaphenanthren-7-one
			| OtherNames = P4;<ref name="James2015" /> Pregnenedione
			| Verifiedfields = changed
			| Watchedfields = changed
			| verifiedrevid = 444066687
			<!-- Sections -->| Section1 = {{Chembox Identifiers
			| CASNo_Ref = {{cascite|correct|??}}
			| CASNo = 57-83-0
			| ChEBI_Ref = {{ebicite|correct|EBI}}
			| ChEBI = 17026
	| ChEMBL_Ref = {{ebicite|correct|EBI}}		| ChEMBL_Ref = {{ebicite|correct|EBI}}
	| ChEMBL = 103		| ChEMBL = 103
	| UNII_Ref = {{fdacite|correct|FDA}}		| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
			| ChemSpiderID = 5773
	| UNII = 4G7DS2Q64Y
	| InChI1 = 1/C21H30O2/c1-13(22)17-6-7-18-16-5-4-14-12-15(23)8-10-20(14,2)19(16)9-11-21(17,18)3/h12,16-19H,4-11H2,1-3H3/t16-,17+,18-,19-,20-,21+/m0/s1
	| InChIKey1 = RJKFOVLPORLFTN-LEKSSAKUBC
	| smiles = O=C4\C=C2/(1CC3((C(=O)C)CC31CC2)C)(C)CC4
	| CAS_number = 57-83-0
	| CASNo_Ref = {{cascite|correct|CAS}}
	| ATC_prefix = G03
	| ATC_suffix =DA04
	| ChEBI = 17026
	| StdInChI = 1S/C21H30O2/c1-13(22)17-6-7-18-16-5-4-14-12-15(23)8-10-20(14,2)19(16)9-11-21(17,18)3/h12,16-19H,4-11H2,1-3H3/t16-,17+,18-,19-,20-,21+/m0/s1
	| StdInChIKey = RJKFOVLPORLFTN-LEKSSAKUSA-N
	| PubChem = 5994
	| IUPHAR_ligand = 2377
	| DrugBank_Ref = {{drugbankcite|correct|drugbank}}		| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
	| DrugBank = DB00396		| DrugBank = DB00396
			| KEGG_Ref = {{keggcite|changed|kegg}}
			| KEGG = C00410
			| PubChem = 5994
			| SMILES = CC(=O)1CC21(CC32CCC4=CC(=O)CC34C)C
			| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
			| StdInChI = InChI=1S/C21H30O2/c1-13(22)17-6-7-18-16-5-4-14-12-15(23)8-10-20(14,2)19(16)9-11-21(17,18)3/h12,16-19H,4-11H2,1-3H3/t16-,17+,18-,19-,20-,21+/m0/s1
			| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
			| StdInChIKey = RJKFOVLPORLFTN-LEKSSAKUSA-N
			| UNII_Ref = {{fdacite|correct|FDA}}
			| UNII = 4G7DS2Q64Y
			}}
			| Section2 = {{Chembox Properties
	| C=21 | H=30 | O=2		| C=21 | H=30 | O=2
	| molecular_weight = 314.46		| MolarMass = 314.469 g/mol
			| Appearance =
	| melting_point = 126
			| Density = 1.171
	| specific_rotation = <sub>D</sub>
			| MeltingPt = 126
	| synonyms = 4-pregnene-3,20-dione
			| BoilingPt =
	| bioavailability = prolonged absorption, half-life approx 25-50 hours
			| Solubility =
	| protein_bound = 96%-99%
			| LogP = 4.04<ref name="chemsrc">{{cite web|url=https://www.chemsrc.com/en/cas/57-83-0_1068061.html|title=Progesterone_msds|access-date=19 April 2018|archive-date=12 February 2021|archive-url=https://web.archive.org/web/20210212022152/https://www.chemsrc.com/en/cas/57-83-0_1068061.html|url-status=live}}</ref>
	| metabolism = ] to pregnanediols and pregnanolones
			}}
	| elimination_half-life = 34.8-55.13 hours
			| Section3 = {{Chembox Hazards
	| excretion = renal
			| MainHazards =
	| pregnancy_category = B (])
	| legal_status =		| FlashPt =
			| AutoignitionPt =
	| routes_of_administration = oral, ]
			}}
			| Section4 =
			| Section5 =
			| Section6 = {{Chembox Pharmacology
			| ATCvet =
			| ATCCode_prefix = G03
			| ATCCode_suffix = DA04
			| ATC_Supplemental =
			| AdminRoutes = ], ]/], ], ], ], ]
			| Bioavail = {{abbr|OMP|oral micronized progesterone}}: <10%<ref name="pmid12215716" /><ref name="pmid8513955" />
			| Excretion = ]
			| HalfLife = {{abbr|OMP|oral micronized progesterone}}: 16–18 hours<ref name="pmid12215716" /><ref name="pmid8513955" /><ref name="Zutshi-2005">{{cite book | vauthors = Zutshi V, Rathore AM, Sharma K | title = Hormones in Obstetrics and Gynaecology | url = https://books.google.com/books?id=IBxBbaDjXw0C&pg=PA74 | date = 1 January 2005 | publisher = Jaypee Brothers Publishers | isbn = 978-81-8061-427-9 | page = 74 }}{{Dead link|date=February 2023 |bot=InternetArchiveBot |fix-attempted=yes }}</ref><br />{{abbr|IM|Intramuscular}}: 22–26 hours<ref name="pmid8513955" /><ref name="pmid26342177">{{cite journal | vauthors = Cometti B | title = Pharmaceutical and clinical development of a novel progesterone formulation | journal = Acta Obstetricia et Gynecologica Scandinavica | volume = 94 | issue = Suppl 161 | pages = 28–37 | date = November 2015 | pmid = 26342177 | doi = 10.1111/aogs.12765 | s2cid = 31974637 | doi-access = free }}</ref><br />{{abbr|SC|Subcutaneous}}: 13–18 hours<ref name="pmid26342177" />
			| Metabolism = ] (], ], ], ], {{abbrlink|3α-HSD|3α-hydroxysteroid dehydrogenase}}, ], ], {{abbrlink|20α-HSD|20α-hydroxysteroid dehydrogenase}})<ref name="pmid9328296">{{cite journal | vauthors = Yamazaki H, Shimada T | title = Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes | journal = Archives of Biochemistry and Biophysics | volume = 346 | issue = 1 | pages = 161–169 | date = October 1997 | pmid = 9328296 | doi = 10.1006/abbi.1997.0302 }}</ref><ref name="McKayWalters2013">{{cite book | vauthors = McKay GA, Walters MR | title = Lecture Notes: Clinical Pharmacology and Therapeutics | url = https://books.google.com/books?id=OGOqcfN_Cc8C&pg=PT33 | date = 6 February 2013 | publisher = John Wiley & Sons | isbn = 978-1-118-34489-7 | page = 33 | access-date = 27 June 2015 | archive-date = 14 January 2023 | archive-url = https://web.archive.org/web/20230114024939/https://books.google.com/books?id=OGOqcfN_Cc8C&pg=PT33 | url-status = live }}</ref>
			| ProteinBound = • ]: 80%<br />• ]: 18%<br />• ]: <1%<br />• Free: 1–2%<ref name="FritzSperoff2012">{{cite book | vauthors = Fritz MA, Speroff L | title = Clinical Gynecologic Endocrinology and Infertility | url = https://books.google.com/books?id=KZLubBxJEwEC&pg=PA44 | date = 28 March 2012 | publisher = Lippincott Williams & Wilkins | isbn = 978-1-4511-4847-3 | pages = 44– }}</ref><ref name="MarshallD.2008">{{cite book | vauthors = Marshall WJ, Bangert SK | title = Clinical Chemistry | url = https://books.google.com/books?id=Gjc704GR5YEC&pg=PA192 | year = 2008 | publisher = Elsevier Health Sciences | isbn = 978-0-7234-3455-9 | pages = 192– | access-date = 5 October 2016 | archive-date = 14 January 2023 | archive-url = https://web.archive.org/web/20230114024953/https://books.google.com/books?id=Gjc704GR5YEC&pg=PA192 | url-status = live }}</ref>
			}}
	}}		}}
	'''Progesterone''' also known as '''P4''' ('''p'''regn-'''4'''-ene-3,20-dione) is a C-21 ] involved in the ] ], ] (supports '']'') and ] of humans and other species. Progesterone belongs to a class of hormones called ], and is the major naturally occurring human progestogen.
			'''Progesterone''' ({{IPAc-en|p|r|oʊ|ˈ|dʒ|ɛ|s|t|ər|oʊ|n|audio=LL-Q1860 (eng)-Flame, not lame-progesterone.wav}}; '''P4''') is an ] ] and ] ] involved in the ], ], and ] of humans and other species.<ref name="James2015" /><ref name="KingBrucker2010" /> It belongs to a group of steroid hormones called the ]s<ref name="KingBrucker2010" /> and is the major progestogen in the body. Progesterone has a variety of important functions in the body. It is also a crucial ] in the production of other endogenous ]s, including the ]s and the ]s, and plays an important role in brain function as a ].<ref name="pmid11108866">{{cite journal | vauthors = Baulieu E, Schumacher M | title = Progesterone as a neuroactive neurosteroid, with special reference to the effect of progesterone on myelination | journal = Steroids | volume = 65 | issue = 10–11 | pages = 605–612 | year = 2000 | pmid = 11108866 | doi = 10.1016/s0039-128x(00)00173-2 | s2cid = 14952168 }}</ref>
	Progesterone is commonly manufactured from the ], ]. Dioscorea produces large amounts of a steroid called ], which can be converted into progesterone in the laboratory.
			In addition to its role as a natural hormone, progesterone is also used as a medication, such as in combination with ] for ], to reduce the risk of ] or ], in ], and in ].<ref name="pmid30608551">{{cite journal | vauthors = Prior JC | title = Progesterone Is Important for Transgender Women's Therapy-Applying Evidence for the Benefits of Progesterone in Ciswomen | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 104 | issue = 4 | pages = 1181–1186 | date = April 2019 | pmid = 30608551 | doi = 10.1210/jc.2018-01777 | quote = Evidence has accrued that normal progesterone (and ovulation), as well as physiological estradiol levels, is necessary during ciswomen's premenopausal menstrual cycles for current fertility and long-term health; transgender women may require progesterone therapy and similar potential physiological benefits | s2cid = 58620122 | doi-access = free }}</ref> It was first prescribed in 1934.<ref name=Fis2006>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=47X |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA47X }}</ref>
	== Chemistry ==
			{{TOC limit}}
			==Biological activity==
	Progesterone was independently discovered by four research groups.<ref name="pmid17747122">{{cite journal | author = Allen WM | title = The isolation of crystalline progestin | journal = Science | volume = 82 | issue = 2118 | pages = 89–93 | year = 1935 | pmid = 17747122 | doi = 10.1126/science.82.2118.89 }}</ref><ref name="Butenandt_1934">{{cite journal | author = Butenandt A, Westphal U | title = Zur Isolierung und Charakterisierung des Corpusluteum-Hormons | journal = Berichte Deutsche chemische Gesellschaft | volume = 67 | issue = | pages = 1440–1442 | year = 1934| doi = 10.1002/cber.19340670831 }}</ref><ref name="Hartmann_1934">{{cite journal | author = Hartmann M, Wettstein A | title = Ein krystallisiertes Hormon aus Corpus luteum | journal = Helvetica Chimica Acta | volume = 17 | issue = | pages = 878–882 | year = 1934| doi = 10.1002/hlca.193401701111 }}</ref><ref name="Slotta_1934">{{cite journal | author = Slotta KH, Ruschig H, Fels E | title = Reindarstellung der Hormone aus dem Corpusluteum | journal = Berichte Deutsche chemische Gesellschaft | volume = 67 | issue = | pages = 1270–1273 | year = 1934| doi = 10.1002/cber.19340670729 }}</ref>
			{{See also|Pharmacodynamics of progesterone#Mechanism of action}}
	] co-discovered progesterone with his anatomy professor George Washington Corner at the University of Rochester Medical School in 1933. Allen first determined its melting point, molecular weight, and partial molecular structure. He also gave it the name '''Progesterone''' derived from '''Proge'''stational '''Ster'''oidal ket'''one'''.<ref name="pmid4922128">{{cite journal | author = Allen WM | title = Progesterone: how did the name originate? | journal = South. Med. J. | volume = 63 | issue = 10 | pages = 1151–5 | year = 1970 | pmid = 4922128 | doi = | issn = }}</ref>
			Progesterone is the most important progestogen in the body. As a potent ] of the ] (nPR) (with an ] of K<sub>D</sub> = 1 nM) the resulting effects on ribosomal transcription plays a major role in regulation of female reproduction.<ref name="KingBrucker2010" /><ref name="Josimovich2013" /> In addition, progesterone is an agonist of the more recently discovered ]s (mPRs),<ref name="pmid22687885">{{cite journal | vauthors = Thomas P, Pang Y | title = Membrane progesterone receptors: evidence for neuroprotective, neurosteroid signaling and neuroendocrine functions in neuronal cells | journal = Neuroendocrinology | volume = 96 | issue = 2 | pages = 162–171 | year = 2012 | pmid = 22687885 | pmc = 3489003 | doi = 10.1159/000339822 }}</ref> of which the expression has regulation effects in reproduction function (], labor, and ]) and cancer although additional research is required to further define the roles.<ref name="pmid27368976">{{cite journal | vauthors = Valadez-Cosmes P, Vázquez-Martínez ER, Cerbón M, Camacho-Arroyo I | title = Membrane progesterone receptors in reproduction and cancer | journal = Molecular and Cellular Endocrinology | volume = 434 | pages = 166–175 | date = October 2016 | pmid = 27368976 | doi = 10.1016/j.mce.2016.06.027 | s2cid = 3826650 }}</ref> It also functions as a ligand of the ] (progesterone receptor membrane component 1) which impacts ], metabolic regulation, and viability control of ].<ref name="pmid9516722">{{cite journal | vauthors = Meyer C, Schmid R, Schmieding K, Falkenstein E, Wehling M | title = Characterization of high affinity progesterone-binding membrane proteins by anti-peptide antiserum | journal = Steroids | volume = 63 | issue = 2 | pages = 111–116 | date = February 1998 | pmid = 9516722 | doi = 10.1016/s0039-128x(97)00143-8 | s2cid = 40096058 }}</ref><ref name="pmid30087538">{{cite journal | vauthors = Kabe Y, Handa H, Suematsu M | title = Function and structural regulation of the carbon monoxide (CO)-responsive membrane protein PGRMC1 | journal = Journal of Clinical Biochemistry and Nutrition | volume = 63 | issue = 1 | pages = 12–17 | date = July 2018 | pmid = 30087538 | pmc = 6064819 | doi = 10.3164/jcbn.17-132 }}</ref><ref name="pmid28396637">{{cite journal | vauthors = Ryu CS, Klein K, Zanger UM | title = Membrane Associated Progesterone Receptors: Promiscuous Proteins with Pleiotropic Functions - Focus on Interactions with Cytochromes P450 | journal = Frontiers in Pharmacology | volume = 8 | pages = 159 | date = 27 March 2017 | pmid = 28396637 | pmc = 5366339 | doi = 10.3389/fphar.2017.00159 | doi-access = free }}</ref> Moreover, progesterone is also known to be an antagonist of the ] ],<ref name="pmid11744080">{{cite journal | vauthors = Maurice T, Urani A, Phan VL, Romieu P | title = The interaction between neuroactive steroids and the sigma1 receptor function: behavioral consequences and therapeutic opportunities | journal = Brain Research. Brain Research Reviews | volume = 37 | issue = 1–3 | pages = 116–132 | date = November 2001 | pmid = 11744080 | doi = 10.1016/s0165-0173(01)00112-6 | s2cid = 44931783 }}</ref><ref name="pmid21084640">{{cite journal | vauthors = Johannessen M, Fontanilla D, Mavlyutov T, Ruoho AE, Jackson MB | title = Antagonist action of progesterone at σ-receptors in the modulation of voltage-gated sodium channels | journal = American Journal of Physiology. Cell Physiology | volume = 300 | issue = 2 | pages = C328–C337 | date = February 2011 | pmid = 21084640 | pmc = 3043630 | doi = 10.1152/ajpcell.00383.2010 }}</ref> a ] of ]s,<ref name="pmid11108866" /> and a potent antagonist of the ] (MR).<ref name="pmid8282004">{{cite journal | vauthors = Rupprecht R, Reul JM, van Steensel B, Spengler D, Söder M, Berning B, Holsboer F, Damm K | display-authors = 6 | title = Pharmacological and functional characterization of human mineralocorticoid and glucocorticoid receptor ligands | journal = European Journal of Pharmacology | volume = 247 | issue = 2 | pages = 145–154 | date = October 1993 | pmid = 8282004 | doi = 10.1016/0922-4106(93)90072-H }}</ref> Progesterone prevents MR activation by binding to this receptor with an affinity exceeding even those of ] and ]s such as ] and ],<ref name="pmid8282004" /> and produces ] effects, such as ], at physiological concentrations.<ref name="pmid14667981">{{cite journal | vauthors = Elger W, Beier S, Pollow K, Garfield R, Shi SQ, Hillisch A | title = Conception and pharmacodynamic profile of drospirenone | journal = Steroids | volume = 68 | issue = 10–13 | pages = 891–905 | date = November 2003 | pmid = 14667981 | doi = 10.1016/j.steroids.2003.08.008 | s2cid = 41756726 }}</ref> In addition, progesterone binds to and behaves as a ] of the ] (GR), albeit with very low potency (] >100-fold less relative to ]).<ref name="pmid18060946">{{cite journal | vauthors = Attardi BJ, Zeleznik A, Simhan H, Chiao JP, Mattison DR, Caritis SN | title = Comparison of progesterone and glucocorticoid receptor binding and stimulation of gene expression by progesterone, 17-alpha hydroxyprogesterone caproate, and related progestins | journal = American Journal of Obstetrics and Gynecology | volume = 197 | issue = 6 | pages = 599.e1–599.e7 | date = December 2007 | pmid = 18060946 | pmc = 2278032 | doi = 10.1016/j.ajog.2007.05.024 }}</ref><ref name="pmid23209664">{{cite journal | vauthors = Lei K, Chen L, Georgiou EX, Sooranna SR, Khanjani S, Brosens JJ, Bennett PR, Johnson MR | display-authors = 6 | title = Progesterone acts via the nuclear glucocorticoid receptor to suppress IL-1β-induced COX-2 expression in human term myometrial cells | journal = PLOS ONE | volume = 7 | issue = 11 | pages = e50167 | year = 2012 | pmid = 23209664 | pmc = 3509141 | doi = 10.1371/journal.pone.0050167 | doi-access = free | bibcode = 2012PLoSO...750167L }}</ref>
	Like other ]s, progesterone consists of four interconnected ]s. Progesterone contains ] and oxygenated functional groups, as well as two ] branches. Like all steroid hormones, it is ].
			Progesterone, through its ] ]s such as ] and ], acts indirectly as a ] of the ].<ref name="pmid1347506">{{cite journal | vauthors = Paul SM, Purdy RH | title = Neuroactive steroids | journal = FASEB Journal | volume = 6 | issue = 6 | pages = 2311–2322 | date = March 1992 | pmid = 1347506 | doi = 10.1096/fasebj.6.6.1347506 | s2cid = 221753076 | doi-access = free }}</ref>
	== Sources ==
	=== Animal ===
			Progesterone and some of its metabolites, such as ], are agonists of the ] (PXR),<ref name="pmid12372848">{{cite journal | vauthors = Kliewer SA, Goodwin B, Willson TM | title = The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism | journal = Endocrine Reviews | volume = 23 | issue = 5 | pages = 687–702 | date = October 2002 | pmid = 12372848 | doi = 10.1210/er.2001-0038 | doi-access = free }}</ref> albeit weakly so (] >10 μM).<ref name="pmid9727070">{{cite journal | vauthors = Lehmann JM, McKee DD, Watson MA, Willson TM, Moore JT, Kliewer SA | title = The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions | journal = The Journal of Clinical Investigation | volume = 102 | issue = 5 | pages = 1016–1023 | date = September 1998 | pmid = 9727070 | pmc = 508967 | doi = 10.1172/JCI3703 }}</ref> In accordance, progesterone ]s several ] ] ]s,<ref name="Meanwell2014">{{cite book|vauthors=Meanwell NA|title=Tactics in Contemporary Drug Design|url=https://books.google.com/books?id=j2HEBQAAQBAJ&pg=PA161|date=8 December 2014|publisher=Springer|isbn=978-3-642-55041-6|pages=161–|access-date=1 February 2016|archive-date=14 January 2023|archive-url=https://web.archive.org/web/20230114024941/https://books.google.com/books?id=j2HEBQAAQBAJ&pg=PA161|url-status=live}}</ref> such as ],<ref name="LegatoBilezikian2004">{{cite book|vauthors=Legato MJ, Bilezikian JP|title=Principles of Gender-specific Medicine|url=https://books.google.com/books?id=TiLxa8nPbLkC&pg=PA146|year=2004|publisher=Gulf Professional Publishing|isbn=978-0-12-440906-4|pages=146–|access-date=1 February 2016|archive-date=14 January 2023|archive-url=https://web.archive.org/web/20230114024928/https://books.google.com/books?id=TiLxa8nPbLkC&pg=PA146|url-status=live}}</ref><ref name="LemkeWilliams2012 p164">{{cite book | vauthors = Williams DA | chapter = Drug Metabolism | veditors = Lemke TL, Williams DA | title = Foye's Principles of Medicinal Chemistry | chapter-url = https://books.google.com/books?id=Sd6ot9ul-bUC&pg=PA164|date=24 January 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-60913-345-0|page=164}}</ref> especially during ] when concentrations are much higher than usual.<ref name="ScholarlyEditions2013">{{cite book|title=Estrogens—Advances in Research and Application: 2013 Edition: ScholarlyBrief|url=https://books.google.com/books?id=9WdGK_3ujQMC&pg=PA4|date=21 June 2013|publisher=ScholarlyEditions|isbn=978-1-4816-7550-5|pages=4–|access-date=1 February 2016|archive-date=14 January 2023|archive-url=https://web.archive.org/web/20230114024941/https://books.google.com/books?id=9WdGK_3ujQMC&pg=PA4|url-status=live}}</ref> Perimenopausal women have been found to have greater CYP3A4 activity relative to men and postmenopausal women, and it has been inferred that this may be due to the higher progesterone levels present in perimenopausal women.<ref name="LegatoBilezikian2004" />
	Progesterone is produced in the ] (to be specific, after ovulation in the ]), the ]s (near the kidney), and, during pregnancy, in the ]. Progesterone is also stored in adipose (fat) tissue.
			Progesterone modulates the activity of ] (cation channels of sperm) ] Ca<sup>2+</sup> channels. Since eggs release progesterone, sperm may use progesterone as a homing signal to swim toward eggs (]). As a result, it has been suggested that substances that block the progesterone binding site on CatSper channels could potentially be used in ].<ref name="pmid21412338">{{cite journal | vauthors = Strünker T, Goodwin N, Brenker C, Kashikar ND, Weyand I, Seifert R, Kaupp UB | title = The CatSper channel mediates progesterone-induced Ca2+ influx in human sperm | journal = Nature | volume = 471 | issue = 7338 | pages = 382–386 | date = March 2011 | pmid = 21412338 | doi = 10.1038/nature09769 | s2cid = 4431334 | bibcode = 2011Natur.471..382S }}</ref><ref name="pmid21412339">{{cite journal | vauthors = Lishko PV, Botchkina IL, Kirichok Y | title = Progesterone activates the principal Ca2+ channel of human sperm | journal = Nature | volume = 471 | issue = 7338 | pages = 387–391 | date = March 2011 | pmid = 21412339 | doi = 10.1038/nature09767 | s2cid = 4340309 | bibcode = 2011Natur.471..387L }}</ref>
	In humans, increasing amounts of progesterone are produced during pregnancy:
			==Biological function==
	* At first, the source is the corpus luteum that has been "rescued" by the presence of human chorionic gonadotropins (]) from the conceptus.
			]
			===Hormonal interactions===
	* However, after the 8th week, production of progesterone shifts to the placenta. The placenta utilizes maternal cholesterol as the initial substrate, and most of the produced progesterone enters the maternal circulation, but some is picked up by the fetal circulation and used as substrate for fetal ]. At term the placenta produces about 250&nbsp;mg progesterone per day.
			Progesterone has a number of physiological effects that are amplified in the presence of ]s. Estrogens through ]s (ERs) induce or ] the ] of the PR.<ref name="pmid2328727">{{cite journal | vauthors = Kastner P, Krust A, Turcotte B, Stropp U, Tora L, Gronemeyer H, Chambon P | title = Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B | journal = The EMBO Journal | volume = 9 | issue = 5 | pages = 1603–1614 | date = May 1990 | pmid = 2328727 | pmc = 551856 | doi = 10.1002/j.1460-2075.1990.tb08280.x }}</ref> One example of this is in ] tissue, where estrogens allow progesterone to mediate ] development.<ref name="pmid16917139">{{cite journal | vauthors = Cline JM, Wood CE | title = Hormonal effects on the mammary gland of postmenopausal nonhuman primates | journal = Breast Disease | volume = 24 | pages = 59–70 | date = 1 January 2006 | pmid = 16917139 | doi = 10.3233/bd-2006-24105 | publisher = IOS Press | isbn = 978-1-58603-653-9 | veditors = Hallam SZ, Osuch JR | url = https://books.google.com/books?id=wGaKtDw50K0C&pg=PA61 | url-access = subscription | access-date = 2 August 2023 | archive-date = 27 November 2023 | archive-url = https://web.archive.org/web/20231127222130/https://books.google.com/books?id=wGaKtDw50K0C&pg=PA61 | url-status = live }}</ref><ref name="Johnson2003">{{cite book | vauthors = Johnson LR | title = Essential Medical Physiology | url = https://books.google.com/books?id=j9e-tkdHeUoC&pg=PA770 | year = 2003 | publisher = Academic Press | isbn = 978-0-12-387584-6 | pages = 770 | access-date = 1 February 2016 | archive-date = 14 January 2023 | archive-url = https://web.archive.org/web/20230114025047/https://books.google.com/books?id=j9e-tkdHeUoC&pg=PA770 | url-status = live }}</ref><ref name="CoadDunstall2011">{{cite book| vauthors = Coad J, Dunstall M | title = Anatomy and Physiology for Midwives, with Pageburst online access,3: Anatomy and Physiology for Midwives|url=https://books.google.com/books?id=OmSKoYD-iW0C&pg=PA413|year=2011|publisher=Elsevier Health Sciences|isbn=978-0-7020-3489-3|pages=413}}</ref>
			Elevated levels of progesterone potently reduce the sodium-retaining activity of aldosterone, resulting in natriuresis and a reduction in extracellular fluid volume. Progesterone withdrawal, on the other hand, is associated with a temporary increase in sodium retention (reduced natriuresis, with an increase in extracellular fluid volume) due to the compensatory increase in aldosterone production, which combats the blockade of the mineralocorticoid receptor by the previously elevated level of progesterone.<ref name="pmid13263410">{{cite journal | vauthors = Landau RL, Bergenstal DM, Lugibihl K, Kascht ME | title = The metabolic effects of progesterone in man | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 15 | issue = 10 | pages = 1194–1215 | date = October 1955 | pmid = 13263410 | doi = 10.1210/jcem-15-10-1194 }}</ref>
	* An additional source of progesterone is milk products. They contain much progesterone because on dairy farms cows are milked during pregnancy, when the progesterone content of the milk is high. After consumption of milk products the level of bioavailable progesterone goes up.<ref name="titleResult Content View">{{cite web | url =http://www.docguide.com/news/content.nsf/news/852571020057CCF6852573B1007803AD | title = Milk products are a source of dietary progesterone | accessdate = 2008-03-12 | author = Goodson III WH, Handagama P, Moore II DH, Dairkee S | authorlink = | coauthors = | date = 2007-12-13 | format = | work = | publisher = 30th Annual San Antonio Breast Cancer Symposium | pages = abstract # 2028 | language = | archiveurl = | archivedate = | quote = }}</ref>
	=== Plants ===		===Early sexual differentiation===
			Progesterone plays a role in early human sexual differentiation.<ref name=wj>{{cite journal|doi=10.15347/WJM/2023.003 |doi-access=free |title=Alternative androgen pathways |year=2023 | vauthors = Masiutin M, Yadav M |journal=WikiJournal of Medicine |volume=10 |pages=X |s2cid=257943362}}</ref> ]l progesterone is the feedstock for the ] (DHT) produced via the ] found operating in multiple non-gonadal tissues of the ],<ref name="pmid30763313">{{cite journal | vauthors = O'Shaughnessy PJ, Antignac JP, Le Bizec B, Morvan ML, Svechnikov K, Söder O, Savchuk I, Monteiro A, Soffientini U, Johnston ZC, Bellingham M, Hough D, Walker N, Filis P, Fowler PA | display-authors = 6 | title = Alternative (backdoor) androgen production and masculinization in the human fetus | journal = PLOS Biology | volume = 17 | issue = 2 | pages = e3000002 | date = February 2019 | pmid = 30763313 | pmc = 6375548 | doi = 10.1371/journal.pbio.3000002 | doi-access = free }}</ref> whereas deficiencies in this pathway lead to undervirilization of the male fetus, resulting in incomplete development of the male genitalia.<ref name="pmid24793988">{{cite journal | vauthors = Flück CE, Pandey AV | title = Steroidogenesis of the testis -- new genes and pathways | journal = Annales d'Endocrinologie | volume = 75 | issue = 2 | pages = 40–47 | date = May 2014 | pmid = 24793988 | doi = 10.1016/j.ando.2014.03.002 }}</ref><ref name="pmid8636249">{{cite journal | vauthors = Zachmann M | title = Prismatic cases: 17,20-desmolase (17,20-lyase) deficiency | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 81 | issue = 2 | pages = 457–459 | date = February 1996 | pmid = 8636249 | doi = 10.1210/jcem.81.2.8636249 | doi-access = free }}</ref> DHT is a potent ] that is responsible for the development of male genitalia, including the ] and ].
			During early fetal development, the undifferentiated gonads can develop into either testes or ovaries. The presence of the ] leads to the development of testes. The testes then produce testosterone, which is converted to DHT via the enzyme ]. DHT is a potent androgen that is responsible for the masculinization of the external genitalia and the development of the prostate gland. Progesterone, produced by the placenta during pregnancy, plays a role in fetal sexual differentiation by serving as a precursor molecule for the synthesis of DHT via the backdoor pathway. In the absence of adequate levels of ] during fetal development, the ] can become deficient, leading to undermasculinization of the male fetus. This can result in the development of ambiguous genitalia or even female genitalia in some cases. Therefore, both DHT and progesterone play crucial roles in early fetal sexual differentiation, with progesterone acting as a precursor molecule for DHT synthesis and DHT promoting the development of male genitalia.<ref name=wj/>
	In at least one plant, '']'', progesterone has been detected.<ref name="pmid20108949">{{cite journal | author = Pauli GF, Friesen JB, Gödecke T, Farnsworth NR, Glodny B | title = Occurrence of Progesterone and Related Animal Steroids in Two Higher Plants | journal = J Nat Prod | volume = 73| issue = 3| pages = 338–45| year = 2010 | month = January | pmid = 20108949 | doi = 10.1021/np9007415 | url = | issn = }}</ref> In addition, progesterone-like ]s are found in '']''. ''Dioscorea mexicana'' is a plant that is part of the ] family native to ].<ref name="pmid12255132">{{cite journal | author = Applezweig N | title = Steroids | journal = Chem Week | volume = 104 | issue = | pages = 57–72 | year = 1969 | month = May | pmid = 12255132 | doi = | url = | issn = }}</ref> It contains a steroid called ] that is taken from the plant and is converted into progesterone.<ref name="pmid16946542">{{cite journal | author = Noguchi E, Fujiwara Y, Matsushita S, Ikeda T, Ono M, Nohara T | title = Metabolism of tomato steroidal glycosides in humans | journal = Chem. Pharm. Bull. | volume = 54 | issue = 9 | pages = 1312–4 | year = 2006 | month = September | pmid = 16946542 | doi = 10.1248/cpb.54.1312 }}</ref> Diosgenin and progesterone are found in other '']'' species as well.
			===Reproductive system===
	Another plant that contains substances readily convertible to progesterone is '']'' native to ]. Research has shown that the Taiwanese yam contains ]s — steroids that can be converted to diosgenin and thence to progesterone.<ref name="pmid14558759">{{cite journal | author = Yang DJ, Lu TJ, Hwang LS | title = Isolation and identification of steroidal saponins in Taiwanese yam cultivar (Dioscorea pseudojaponica Yamamoto) | journal = J. Agric. Food Chem. | volume = 51 | issue = 22 | pages = 6438–44 | year = 2003 | month = October | pmid = 14558759 | doi = 10.1021/jf030390j | url = }}</ref>
			] showing changes to the ] due to progesterone (]) ].]]
			Progesterone has key effects via non-genomic signalling on human sperm as they migrate through the female reproductive tract before ] occurs, though the receptor(s) as yet remain unidentified.<ref name="pmid17447210">{{cite journal | vauthors = Correia JN, Conner SJ, Kirkman-Brown JC | title = Non-genomic steroid actions in human spermatozoa. "Persistent tickling from a laden environment" | journal = Seminars in Reproductive Medicine | volume = 25 | issue = 3 | pages = 208–219 | date = May 2007 | pmid = 17447210 | doi = 10.1055/s-2007-973433 | s2cid = 260318879 }}</ref> Detailed characterisation of the events occurring in sperm in response to progesterone has elucidated certain events including intracellular calcium transients and maintained changes,<ref name="pmid10837122">{{cite journal | vauthors = Kirkman-Brown JC, Bray C, Stewart PM, Barratt CL, Publicover SJ | title = Biphasic elevation of (i) in individual human spermatozoa exposed to progesterone | journal = Developmental Biology | volume = 222 | issue = 2 | pages = 326–335 | date = June 2000 | pmid = 10837122 | doi = 10.1006/dbio.2000.9729 | doi-access = free }}</ref> slow calcium oscillations,<ref name="pmid14606954">{{cite journal | vauthors = Kirkman-Brown JC, Barratt CL, Publicover SJ | title = Slow calcium oscillations in human spermatozoa | journal = The Biochemical Journal | volume = 378 | issue = Pt 3 | pages = 827–832 | date = March 2004 | pmid = 14606954 | pmc = 1223996 | doi = 10.1042/BJ20031368 }}</ref> now thought to possibly regulate motility.<ref name="pmid15322137">{{cite journal | vauthors = Harper CV, Barratt CL, Publicover SJ | title = Stimulation of human spermatozoa with progesterone gradients to simulate approach to the oocyte. Induction of (i) oscillations and cyclical transitions in flagellar beating | journal = The Journal of Biological Chemistry | volume = 279 | issue = 44 | pages = 46315–46325 | date = October 2004 | pmid = 15322137 | doi = 10.1074/jbc.M401194200 | doi-access = free }}</ref> It is produced by the ovaries.<ref name=Marieb>{{cite book | vauthors = Marieb E | title = Anatomy & physiology | publisher = Benjamin-Cummings | page= 903 | year = 2013 | isbn = 9780321887603 }}</ref> Progesterone has also been shown to demonstrate effects on octopus spermatozoa.<ref name="pmid11335951">{{cite journal | vauthors = Tosti E, Di Cosmo A, Cuomo A, Di Cristo C, Gragnaniello G | title = Progesterone induces activation in Octopus vulgaris spermatozoa | journal = Molecular Reproduction and Development | volume = 59 | issue = 1 | pages = 97–105 | date = May 2001 | pmid = 11335951 | doi = 10.1002/mrd.1011 | s2cid = 28390608 }}</ref>
			Progesterone is sometimes called the "hormone of ]",<ref name="colostate">{{cite web | url = http://www.vivo.colostate.edu/hbooks/pathphys/reprod/placenta/endocrine.html | title = Placental Hormones | access-date = 12 March 2008 | last = Bowen | first = R. | date = 6 August 2000 | archive-date = 17 May 2007 | archive-url = https://web.archive.org/web/20070517165244/http://www.vivo.colostate.edu/hbooks/pathphys/reprod/placenta/endocrine.html | url-status = dead }}</ref> and it has many roles relating to the development of the fetus:
	Many other ''Dioscorea'' species of the yam family contain steroidal substances from which progesterone can be produced. Among the more notable of these are '']'' and '']''. One study showed that the ''Dioscorea villosa'' contains 3.5% diosgenin.<ref name="pmid15513824">{{cite journal | author = Hooker E | title = Final report of the amended safety assessment of Dioscorea Villosa (Wild Yam) root extract | journal = Int. J. Toxicol. | volume = 23 Suppl 2 | issue = | pages = 49–54 | year = 2004 | pmid = 15513824 | doi = 10.1080/10915810490499055 | url = }}</ref> '']'' has been found to contain 2.64% diosgenin as shown by ].<ref>{{cite journal | title = Diosgenin quantification by HPLC in a Dioscorea polygonoides tuber collection from colombian flora | year = 2007 | journal = Journal of the Brazilian Chemical Society | pages = 1073–1076 | volume = 18 | issue = 5 | doi = 10.1590/S0103-50532007000500030 | author = Niño J, Jiménez DA, Mosquera OM, Correa YM }}</ref> Many of the ''Dioscorea'' species that originate from the yam family grow in countries that have tropical and subtropical climates.<ref>{{Cite book | title = Properties of starches in yam (Dioscorea spp.) tuber | year = 2005 | journal = Current Topics in Food Science and Technology | pages = 105–114 | isbn = 81-308-0003-9 | author = Myoda T, Nagai T, Nagashima T | postscript = <!--None--> }}</ref>
			* Progesterone converts the ] to its secretory stage to prepare the uterus for implantation. At the same time progesterone affects the ] and ], making it thick and impenetrable to ]. Progesterone is anti-] in endometrial epithelial cells, and as such, mitigates the tropic effects of ].<ref name="pmid25406186">{{cite journal | vauthors = Patel B, Elguero S, Thakore S, Dahoud W, Bedaiwy M, Mesiano S | title = Role of nuclear progesterone receptor isoforms in uterine pathophysiology | journal = Human Reproduction Update | volume = 21 | issue = 2 | pages = 155–173 | year = 2014 | pmid = 25406186 | pmc = 4366574 | doi = 10.1093/humupd/dmu056 }}</ref> If pregnancy does not occur, progesterone levels will decrease, leading to ]. Normal menstrual bleeding is progesterone-withdrawal bleeding. If ovulation does not occur and the ] does not develop, levels of progesterone may be low, leading to ]
			* During implantation and ], progesterone appears to decrease the maternal ] response to allow for the acceptance of the pregnancy.<ref name="pmid27662646">{{cite journal | vauthors = Di Renzo GC, Giardina I, Clerici G, Brillo E, Gerli S | title = Progesterone in normal and pathological pregnancy | journal = Hormone Molecular Biology and Clinical Investigation | volume = 27 | issue = 1 | pages = 35–48 | date = July 2016 | pmid = 27662646 | doi = 10.1515/hmbci-2016-0038 | s2cid = 32239449 }}</ref>
			* Progesterone decreases contractility of the uterine ].<ref name="colostate"/> This effect contributes to prevention of ].<ref name="pmid27662646" /> Studies have shown that in individuals who are pregnant with a single fetus, asymptomatic in the prenatal stage, and at a high risk of giving pre-term birth spontaneously, vaginal progesterone medication has been found to be effective in preventing spontaneous pre-term birth. Individuals who are at a high risk of giving pre-term birth spontaneously are those who have a short cervix of less than 25&nbsp;mm or have previously given pre-term birth spontaneously. Although pre-term births are generally considered to be less than 37 weeks, these studies found that vaginal progesterone is associated with fewer pre-term births of less than 34 weeks.<ref name="pmid35168930">{{cite journal | vauthors = Care A, Nevitt SJ, Medley N, Donegan S, Good L, Hampson L, Tudur Smith C, Alfirevic Z | display-authors = 6 | title = Interventions to prevent spontaneous preterm birth in women with singleton pregnancy who are at high risk: systematic review and network meta-analysis | journal = BMJ | volume = 376 | pages = e064547 | date = February 2022 | pmid = 35168930 | pmc = 8845039 | doi = 10.1136/bmj-2021-064547 }}</ref>
			* A drop in progesterone levels is possibly one step that facilitates the onset of ].
			* In addition, progesterone inhibits ] during pregnancy. The fall in progesterone levels following delivery is one of the triggers for milk production.
			The ] ]s placental progesterone in the production of ] steroids.<ref name="pmid30763313"/>
	== Synthesis ==
	=== Biosynthesis ===
	] (]) synthesis, as ] is for ] (]), and ] for ].]]
			===Breasts===
	In mammals, progesterone ('''<u>6</u>'''), like all other ] ]s, is synthesized from ] ('''<u>3</u>'''), which in turn is derived from ] ('''<u>1</u>''') (see the upper half of the figure to the right).
			{{See also|Breast development#Biochemistry}}
			====Lobuloalveolar development====
	Cholesterol ('''<u>1</u>''') undergoes double oxidation to produce 20,22-dihydroxycholesterol ('''<u>2</u>'''). This vicinal ] is then further oxidized with loss of the side chain starting at position C-22 to produce pregnenolone ('''<u>3</u>'''). This reaction is catalyzed by ] ].
			Progesterone plays an important role in ]. In conjunction with ], it mediates ] maturation of the ]s during pregnancy to allow for milk production and thus ] and ] of ] following ] (childbirth).<ref name="pmid22844349">{{cite journal | vauthors = Macias H, Hinck L | title = Mammary gland development | journal = Wiley Interdisciplinary Reviews. Developmental Biology | volume = 1 | issue = 4 | pages = 533–557 | year = 2012 | pmid = 22844349 | pmc = 3404495 | doi = 10.1002/wdev.35 }}</ref> ] induces expression of the PR in breast tissue and hence progesterone is dependent on estrogen to mediate lobuloalveolar development.<ref name="pmid16917139" /><ref name="Johnson2003" /><ref name="CoadDunstall2011" /> It has been found that {{abbrlink|RANKL|Receptor activator of nuclear factor kappa-B ligand}} is a critical downstream mediator of progesterone-induced lobuloalveolar maturation.<ref name="pmid26266959">{{cite journal | vauthors = Hilton HN, Graham JD, Clarke CL | title = Minireview: Progesterone Regulation of Proliferation in the Normal Human Breast and in Breast Cancer: A Tale of Two Scenarios? | journal = Molecular Endocrinology | volume = 29 | issue = 9 | pages = 1230–1242 | date = September 2015 | pmid = 26266959 | pmc = 5414684 | doi = 10.1210/me.2015-1152 }}</ref> RANKL ] show an almost identical mammary phenotype to PR knockout mice, including normal mammary ductal development but complete failure of the development of lobuloalveolar structures.<ref name="pmid26266959" />
	The conversion of pregnenolone to progesterone takes place in two steps. First, the 3-] group is oxidized to a ] group ('''<u>4</u>''') and second, the ] is moved to C-4, from C-5 through a keto/] ]ization reaction.<ref name="isbn0-471-49641-3">{{cite book | author = Dewick, Paul M. | authorlink = | editor = | others = | title = Medicinal natural products: a biosynthetic approach | edition = | language = | publisher = Wiley | location = New York | year = 2002 | origyear = | pages = 244 | quote = | isbn = 0-471-49641-3 | oclc = | doi = | url = | accessdate = }}</ref> This reaction is catalyzed by ].
			====Ductal development====
	Progesterone in turn (see lower half of figure to the right) is the precursor of the mineralocorticoid ], and after conversion to ] (another natural progestogen) of ] and ]. Androstenedione can be converted to ], ] and ].
			Though to a far lesser extent than estrogen, which is the major mediator of mammary ductal development (via the ]),<ref name="StraussBarbieri2013">{{cite book|vauthors=Barbieri RL|chapter=The Breast|veditors=Strauss JF, Barbieri RL|title=Yen and Jaffe's Reproductive Endocrinology|chapter-url=https://books.google.com/books?id=KZ95AAAAQBAJ&pg=PA236|date=13 September 2013|publisher=Elsevier Health Sciences|isbn=978-1-4557-2758-2|pages=236–|access-date=1 February 2016|archive-date=14 January 2023|archive-url=https://web.archive.org/web/20230114025044/https://books.google.com/books?id=KZ95AAAAQBAJ&pg=PA236|url-status=live}}</ref><ref name="pmid24718936">{{cite journal | vauthors = Scaling AL, Prossnitz ER, Hathaway HJ | title = GPER mediates estrogen-induced signaling and proliferation in human breast epithelial cells and normal and malignant breast | journal = Hormones & Cancer | volume = 5 | issue = 3 | pages = 146–160 | date = June 2014 | pmid = 24718936 | pmc = 4091989 | doi = 10.1007/s12672-014-0174-1 }}</ref> progesterone may be involved in ductal development of the mammary glands to some extent as well.<ref name="pmid23705924">{{cite journal | vauthors = Aupperlee MD, Leipprandt JR, Bennett JM, Schwartz RC, Haslam SZ | title = Amphiregulin mediates progesterone-induced mammary ductal development during puberty | journal = Breast Cancer Research | volume = 15 | issue = 3 | pages = R44 | date = May 2013 | pmid = 23705924 | pmc = 3738150 | doi = 10.1186/bcr3431 | doi-access = free }}</ref> PR knockout mice or mice treated with the ] ] show delayed although otherwise normal mammary ductal development at puberty.<ref name="pmid23705924" /> In addition, mice modified to have ] of ] display ductal hyperplasia,<ref name="pmid26266959" /> and progesterone induces ductal growth in the mouse mammary gland.<ref name="pmid23705924" /> Progesterone mediates ductal development mainly via induction of the ] of ], the same ] that estrogen primarily induces the expression of to mediate ductal development.<ref name="pmid23705924" /> These animal findings suggest that, while not essential for full mammary ductal development, progesterone seems to play a potentiating or accelerating role in estrogen-mediated mammary ductal development.<ref name="pmid23705924" />
			====Breast cancer risk====
	Pregenolone and progesterone can also be synthesized by yeast.<ref name="pmid9487528">{{cite journal | author = Duport C, Spagnoli R, Degryse E, Pompon D | title = Self-sufficient biosynthesis of pregnenolone and progesterone in engineered yeast | journal = Nat. Biotechnol. | volume = 16 | issue = 2 | pages = 186–9 | year = 1998 | month = February | pmid = 9487528 | doi = 10.1038/nbt0298-186 | url = }}</ref>
			Progesterone also appears to be involved in the ] of ], though its role, and whether it is a promoter or inhibitor of breast cancer risk, has not been fully elucidated.<ref name="pmid23336704">{{cite journal | vauthors = Kuhl H, Schneider HP | title = Progesterone--promoter or inhibitor of breast cancer | journal = Climacteric | volume = 16 | issue = Suppl 1 | pages = 54–68 | date = August 2013 | pmid = 23336704 | doi = 10.3109/13697137.2013.768806 | s2cid = 20808536 }}</ref><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 }}</ref> Most ]s, or ] progestogens, like ], have been found to increase the risk of breast cancer in postmenopausal people in combination with estrogen as a component of ].<ref name="pmid31474332">{{cite journal | title = Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence | journal = Lancet | volume = 394 | issue = 10204 | pages = 1159–1168 | date = September 2019 | pmid = 31474332 | pmc = 6891893 | doi = 10.1016/S0140-6736(19)31709-X | author1 = Collaborative Group on Hormonal Factors in Breast Cancer }}</ref><ref name="pmid31512725" /> The combination of natural oral progesterone or the atypical progestin ] with estrogen has been associated with less risk of breast cancer than progestins plus estrogen.<ref name="pmid29384406">{{cite journal | vauthors = Stute P, Wildt L, Neulen J | title = The impact of micronized progesterone on breast cancer risk: a systematic review | journal = Climacteric | volume = 21 | issue = 2 | pages = 111–122 | date = April 2018 | pmid = 29384406 | doi = 10.1080/13697137.2017.1421925 | s2cid = 3642971 | doi-access = free | url = https://boris.unibe.ch/125894/1/29384406.pdf | access-date = 2 February 2024 | archive-date = 2 February 2024 | archive-url = https://web.archive.org/web/20240202143017/https://boris.unibe.ch/125894/1/29384406.pdf | url-status = live }}</ref><ref name="pmid27456847">{{cite journal | vauthors = Asi N, Mohammed K, Haydour Q, Gionfriddo MR, Vargas OL, Prokop LJ, Faubion SS, Murad MH | display-authors = 6 | title = Progesterone vs. synthetic progestins and the risk of breast cancer: a systematic review and meta-analysis | journal = Systematic Reviews | volume = 5 | issue = 1 | pages = 121 | date = July 2016 | pmid = 27456847 | pmc = 4960754 | doi = 10.1186/s13643-016-0294-5 | doi-access = free }}</ref><ref name="pmid29852797">{{cite journal | vauthors = Gompel A, Plu-Bureau G | title = Progesterone, progestins and the breast in menopause treatment | journal = Climacteric | volume = 21 | issue = 4 | pages = 326–332 | date = August 2018 | pmid = 29852797 | doi = 10.1080/13697137.2018.1476483 | s2cid = 46922084 }}</ref> However, this may simply be an artifact of the low progesterone levels produced with oral progesterone.<ref name="pmid23336704" /><ref name="pmid29526116">{{cite journal | vauthors = Davey DA | title = Menopausal hormone therapy: a better and safer future | journal = Climacteric | volume = 21 | issue = 5 | pages = 454–461 | date = October 2018 | pmid = 29526116 | doi = 10.1080/13697137.2018.1439915 | s2cid = 3850275 }}</ref> More research is needed on the role of progesterone in breast cancer.<ref name="pmid31512725" />
	{{-}}
	=== Laboratory ===		===Skin health===
			The ], as well as the ], have been detected in the ], including in ]s and ]s.<ref name="pmid12762829">{{cite journal | vauthors = Raine-Fenning NJ, Brincat MP, Muscat-Baron Y | title = Skin aging and menopause : implications for treatment | journal = American Journal of Clinical Dermatology | volume = 4 | issue = 6 | pages = 371–378 | year = 2003 | pmid = 12762829 | doi = 10.2165/00128071-200304060-00001 | s2cid = 20392538 }}</ref><ref name="pmid16120154">{{cite journal | vauthors = Holzer G, Riegler E, Hönigsmann H, Farokhnia S, Schmidt JB | title = Effects and side-effects of 2% progesterone cream on the skin of peri- and postmenopausal women: results from a double-blind, vehicle-controlled, randomized study | journal = The British Journal of Dermatology | volume = 153 | issue = 3 | pages = 626–634 | date = September 2005 | pmid = 16120154 | doi = 10.1111/j.1365-2133.2005.06685.x | s2cid = 6077829 }}</ref> At ] and thereafter, decreased levels of female ]s result in ], thinning, and increased ] of the skin and a reduction in skin ], firmness, and strength.<ref name="pmid12762829" /><ref name="pmid16120154" /> These skin changes constitute an acceleration in ] and are the result of decreased ] content, irregularities in the ] of ] ]s, decreased ] between ]s, and reduced ] and ].<ref name="pmid12762829" /><ref name="pmid16120154" /> The skin also becomes more ] during menopause, which is due to reduced skin ] and ] (sebum production).<ref name="pmid12762829" /> Along with chronological aging and photoaging, estrogen deficiency in menopause is one of the three main factors that predominantly influences skin aging.<ref name="pmid12762829" />
	] of progesterone from ].<ref name="Marker_1940"/>]]
	An economical ] of progesterone from the plant steroid ] isolated from yams was developed by ] in 1940 for the ] pharmaceutical company (see figure to the right).<ref name="Marker_1940"/> This synthesis is known as the ]. Additional semisyntheses of progesterone have also been reported starting from a variety of steroids. For the example, ] can be simultaneously deoxygenated at the C-17 and C-21 position by treatment with iodotrimethylsilane in ] to produce 11-keto-progesterone (ketogestin), which in turn can be reduced at position-11 to yield progesterone.<ref name="pmid3815593">{{cite journal| author = Numazawa M, Nagaoka M, Kunitama Y | title = Regiospecific deoxygenation of the dihydroxyacetone moiety at C-17 of corticoid steroids with iodotrimethylsilane | journal = Chem. Pharm. Bull. | volume = 34 | issue = 9 | pages = 3722–6 | year = 1986 | month = September | pmid = 3815593 | doi = | url =http://www.journalarchive.jst.go.jp/english/jnlabstract_en.php?cdjournal=cpb1958&cdvol=34&noissue=9&startpage=3722 | issn = }}</ref>
	]
			Hormone replacement therapy, consisting of systemic treatment with estrogen alone or in combination with a progestogen, has well-documented and considerable beneficial effects on the skin of postmenopausal people.<ref name="pmid12762829" /><ref name="pmid16120154" /> These benefits include increased skin collagen content, skin thickness and elasticity, and skin hydration and surface lipids.<ref name="pmid12762829" /><ref name="pmid16120154" /> Topical estrogen has been found to have similar beneficial effects on the skin.<ref name="pmid12762829" /> In addition, a study has found that topical 2% progesterone cream significantly increases skin elasticity and firmness and observably decreases wrinkles in peri- and postmenopausal people.<ref name="pmid16120154" /> Skin hydration and surface lipids, on the other hand, did not significantly change with topical progesterone.<ref name="pmid16120154" />
	A ] of progesterone was reported in 1971 by ] (see figure to the right).<ref name="pmid5131151">{{cite journal | author = Johnson WS, Gravestock MB, McCarry BE | title = Acetylenic bond participation in biogenetic-like olefinic cyclizations. II. Synthesis of dl-progesterone | journal = J. Am. Chem. Soc. | volume = 93 | issue = 17 | pages = 4332–4 | year = 1971 | month = August | pmid = 5131151 | doi = 10.1021/ja00746a062 | url = | issn = }}</ref> The synthesis begins with reacting the ] '''<u>7</u>''' with ] to produce the ] '''<u>8</u>'''. The ylide '''<u>8</u>''' is reacted with an ] to produce the ] '''<u>9</u>'''. The ] ]s of '''<u>9</u>''' are hydrolyzed to produce the diketone '''<u>10</u>''', which in turn is cyclized to form the cyclopentenone '''<u>11</u>'''. The ketone of '''<u>11</u>''' is reacted with methyl lithium to yield the tertiary alcohol '''<u>12</u>''', which in turn is treated with acid to produce the tertiary cation '''<u>13</u>'''. The key step of the synthesis is the π-cation cyclization of '''<u>13</u>''' in which the B-, C-, and D-rings of the steroid are simultaneously formed to produce '''<u>14</u>'''. This step resembles the cationic cyclization reaction used in the biosynthesis of steroids and hence is referred to as ''biomimetic''. In the next step the ] ] is hydrolyzed to produce the ketone '''<u>15</u>'''. The cyclopentene A-ring is then opened by oxidizing with ozone to produce '''<u>16</u>'''. Finally, the diketone '''<u>17</u>''' undergoes an intramolecular ] by treating with aqueous potassium hydroxide to produce progesterone.<ref name="pmid5131151"/>
			These findings suggest that progesterone, like estrogen, also has beneficial effects on the skin, and may be independently protective against skin aging.<ref name="pmid16120154" />
	== Levels ==
	In women, progesterone levels are relatively low during the preovulatory phase of the ], rise after ], and are elevated during the luteal phase, as shown in diagram below. Progesterone levels tend to be < 2&nbsp;ng/ml prior to ovulation, and > 5&nbsp;ng/ml after ovulation. If ] occurs, progesterone levels are initially maintained at luteal levels. With the onset of the luteal-placental shift in progesterone support of the pregnancy, levels start to rise further and may reach 100-200&nbsp;ng/ml at term. Whether a decrease in progesterone levels is critical for the initiation of ] has been argued and may be species-specific. After delivery of the placenta and during lactation, progesterone levels are very low.
			===Sexuality===
			====Libido====
			{{See also|Sexual motivation and hormones}}
			Progesterone and its ] ] ] appear to be importantly involved in ] in females.<ref name="King2012">{{cite book |vauthors=King SR |title=Neurosteroids and the Nervous System |url=https://books.google.com/books?id=D1fOTC6CP3kC&pg=PA44 |date=9 November 2012 |publisher=Springer Science & Business Media |isbn=978-1-4614-5559-2 |pages=44–46}}</ref>
			====Homosexuality====
			Dr. ], of the ], and colleagues looked for a relationship between progesterone and sexual attitudes in 92 women. Their research, published in the ] found that women who had higher levels of progesterone scored higher on a questionnaire measuring homoerotic motivation. They also found that men who had high levels of progesterone were more likely to have higher homoerotic motivation scores after affiliative priming compared to men with low levels of progesterone.<ref name="pmid25420899">{{cite journal | vauthors = Fleischman DS, Fessler DM, Cholakians AE | title = Testing the Affiliation Hypothesis of Homoerotic Motivation in Humans: The Effects of Progesterone and Priming | journal = Archives of Sexual Behavior | volume = 44 | issue = 5 | pages = 1395–1404 | date = July 2015 | pmid = 25420899 | doi = 10.1007/s10508-014-0436-6 | s2cid = 9864224 | url = https://researchportal.port.ac.uk/portal/en/publications/testing-the-affiliation-hypothesis-of-homoerotic-motivation-in-humans(d1eb5448-5664-4d2d-8694-18f970836cbb).html | access-date = 2 August 2023 | archive-date = 23 September 2020 | archive-url = https://web.archive.org/web/20200923005905/https://researchportal.port.ac.uk/portal/en/publications/testing-the-affiliation-hypothesis-of-homoerotic-motivation-in-humans(d1eb5448-5664-4d2d-8694-18f970836cbb).html | url-status = live }}</ref><ref name="UoP-News-Homos">{{cite news |title=Homosexuality may help us bond | work = UoP News |url=https://uopnews.port.ac.uk/2014/11/25/homosexuality-may-help-us-bond/ |access-date=2 July 2019 |archive-date=2 July 2019 |archive-url=https://web.archive.org/web/20190702203503/https://uopnews.port.ac.uk/2014/11/25/homosexuality-may-help-us-bond/ |url-status=dead }}</ref><ref name="The-Telegraph-2014">{{Cite web|url=https://www.telegraph.co.uk/news/science/11251206/Having-homosexual-thoughts-is-an-essential-part-of-human-evolution-study-suggests.html|title=Having homosexual thoughts 'is an essential part of human evolution' study suggests|date=25 November 2014|website=The Telegraph|access-date=4 April 2018|archive-date=15 February 2018|archive-url=https://web.archive.org/web/20180215160336/http://www.telegraph.co.uk/news/science/11251206/Having-homosexual-thoughts-is-an-essential-part-of-human-evolution-study-suggests.html|url-status=live}}</ref><ref name="HuffPost-2014">{{Cite web|url=https://www.huffpost.com/entry/homosexuality-evolution-social-bonding_n_6218406|title=New Study Identifies Evolutionary Basis Of Homosexuality|date=26 November 2014|website=HuffPost|access-date=21 October 2023|archive-date=27 November 2023|archive-url=https://web.archive.org/web/20231127222130/https://www.huffpost.com/entry/homosexuality-evolution-social-bonding_n_6218406|url-status=live}}</ref>
			===Nervous system===
			Progesterone, like ] and ] (DHEA), belongs to an important group of endogenous steroids called ]s. It can be metabolized within all parts of the ].<ref name="pmid558037">{{cite journal | vauthors = Hanukoglu I, Karavolas HJ, Goy RW | title = Progesterone metabolism in the pineal, brain stem, thalamus and corpus callosum of the female rat | journal = Brain Research | volume = 125 | issue = 2 | pages = 313–324 | date = April 1977 | pmid = 558037 | doi = 10.1016/0006-8993(77)90624-2 | s2cid = 35814845 | url = https://zenodo.org/record/890908 | access-date = 28 June 2019 | archive-date = 5 March 2021 | archive-url = https://web.archive.org/web/20210305233844/https://zenodo.org/record/890908 | url-status = live }}</ref>
			Neurosteroids are ]s, and are ], ], and regulate ] and ]ation.<ref name="pmid15135772">{{cite journal | vauthors = Schumacher M, Guennoun R, Robert F, Carelli C, Gago N, Ghoumari A, Gonzalez Deniselle MC, Gonzalez SL, Ibanez C, Labombarda F, Coirini H, Baulieu EE, De Nicola AF | display-authors = 6 | title = Local synthesis and dual actions of progesterone in the nervous system: neuroprotection and myelination | journal = Growth Hormone & IGF Research | volume = 14 | issue = Suppl A | pages = S18–S33 | date = June 2004 | pmid = 15135772 | doi = 10.1016/j.ghir.2004.03.007 }}</ref> The effects of progesterone as a neurosteroid are mediated predominantly through its interactions with non-nuclear PRs, namely the mPRs and ], as well as certain other receptors, such as the σ<sub>1</sub> and nACh receptors.<ref name="pmid24065876">{{cite journal | vauthors = Singh M, Su C, Ng S | title = Non-genomic mechanisms of progesterone action in the brain | journal = Frontiers in Neuroscience | volume = 7 | pages = 159 | date = September 2013 | pmid = 24065876 | pmc = 3776940 | doi = 10.3389/fnins.2013.00159 | doi-access = free }}</ref>
			===Brain damage===
			{{See also|Progesterone (medication)#Other uses}}
			Previous studies have shown that progesterone supports the normal development of neurons in the brain, and that the hormone has a protective effect on damaged brain tissue. It has been observed in animal models that females have reduced susceptibility to ] and this protective effect has been hypothesized to be caused by increased circulating levels of ] and progesterone in females.<ref name="pmid10833057">{{cite journal | vauthors = Roof RL, Hall ED | title = Gender differences in acute CNS trauma and stroke: neuroprotective effects of estrogen and progesterone | journal = Journal of Neurotrauma | volume = 17 | issue = 5 | pages = 367–388 | date = May 2000 | pmid = 10833057 | doi = 10.1089/neu.2000.17.367 }}</ref>
			====Proposed mechanism====
			The mechanism of progesterone protective effects may be the reduction of inflammation that follows brain trauma and hemorrhage.<ref name="pmid18188998">{{cite journal | vauthors = Pan DS, Liu WG, Yang XF, Cao F | title = Inhibitory effect of progesterone on inflammatory factors after experimental traumatic brain injury | journal = Biomedical and Environmental Sciences | volume = 20 | issue = 5 | pages = 432–438 | date = October 2007 | pmid = 18188998 }}</ref><ref name="pmid27143417">{{cite journal | vauthors = Jiang C, Zuo F, Wang Y, Wan J, Yang Z, Lu H, Chen W, Zang W, Yang Q, Wang J | display-authors = 6 | title = Progesterone exerts neuroprotective effects and improves long-term neurologic outcome after intracerebral hemorrhage in middle-aged mice | journal = Neurobiology of Aging | volume = 42 | pages = 13–24 | date = June 2016 | pmid = 27143417 | pmc = 4857017 | doi = 10.1016/j.neurobiolaging.2016.02.029 }}</ref>
			Damage incurred by traumatic brain injury is believed to be caused in part by mass ] leading to ]. One way in which progesterone helps to alleviate some of this excitotoxicity is by blocking the ]s that trigger ] release.<ref name="pmid22101209">{{cite journal | vauthors = Luoma JI, Stern CM, Mermelstein PG | title = Progesterone inhibition of neuronal calcium signaling underlies aspects of progesterone-mediated neuroprotection | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 131 | issue = 1–2 | pages = 30–36 | date = August 2012 | pmid = 22101209 | pmc = 3303940 | doi = 10.1016/j.jsbmb.2011.11.002 }}</ref> It does so by manipulating the signaling pathways of ]s involved in this release. Another method for reducing the excitotoxicity is by up-regulating the ], a widespread inhibitory neurotransmitter receptor.<ref name="pmid17826842">{{cite journal | vauthors = Stein DG | title = Progesterone exerts neuroprotective effects after brain injury | journal = Brain Research Reviews | volume = 57 | issue = 2 | pages = 386–397 | date = March 2008 | pmid = 17826842 | pmc = 2699575 | doi = 10.1016/j.brainresrev.2007.06.012 }}</ref>
			Progesterone has also been shown to prevent ] in neurons, a common consequence of brain injury.<ref name="pmid22088981">{{cite journal | vauthors = Espinoza TR, Wright DW | title = The role of progesterone in traumatic brain injury | journal = The Journal of Head Trauma Rehabilitation | volume = 26 | issue = 6 | pages = 497–499 | year = 2011 | pmid = 22088981 | pmc = 6025750 | doi = 10.1097/HTR.0b013e31823088fa }}</ref> It does so by inhibiting enzymes involved in the apoptosis pathway specifically concerning the mitochondria, such as activated ] and ].
			Not only does progesterone help prevent further damage, it has also been shown to aid in ].<ref name="pmid26746666">{{cite journal | vauthors = Jiang C, Zuo F, Wang Y, Lu H, Yang Q, Wang J | title = Progesterone Changes VEGF and BDNF Expression and Promotes Neurogenesis After Ischemic Stroke | journal = Molecular Neurobiology | volume = 54 | issue = 1 | pages = 571–581 | date = January 2016 | pmid = 26746666 | pmc = 4938789 | doi = 10.1007/s12035-015-9651-y }}</ref> One of the serious effects of traumatic brain injury includes edema. Animal studies show that progesterone treatment leads to a decrease in ] levels by increasing the concentration of ]s and ] sent to the injured tissue.<ref name="pmid22101209"/><ref name="pmid19401954">{{cite journal | vauthors = Herson PS, Koerner IP, Hurn PD | title = Sex, sex steroids, and brain injury | journal = Seminars in Reproductive Medicine | volume = 27 | issue = 3 | pages = 229–239 | date = May 2009 | pmid = 19401954 | pmc = 2675922 | doi = 10.1055/s-0029-1216276 }}</ref> This was observed in the form of reduced leakage from the ] in secondary recovery in progesterone treated rats. In addition, progesterone was observed to have ] properties, reducing the concentration of ] faster than without.<ref name="pmid17826842"/> There is also evidence that the addition of progesterone can also help re]ate damaged ] due to trauma, restoring some lost neural signal conduction.<ref name="pmid17826842"/> Another way progesterone aids in regeneration includes increasing the circulation of endothelial progenitor cells in the brain.<ref name="pmid21534727">{{cite journal | vauthors = Li Z, Wang B, Kan Z, Zhang B, Yang Z, Chen J, Wang D, Wei H, Zhang JN, Jiang R | display-authors = 6 | title = Progesterone increases circulating endothelial progenitor cells and induces neural regeneration after traumatic brain injury in aged rats | journal = Journal of Neurotrauma | volume = 29 | issue = 2 | pages = 343–353 | date = January 2012 | pmid = 21534727 | pmc = 3261789 | doi = 10.1089/neu.2011.1807 }}</ref> This helps new ] to grow around scar tissue which helps repair the area of insult.
			===Addiction===
			Progesterone enhances the function of ]s in the brain, so an excess or deficit of progesterone has the potential to result in significant neurochemical issues. This provides an explanation for why some people resort to substances that enhance ] activity such as ], ], and ] when their progesterone levels fall below optimal levels.<ref name="pmid21186920">{{cite journal | vauthors = Lynch WJ, Sofuoglu M | title = Role of progesterone in nicotine addiction: evidence from initiation to relapse | journal = Experimental and Clinical Psychopharmacology | volume = 18 | issue = 6 | pages = 451–461 | date = December 2010 | pmid = 21186920 | pmc = 3638762 | doi = 10.1037/a0021265 }}</ref>
			* Sex differences in hormone levels may induce women to respond differently than men to nicotine. When women undergo cyclic changes or different hormonal transition phases (menopause, pregnancy, adolescence), there are changes in their progesterone levels.<ref name="pmid22474108">{{cite journal | vauthors = Cosgrove KP, Esterlis I, McKee SA, Bois F, Seibyl JP, Mazure CM, Krishnan-Sarin S, Staley JK, Picciotto MR, O'Malley SS | display-authors = 6 | title = Sex differences in availability of β2*-nicotinic acetylcholine receptors in recently abstinent tobacco smokers | journal = Archives of General Psychiatry | volume = 69 | issue = 4 | pages = 418–427 | date = April 2012 | pmid = 22474108 | pmc = 3508698 | doi = 10.1001/archgenpsychiatry.2011.1465 }}</ref> Therefore, females have an increased biological vulnerability to nicotine's reinforcing effects compared to males and progesterone may be used to counter this enhanced vulnerability. This information supports the idea that progesterone can affect behavior.<ref name="pmid21186920"/>
			* Similar to nicotine, cocaine also increases the release of dopamine in the brain. The neurotransmitter is involved in the reward center and is one of the main neurotransmitters involved with substance abuse and reliance. In a study of cocaine users, it was reported that progesterone reduced craving and the feeling of being stimulated by cocaine. Thus, progesterone was suggested as an agent that decreases cocaine craving by reducing the dopaminergic properties of the drug.<ref name="pmid21796112">{{cite journal | vauthors = Mello NK, Knudson IM, Kelly M, Fivel PA, Mendelson JH | title = Effects of progesterone and testosterone on cocaine self-administration and cocaine discrimination by female rhesus monkeys | journal = Neuropsychopharmacology | volume = 36 | issue = 11 | pages = 2187–2199 | date = October 2011 | pmid = 21796112 | pmc = 3176575 | doi = 10.1038/npp.2011.130 }}</ref>
			===Societal===
			In a 2012 University of Amsterdam study of 120 women, women's luteal phase (higher levels of progesterone, and increasing levels of estrogen) was correlated with a lower level of competitive behavior in gambling and math contest scenarios, while their premenstrual phase (sharply-decreasing levels of progesterone, and decreasing levels of estrogen) was correlated with a higher level of competitive behavior.<ref name="Buser-2012">{{Cite journal|vauthors=Buser T|date=1 June 2012|title=The impact of the menstrual cycle and hormonal contraceptives on competitiveness|journal=Journal of Economic Behavior & Organization|series=Gender Differences in Risk Aversion and Competition|volume=83|issue=1|pages=1–10|doi=10.1016/j.jebo.2011.06.006|issn=0167-2681|url=https://pure.uva.nl/ws/files/1864146/117489_376503.pdf|access-date=2 February 2024|archive-date=2 February 2024|archive-url=https://web.archive.org/web/20240202143019/https://pure.uva.nl/ws/files/1864146/117489_376503.pdf|url-status=live}}</ref>
			===Other effects===
			* Progesterone also has a role in skin elasticity and bone strength, in ], in nerve tissue and in ], and the presence of progesterone receptors in certain muscle and fat tissue may hint at a role in ] proportions of those.<ref name="medicinalchem">{{cite book |title= Medicinal Chemistry| vauthors = Sriram D |year=2007 |publisher=Dorling Kindersley India Pvt. Ltd.|location= New Delhi| isbn= 978-81-317-0031-0 |page=432}}<!--this seems to have copied from WP?, see ]--></ref>
			* During pregnancy, progesterone is said to decrease uterine irritability.<ref name="Blackburn2014">{{cite book | vauthors = Blackburn S | title = Maternal, Fetal, & Neonatal Physiology | url = https://books.google.com/books?id=RNLsAwAAQBAJ&pg=PA92|date=14 April 2014|publisher=Elsevier Health Sciences|isbn=978-0-323-29296-2|pages=92–}}</ref>
			* During pregnancy, progesterone helps to suppress immune responses of the mother to fetal antigens, which prevents rejection of the fetus.<ref name="Blackburn2014" />
			* Progesterone raises ] (EGF-1) levels, a factor often used to induce proliferation, and used to sustain cultures, of ]s.<ref name="pmid17074804">{{cite journal | vauthors = Faivre EJ, Lange CA | title = Progesterone receptors upregulate Wnt-1 to induce epidermal growth factor receptor transactivation and c-Src-dependent sustained activation of Erk1/2 mitogen-activated protein kinase in breast cancer cells | journal = Molecular and Cellular Biology | volume = 27 | issue = 2 | pages = 466–480 | date = January 2007 | pmid = 17074804 | pmc = 1800800 | doi = 10.1128/MCB.01539-06 }}</ref>
			* Progesterone increases core temperature (thermogenic function) during ovulation.<ref name="GeorgiaPhysiology">{{cite book| title= Essentials of Human Physiology| vauthors = Nosek TM | chapter=Section 5/5ch9/s5ch9_13 |chapter-url=http://humanphysiology.tuars.com/program/section5/5ch9/s5ch9_13.htm |archive-url=https://web.archive.org/web/20160324124828/http://humanphysiology.tuars.com/program/section5/5ch9/s5ch9_13.htm|archive-date=24 March 2016}}</ref><ref name="Rothchild-1969">{{Citation|vauthors=Rothchild I|title=The Physiologic Basis for the Temperature Raising Effect of Progesterone|date=1969|url=https://doi.org/10.1007/978-1-4684-1782-1_49|work=Metabolic Effects of Gonadal Hormones and Contraceptive Steroids|pages=668–675|veditors=Salhanick HA, Kipnis DM, Wiele RL|place=Boston, MA|publisher=Springer US|language=en|doi=10.1007/978-1-4684-1782-1_49|isbn=978-1-4684-1782-1|access-date=22 March 2021|url-access=subscription|archive-date=29 August 2021|archive-url=https://web.archive.org/web/20210829011027/https://link.springer.com/chapter/10.1007%2F978-1-4684-1782-1_49|url-status=live}}</ref>
			* Progesterone reduces ] and relaxes ]. ] are widened and ] regulated. (PRs are widely present in ].)
			* Progesterone acts as an ] agent and regulates the ].
			* Progesterone reduces ] activity.<ref name="pmid3184927">{{cite journal | vauthors = Hould FS, Fried GM, Fazekas AG, Tremblay S, Mersereau WA | title = Progesterone receptors regulate gallbladder motility | journal = The Journal of Surgical Research | volume = 45 | issue = 6 | pages = 505–512 | date = December 1988 | pmid = 3184927 | doi = 10.1016/0022-4804(88)90137-0 }}</ref>
			* Progesterone normalizes ] clotting and vascular tone, ] and ] levels, ] ] levels, and use of fat stores for energy.
			* Progesterone may affect gum health, increasing risk of gingivitis (gum inflammation).<ref name="WebMD-Hormones-Oral-Health">{{cite web|url=http://www.webmd.com/oral-health/hormones-oral-health|title=Hormones and Oral Health|website=WebMD|access-date=22 July 2013|archive-date=18 June 2016|archive-url=https://web.archive.org/web/20160618171445/http://www.webmd.com/oral-health/hormones-oral-health|url-status=live}}</ref>
			* Progesterone appears to prevent ] (involving the uterine lining) by regulating the effects of estrogen.
			* Progesterone plays an important role in the signaling of insulin release and pancreatic function, and may affect the susceptibility to diabetes or gestational diabetes.<ref name="pmid12438645">{{cite journal | vauthors = Picard F, Wanatabe M, Schoonjans K, Lydon J, O'Malley BW, Auwerx J | title = Progesterone receptor knockout mice have an improved glucose homeostasis secondary to beta -cell proliferation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 24 | pages = 15644–15648 | date = November 2002 | pmid = 12438645 | pmc = 137770 | doi = 10.1073/pnas.202612199 | doi-access = free }}</ref><ref name="pmid12591170">{{cite journal | vauthors = Brănişteanu DD, Mathieu C | title = Progesterone in gestational diabetes mellitus: guilty or not guilty? | journal = Trends in Endocrinology and Metabolism | volume = 14 | issue = 2 | pages = 54–56 | date = March 2003 | pmid = 12591170 | doi = 10.1016/S1043-2760(03)00003-1 | s2cid = 38209977 }}</ref>
			* Progesterone levels in the blood were found to be lower in those who had higher weight and higher BMI among those who became pregnant through in vitro fertilization.<ref name="pmid34278354">{{cite journal | vauthors = Whynott RM, Summers KM, Jakubiak M, Van Voorhis BJ, Mejia RB | title = The effect of weight and body mass index on serum progesterone values and live birth rate in cryopreserved in vitro fertilization cycles | journal = F&S Reports | volume = 2 | issue = 2 | pages = 195–200 | date = June 2021 | pmid = 34278354 | pmc = 8267385 | doi = 10.1016/j.xfre.2021.02.005 }}</ref>
			* Current data shows that micronized progesterone, which is chemically identical to the progesterone produced in people's bodies, in combination with estrogen in menopausal hormone therapy does not seem to have significant effects on venous thromboembolism (blood clots in veins) and ischemic stroke (lack of blood flow to the brain due to blockage of a blood vessel that supplies the brain). However, more studies need to be conducted to see whether or not micronized progesterone alone or in combined menopausal hormone therapy changes the risk of myocardial infarctions (heart attacks).<ref name="pmid35112635">{{cite journal | vauthors = Kaemmle LM, Stadler A, Janka H, von Wolff M, Stute P | title = The impact of micronized progesterone on cardiovascular events - a systematic review | journal = Climacteric | volume = 25 | issue = 4 | pages = 327–336 | date = August 2022 | pmid = 35112635 | doi = 10.1080/13697137.2021.2022644 | s2cid = 246487187 }}</ref>
			* There have not been any studies done yet on the effects of micronized progesterone on hair loss due to menopause.<ref name="pmid33527841">{{cite journal | vauthors = Gasser S, Heidemeyer K, von Wolff M, Stute P | title = Impact of progesterone on skin and hair in menopause - a comprehensive review | journal = Climacteric | volume = 24 | issue = 3 | pages = 229–235 | date = June 2021 | pmid = 33527841 | doi = 10.1080/13697137.2020.1838476 | s2cid = 231757325 }}</ref>
			* Despite suggestions for using hormone therapy to prevent loss of muscle mass in post-menopausal individuals (50 and older), menopausal hormone therapy involving either estrogen alone or estrogen and progesterone has not been found to preserve muscle mass.<ref name="pmid31461147">{{cite journal | vauthors = Javed AA, Mayhew AJ, Shea AK, Raina P | title = Association Between Hormone Therapy and Muscle Mass in Postmenopausal Women: A Systematic Review and Meta-analysis | journal = JAMA Network Open | volume = 2 | issue = 8 | pages = e1910154 | date = August 2019 | pmid = 31461147 | pmc = 6716293 | doi = 10.1001/jamanetworkopen.2019.10154 }}</ref> Menopausal hormone therapy also does not result in body weight reduction, BMI reduction, or change in glucose metabolism.<ref name="pmid30477366">{{cite journal | vauthors = Coquoz A, Gruetter C, Stute P | title = Impact of micronized progesterone on body weight, body mass index, and glucose metabolism: a systematic review | journal = Climacteric | volume = 22 | issue = 2 | pages = 148–161 | date = April 2019 | pmid = 30477366 | doi = 10.1080/13697137.2018.1514003 | s2cid = 53782622 }}</ref>
			==Biochemistry==
			===Biosynthesis===
			], showing progesterone among the progestogens in yellow area.<ref name="HäggströmRichfield2014">{{cite journal | vauthors = Häggström M, Richfield D |year=2014|title=Diagram of the pathways of human steroidogenesis|journal=WikiJournal of Medicine|volume=1|issue=1|doi=10.15347/wjm/2014.005|issn=2002-4436|doi-access=free}}</ref>]]
			In mammals, progesterone, like all other ] ]s, is synthesized from ], which itself is derived from ].
			Cholesterol undergoes double oxidation to produce ] and then ]. This vicinal ] is then further oxidized with loss of the side chain starting at position C22 to produce pregnenolone. This reaction is catalyzed by ] ].
			The conversion of pregnenolone to progesterone takes place in two steps. First, the 3β-] group is oxidized to a ] group and second, the ] is moved to C4, from C5 through a keto/] ]ization reaction.<ref name="isbn0-471-49641-3">{{cite book | vauthors = Bewick PM | title = Medicinal natural products: a biosynthetic approach | publisher = Wiley | location = New York | year = 2002 | pages = 244 | isbn = 0-471-49641-3 }}</ref> This reaction is catalyzed by ].
			Progesterone in turn is the precursor of the mineralocorticoid ], and after conversion to ], of ] and ]. Androstenedione can be converted to ], ], and ], highlighting the critical role of progesterone in testosterone synthesis.
			Pregnenolone and progesterone can also be synthesized by ].<ref name="pmid9487528">{{cite journal | vauthors = Duport C, Spagnoli R, Degryse E, Pompon D | title = Self-sufficient biosynthesis of pregnenolone and progesterone in engineered yeast | journal = Nature Biotechnology | volume = 16 | issue = 2 | pages = 186–189 | date = February 1998 | pmid = 9487528 | doi = 10.1038/nbt0298-186 | s2cid = 852617 }}</ref>
			Approximately 25&nbsp;mg of progesterone is secreted from the ovaries per day, while the adrenal glands produce about 2&nbsp;mg of progesterone per day.<ref name="LemkeWilliams2012 p1397">{{cite book|vauthors=Zavod RM|chapter=Women's Health|veditors=Lemke TL, Williams DA|title=Foye's Principles of Medicinal Chemistry|chapter-url=https://books.google.com/books?id=Sd6ot9ul-bUC&pg=PA1397|date=24 January 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-60913-345-0|pages=1397–|access-date=19 July 2018|archive-date=14 January 2023|archive-url=https://web.archive.org/web/20230114025043/https://books.google.com/books?id=Sd6ot9ul-bUC&pg=PA1397|url-status=live}}</ref>
			{{Production rates, secretion rates, clearance rates, and blood levels of major sex hormones}}
			===Distribution===
			Progesterone binds extensively to ]s, including ] (50–54%) and ] (43–48%).<ref name="Drugs.com">{{citation | url = https://www.drugs.com/pro/progesterone.html | title = Progesterone - Drugs.com | access-date = 23 August 2015 | archive-date = 27 March 2019 | archive-url = https://web.archive.org/web/20190327091744/https://www.drugs.com/pro/progesterone.html | url-status = live }}</ref> It has similar affinity for albumin relative to the PR.<ref name="Josimovich2013" />
			===Metabolism===
			The ] of progesterone is rapid and extensive and occurs mainly in the ],<ref name="FalconeHurd2007">{{cite book|vauthors=Falcone T, Hurd WW|title=Clinical Reproductive Medicine and Surgery|url=https://books.google.com/books?id=fOPtaEIKvcIC&pg=PA22|year=2007|publisher=Elsevier Health Sciences|isbn=978-0-323-03309-1|pages=22–|access-date=6 November 2016|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110014156/https://books.google.com/books?id=fOPtaEIKvcIC&pg=PA22|url-status=live}}</ref><ref name="Cupps1991">{{cite book | vauthors = Cupps PT |title=Reproduction in Domestic Animals|url=https://books.google.com/books?id=bbb-ow0N7K4C&pg=PA101|date=20 February 1991|publisher=Elsevier|isbn=978-0-08-057109-6|pages=101–}}</ref><ref name="pmid14667980" /> though ]s that metabolize progesterone are also expressed widely in the ], ], and various other ] ]s.<ref name="pmid558037" /><ref name="DowdJohnson2016">{{cite book | vauthors = Dowd FJ, Johnson B, Mariotti A | title = Pharmacology and Therapeutics for Dentistry|url=https://books.google.com/books?id=6xT7DAAAQBAJ&pg=PA448|date=3 September 2016|publisher=Elsevier Health Sciences|isbn=978-0-323-44595-5|pages=448–}}</ref> Progesterone has an ] of only approximately 5&nbsp;minutes in ].<ref name="FalconeHurd2007" /> The metabolism of progesterone is complex, and it may form as many as 35 different ] ]s when it is ingested orally.<ref name="pmid14667980" /><ref name="pmid16112947" /> Progesterone is highly susceptible to enzymatic ] via ]s and ]s due to its ] (between the C4 and C5 positions) and its two ]s (at the C3 and C20 positions).<ref name="pmid14667980" />
			The major ] of progesterone is reduction by ]<ref name="pmid558037" /> and ] into the dihydrogenated ] and ], respectively.<ref name="Cupps1991" /><ref name="pmid14667980">{{cite journal | vauthors = Stanczyk FZ | title = All progestins are not created equal | journal = Steroids | volume = 68 | issue = 10–13 | pages = 879–890 | date = November 2003 | pmid = 14667980 | doi = 10.1016/j.steroids.2003.08.003 | s2cid = 44601264 }}</ref><ref name="PlantZeleznik2014">{{cite book| vauthors = Plant TM, Zeleznik AJ |title=Knobil and Neill's Physiology of Reproduction|url=https://books.google.com/books?id=I1ACBAAAQBAJ&pg=PA304|date=15 November 2014|publisher=Academic Press|isbn=978-0-12-397769-4|pages=304–}}</ref><ref name="SantoroNeal-Perry2010">{{cite book|vauthors=Santoro NF, Neal-Perry G|title=Amenorrhea: A Case-Based, Clinical Guide|url=https://books.google.com/books?id=4836MLkPoIYC&pg=PA13|date=11 September 2010|publisher=Springer Science & Business Media|isbn=978-1-60327-864-5|pages=13–|access-date=6 November 2016|archive-date=14 January 2023|archive-url=https://web.archive.org/web/20230114025033/https://books.google.com/books?id=4836MLkPoIYC&pg=PA13|url-status=live}}</ref> This is followed by the further reduction of these metabolites via ] and ] into the tetrahydrogenated ], ], ], and ].<ref name="pmid21094889">{{cite book | vauthors = Reddy DS | title = Sex Differences in the Human Brain, their Underpinnings and Implications | chapter = Neurosteroids | series = Progress in Brain Research | volume = 186 | pages = 113–37 | year = 2010 | publisher = Elsevier | pmid = 21094889 | pmc = 3139029 | doi = 10.1016/B978-0-444-53630-3.00008-7 | isbn = 9780444536303 }}</ref><ref name="Cupps1991" /><ref name="pmid14667980" /><ref name="PlantZeleznik2014" /> Subsequently, ] and ] reduce these metabolites to form the corresponding hexahydrogenated ]s (eight different ]s in total),<ref name="Cupps1991" /><ref name="SantoroNeal-Perry2010" /> which are then conjugated via ] and/or ], released from the liver into circulation, and ] by the ]s into the ].<ref name="FalconeHurd2007" /><ref name="pmid14667980" /> The major metabolite of progesterone in the urine is the 3α,5β,20α isomer of ], which has been found to constitute 15 to 30% of an injection of progesterone.<ref name="Josimovich2013" /><ref name="BaulieuKelly1990">{{cite book| vauthors = Baulieu E, Kelly PA |title=Hormones: From Molecules to Disease|url=https://books.google.com/books?id=Seddp4-dulIC&pg=PA401|date=30 November 1990|publisher=Springer Science & Business Media|isbn=978-0-412-02791-8|pages=401–}}</ref> Other metabolites of progesterone formed by the enzymes in this pathway include ], ], ], and ], as well as various combination products of the enzymes aside from those already mentioned.<ref name="Josimovich2013" /><ref name="pmid14667980" /><ref name="BaulieuKelly1990" /><ref name="pmid21182831">{{cite journal | vauthors = Beranič N, Gobec S, Rižner TL | title = Progestins as inhibitors of the human 20-ketosteroid reductases, AKR1C1 and AKR1C3 | journal = Chemico-Biological Interactions | volume = 191 | issue = 1–3 | pages = 227–233 | date = May 2011 | pmid = 21182831 | doi = 10.1016/j.cbi.2010.12.012 | bibcode = 2011CBI...191..227B }}</ref> Progesterone can also first be ] (see below) and then reduced.<ref name="pmid14667980" /> Endogenous progesterone is metabolized approximately 50% into 5α-dihydroprogesterone in the ], 35% into 3β-dihydroprogesterone in the liver, and 10% into 20α-dihydroprogesterone.<ref name="pmid15492972">{{cite journal | vauthors = Anderson GD, Odegard PS | title = Pharmacokinetics of estrogen and progesterone in chronic kidney disease | journal = Advances in Chronic Kidney Disease | volume = 11 | issue = 4 | pages = 357–360 | date = October 2004 | pmid = 15492972 | doi = 10.1053/j.ackd.2004.07.001 }}</ref>
			Relatively small portions of progesterone are ] via ] (CYP17A1) and ] (CYP21A2) into ] and ] (21-hydroxyprogesterone), respectively,<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 }}</ref> and ]s are formed secondarily to 17α-hydroxylation.<ref name="GreenblattBrogan2016">{{cite book| vauthors = Greenblatt JM, Brogan K |title=Integrative Therapies for Depression: Redefining Models for Assessment, Treatment and Prevention|url=https://books.google.com/books?id=GpHwCgAAQBAJ&pg=PA201|date=27 April 2016|publisher=CRC Press|isbn=978-1-4987-0230-0|pages=201–}}</ref><ref name="Graham2012">{{cite book|vauthors=Graham C|title=Reproductive Biology of the Great Apes: Comparative and Biomedical Perspectives|url=https://books.google.com/books?id=iUA0CdGhYksC&pg=PA179|date=2 December 2012|publisher=Elsevier|isbn=978-0-323-14971-6|pages=179–|access-date=6 November 2016|archive-date=14 January 2023|archive-url=https://web.archive.org/web/20230114024936/https://books.google.com/books?id=iUA0CdGhYksC&pg=PA179|url-status=live}}</ref> Even smaller amounts of progesterone may be also hydroxylated via ] (CYP11B1) and to a lesser extent via ] (CYP11B2) into ].<ref name="pmid23322723">{{cite journal | vauthors = Strushkevich N, Gilep AA, Shen L, Arrowsmith CH, Edwards AM, Usanov SA, Park HW | title = Structural insights into aldosterone synthase substrate specificity and targeted inhibition | journal = Molecular Endocrinology | volume = 27 | issue = 2 | pages = 315–324 | date = February 2013 | pmid = 23322723 | pmc = 5417327 | doi = 10.1210/me.2012-1287 }}</ref><ref name="pmid29277707">{{cite journal | vauthors = van Rooyen D, Gent R, Barnard L, Swart AC | title = The in vitro metabolism of 11β-hydroxyprogesterone and 11-ketoprogesterone to 11-ketodihydrotestosterone in the backdoor pathway | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 178 | pages = 203–212 | date = April 2018 | pmid = 29277707 | doi = 10.1016/j.jsbmb.2017.12.014 | s2cid = 3700135 }}</ref><ref name=wj/> In addition, progesterone can be hydroxylated in the liver by other ] enzymes which are not steroid-specific.<ref name="Piccinato2008">{{cite book| vauthors = de Azevedo Piccinato C |title=Regulation of Steroid Metabolism and the Hepatic Transcriptome by Estradiol and Progesterone|url=https://books.google.com/books?id=2nlbQ12QrSsC&pg=PA24|year=2008|isbn=978-1-109-04632-8|pages=24–25}}{{Dead link|date=February 2023 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> 6β-Hydroxylation, which is catalyzed mainly by ], is the major transformation, and is responsible for approximately 70% of cytochrome P450-mediated progesterone metabolism.<ref name="Piccinato2008" /> Other routes include 6α-, 16α-, and 16β-hydroxylation.<ref name="pmid14667980" /> However, treatment of women with ], a strong CYP3A4 inhibitor, had minimal effects on progesterone levels, producing only a slight and non-significant increase, and this suggests that cytochrome P450 enzymes play only a small role in progesterone metabolism.<ref name="pmid1825737">{{cite journal | vauthors = Akalin S | title = Effects of ketoconazole in hirsute women | journal = Acta Endocrinologica | volume = 124 | issue = 1 | pages = 19–22 | date = January 1991 | pmid = 1825737 | doi = 10.1530/acta.0.1240019 | s2cid = 9831739 }}</ref>
			{{Progesterone metabolism||align=center|caption=This diagram illustrates the ]s involved in the ] of progesterone in humans. In addition to the ]s shown in the diagram, ], specifically ] and ], occurs with ]s of progesterone that have one or more available ] (–OH) ]s.}}
			===Levels===
			]
			Progesterone levels are relatively low during the preovulatory phase of the ], rise after ], and are elevated during the ], as shown in the diagram above. Progesterone levels tend to be less than 2&nbsp;ng/mL prior to ovulation and greater than 5&nbsp;ng/mL after ovulation. If ] occurs, ] is released, maintaining the corpus luteum and allowing it to maintain levels of progesterone. Between 7 and 9&nbsp;weeks, the placenta begins to produce progesterone in place of the corpus luteum in a process called the luteal-placental shift.<ref name="pmid4688578">{{cite journal | vauthors = Csapo AI, Pulkkinen MO, Wiest WG | title = Effects of luteectomy and progesterone replacement therapy in early pregnant patients | journal = American Journal of Obstetrics and Gynecology | volume = 115 | issue = 6 | pages = 759–765 | date = March 1973 | pmid = 4688578 | doi = 10.1016/0002-9378(73)90517-6 }}</ref>
			After the luteal-placental shift, progesterone levels start to rise further and may reach 100 to 200&nbsp;ng/mL at term. Whether a decrease in progesterone levels is critical for the initiation of ] has been argued and may be species-specific. After delivery of the placenta and during lactation, progesterone levels are very low.
			Progesterone levels are low in children and postmenopausal people.<ref>{{cite web |title=Progesterone Historical Reference Ranges |author=NIH Clinical Center |date=16 August 2004 |publisher=United States National Institutes of Health |url=http://cclnprod.cc.nih.gov/dlm/testguide.nsf/Index/CB26894E1EB28DEF85256BA5005B000E?OpenDocument |archive-url=https://web.archive.org/web/20090109072721/http://cclnprod.cc.nih.gov/dlm/testguide.nsf/Index/CB26894E1EB28DEF85256BA5005B000E?OpenDocument |archive-date=9 January 2009 |access-date=12 March 2008}}</ref> Adult males have levels similar to those in women during the follicular phase of the menstrual cycle.
			{{clear}}
			{| class="wikitable sortable mw-collapsible" style="text-align:left; margin-left:auto; margin-right:auto; border:none;"
			|+ class="nowrap" | Endogenous <noinclude>]</noinclude><includeonly>progesterone</includeonly> production rates and plasma progesterone levels
			|-
			! Group !! {{abbr|P4|Progesterone}} production !! {{abbr|P4|Progesterone}} levels
			|-
			| ] children || {{abbr|ND|No data}} || 0.06–0.5&nbsp;ng/mL
			|-
			| ] girls<br />&nbsp;&nbsp;] (childhood)<br />&nbsp;&nbsp;] (ages 8–12)<br />&nbsp;&nbsp;] (ages 10–13)<br />&nbsp;&nbsp;] (ages 11–14)<br />&nbsp;&nbsp;] (ages 12–15)<br />&nbsp;&nbsp;&nbsp;&nbsp;] (days 1–14)<br />&nbsp;&nbsp;&nbsp;&nbsp;] (days 15–28) || &nbsp;<br />{{abbr|ND|No data}}<br />{{abbr|ND|No data}}<br />{{abbr|ND|No data}}<br />{{abbr|ND|No data}}<br />&nbsp;<br />{{abbr|ND|No data}}<br />{{abbr|ND|No data}} || &nbsp;<br />0.22 (<0.10–0.32) ng/mL<br />0.30 (0.10–0.51) ng/mL<br />0.36 (0.10–0.75) ng/mL<br />1.75 (<0.10–25.0) ng/mL<br />&nbsp;<br />0.35 (0.13–0.75) ng/mL<br />2.0–25.0&nbsp;ng/mL
			|-
			| ] women<br />&nbsp;&nbsp;] (days 1–14)<br />&nbsp;&nbsp;] (days 15–28)<br />&nbsp;&nbsp;] (]) || &nbsp;<br />0.75–5.4&nbsp;mg/day<br />15–50&nbsp;mg/day<br />{{abbr|ND|No data}} || &nbsp;<br />0.02–1.2&nbsp;ng/mL<br />4–30&nbsp;ng/mL<br />0.1–0.3&nbsp;ng/mL
			|-
			| ] women<br />] women<br />] and ] women || {{abbr|ND|No data}}<br />1.2&nbsp;mg/day<br /><0.3&nbsp;mg/day || 0.03–0.3&nbsp;ng/mL<br />0.39&nbsp;ng/mL<br />{{abbr|ND|No data}}
			|-
			| ] women<br />&nbsp;&nbsp;] (weeks 1–12)<br />&nbsp;&nbsp;] (weeks 13–26)<br />&nbsp;&nbsp;] (weeks 27–40)<br />&nbsp;&nbsp;] (at 24 hours) || &nbsp;<br />55&nbsp;mg/day<br />92–100&nbsp;mg/day<br />190–563&nbsp;mg/day<br />{{abbr|ND|No data}} || &nbsp;<br />9–75&nbsp;ng/mL<br />17–146&nbsp;ng/mL<br />55–255&nbsp;ng/mL<br />19&nbsp;ng/mL
			|-
			| Men || 0.75–3&nbsp;mg/day || 0.1–0.3&nbsp;ng/mL
			|- class="sortbottom"
			| colspan="5" style="width: 1px; background-color:#eaecf0; text-align: center;" | '''Notes:''' Mean levels are given as a single value and ranges are given after in parentheses. '''Sources:''' <noinclude><ref name="pmid945344" /><ref name="Chernecky_Berger_2012">{{cite book|vauthors=Chernecky CC, Berger BJ|title=Laboratory Tests and Diagnostic Procedures - E-Book|url=https://books.google.com/books?id=dWHYcOJK-cgC&pg=PA908|date=31 October 2012|publisher=Elsevier Health Sciences|isbn=978-1-4557-4502-9|pages=908–|access-date=23 August 2023|archive-date=27 February 2024|archive-url=https://web.archive.org/web/20240227031646/https://books.google.com/books?id=dWHYcOJK-cgC&pg=PA908#v=onepage&q&f=false|url-status=live}}</ref><ref name="Becker_2001">{{cite book|vauthors=Becker KL|title=Principles and Practice of Endocrinology and Metabolism|url=https://books.google.com/books?id=FVfzRvaucq8C&pg=PA940|year=2001|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-1750-2|pages=889, 940|access-date=23 August 2023|archive-date=27 February 2024|archive-url=https://web.archive.org/web/20240227031703/https://books.google.com/books?id=FVfzRvaucq8C&pg=PA940#v=onepage&q&f=false|url-status=live}}</ref><ref name="Josimovich2013b" /><ref name="KeepUtian2012">{{cite book|vauthors=van Keep P, Utian W|title=The Premenstrual Syndrome: Proceedings of a workshop held during the Sixth International Congress of Psychosomatic Obstetrics and Gynecology, Berlin, September 1980|url=https://books.google.com/books?id=0IAJBgAAQBAJ&pg=PA51|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-6255-5|pages=51–52|access-date=1 February 2016|archive-date=14 January 2023|archive-url=https://web.archive.org/web/20230114025337/https://books.google.com/books?id=0IAJBgAAQBAJ&pg=PA51|url-status=live}}</ref><ref name="StraussBarbieri2009">{{cite book|vauthors=Strauss JF, Barbieri RL|title=Yen and Jaffe's Reproductive Endocrinology: Physiology, Pathophysiology, and Clinical Management|url=https://books.google.com/books?id=NudwnhxY8kYC&pg=PA807|year=2009|publisher=Elsevier Health Sciences|isbn=978-1-4160-4907-4|pages=807–|access-date=23 August 2023|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110014157/https://books.google.com/books?id=NudwnhxY8kYC&pg=PA807|url-status=live}}</ref><ref name="Bajaj_Berman2011">{{cite book|vauthors=Bajaj L, Berman S|title=Berman's Pediatric Decision Making|url=https://books.google.com/books?id=NPhnHrDQ1_kC&pg=PA160|date=1 January 2011|publisher=Elsevier Health Sciences|isbn=978-0-323-05405-8|pages=160–|access-date=23 August 2023|archive-date=11 January 2023|archive-url=https://web.archive.org/web/20230111143033/https://books.google.com/books?id=NPhnHrDQ1_kC&pg=PA160|url-status=live}}</ref><ref name="Lauritzen1988">{{cite book | vauthors = Lauritzen C | chapter = Natürliche und Synthetische Sexualhormone – Biologische Grundlagen und Behandlungsprinzipien | pages = 229–306 | trans-chapter = Natural and Synthetic Sexual Hormones – Biological Basis and Medical Treatment Principles | editor1 = Hermann P. G. Schneider | editor2 = Christian Lauritzen | editor3 = Eberhard Nieschlag | title = Grundlagen und Klinik der Menschlichen Fortpflanzung | trans-title = Foundations and Clinic of Human Reproduction | language = de | year = 1988 | publisher = Walter de Gruyter | isbn = 978-3110109689 | oclc = 35483492 | url = https://books.google.com/books?id=v4HvAQAACAAJ | access-date = 23 August 2023 | archive-date = 1 October 2023 | archive-url = https://web.archive.org/web/20231001111615/https://books.google.com/books?id=v4HvAQAACAAJ | url-status = live }}</ref><ref name="LittleBilliar1983">Little, A. B., & Billiar, R. B. (1983). Progestagens. In Endocrinology of Pregnancy, 3rd Edition (pp. 92–111). Harper and Row Philadelphia. https://scholar.google.com/scholar?cluster=2512291948467467634 {{Webarchive|url=https://web.archive.org/web/20220222083312/https://scholar.google.com/scholar?cluster=2512291948467467634 |date=22 February 2022 }}</ref></noinclude><includeonly>See template.</includeonly>
			|}
			====Ranges====
	Progesterone levels are relatively low in children and postmenopausal women.<ref name="titleHistorical Reference Ranges">{{cite web | url = http://cclnprod.cc.nih.gov/dlm/testguide.nsf/Index/CB26894E1EB28DEF85256BA5005B000E?OpenDocument | title = Progesterone Historical Reference Ranges | accessdate = 2008-03-12 | author = NIH Clinical Center | authorlink = | coauthors = | date = 2004-08-16 | format = | work = | publisher = United States National Institutes of Health | pages = | language = | archiveurl = | archivedate = | quote = }}</ref> Adult males have levels similar to those in women during the follicular phase of the menstrual cycle.
			Blood test results should always be interpreted using the reference ranges provided by the laboratory that performed the results. Example reference ranges are listed below.
	{|class="wikitable" align="center"		{|class="wikitable" align="center"
Line 106:		Line 257:
	| Female - menstrual cycle ||colspan=3| (see diagram below)		| Female - menstrual cycle ||colspan=3| (see diagram below)
	|-		|-
	|rowspan=2| Female - postmenopausal || ]0.2<ref name=nih2009>, Performed at the Clinical Center at the National Institutes of Health, Bethesda MD, 03Feb09</ref> || 1<ref name=nih2009/> || ]/]		| rowspan=2| Female - postmenopausal || ]0.2<ref name=nih2009>, Performed at the Clinical Center at the National Institutes of Health, Bethesda MD, 03Feb09</ref> || 1<ref name=nih2009/> || ]/]
	|-		|-
	| <0,6<ref name=mass>Converted from mass values using molar mass of 314.46 g/mol</ref> || 3<ref name=mass/> || ]/]		| <0.6<ref name="mass-converted">Converted from mass values using molar mass of 314.46 g/mol</ref> || 3<ref name="mass-converted"/> || ]/]
	|-		|-
	|rowspan=2| Female on ]s || 0.34<ref name=nih2009/> || 0.92<ref name=nih2009/> || ng/mL		| rowspan=2| Female on ]s || 0.34<ref name=nih2009/> || 0.92<ref name=nih2009/> || ng/mL
	|-		|-
	| 1.1<ref name=mass/> || 2.9<ref name=mass/> || nmol/L		| 1.1<ref name="mass-converted"/> || 2.9<ref name="mass-converted"/> || nmol/L
	|-		|-
	|rowspan=2| Males ]16 years || 0.27<ref name=nih2009/> || 0.9<ref name=nih2009/> || ng/mL		| rowspan=2| Males ]16 years || 0.27<ref name=nih2009/> || 0.9<ref name=nih2009/> || ng/mL
	|-		|-
	| 0.86<ref name=mass/> || 2.9<ref name=mass/> || nmol/L		| 0.86<ref name="mass-converted"/> || 2.9<ref name="mass-converted"/> || nmol/L
	|-		|-
	|rowspan=2| Female or male 1-9 years || 0.1<ref name=nih2009/> || 4.1<ref name=nih2009/> or 4.5<ref name=nih2009/> || ng/mL		| rowspan=2| Female or male 1–9 years || 0.1<ref name=nih2009/> || 4.1<ref name=nih2009/> or 4.5<ref name=nih2009/> || ng/mL
	|-		|-
	| 0.3<ref name=mass/> || 13<ref name=mass/> || nmol/L		| 0.3<ref name="mass-converted"/> || 13<ref name="mass-converted"/> || nmol/L
	|}		|}
			{{Hidden begin|toggle=left|title=Reference ranges for the blood content of progesterone during the menstrual cycle}}
	].<ref>References and further description of values are given in image page in Wikimedia Commons at ].</ref>
			].<ref name="Häggström2014">{{cite journal|year=2014|title=Reference ranges for estradiol, progesterone, luteinizing hormone and follicle-stimulating hormone during the menstrual cycle|journal=WikiJournal of Medicine|volume=1|issue=1|doi=10.15347/wjm/2014.001|issn=2002-4436| vauthors = Häggström M |doi-access=free|s2cid=88035135 }}</ref>
	<br>- The ranges denoted '''By biological stage''' may be used in closely monitored menstrual cycles in regard to other markers of its biological progression, with the time scale being compressed or stretched to how much faster or slower, respectively, the cycle progresses compared to an average cycle.
	<br>- The ranges denoted '''Inter-cycle variability''' are more appropriate to use in non-monitored cycles with only the beginning of menstruation known, but where the woman accurately knows her average cycle lengths and time of ovulation, and that they are somewhat averagely regular, with the time scale being compressed or stretched to how much a woman's average cycle length is shorter or longer, respectively, than the average of the population.		<small><br />• The ranges denoted '''By biological stage''' may be used in closely monitored menstrual cycles in regard to other markers of its biological progression, with the time scale being compressed or stretched to how much faster or slower, respectively, the cycle progresses compared to an average cycle.
	<br>- The ranges denoted '''Inter-woman variability''' are more appropriate to use when the average cycle lengths and time of ovulation are unknown, but only the beginning of menstruation is given.]]		<br />• The ranges denoted '''Inter-cycle variability''' are more appropriate to use in non-monitored cycles with only the beginning of menstruation known, but where the woman accurately knows her average cycle lengths and time of ovulation, and that they are somewhat averagely regular, with the time scale being compressed or stretched to how much a woman's average cycle length is shorter or longer, respectively, than the average of the population.
			<br />• The ranges denoted '''Inter-woman variability''' are more appropriate to use when the average cycle lengths and time of ovulation are unknown, but only the beginning of menstruation is given.</small>]]{{Clear}}
			{{Hidden end}}
	== Effects ==		===Sources===
			====Animal====
	] showing changes to the ] due to progesterone (]) ].]]
			Progesterone is produced in high amounts in the ] (by the ]) from the onset of ] to ], and is also produced in smaller amounts by the ]s after the onset of ] in both males and females. To a lesser extent, progesterone is produced in ], especially in the brain, and in ], as well.
	Progesterone exerts its primary action through the intracellular ] although a distinct, membrane bound progesterone receptor has also been postulated.<ref name="pmid9506743">{{cite journal | author = Luconi M, Bonaccorsi L, Maggi M, Pecchioli P, Krausz C, Forti G, Baldi E | title = Identification and characterization of functional nongenomic progesterone receptors on human sperm membrane | journal = J. Clin. Endocrinol. Metab. | volume = 83 | issue = 3 | pages = 877–85 | year = 1998 | pmid = 9506743 | doi = 10.1210/jc.83.3.877 }}</ref><ref name="pmid15684349">{{cite journal | author = Jang S, Yi LS | title = Identification of a 71 kDa protein as a putative non-genomic membrane progesterone receptor in boar spermatozoa | journal = J. Endocrinol. | volume = 184 | issue = 2 | pages = 417–25 | year = 2005 | pmid = 15684349 | doi = 10.1677/joe.1.05607 }}</ref> In addition, progesterone is a highly potent antagonist of the ] (MR, the receptor for ] and other mineralocorticosteroids). It prevents MR activation by binding to this receptor with an affinity exceeding even those of aldosterone and other corticosteroids such as cortisol and corticosterone.<ref name="pmid8282004">{{cite journal | author = Rupprecht R, Reul JM, van Steensel B, Spengler D, Söder M, Berning B, Holsboer F, Damm K | title = Pharmacological and functional characterization of human mineralocorticoid and glucocorticoid receptor ligands | journal = Eur J Pharmacol | volume = 247 | issue = 2 | pages = 145–54 | year = 1993 | pmid = 8282004 | doi = 10.1016/0922-4106(93)90072-H }}</ref>
			During human ], progesterone is produced in increasingly high amounts by the ovaries and ]. At first, the source is the corpus luteum that has been "rescued" by the presence of ] (hCG) from the conceptus. However, after the 8th week, production of progesterone shifts to the placenta. The placenta utilizes maternal cholesterol as the initial substrate, and most of the produced progesterone enters the maternal circulation, but some is picked up by the fetal circulation and used as substrate for fetal corticosteroids. At term the placenta produces about 250&nbsp;mg progesterone per day.
	Progesterone has a number of physiological effects that are amplified in the presence of ]. Estrogen through estrogen receptors ] the ] of progesterone receptors.<ref name="pmid2328727">{{cite journal | author = Kastner P, Krust A, Turcotte B, Stropp U, Tora L, Gronemeyer H, Chambon P | title = Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B | journal = EMBO J. | volume = 9 | issue = 5 | pages = 1603–14 | year = 1990 | pmid = 2328727 | doi = | issn = | pmc = 551856 }}</ref> Also, elevated levels of progesterone potently reduce the sodium-retaining activity of aldosterone, resulting in natriuresis and a reduction in extracellular fluid volume. Progesterone withdrawal, on the other hand, is associated with a temporary increase in sodium retention (reduced natriuresis, with an increase in extracellular fluid volume) due to the compensatory increase in aldosterone production, which combats the blockade of the mineralocorticoid receptor by the previously elevated level of progesterone.<ref name="pmid13263410">{{cite journal | doi = 10.1210/jcem-15-10-1194 | author = Landau RL, Bergenstal DM, Lugibihl K, Kascht ME. | title = The metabolic effects of progesterone in man | journal = J Clin Endocrinol Metab | volume = 15 | issue = 10 | pages = 1194–215 | year = 1955 | pmid = 13263410 }}</ref>
			An additional animal source of progesterone is milk products. After consumption of milk products the level of bioavailable progesterone goes up.<ref name="titleResult Content View">{{cite web | url = http://www.docguide.com/news/content.nsf/news/852571020057CCF6852573B1007803AD | title = Milk products are a source of dietary progesterone | access-date = 12 March 2008 | vauthors = Goodson III WH, Handagama P, Moore II DH, Dairkee S | date = 13 December 2007 | publisher = 30th Annual San Antonio Breast Cancer Symposium | pages = abstract # 2028 | archive-date = 20 September 2008 | archive-url = https://web.archive.org/web/20080920110341/http://www.docguide.com/news/content.nsf/news/852571020057CCF6852573B1007803AD | url-status = live }}</ref>
	=== Reproductive system ===
			====Plants====
	Progesterone has key effects via non-genomic signalling on human sperm as they migrate through the female tract before fertilization occurs, though the receptor(s) as yet remain unidentified.<ref name="pmid17447210">{{cite journal | author = Correia JN, Conner SJ, Kirkman-Brown JC | title = Non-genomic steroid actions in human spermatozoa. "Persistent tickling from a laden environment" | journal = Semin. Reprod. Med. | volume = 25 | issue = 3 | pages = 208–19 | year = 2007 | month = May | pmid = 17447210 | doi = 10.1055/s-2007-973433 | url = | issn = }}</ref> Detailed characterisation of the events occurring in sperm in response to progesterone has elucidated certain events including intracellular calcium transients and maintained changes,<ref name=pmid10837122>{{cite journal |author=Kirkman-Brown JC, Bray C, Stewart PM, Barratt CL, Publicover SJ |title=Biphasic elevation of (i) in individual human spermatozoa exposed to progesterone |journal=Developmental Biology |volume=222 |issue=2 |pages=326–35 |year=2000 |month=June |pmid=10837122 |doi=10.1006/dbio.2000.9729 |issn=0012-1606}}</ref> slow calcium oscillations,<ref name=pmid14606954>{{cite journal |author=Kirkman-Brown JC, Barratt CL, Publicover SJ |title=Slow calcium oscillations in human spermatozoa |journal=The Biochemical Journal |volume=378 |issue=Pt 3 |pages=827–32 |year=2004 |month=March |pmid=14606954 |pmc=1223996 |doi=10.1042/BJ20031368 }}</ref> now thought to possibly regulate motility.<ref name=pmid15322137>{{cite journal |author=Harper CV, Barratt CL, Publicover SJ |title=Stimulation of human spermatozoa with progesterone gradients to simulate approach to the oocyte. Induction of (i) oscillations and cyclical transitions in flagellar beating |journal=The Journal of Biological Chemistry |volume=279 |issue=44 |pages=46315–25 |year=2004 |month=October |pmid=15322137 |doi=10.1074/jbc.M401194200 }}</ref> Interestingly progesterone has also been shown to demonstrate effects on octopus spermatozoa.<ref name="pmid11335951">{{cite journal | author = Tosti E, Di Cosmo A, Cuomo A, Di Cristo C, Gragnaniello G | title = Progesterone induces activation in Octopus vulgaris spermatozoa | journal = Mol. Reprod. Dev. | volume = 59 | issue = 1 | pages = 97–105 | year = 2001 | month = May | pmid = 11335951 | doi = 10.1002/mrd.1011 | url = | issn = }}</ref>
			In at least one plant, '']'', progesterone has been detected.<ref name="pmid20108949">{{cite journal | vauthors = Pauli GF, Friesen JB, Gödecke T, Farnsworth NR, Glodny B | title = Occurrence of progesterone and related animal steroids in two higher plants | journal = Journal of Natural Products | volume = 73 | issue = 3 | pages = 338–345 | date = March 2010 | pmid = 20108949 | doi = 10.1021/np9007415 | s2cid = 26467578 }}</ref> In addition, progesterone-like ]s are found in '']''. ''Dioscorea mexicana'' is a plant that is part of the ] family native to ].<ref name="pmid12255132">{{cite journal | vauthors = Applezweig N | title = Steroids | journal = Chemical Week | volume = 104 | pages = 57–72 | date = May 1969 | pmid = 12255132 }}</ref> It contains a steroid called ] that is taken from the plant and is converted into progesterone.<ref name="pmid16946542">{{cite journal | vauthors = Noguchi E, Fujiwara Y, Matsushita S, Ikeda T, Ono M, Nohara T | title = Metabolism of tomato steroidal glycosides in humans | journal = Chemical & Pharmaceutical Bulletin | volume = 54 | issue = 9 | pages = 1312–1314 | date = September 2006 | pmid = 16946542 | doi = 10.1248/cpb.54.1312 | doi-access = free }}</ref> Diosgenin and progesterone are also found in other '']'' species, as well as in other plants that are not closely related, such as ].
			Another plant that contains substances readily convertible to progesterone is '']'' native to ]. Research has shown that the Taiwanese yam contains ]s — steroids that can be converted to diosgenin and thence to progesterone.<ref name="pmid14558759">{{cite journal | vauthors = Yang DJ, Lu TJ, Hwang LS | title = Isolation and identification of steroidal saponins in Taiwanese yam cultivar (Dioscorea pseudojaponica Yamamoto) | journal = Journal of Agricultural and Food Chemistry | volume = 51 | issue = 22 | pages = 6438–6444 | date = October 2003 | pmid = 14558759 | doi = 10.1021/jf030390j | bibcode = 2003JAFC...51.6438Y | url = http://ntur.lib.ntu.edu.tw/bitstream/246246/189462/1/58.pdf | access-date = 2 April 2022 | archive-date = 3 August 2022 | archive-url = https://web.archive.org/web/20220803163123/http://ntur.lib.ntu.edu.tw/bitstream/246246/189462/1/58.pdf | url-status = live }}</ref>
	Progesterone modulates the activity of ] (cation channels of sperm) ] Ca<sup>2+</sup> channels. Since eggs release progesterone, sperm may use progesterone as a homing signal to swim toward eggs (]). Hence substances that block the progesterone binding site on CatSper channels could potentially be used in ].<ref name="pmid21412338">{{cite journal | author = Strünker T, Goodwin N, Brenker C, Kashikar ND, Weyand I, Seifert R, Kaupp UB | title = The CatSper channel mediates progesterone-induced Ca2+ influx in human sperm | journal = Nature | volume = 471 | issue = 7338 | pages = 382–6 | year = 2011 | month = March | pmid = 21412338 | doi = 10.1038/nature09769 | laysummary = http://www.nature.com/news/2011/110316/full/news.2011.163.html | laysource = Nature News }}</ref><ref name="pmid21412339">{{cite journal | author = Lishko PV, Botchkina IL, Kirichok Y | title = Progesterone activates the principal Ca2+ channel of human sperm | journal = Nature | volume = 471 | issue = 7338 | pages = 387–91 | year = 2011 | month = March | pmid = 21412339 | doi = 10.1038/nature09767 }}</ref>
			Many other ''Dioscorea'' species of the yam family contain steroidal substances from which progesterone can be produced. Among the more notable of these are '']'' and '']''. One study showed that the ''Dioscorea villosa'' contains 3.5% diosgenin.<ref name="pmid15513824">{{cite journal | vauthors = | title = Final report of the amended safety assessment of Dioscorea Villosa (Wild Yam) root extract | journal = International Journal of Toxicology | volume = 23 | issue = Suppl 2 | pages = 49–54 | year = 2004 | pmid = 15513824 | doi = 10.1080/10915810490499055 | s2cid = 962216 | doi-access = free }}</ref> '']'' has been found to contain 2.64% diosgenin as shown by ].<ref name="Nino-2007">{{cite journal | title = Diosgenin quantification by HPLC in a Dioscorea polygonoides tuber collection from colombian flora | year = 2007 | journal = Journal of the Brazilian Chemical Society | pages = 1073–1076 | volume = 18 | issue = 5 | doi = 10.1590/S0103-50532007000500030 |vauthors=Niño J, Jiménez DA, Mosquera OM, Correa YM | doi-access = free | s2cid = 95193700 }}</ref> Many of the ''Dioscorea'' species that originate from the yam family grow in countries that have tropical and subtropical climates.<ref name="Myoda-2005">{{Cite journal | title = Properties of starches in yam (Dioscorea spp.) tuber | year = 2005 | journal = Current Topics in Food Science and Technology | pages = 105–114 | isbn = 81-308-0003-9 |vauthors=Myoda T, Nagai T, Nagashima T }}</ref>
	Progesterone is sometimes called the "hormone of pregnancy",<ref name="colostate">{{cite web | url = http://www.vivo.colostate.edu/hbooks/pathphys/reprod/placenta/endocrine.html | title = Placental Hormones | accessdate = 2008-03-12 | author = Bowen R | authorlink = | coauthors = | date = 2000-08-06 | work = | publisher = | pages = | language = | archiveurl = | archivedate = | quote = }}</ref> and it has many roles relating to the development of the fetus:
	* Progesterone converts the ] to its secretory stage to prepare the uterus for implantation. At the same time progesterone affects the vaginal ] and ], making it thick and impenetrable to ]. If pregnancy does not occur, progesterone levels will decrease, leading, in the human, to ]. Normal menstrual bleeding is progesterone-withdrawal bleeding. If ovulation does not occur and the corpus luteum does not develop, levels of progesterone may be low, leading to ]
	* During implantation and ], progesterone appears to decrease the maternal ] response to allow for the acceptance of the pregnancy.
	* Progesterone decreases contractility of the uterine ].<ref name="colostate"/>
	* In addition progesterone inhibits ] during pregnancy. The fall in progesterone levels following delivery is one of the triggers for milk production.
	* A drop in progesterone levels is possibly one step that facilitates the onset of ].
			==Medical use==
	The ] ]s placental progesterone in the production of ] steroids.
			{{Main|Progesterone (medication)|Pharmacodynamics of progesterone|Pharmacokinetics of progesterone}}
			Progesterone is used as a ]. It is used in combination with ]s mainly in ] for ] ]s and ].<ref name="pmid16112947" /><ref name="pmid28159148">{{cite journal | vauthors = Wesp LM, Deutsch MB | title = Hormonal and Surgical Treatment Options for Transgender Women and Transfeminine Spectrum Persons | journal = The Psychiatric Clinics of North America | volume = 40 | issue = 1 | pages = 99–111 | date = March 2017 | pmid = 28159148 | doi = 10.1016/j.psc.2016.10.006 }}</ref> It may also be used alone to treat menopausal symptoms. Studies have shown that transdermal progesterone (skin patch) and oral micronized progesterone are effective treatments for certain symptoms of menopause such as hot flashes and night sweats, which are otherwise referred to as vasomotor symptoms or VMS.<ref name="pmid33109992">{{cite journal | vauthors = Dolitsky SN, Cordeiro Mitchell CN, Stadler SS, Segars JH | title = Efficacy of progestin-only treatment for the management of menopausal symptoms: a systematic review | journal = Menopause | volume = 28 | issue = 2 | pages = 217–224 | date = November 2020 | pmid = 33109992 | doi = 10.1097/GME.0000000000001676 | s2cid = 225100434 }}</ref>
	=== Nervous system ===
			It is also used to support ] and ] and to treat ]s.<ref name="pmid25113944">{{cite journal | vauthors = Ruan X, Mueck AO | title = Systemic progesterone therapy--oral, vaginal, injections and even transdermal? | journal = Maturitas | volume = 79 | issue = 3 | pages = 248–255 | date = November 2014 | pmid = 25113944 | doi = 10.1016/j.maturitas.2014.07.009 }}</ref><ref name="pmid26443945">{{cite journal | vauthors = Filicori M | title = Clinical roles and applications of progesterone in reproductive medicine: an overview | journal = Acta Obstetricia et Gynecologica Scandinavica | volume = 94 | issue = Suppl 161 | pages = 3–7 | date = November 2015 | pmid = 26443945 | doi = 10.1111/aogs.12791 | doi-access = free }}</ref><ref name="pmid26345161">{{cite journal | vauthors = Ciampaglia W, Cognigni GE | title = Clinical use of progesterone in infertility and assisted reproduction | journal = Acta Obstetricia et Gynecologica Scandinavica | volume = 94 | issue = Suppl 161 | pages = 17–27 | date = November 2015 | pmid = 26345161 | doi = 10.1111/aogs.12770 | s2cid = 40753277 | doi-access = free }}</ref><ref name="pmid28989916">{{cite journal | vauthors = Choi SJ | title = Use of progesterone supplement therapy for prevention of preterm birth: review of literatures | journal = Obstetrics & Gynecology Science | volume = 60 | issue = 5 | pages = 405–420 | date = September 2017 | pmid = 28989916 | pmc = 5621069 | doi = 10.5468/ogs.2017.60.5.405 }}</ref> Progesterone has been shown to prevent miscarriage in those with 1) vaginal bleeding early in their current pregnancy and 2) a previous history of miscarriage.<ref name="pmid32609084">{{cite journal | vauthors = Coomarasamy A, Harb HM, Devall AJ, Cheed V, Roberts TE, Goranitis I, Ogwulu CB, Williams HM, Gallos ID, Eapen A, Daniels JP, Ahmed A, Bender-Atik R, Bhatia K, Bottomley C, Brewin J, Choudhary M, Crosfill F, Deb S, Duncan WC, Ewer A, Hinshaw K, Holland T, Izzat F, Johns J, Lumsden MA, Manda P, Norman JE, Nunes N, Overton CE, Kriedt K, Quenby S, Rao S, Ross J, Shahid A, Underwood M, Vaithilingham N, Watkins L, Wykes C, Horne AW, Jurkovic D, Middleton LJ | display-authors = 6 | title = Progesterone to prevent miscarriage in those with early pregnancy bleeding: the PRISM RCT | language = EN | journal = Health Technology Assessment | volume = 24 | issue = 33 | pages = 1–70 | date = June 2020 | pmid = 32609084 | pmc = 7355406 | doi = 10.3310/hta24330 | doi-access = free }}</ref> Progesterone can be taken ], ], and by ] into ] or ], among other ]s.<ref name="pmid16112947" />
	Progesterone, like ] and ], belongs to the group of ]s. It can be synthesized within the ] and also serves as a precursor to another major neurosteroid, ].
			==Chemistry==
	] affect ], are neuroprotective, and affect ]ation.<ref name="pmid15135772">{{cite journal | author = Schumacher M, Guennoun R, Robert F, ''et al.'' | title = Local synthesis and dual actions of progesterone in the nervous system: neuroprotection and myelination | journal = Growth Horm. IGF Res. | volume = 14 Suppl A | issue = | pages = S18–33 | year = 2004 | pmid = 15135772 | doi = 10.1016/j.ghir.2004.03.007| accessdate = }}</ref> They are investigated for their potential to improve ] and ]. Progesterone affects regulation of ] genes.
			]
			{{See also|List of neurosteroids}}
			Progesterone is a ] ] ] and is also known as pregn-4-ene-3,20-dione.<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=PA1024 |date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=1024–}}</ref><ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory |url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA880 |date=January 2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=880–}}</ref> It has a ] (]) between the C4 and C5 positions and two ] ]s (3,20-]), one at the C3 position and the other at the C20 position.<ref name="Elks2014" /><ref name="IndexNominum2000" />
	Its effect as a neurosteroid works predominantly through the ] beta pathway, as an inhibitor. (Other GSK-3 beta inhibitors include ] mood stabilizers, ] and ].)
	===Other syndromes===		===Synthesis===
			Progesterone is commercially produced by semisynthesis. Two main routes are used: one from yam ] first pioneered by Marker in 1940, and one based on soy ]s scaled up in the 1970s. Additional (not necessarily economical) semisyntheses of progesterone have also been reported starting from a variety of steroids. For the example, ] can be simultaneously deoxygenated at the C-17 and C-21 position by treatment with iodotrimethylsilane in ] to produce 11-keto-progesterone (ketogestin), which in turn can be reduced at position-11 to yield progesterone.<ref name="pmid3815593">{{cite journal | vauthors = Numazawa M, Nagaoka M, Kunitama Y | title = Regiospecific deoxygenation of the dihydroxyacetone moiety at C-17 of corticoid steroids with iodotrimethylsilane | journal = Chemical & Pharmaceutical Bulletin | volume = 34 | issue = 9 | pages = 3722–3726 | date = September 1986 | pmid = 3815593 | doi = 10.1248/cpb.34.3722 | doi-access = free }}</ref>
			====Marker semisynthesis====
	* It raises ] levels, a factor often used to induce proliferation, and used to sustain cultures, of ]s.
			{{main|Marker degradation}}
	* It increases core temperature (thermogenic function) during ovulation.<ref name="GeorgiaPhysiology">{{GeorgiaPhysiology|5/5ch9/s5ch9_13}}</ref>
			An economical ] of progesterone from the plant steroid ] isolated from yams was developed by ] in 1940 for the ] pharmaceutical company.<ref name="Marker1940">{{cite journal |vauthors=Marker RE, Krueger J | title = Sterols. CXII. Sapogenins. XLI. The Preparation of Trillin and its Conversion to Progesterone | journal = J. Am. Chem. Soc. | volume = 62 | issue = 12 | pages = 3349–3350 | year = 1940| doi = 10.1021/ja01869a023 }}</ref> This synthesis is known as the ].
	* It reduces ] and relaxes ]. ] are widened and ] regulated. (]s are widely present in ].)
			] of progesterone from ].<ref name="Marker1940"/>]]
	* It acts as an ] agent and regulates the ].
	* It reduces ] activity.<ref name="pmid3184927">{{cite journal | author = Hould FS, Fried GM, Fazekas AG, Tremblay S, Mersereau WA | title = Progesterone receptors regulate gallbladder motility | journal = J. Surg. Res. | volume = 45 | issue = 6 | pages = 505–12 | year = 1988 | pmid = 3184927| doi = 10.1016/0022-4804(88)90137-0 }}</ref>
	* It normalizes ] clotting and vascular tone, ] and ] levels, ] ] levels, and use of fat stores for energy.
	* It may affect gum health, increasing risk of gingivitis (gum inflammation) and tooth decay.
	* It appears to prevent ] (involving the uterine lining) by regulating the effects of estrogen.
			The ] intermediate is important to the synthesis of many other medically important steroids. A very similar approach can produce 16-DPA from ].<ref name="Goswami-2003">{{cite journal | vauthors = Goswami A, Kotoky R, Rastogi RC, Ghosh AC |title=A One-Pot Efficient Process for 16-Dehydropregnenolone Acetate |journal=Organic Process Research & Development |date=1 May 2003 |volume=7 |issue=3 |pages=306–308 |doi=10.1021/op0200625}}</ref>
	==Adverse effects==
			====Soy semisynthesis====
	Pill form of progesterone (actually a synthetic version such as Progestogen) taken at 400&nbsp;mg as cited by the following patent can cause increased fluid retention, which may result in epilepsy, ], asthma, cardiac or renal dysfunction. Blood clots that can result in strokes and heart attacks, which may lead to death or long-term disability, may develop; pulmonary embolus or ] can also develop as a result of progesterone therapy. Progesterone is associated with an increased risk of thrombotic disorders such as ], ]s, ], and ].<ref name=ppg2004>{{cite web |url=http://www.prometrium.com/pdf/Prometrium_Patient_Information.pdf |title=Prometrium(progesterone) |author=Columbia Laboratories, Inc. |month=November |year=2004 |format=PDF }}</ref>
			Progesterone can also be made from the ] found in ] also. c.f. ].
			] to progesterone synthesis.<ref name=Heyl>{{cite journal | vauthors = Heyl FW | title = Progesterone from 3-Acetoxybisnor-5-cholenaldehyde and 3-Ketobisnor-4-cholenaldehyde | journal = Journal of the American Chemical Society | volume = 72 | issue = 6 | pages = 2617–2619 | date = 1950 | doi = 10.1021/ja01162a076 }}</ref><ref name="Slomp-1958">{{cite journal | vauthors = Slomp G | title = Ozonolysis. II. 1 The Effect of Pyridine on the Ozonolysis of 4,22-Stigmastadien-3-one 2 | journal = Journal of the American Chemical Society | volume = 80 | issue = 4 | pages = 915–921 | date = 1958 | doi = 10.1021/ja01537a041 }}</ref><ref name="pmid915584">{{cite journal | vauthors = Sundararaman P, Djerassi C | title = A convenient synthesis of progesterone from stigmasterol | journal = The Journal of Organic Chemistry | volume = 42 | issue = 22 | pages = 3633–3634 | date = October 1977 | pmid = 915584 | doi = 10.1021/jo00442a044 }}</ref><ref name="PBS.org-2007">{{cite web | url = https://www.pbs.org/wgbh/nova/transcripts/3402_julian.html | date = 6 February 2007 | title = Nova Transcripts: Forgotten Genius | publisher = PBS.org | access-date = 8 September 2017 | archive-date = 11 October 2018 | archive-url = https://web.archive.org/web/20181011224654/http://www.pbs.org/wgbh/nova/transcripts/3402_julian.html | url-status = live }}</ref><ref name="lipidlibrary.aocs.org">{{cite web | url = http://lipidlibrary.aocs.org/history/Julian/index.htm | title = Giants of the Past | publisher = lipidlibrary.aocs.org | url-status = dead | archive-url = https://web.archive.org/web/20120415001340/http://lipidlibrary.aocs.org/history/Julian/index.htm | archive-date = 15 April 2012 }}</ref>]]
	Common adverse effects include cramps, abdominal pain, skeletal pain, perineal pain, headache, arthralgia, constipation, ], ], diarrhea, nausea, vomiting, breast enlargement, joint pain, flatulence, hot flushes, decreased libido, thirst, increased appetite, ], drowsiness, excessive urination at night. Psychiatric effects including ], mood swings, emotional instability, aggression, abnormal crying, insomnia, forgetfulness, sleep disorders.<ref name=ppg2004/>
			====Total synthesis====
	Less frequent adverse effects that may occur include allergy, anemia, bloating, fatigue, tremor, ], pain, conjunctivitis, dizziness, vomiting, myalgia, back pain, breast pain, genital itching, genital yeast infection, upper respiratory tract infection, ], ], ], ], ], ], premenstrual tension, ], urinary tract infection, vaginal discharge, ], sweating, hyperventilation, vaginal dryness, ], fever, ], flu-like symptoms, dry mouth, rhinitis, leg pain, skin discoloration, skin disorders, ], sinusitis, acne.<ref name=ppg2004/>
			]
			A ] of progesterone was reported in 1971 by ].<ref name="pmid5131151">{{cite journal | vauthors = Johnson WS, Gravestock MB, McCarry BE | title = Acetylenic bond participation in biogenetic-like olefinic cyclizations. II. Synthesis of dl-progesterone | journal = Journal of the American Chemical Society | volume = 93 | issue = 17 | pages = 4332–4334 | date = August 1971 | pmid = 5131151 | doi = 10.1021/ja00746a062 }}</ref> The synthesis begins with reacting the ] '''<u>7</u>''' with ] to produce the ] '''<u>8</u>'''. The ylide '''<u>8</u>''' is reacted with an ] to produce the ] '''<u>9</u>'''. The ] ]s of '''<u>9</u>''' are hydrolyzed to produce the diketone '''<u>10</u>''', which in turn is cyclized to form the cyclopentenone '''<u>11</u>'''. The ketone of '''<u>11</u>''' is reacted with methyl lithium to yield the tertiary alcohol '''<u>12</u>''', which in turn is treated with acid to produce the tertiary cation '''<u>13</u>'''. The key step of the synthesis is the π-cation cyclization of '''<u>13</u>''' in which the B-, C-, and D-rings of the steroid are simultaneously formed to produce '''<u>14</u>'''. This step resembles the cationic cyclization reaction used in the biosynthesis of steroids and hence is referred to as ''biomimetic''. In the next step the ] ] is hydrolyzed to produce the ketone '''<u>15</u>'''. The cyclopentene A-ring is then opened by oxidizing with ozone to produce '''<u>16</u>'''. Finally, the diketone '''<u>17</u>''' undergoes an intramolecular ] by treating with aqueous potassium hydroxide to produce progesterone.<ref name="pmid5131151"/>
	Current research suggests that progesterone plays an important role in the signaling of insulin release and pancreatic function, and may affect the susceptibility to diabetes.<ref>{{cite web |url=http://www.pnas.org/content/99/24/15644.full.pdf |title=Progesterone receptor knockout mice have an improved glucose homeostasis secondary to beta -cell proliferation |author=Picard F, Wanatabe M, Schoonjans K, Lydon J, O'Malley BW, Auwerx J |month=November |year=2002 |format=PDF }}</ref> It has been shown that women with high levels of progesterone during pregnancy are more likely to develop glucose abnormalities.<ref>{{cite web |url=http://www.ncbi.nlm.nih.gov/pubmed/12591170 |title=Progesterone in gestational diabetes mellitus: guilty or not guilty? |author=Brănişteanu DD, Mathieu C |month=March |year=2003 }}</ref>
			==History==
	== Medical applications ==
			] and ] discovered the hormonal action of progesterone in 1929.<ref name="Josimovich2013" /><ref name="Corner-1929">{{Cite journal|vauthors=Corner GW, Allen WM|date=1 March 1929|title=Physiology of the corpus luteum|journal=American Journal of Physiology. Legacy Content|volume=88|issue=2|pages=326–339|url=https://journals.physiology.org/doi/abs/10.1152/ajplegacy.1929.88.2.326|doi=10.1152/ajplegacy.1929.88.2.326|issn=0002-9513|url-access=subscription|access-date=12 August 2021|archive-date=12 August 2021|archive-url=https://web.archive.org/web/20210812022335/https://journals.physiology.org/doi/abs/10.1152/ajplegacy.1929.88.2.326|url-status=live}}</ref><ref name="CoutinhoSegal1999">{{cite book | vauthors = Coutinho EM, Segal SJ | title = Is Menstruation Obsolete? | url = https://books.google.com/books?id=1ZzmCwAAQBAJ&pg=PA31 | year = 1999 | publisher = Oxford University Press | isbn = 978-0-19-513021-8 | pages = 31– | access-date = 5 October 2016 | archive-date = 14 January 2023 | archive-url = https://web.archive.org/web/20230114024937/https://books.google.com/books?id=1ZzmCwAAQBAJ&pg=PA31 | url-status = live }}</ref><ref name="Walker2008">{{cite book | vauthors = Walker A | title = The Menstrual Cycle |url=https://books.google.com/books?id=7HQBAwAAQBAJ&pg=PA49 |date=7 March 2008 |publisher=Routledge |isbn=978-1-134-71411-7 |pages=49–}}</ref> By 1931–1932, nearly pure crystalline material of high progestational activity had been isolated from the ] of animals, and by 1934, pure crystalline progesterone had been refined and obtained and the ] of progesterone was determined.<ref name="Josimovich2013" /><ref name="CoutinhoSegal1999" /> This was achieved by ] at the ] of ] in ], who extracted this new compound from several thousand liters of ].<ref name="Piosik-2003">{{Cite journal | vauthors = Piosik R | title = Adolf Butenandt und sein Wirken an der Technischen Hochschule Danzig | doi = 10.1002/ckon.200390038 | journal = CHEMKON | volume = 10 | issue = 3 | pages = 135–138 | year = 2003 }}</ref>
	]
	The use of progesterone and its analogues have many medical applications, both to address acute situations and to address the long-term decline of natural progesterone levels. Because of the poor bioavailability of progesterone when taken orally, many synthetic progestins have been designed with improved oral bioavailability.<ref name="pmid19434889">{{cite journal | author = Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH | title = Classification and pharmacology of progestins | journal = Maturitas | volume = 61 | issue = 1-2 | pages = 171–80 | year = 2008 | pmid = 19434889 | doi = 10.1016/j.maturitas.2003.09.014 | url = http://www1.elsevier.com/homepage/sab/womenshealth/doc/journals/maturitas_si/2.pdf | issn = }}</ref> Progesteone was approved by the United States ] as vaginal ] on July 31, 1997,<ref>{{cite web | url = http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=020701&TABLE1=OB_Rx | title = Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations: 020701 | accessdate = 2010-07-07 | date = 2010-07-02 | publisher = ] }}</ref> an oral ] on May 14, 1998<ref>{{cite web | url = http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=019781&TABLE1=OB_Rx | title = Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations: 019781 | accessdate = 2010-07-07 | date = 2010-07-02 | publisher = ] }}</ref> in an ] form on April 25, 2001<ref>{{cite web | url = http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=075906&TABLE1=OB_Rx | title = Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations: 075906 | accessdate = 2010-07-07 | date = 2010-07-02 | publisher = ] }}</ref> and as a vaginal insert on June 21, 2007.<ref>{{cite web | url = http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=022057&TABLE1=OB_Rx | title = Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations: 022057 | accessdate = 2010-07-07 | date = 2010-07-02 | publisher = ] }}</ref> In Italy and Spain, Progesterone is sold under the trademark Progeffik.
			] of progesterone from ] and ] was accomplished later that year.<ref name="CoutinhoSegal1999"/><ref name="Ginsburg2012">{{cite book|vauthors=Ginsburg B|title=Premenstrual Syndrome: Ethical and Legal Implications in a Biomedical Perspective|url=https://books.google.com/books?id=HTLoBwAAQBAJ&pg=PA274|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4684-5275-4|pages=274–|access-date=5 October 2016|archive-date=14 January 2023|archive-url=https://web.archive.org/web/20230114025025/https://books.google.com/books?id=HTLoBwAAQBAJ&pg=PA274|url-status=live}}</ref> Up to this point, progesterone, known generically as corpus luteum hormone, had been being referred to by several groups by different names, including corporin, lutein, luteosterone, and progestin.<ref name="Josimovich2013" /><ref name="Rolleston1936">{{cite book |vauthors=Rolleston HD |title=The Endocrine Organs in Health and Disease: With an Historical Review |url=https://books.google.com/books?id=tkgbAAAAIAAJ |year=1936 |publisher=Oxford University Press, H. Milford |page=406 |access-date=5 October 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114024937/https://books.google.com/books?id=tkgbAAAAIAAJ |url-status=live }}</ref> In 1935, at the time of the Second International Conference on the Standardization of Sex Hormones in ], a compromise was made between the groups and the name progesterone (progestational steroidal ketone) was created.<ref name="Josimovich2013" /><ref name="pmid4922128">{{cite journal | vauthors = Allen WM | title = Progesterone: how did the name originate? | journal = Southern Medical Journal | volume = 63 | issue = 10 | pages = 1151–1155 | date = October 1970 | pmid = 4922128 | doi = 10.1097/00007611-197010000-00012 | s2cid = 35867375 }}</ref>
	=== Bioavailability ===
	The route of administration impacts the effect of the drug. Given orally, progesterone has a wide person-to-person variability in absorption and ] while synthetic progestins are rapidly absorbed with a longer ] than progesterone and maintain stable levels in the blood.<ref>{{cite pmid | 14670641 }}</ref>
			===Veterinary use===
	Progesterone does not dissolve in water and is poorly absorbed when taken orally unless ] in oil. Products are often sold as ] containing micronised progesterone in oil. Progesterone can also be administered through vaginal or rectal ] or ], ]ly through a gel or cream,<ref name=Lark1999>{{cite book |title=Making the Estrogen Decision |last=Lark |first=Susan |authorlink=Susan Lark |coauthors= |year=1999 |publisher=McGraw-Hill Professional |location= |isbn=0879836962, 9780879836962 |page=22 |url=http://books.google.com/?id=d3IP-dmpoNsC&pg=PA22&dq=progesterone+%22skin+cream%22+liver&cd=3#v=onepage&q=progesterone%20%22skin%20cream%22%20liver }}</ref> or via ] (though the latter has a short ] requiring daily administration).
			The use of progesterone tests in dog breeding to pinpoint ovulation is becoming more widely used. There are several tests available but the most reliable test is a blood test with blood drawn by a veterinarian and sent to a lab for processing. Results can usually be obtained with 24 to 72 hours. The rationale for using progesterone tests is that increased numbers begin in close proximity to preovulatory surge in gonadotrophins and continue through ovulation and estrus. When progesterone levels reach certain levels they can signal the stage of estrus the female is. Prediction of birth date of the pending litter can be very accurate if ovulation date is known. Puppies deliver with a day or two of 9 weeks gestation in most cases. It is not possible to determine pregnancy using progesterone tests once a breeding has taken place, however. This is due to the fact that, in dogs, progesterone levels remain elevated throughout the estrus period.<ref name="Refsal-2009">{{Cite journal|vauthors=Refsal K|date=February 2009|title=Interpretation of Serum Progesterone Results for Management of Breeding in Dogs|url=https://www.dcpah.msu.edu/sections/endocrinology/Progesterone_Guidelines.pdf|journal=Webcd.endo.ref|access-date=26 February 2018|archive-date=29 August 2021|archive-url=https://web.archive.org/web/20210829011032/https://cvm.msu.edu/vdl|url-status=live}}</ref>
			=== Pricing ===
	"Natural progesterone" products derived from ] do not require a prescription, but there is no evidence that the human body can convert its active ingredient (], the plant steroid that is chemically converted to produce progesterone industrially<ref name="Marker_1940">{{cite journal | author = Marker RE, Krueger J | title = Sterols. CXII. Sapogenins. XLI. The Preparation of Trillin and its Conversion to Progesterone | journal = J. Am. Chem. Soc. | volume = 62 | issue = 12 | pages = 3349–3350 | year = 1940| doi = 10.1021/ja01869a023 }}</ref>) into progesterone.<ref name="pmid9492350">{{cite journal | author = Zava DT, Dollbaum CM, Blen M | title = Estrogen and progestin bioactivity of foods, herbs, and spices | journal = Proc. Soc. Exp. Biol. Med. | volume = 217 | issue = 3 | pages = 369–78 | year = 1998 | pmid = 9492350 | doi = | issn = | url = http://www.cancersupportivecare.com/estrogenherbref.html#31 }}</ref><ref name="pmid11428178">{{cite journal | author = Komesaroff PA, Black CV, Cable V, Sudhir K | title = Effects of wild yam extract on menopausal symptoms, lipids and sex hormones in healthy menopausal women | journal = Climacteric | volume = 4 | issue = 2 | pages = 144–50 | year = 2001 | pmid = 11428178| doi = 10.1080/713605087 }}</ref>
			Pricing for progesterone can vary depending location, insurance coverage, discount coupons, quantity, shortages, manufacturers, brand or generic versions, different pharmacies, and so on. As of currently, 30 capsules of 100&nbsp;mg of the generic version, Prometrium, from CVS Pharmacy is around $40 without any discounts or insurance applied. The brand version, Progesterone, is around $450 for 30 capsules without any discounts or insurance applied.<ref name="www.goodrx.com-prices">{{cite web |title=Progesterone Prices, Coupons & Savings Tips - GoodRx |url=https://www.goodrx.com/progesterone |access-date=1 August 2023 |website=www.goodrx.com |archive-date=30 March 2023 |archive-url=https://web.archive.org/web/20230330054318/https://www.goodrx.com/progesterone |url-status=live }}</ref> In comparison, Walgreens offers 30 capsules of 100&nbsp;mg in the generic version for $51 without insurance or coupons applied. The brand name costs around $431 for 30 capsules of 100&nbsp;mg.<ref name="www.goodrx.com-prices-2">{{Cite web |title=Progesterone Prices, Coupons & Savings Tips - GoodRx |url=https://www.goodrx.com/progesterone |access-date=1 August 2023 |website=www.goodrx.com |archive-date=30 March 2023 |archive-url=https://web.archive.org/web/20230330054318/https://www.goodrx.com/progesterone |url-status=live }}</ref> {{Clear}}
	=== Specific uses ===		== References ==
			* {{Creative Commons text attribution notice|cc=bysa3|url=https://en.wikiversity.org/wiki?curid=269289}}
			{{reflist|refs=
			<ref name="James2015">{{cite book |vauthors=Jameson JL, De Groot LJ |title=Endocrinology: Adult and Pediatric E-Book |url=https://books.google.com/books?id=xmLeBgAAQBAJ&pg=PA2179 |date=25 February 2015 |publisher=Elsevier Health Sciences |isbn=978-0-323-32195-2 |page=2179 |access-date=29 October 2017 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114025031/https://books.google.com/books?id=xmLeBgAAQBAJ&pg=PA2179 |url-status=live }}</ref>
	*Progesterone is used to support pregnancy in Assisted Reproductive Technology (ART) cycles such as In-vitro Fertilization (IVF). While daily intramuscular injections of progesterone-in-oil (PIO) have been the standard route of administration, PIO injections are not FDA-approved for use in pregnancy. A recent meta-analysis showed that the intravaginal route with an appropriate dose and dosing frequency is equivalent to daily intramuscular injections.<ref name="Zarutskiea_2007">{{cite journal | author = Zarutskiea PW, Phillips JA | title = Re-analysis of vaginal progesterone as luteal phase support (LPS) in assisted reproduction (ART) cycles | journal = Fertility and Sterility | volume = 88 | issue = supplement 1 | pages = S113 | year = 2007| doi = 10.1016/j.fertnstert.2007.07.365 }}</ref> In addition, a recent case-matched study comparing vaginal progesterone with PIO injections showed that live birth rates were nearly identical with both methods.<ref>Khan N, Richter KS, Blake EJ, et al. Case-matched comparison of intramuscular versus vaginal progesterone for luteal phase support after in vitro fertilization and embryo transfer. Presented at: 55th Annual Meeting of the Pacific Coast Reproductive Society; April 18–22, 2007; Rancho Mirage, CA.</ref>
	*Progesterone is used to control persistent ]. It is also used to prepare uterine lining in ] therapy and to support early pregnancy. Patients with ] due to inadequate progesterone production may receive progesterone.
	*Progesterone is also used in nonpregnant women with a delayed menstruation of one or more weeks, in order to allow the thickened endometrial lining to slough off. This process is termed a progesterone withdrawal bleed. The progesterone is taken orally for a short time (usually one week), after which the progesterone is discontinued and bleeding should occur.
	*Progesterone is being investigated as potentially beneficial in treating ], since the characteristic deterioration of nerve ] insulation halts during pregnancy, when progesterone levels are raised; deterioration commences again when the levels drop.
	*Vaginally dosed progesterone is being investigated as potentially beneficial in preventing preterm birth in women at risk for preterm birth. The initial study by Fonseca suggested that vaginal progesterone could prevent preterm birth in women with a history of preterm birth.<ref name="pmid12592250">{{cite journal | author = da Fonseca EB, Bittar RE, Carvalho MH, Zugaib M | title = Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study | journal = Am. J. Obstet. Gynecol. | volume = 188 | issue = 2 | pages = 419–24 | year = 2003 | pmid = 12592250 | doi = 10.1067/mob.2003.41 }}</ref> According to a recent study, women with a short cervix that received hormonal treatment with a progesterone gel had their risk of prematurely giving birth reduced. The hormone treatment was administered vaginally every day during the second half of a pregnancy. <ref>{{cite web|last=Harris|first=Gardiner|title=Hormone Is Said to Cut Risk of Premature Birth|url=http://www.nytimes.com/2011/05/03/health/research/03preemie.html|publisher=New York Times|accessdate=5 May 2011}}</ref>
			<ref name="Josimovich2013">{{cite book |vauthors=Josimovich JB |title=Gynecologic Endocrinology |url=https://books.google.com/books?id=9vv2BwAAQBAJ&pg=PA25 |date=11 November 2013 |publisher=Springer Science & Business Media |isbn=978-1-4613-2157-6 |pages=9, 25–29 |access-date=1 February 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114024947/https://books.google.com/books?id=9vv2BwAAQBAJ&pg=PA25 |url-status=live }}</ref>
	A subsequent and larger study showed that vaginal progesterone was no better than placebo in preventing recurrent preterm birth in women with a history of a previous preterm birth,<ref name="pmid17899572">{{cite journal | author = O'Brien JM, Adair CD, Lewis DF, Hall DR, Defranco EA, Fusey S, Soma-Pillay P, Porter K, How H, Schackis R, Eller D, Trivedi Y, Vanburen G, Khandelwal M, Trofatter K, Vidyadhari D, Vijayaraghavan J, Weeks J, Dattel B, Newton E, Chazotte C, Valenzuela G, Calda P, Bsharat M, Creasy GW | title = Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial | journal = Ultrasound Obstet Gynecol | volume = 30 | issue = 5 | pages = 687–96 | year = 2007 | pmid = 17899572 | doi = 10.1002/uog.5158 }}</ref> but a planned secondary analysis of the data in this trial showed that women with a short cervix at baseline in the trial had benefit in two ways: a reduction in births less than 32 weeks and a reduction in both the frequency and the time their babies were in intensive care.<ref name="pmid17899571">{{cite journal | author = DeFranco EA, O'Brien JM, Adair CD, Lewis DF, Hall DR, Fusey S, Soma-Pillay P, Porter K, How H, Schakis R, Eller D, Trivedi Y, Vanburen G, Khandelwal M, Trofatter K, Vidyadhari D, Vijayaraghavan J, Weeks J, Dattel B, Newton E, Chazotte C, Valenzuela G, Calda P, Bsharat M, Creasy GW | title = Vaginal progesterone is associated with a decrease in risk for early preterm birth and improved neonatal outcome in women with a short cervix: a secondary analysis from a randomized, double-blind, placebo-controlled trial | journal = Ultrasound Obstet Gynecol | volume = 30 | issue = 5 | pages = 697–705 | year = 2007 | pmid = 17899571 | doi = 10.1002/uog.5159 }}</ref> In another trial, vaginal progesterone was shown to be better than placebo in reducing preterm birth prior to 34 weeks in women with an extremely short cervix at baseline.<ref name="pmid17671254">{{cite journal | author = Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH | title = Progesterone and the risk of preterm birth among women with a short cervix | journal = N. Engl. J. Med. | volume = 357 | issue = 5 | pages = 462–9 | year = 2007 | pmid = 17671254 | doi = 10.1056/NEJMoa067815 }}</ref> An editorial by Roberto Romero discusses the role of sonographic cervical length in identifying patients who may benefit from progesterone treatment.<ref name="pmid17899585">{{cite journal | author = Romero R | title = Prevention of spontaneous preterm birth: the role of sonographic cervical length in identifying patients who may benefit from progesterone treatment | journal = Ultrasound Obstet Gynecol | volume = 30 | issue = 5 | pages = 675–86 | year = 2007 | pmid = 17899585 | doi = 10.1002/uog.5174 }}</ref>
	* Progesterone also has a role in skin elasticity and bone strength, in ], in nerve tissue and in ], and the presence of progesterone receptors in certain muscle and fat tissue may hint at a role in ] proportions of those.<ref name="medicinalchem">{{cite book |title= Medicinal Chemistry|last= Sriram|first= D|year= 2007|publisher= Dorling Kindersley India Pvt. Ltd.|location= New Delhi|isbn= 81-317-0031-3|page= 432 |url= |accessdate=02:42, 15 April 2010 (UTC)}}</ref>
	* Progesterone ]s, or ]s (SPRM)s, such as ] (]), can be used to prevent conception or induce ]s.
			<ref name="Josimovich2013b">{{cite book |vauthors=Josimovich JB |title=Gynecologic Endocrinology |url=https://books.google.com/books?id=9vv2BwAAQBAJ&pg=PA25 |date=11 November 2013 |publisher=Springer Science & Business Media |isbn=978-1-4613-2157-6 |pages=9, 25–29, 139 |access-date=1 February 2016 |archive-date=14 January 2023 |archive-url=https://web.archive.org/web/20230114024947/https://books.google.com/books?id=9vv2BwAAQBAJ&pg=PA25 |url-status=live }}</ref>
	Note that methods of ] do not contain progesterone but a ].
			<ref name="KingBrucker2010">{{cite book |vauthors=King TL, Brucker MC |title=Pharmacology for Women's Health |url=https://books.google.com/books?id=E9qVyrNPsBkC&pg=PA373 |date=25 October 2010 |publisher=Jones & Bartlett Publishers |isbn=978-1-4496-5800-7 |pages=372–373}}</ref>
	Progesterone may affect male behavior.<ref name="pmid12601162">{{cite journal | author = Schneider JS, Stone MK, Wynne-Edwards KE, Horton TH, Lydon J, O'Malley B, Levine JE | title = Progesterone receptors mediate male aggression toward infants | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 100 | issue = 5 | pages = 2951–6 | year = 2003 | pmid = 12601162 | doi = 10.1073/pnas.0130100100 | pmc = 151447 }}</ref>
			<!--This ref is defined in a template <ref name="pmid945344">{{cite journal |vauthors=Aufrère MB, Benson H |title=Progesterone: an overview and recent advances |journal=J Pharm Sci |volume=65 |issue=6 |pages=783–800 |date=June 1976 |pmid=945344 |doi=10.1002/jps.2600650602}}</ref>-->
	Progesterone is starting to be used in the treatment of the skin condition ].{{Citation needed|date=November 2008}}
			<ref name="pmid8513955">{{cite journal |vauthors=Simon JA, Robinson DE, Andrews MC, Hildebrand JR, Rocci ML, Blake RE, Hodgen GD |title=The absorption of oral micronized progesterone: the effect of food, dose proportionality, and comparison with intramuscular progesterone |journal=Fertility and Sterility |volume=60 |issue=1 |pages=26–33 |date=July 1993 |pmid=8513955 |doi=10.1016/S0015-0282(16)56031-2 |doi-access=free}}</ref>
	=== Aging ===
			<ref name="pmid12215716">{{cite journal |vauthors=Stanczyk FZ |title=Pharmacokinetics and potency of progestins used for hormone replacement therapy and contraception |journal=Reviews in Endocrine & Metabolic Disorders |volume=3 |issue=3 |pages=211–224 |date=September 2002 |pmid=12215716 |doi=10.1023/A:1020072325818 |s2cid=27018468}}</ref>
	Since most progesterone in males is created during testicular production of ], and most in females by the ], the shutting down (whether by natural or chemical means), or removal, of those inevitably causes a considerable reduction in progesterone levels. Previous concentration upon the role of ]s (progesterone and molecules with similar effects) in female reproduction, when progesterone was simply considered a "female hormone", obscured the significance of progesterone elsewhere in both sexes.
	The tendency for progesterone to have a regulatory effect, the presence of progesterone ]s in many types of body tissue, and the pattern of deterioration (or ] formation) in many of those increasing in later years when progesterone levels have dropped, is prompting widespread research into the potential value of maintaining progesterone levels in both males and females.
	=== Brain damage ===
	Previous studies have shown that progesterone supports the normal development of neurons in the brain, and that the hormone has a protective effect on damaged brain tissue. It has been observed in animal models that females have reduced susceptibility to ] and this protective effect has been hypothesized to be caused by increased circulating levels of ] and progesterone in females.<ref name="pmid10833057">{{cite journal | author = Roof RL, Hall ED | title = Gender differences in acute CNS trauma and stroke: neuroprotective effects of estrogen and progesterone | journal = J. Neurotrauma | volume = 17 | issue = 5 | pages = 367–88 | year = 2000 | month = May | pmid = 10833057 | doi = 10.1089/neu.2000.17.367| url = }}</ref> A number of additional animal studies have confirmed that progesterone has neuroprotective effects when administered shortly after traumatic brain injury.<ref name="pmid17715141">{{cite journal | author = Gibson CL, Gray LJ, Bath PM, Murphy SP | title = Progesterone for the treatment of experimental brain injury; a systematic review | journal = Brain | volume = 131 | issue = Pt 2 | pages = 318–28 | year = 2008 | month = February | pmid = 17715141 | doi = 10.1093/brain/awm183 | url = }}</ref> Encouraging results have also been reported in human clinical trials.<ref name="pmid17011666">{{cite journal | author = Wright DW, Kellermann AL, Hertzberg VS, Clark PL, Frankel M, Goldstein FC, Salomone JP, Dent LL, Harris OA, Ander DS, Lowery DW, Patel MM, Denson DD, Gordon AB, Wald MM, Gupta S, Hoffman SW, Stein DG | title = ProTECT: a randomized clinical trial of progesterone for acute traumatic brain injury | journal = Ann Emerg Med | volume = 49 | issue = 4 | pages = 391–402, 402.e1–2 | year = 2007 | month = April | pmid = 17011666 | doi = 10.1016/j.annemergmed.2006.07.932 | url = }}</ref><ref name="pmid18447940">{{cite journal | author = Xiao G, Wei J, Yan W, Wang W, Lu Z | title = Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial | journal = Crit Care | volume = 12 | issue = 2 | pages = R61 | year = 2008 | month = April | pmid = 18447940 | doi = 10.1186/cc6887 | url = | pmc = 2447617 }}</ref>
	The mechanism of progesterone protective effects may be the reduction of inflammation that follows brain trauma.<ref name="pmid18188998">{{cite journal | author = Pan DS, Liu WG, Yang XF, Cao F | title = Inhibitory effect of progesterone on inflammatory factors after experimental traumatic brain injury | journal = Biomed. Environ. Sci. | volume = 20 | issue = 5 | pages = 432–8 | year = 2007 | month = October | pmid = 18188998 | doi = | url = | issn = }}</ref>
	== See also ==
	*]
	*]
	*]
	*] - the enzyme that deactivates progesterone
	*]
	== References ==
	{{Reflist|2}}
	== Additional images ==
	], showing progesterone among the progestagens in yellow area.]]
	{{Gallery
	|title=
	|footer=
	|width=150
	|lines=1
	<!-- |Image:Steroidogenesis.png|], showing progesterone among the progestagens in yellow area. -->
	|Image:Pregnenolone.png|]
	|Image:11-Deoxycorticosterone.svg|]
	}}		}}
	{{-}}
	== External links ==		== External links ==
			*
	* {{MeshName|Progesterone}}		* {{MeshName|Progesterone}}
	* {{Cite web | url = http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Progesterone.html | title = Progesterone | author = Kimball JW | authorlink = | coauthors = | date = 2007-05-27 | work = Kimball's Biology Pages | publisher = | pages = | language = | archiveurl = | archivedate = | quote = | accessdate = 2008-06-18 }}		* {{Cite web | url = http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Progesterone.html | title = Progesterone | vauthors = Kimball JW | date = 27 May 2007 | work = Kimball's Biology Pages | access-date = 18 June 2008 | archive-url = https://web.archive.org/web/20080618062909/http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Progesterone.html | archive-date = 18 June 2008 | url-status = dead }}
	* {{Cite web | url = http://www.pms-menopause-progesterone.org/progesterone/ | title = Progesterone Resource Center | author = | authorlink = | coauthors = | date = | format = | work = PMS, Menopause, and Progesterone Resource Center | publisher = Oasis Advanced Wellness, Inc | pages = | language = | archiveurl = | archivedate = | quote = | accessdate = 2008-06-18}}
	*
			{{Progesterone}}
	{{Hormones}}		{{Hormones}}
	{{Sex hormones}}		{{Endogenous steroids}}
	{{Cholesterol and steroid intermediates}}		{{Progestogens and antiprogestogens}}
			{{Mineralocorticoids and antimineralocorticoids}}
			{{Navboxes
			| title = ]
			| titlestyle = background:#ccccff
			| list1 =
			{{GABAA receptor positive modulators}}
			{{Glucocorticoid receptor modulators}}
			{{Mineralocorticoid receptor modulators}}
			{{Nicotinic acetylcholine receptor modulators}}
			{{Progesterone receptor modulators}}
			{{Sigma receptor modulators}}
			{{Xenobiotic-sensing receptor modulators}}
			}}
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