Editing Progesterone (section)

==Biochemistry==

===Biosynthesis===
[[File:Steroidogenesis.svg|thumb|right|upright=1.8|[[Steroidogenesis]], 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 [[steroid]] [[hormone]]s, is synthesized from [[pregnenolone]], which itself is derived from [[cholesterol]].{{cn|date=February 2025}}

Cholesterol undergoes double oxidation to produce [[22R-hydroxycholesterol|22''R''-hydroxycholesterol]] and then [[20α,22R-dihydroxycholesterol|20α,22''R''-dihydroxycholesterol]]. This vicinal [[diol]] is then further oxidized with loss of the side chain starting at position C22 to produce pregnenolone. This reaction is catalyzed by [[cytochrome]] [[P450scc]].{{cn|date=February 2025}}

The conversion of pregnenolone to progesterone takes place in two steps. First, the 3β-[[hydroxyl]] group is oxidized to a [[ketone|keto]] group and second, the [[double bond]] is moved to C4, from C5 through a keto/[[enol]] [[tautomer]]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 [[3β-hydroxysteroid dehydrogenase|3β-hydroxysteroid dehydrogenase/δ<sup>5-4</sup>-isomerase]].{{cn|date=February 2025}}

Progesterone in turn is the precursor of the mineralocorticoid [[aldosterone]], and after conversion to [[17α-hydroxyprogesterone]], of [[cortisol]] and [[androstenedione]]. Androstenedione can be converted to [[testosterone]], [[estrone]], and [[estradiol]], highlighting the critical role of progesterone in testosterone synthesis.{{cn|date=February 2025}}

Pregnenolone and progesterone can also be synthesized by [[yeast]].<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 30&nbsp;mg of progesterone is secreted from the ovaries per day in reproductive-age women, while the adrenal glands produce about 1&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 [[plasma protein]]s, including [[albumin]] (50–54%) and [[transcortin]] (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 [[metabolism]] of progesterone is rapid and extensive and occurs mainly in the [[liver]],<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 [[enzyme]]s that metabolize progesterone are also expressed widely in the [[brain]], [[skin]], and various other [[wikt:extrahepatic|extrahepatic]] [[tissue (biology)|tissue]]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 [[elimination half-life]] of only approximately 5&nbsp;minutes in [[circulatory system|circulation]].<ref name="FalconeHurd2007" /> The metabolism of progesterone is complex, and it may form as many as 35 different [[conjugation (biochemistry)|unconjugated]] [[metabolite]]s when it is ingested orally.<ref name="pmid14667980" /><ref name="pmid16112947" /> Progesterone is highly susceptible to enzymatic [[redox|reduction]] via [[reductase]]s and [[hydroxysteroid dehydrogenase]]s due to its [[double bond]] (between the C4 and C5 positions) and its two [[ketone]]s (at the C3 and C20 positions).<ref name="pmid14667980" />

The major [[metabolic pathway]] of progesterone is reduction by [[5α-reductase]]<ref name="pmid558037" /> and [[5β-reductase]] into the dihydrogenated [[5α-dihydroprogesterone]] and [[5β-dihydroprogesterone]], 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 [[3α-hydroxysteroid dehydrogenase]] and [[3β-hydroxysteroid dehydrogenase]] into the tetrahydrogenated [[allopregnanolone]], [[pregnanolone]], [[isopregnanolone]], and [[epipregnanolone]].<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, [[20α-hydroxysteroid dehydrogenase]] and [[20β-hydroxysteroid dehydrogenase]] reduce these metabolites to form the corresponding hexahydrogenated [[pregnanediol]]s (eight different [[isomer]]s in total),<ref name="Cupps1991" /><ref name="SantoroNeal-Perry2010" /> which are then conjugated via [[glucuronidation]] and/or [[sulfation]], released from the liver into circulation, and [[excretion|excreted]] by the [[kidney]]s into the [[urine]].<ref name="FalconeHurd2007" /><ref name="pmid14667980" /> The major metabolite of progesterone in the urine is the 3α,5β,20α isomer of [[pregnanediol glucuronide]], 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 [[3α-dihydroprogesterone]], [[3β-dihydroprogesterone]], [[20α-dihydroprogesterone]], and [[20β-dihydroprogesterone]], 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 [[hydroxylation|hydroxylated]] (see below) and then reduced.<ref name="pmid14667980" /> Endogenous progesterone is metabolized approximately 50% into 5α-dihydroprogesterone in the [[corpus luteum]], 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 [[hydroxylation|hydroxylated]] via [[17α-hydroxylase]] (CYP17A1) and [[21-hydroxylase]] (CYP21A2) into [[17α-hydroxyprogesterone]] and [[11-deoxycorticosterone]] (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 [[pregnanetriol]]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 [[11β-hydroxylase]] (CYP11B1) and to a lesser extent via [[aldosterone synthase]] (CYP11B2) into [[11β-hydroxyprogesterone]].<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 [[cytochrome P450]] 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 [[CYP3A4]], 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 [[ketoconazole]], 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 [[metabolic pathway]]s involved in the [[metabolism]] of progesterone in humans. In addition to the [[biotransformation|transformation]]s shown in the diagram, [[conjugation (biochemistry)|conjugation]], specifically [[glucuronidation]] and [[sulfation]], occurs with [[metabolite]]s of progesterone that have one or more available [[hydroxyl group|hydroxyl]] (–OH) [[functional group|group]]s.}}

===Levels===
[[File:Progesterone levels across the normal menstrual cycle in women.png|class=skin-invert-image|thumb|right|upright=2.25|Progesterone levels across the menstrual cycle in normally cycling and ovulatory women.<ref name="pmid16776638">{{cite journal | vauthors = Stricker R, Eberhart R, Chevailler MC, Quinn FA, Bischof P, Stricker R | title = Establishment of detailed reference values for luteinizing hormone, follicle stimulating hormone, estradiol, and progesterone during different phases of the menstrual cycle on the Abbott ARCHITECT analyzer | journal = Clinical Chemistry and Laboratory Medicine | volume = 44 | issue = 7 | pages = 883–887 | date = 2006 | pmid = 16776638 | doi = 10.1515/CCLM.2006.160 | s2cid = 524952 }}</ref> The horizontal lines are the mean integrated levels for each curve. The vertical line is mid-cycle.]]

Progesterone levels are relatively low during the preovulatory phase of the [[menstrual cycle]], rise after [[ovulation]], and are elevated during the [[luteal phase]], 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 [[pregnancy]] occurs, [[human chorionic gonadotropin]] 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 [[labor (childbirth)|labor]] has been argued and may be species-specific. After delivery of the placenta and during lactation, progesterone levels are very low.{{cn|date=February 2025}}

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>[[progesterone (medication)|progesterone]]</noinclude><includeonly>progesterone</includeonly> production rates and plasma progesterone levels
|-
! Group !! {{abbr|P4|Progesterone}} production !! {{abbr|P4|Progesterone}} levels
|-
| [[Prepuberty|Prepubertal]] children || {{abbr|ND|No data}} || 0.06–0.5&nbsp;ng/mL
|-
| [[Puberty|Pubertal]] girls<br />&nbsp;&nbsp;[[Tanner scale#Definitions of stages|Tanner stage I]] (childhood)<br />&nbsp;&nbsp;[[Tanner scale#Definitions of stages|Tanner stage II]] (ages 8–12)<br />&nbsp;&nbsp;[[Tanner scale#Definitions of stages|Tanner stage III]] (ages 10–13)<br />&nbsp;&nbsp;[[Tanner scale#Definitions of stages|Tanner stage IV]] (ages 11–14)<br />&nbsp;&nbsp;[[Tanner scale#Definitions of stages|Tanner stage V]] (ages 12–15)<br />&nbsp;&nbsp;&nbsp;&nbsp;[[Follicular phase]] (days 1–14)<br />&nbsp;&nbsp;&nbsp;&nbsp;[[Luteal phase]] (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
|-
| [[Premenopause|Premenopausal]] women<br />&nbsp;&nbsp;[[Follicular phase]] (days 1–14)<br />&nbsp;&nbsp;[[Luteal phase]] (days 15–28)<br />&nbsp;&nbsp;[[Oral contraceptive]] ([[anovulation|anovulatory]]) || &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
|-
| [[Menopause|Postmenopausal]] women<br />[[Oophorectomy|Oophorectomized]] women<br />[[Oophorectomy|Oophorectomized]] and [[adrenalectomy|adrenalectomized]] 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}}
|-
| [[Pregnancy|Pregnant]] women<br />&nbsp;&nbsp;[[First trimester]] (weeks 1–12)<br />&nbsp;&nbsp;[[Second trimester]] (weeks 13–26)<br />&nbsp;&nbsp;[[Third trimester]] (weeks 27–40)<br />&nbsp;&nbsp;[[Postpartum]] (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====
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"
!rowspan=2| Person type !!colspan=3| [[Reference range for blood test]]
|-
! Lower limit !! Upper limit !! Unit
|-
| Female - menstrual cycle ||colspan=3| (see diagram below)
|-
| rowspan=2| Female - postmenopausal || [[less than|<]]0.2<ref name=nih2009>[https://web.archive.org/web/20150701024923/http://cclnprod.cc.nih.gov/dlm/testguide.nsf/0/CB26894E1EB28DEF85256BA5005B000E?OpenDocument Progesterone Reference Ranges], Performed at the Clinical Center at the National Institutes of Health, Bethesda MD, 03Feb09</ref> || 1<ref name=nih2009/> || [[nanogram|ng]]/[[millilitre|mL]]
|-
| <0.6<ref name="mass-converted">Converted from mass values using molar mass of 314.46 g/mol</ref> || 3<ref name="mass-converted"/> || [[nanomole|nmol]]/[[litre|L]]
|-
| rowspan=2| Female on [[oral contraceptive]]s || 0.34<ref name=nih2009/> || 0.92<ref name=nih2009/> || ng/mL
|-
| 1.1<ref name="mass-converted"/> || 2.9<ref name="mass-converted"/> || nmol/L
|-
| rowspan=2| Males [[greater than or equal to|≥]]16 years || 0.27<ref name=nih2009/> || 0.9<ref name=nih2009/> || ng/mL
|-
| 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
|-
| 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}}
[[File:Progesterone during menstrual cycle.png|thumb|upright=4|left|Progesterone levels during the [[menstrual cycle]].<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>
<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-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}}

===Sources===

====Animal====
Progesterone is produced in high amounts in the [[ovaries]] (by the [[corpus luteum]]) from the onset of [[puberty]] to [[menopause]], and is also produced in smaller amounts by the [[adrenal gland]]s after the onset of [[adrenarche]] in both males and females. To a lesser extent, progesterone is produced in [[nervous tissue]], especially in the brain, and in [[adipose tissue|adipose (fat) tissue]], as well.

During human [[pregnancy]], progesterone is produced in increasingly high amounts by the ovaries and [[placenta]]. At first, the source is the corpus luteum that has been "rescued" by the presence of [[human chorionic gonadotropin]] (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.

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>

====Plants====
In at least one plant, ''[[Juglans regia]]'', 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 | bibcode = 2010JNAtP..73..338P | s2cid = 26467578 }}</ref> In addition, progesterone-like [[steroid]]s are found in ''[[Dioscorea mexicana]]''. ''Dioscorea mexicana'' is a plant that is part of the [[yam (vegetable)|yam]] family native to [[Mexico]].<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 [[diosgenin]] 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 ''[[Dioscorea]]'' species, as well as in other plants that are not closely related, such as [[fenugreek]].

Another plant that contains substances readily convertible to progesterone is ''[[Dioscorea pseudojaponica]]'' native to [[Taiwan]]. Research has shown that the Taiwanese yam contains [[saponin]]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>

Many other ''Dioscorea'' species of the yam family contain steroidal substances from which progesterone can be produced. Among the more notable of these are ''[[Dioscorea villosa]]'' and ''[[Dioscorea polygonoides]]''. 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> ''[[Dioscorea polygonoides]]'' has been found to contain 2.64% diosgenin as shown by [[gas chromatography-mass spectrometry]].<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>