Editing Progestogen

{{short description|Steroid hormone that activates the progesterone receptor}}
{{about|progestogens as hormones|their use as medications|Progestogen (medication)}}
{{Infobox drug class
| Image = File:Progesterone.svg
| ImageClass = skin-invert-image
| Alt = 
| Caption = [[Progesterone]], the major progestogen in humans and a widely used medication.
| Width = 225px
| Synonyms = Progestins; Progestagens; Gestagens,
| Use = [[Hormonal contraceptive|Contraception]], [[menopause]], [[hypogonadism]], [[transgender women]], others
| MeshID = D011372
| Consumer_Reports = 
| ATC_prefix = G03D
| Drugs.com = 
| Biological_target = [[Progesterone receptor]]s ([[Progesterone receptor A|PRA]], [[Progesterone receptor B|PRB]], [[Progesterone receptor C|PRC]], [[Membrane progesterone receptor|mPR]]s (e.g., [[mPRα]], [[mPRβ]], [[mPRγ]], [[mPRδ]], others))
}}

'''Progestogens''', also sometimes written '''progestins''', '''progestagens''' or '''gestagens''',<ref name="KingBrucker2010">{{cite book | author1 = Tekoa L. King | author2 = Mary C. Brucker | 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 = 373}}</ref> are a class of natural or synthetic [[steroid hormone]]s that bind to and activate the [[progesterone receptor]]s (PR).<ref name="ClarkHarvey2011">{{cite book | author1 = Michelle A. Clark | author2 = Richard A. Harvey | author3 = Richard Finkel |author4=Jose A. Rey |author5=Karen Whalen | title = Pharmacology | url = https://books.google.com/books?id=Y558dgp_PjoC&pg=PA322 | date = 15 December 2011 | publisher = Lippincott Williams & Wilkins | isbn = 978-1-4511-1314-3 | page = 322}}</ref><ref name="Bhattacharya2003">{{cite book | author = Bhattacharya | title = Pharmacology, 2/e | url = https://books.google.com/books?id=X3cCZQCrrjcC&pg=PA378 | date = 1 January 2003 | publisher = Elsevier India | isbn = 978-81-8147-009-6 | page = 378}}</ref> [[Progesterone]] is the major and most important progestogen in the body. The progestogens are named for their function in maintaining [[pregnancy]] (i.e., ''progestational''), although they are also present at other phases of the [[estrous cycle|estrous]] and [[menstrual cycle]]s.<ref name="ClarkHarvey2011" /><ref name="Bhattacharya2003" />

The progestogens are one of three types of [[sex hormone]]s, the others being [[estrogen]]s like [[estradiol]] and [[androgen]]s/[[anabolic steroid]]s like [[testosterone]]. In addition, they are one of the five major classes of steroid hormones, the others being the androgens, estrogens, [[glucocorticoid]]s, and [[mineralocorticoid]]s, as well as the [[neurosteroid]]s. All endogenous progestogens are characterized by their basic 21-carbon skeleton, called a [[pregnane]] skeleton (C21). In similar manner, the estrogens possess an [[estrane]] skeleton (C18), and androgens, an [[androstane]] skeleton (C19).

The terms ''progesterone'', ''progestogen'', and ''progestin'' are mistakenly used interchangeably both in the scientific literature and in clinical settings.<ref name="KingBrucker2010" /><ref name="Parker-Pope2008">{{cite book|url=https://books.google.com/books?id=jHn_XSLyvXEC&pg=PA228|title=The Hormone Decision|date=25 March 2008|publisher=Simon and Schuster|isbn=978-1-4165-6201-6|page=228|author=Tara Parker-Pope}}</ref><ref name=":0">{{Cite book|title=Sexual chemistry: understanding your hormones, the Pill and HRT|last=Grant|first=Ellen|publisher=Cedar|year=1994|isbn=978-0749313630|location=Great Britain|pages=39}}</ref> ''[[Progestin]]s'' are ''[[synthetic compound|synthetic]] progestogens'' and are used in medicine.<ref name="ClarkHarvey2011" /> Major examples of progestins include the [[17α-hydroxyprogesterone]] derivative [[medroxyprogesterone acetate]] and the [[19-nortestosterone]] derivative [[norethisterone]]. The progestins are [[structural analog]]ues of progesterone and have progestogenic activity similarly, but differ from progesterone in their pharmacological properties in various ways.<ref name=":0" /> 

In addition to their roles as natural hormones, progestogens are used as [[medication]]s, for instance in [[menopausal hormone therapy]] and [[Transgender hormone therapy (male-to-female)|transgender hormone therapy]] for [[Trans woman|transgender women]]; for information on progestogens as medications, see the [[progesterone (medication)]] and [[progestogen (medication)]] articles.

==Types and examples==
The most important progestogen in the body is [[progesterone]] (P4).<ref name="Okpako1991">{{cite book|author=D. T. Okpako|title=Principles of Pharmacology: A Tropical Approach|url=https://books.google.com/books?id=5GcbwxQTHvMC&pg=PA536|date=22 February 1991|publisher=Cambridge University Press|isbn=978-0-521-34095-3|pages=536–}}</ref><ref name="LaycockMeeran2012">{{cite book|author1=John Laycock|author2=Karim Meeran|title=Integrated Endocrinology|url=https://books.google.com/books?id=v5hk3Ptf6QkC&pg=PT235|date=1 October 2012|publisher=John Wiley & Sons|isbn=978-1-118-45057-4|pages=235–}}</ref> Other [[endogenous]] progestogens, with varying degrees of progestogenic activity, include [[16α-hydroxyprogesterone]] (16α-OHP),<ref name="pmid21095220">{{cite journal | vauthors = Storbeck KH, Swart P, Africander D, Conradie R, Louw R, Swart AC | title = 16α-hydroxyprogesterone: origin, biosynthesis and receptor interaction | journal = Mol. Cell. Endocrinol. | volume = 336 | issue = 1–2 | pages = 92–101 | year = 2011 | pmid = 21095220 | doi = 10.1016/j.mce.2010.11.016 | s2cid = 5503049 }}</ref> [[17α-hydroxyprogesterone]] (17α-OHP) (very weak),<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 = Am. J. Obstet. Gynecol. | volume = 197 | issue = 6 | pages = 599.e1–7 | year = 2007 | pmid = 18060946 | pmc = 2278032 | doi = 10.1016/j.ajog.2007.05.024 }}</ref> [[20α-dihydroprogesterone]] (20α-DHP),<ref name="Legato2009">{{cite book|author=Marianne J. Legato|title=Principles of Gender-Specific Medicine|url=https://books.google.com/books?id=whb9hsUgZtwC&pg=PA617|date=29 October 2009|publisher=Academic Press|isbn=978-0-08-092150-1|pages=617–}}</ref><ref name="Katzung2017">{{cite book|author=Bertram G. Katzung|title=Basic and Clinical Pharmacology 14th Edition|url=https://books.google.com/books?id=-W5ADwAAQBAJ|date=30 November 2017|publisher=McGraw-Hill Education|isbn=978-1-259-64116-9|page=728|quote=In addition to progesterone, 20α- and 20β-hydroxyprogesterone (20α- and 20β-hydroxy-4-pregnene-3-one) also are found. These compounds have about one-fifth the progestational activity of progesterone in humans and other species.}}</ref> [[20β-dihydroprogesterone]] (20β-DHP),<ref name="Katzung2017" /> [[5α-dihydroprogesterone]] (5α-DHP),<ref name="pmid8398145">{{cite journal | vauthors = Rupprecht R, Reul JM, Trapp T, van Steensel B, Wetzel C, Damm K, Zieglgänsberger W, Holsboer F | title = Progesterone receptor-mediated effects of neuroactive steroids | journal = Neuron | volume = 11 | issue = 3 | pages = 523–30 | year = 1993 | pmid = 8398145 | doi = 10.1016/0896-6273(93)90156-l| s2cid = 11205767 }}</ref> [[5β-dihydroprogesterone]] (5β-DHP) (very weak),<ref name="Lima-HernándezBeyer2012">{{cite journal|last1=Lima-Hernández|first1=Francisco J.|last2=Beyer|first2=Carlos|last3=Gómora-Arrati|first3=Porfirio|last4=García-Juárez|first4=Marcos|last5=Encarnación-Sánchez|first5=José L.|last6=Etgen|first6=Anne M.|last7=González-Flores|first7=Oscar|title=Src kinase signaling mediates estrous behavior induced by 5β-reduced progestins, GnRH, prostaglandin E2 and vaginocervical stimulation in estrogen-primed rats|journal=Hormones and Behavior|volume=62|issue=5|year=2012|pages=579–584|issn=0018-506X|doi=10.1016/j.yhbeh.2012.09.004|pmid=23010621|s2cid=40245594}}</ref><ref name="pmid405534">{{cite journal | vauthors = Illingworth DV, Elsner C, De Groot K, Flickinger GL, Mikhail G | title = A specific progesterone receptor of myometrial cytosol from the rhesus monkey | journal = J. Steroid Biochem. | volume = 8 | issue = 2 | pages = 157–60 | date = February 1977 | pmid = 405534 | doi = 10.1016/0022-4731(77)90040-1}}</ref> [[3β-dihydroprogesterone]] (3β-DHP),<ref name="pmid919010">{{cite journal | vauthors = Junkermann H, Runnebaum B, Lisboa BP | title = New progesterone metabolites in human myometrium | journal = Steroids | volume = 30 | issue = 1 | pages = 1–14 | date = July 1977 | pmid = 919010 | doi = 10.1016/0039-128X(77)90131-3 | s2cid = 28420255 | quote = In the Clauberg bioassay the 3β-hydroxy-4-pregnen-20-one shows about the same potency as progesterone (34). In regard to the biological activity of the 3α epimer no data are available.}}</ref><ref name="pmid13480263">{{cite journal | vauthors = Pincus G, Miyake T, Merrill AP, Longo P | title = The bioassay of progesterone | journal = Endocrinology | volume = 61 | issue = 5 | pages = 528–33 | date = November 1957 | pmid = 13480263 | doi = 10.1210/endo-61-5-528 | doi-access = free }}</ref> [[11-deoxycorticosterone]] (DOC),<ref name="Springer2013">{{cite book|title=The Adrenocortical Hormones: Their Origin · Chemistry, Physiology, and Pharmacology|url=https://books.google.com/books?id=BLXoCAAAQBAJ&pg=PA610|date=27 November 2013|publisher=Springer Science & Business Media|isbn=978-3-642-88385-9|pages=610–}}</ref> and [[5α-dihydrodeoxycorticosterone]] (5α-DHDOC).<ref name="pmid16393154">{{cite journal | vauthors = Edwards HE, Vimal S, Burnham WM | title = The acute anticonvulsant effects of deoxycorticosterone in developing rats: role of metabolites and mineralocorticoid-receptor responses | journal = Epilepsia | volume = 46 | issue = 12 | pages = 1888–97 | year = 2005 | pmid = 16393154 | doi = 10.1111/j.1528-1167.2005.00295.x | s2cid = 26030656 | doi-access = free }}</ref> They are all [[metabolite]]s of progesterone, lying downstream of progesterone in terms of biosynthesis.

==Biological function==
The major [[tissue (biology)|tissue]]s affected by progestogens include the [[uterus]], [[vagina]], [[cervix]], [[breast]]s, [[testes]], and [[brain]]. The main biological role of progestogens in the body is in the [[female reproductive system]], and the [[male reproductive system]],<ref>{{cite journal |last1=Oettel |first1=M |last2=Mukhopadhyay |first2=AK |name-list-style=amp |date=2004 |title=Progesterone: the forgotten hormone in men? |journal=Aging Male|volume=7 |issue=3 |pages=236–57 |pmid=15669543 |doi=10.1080/13685530400004199 |s2cid=115377 |doi-access=free }}</ref> with involvement in regulation of the [[menstrual cycle]], maintenance of [[pregnancy]], and preparation of the [[mammary gland]]s for [[lactation]] and [[breastfeeding]] following [[parturition]] in women; in men progesterone affects [[spermiogenesis]], [[sperm capacitation]], and [[testosterone]] synthesis. Progestogens also have effects in other parts of the body. Unlike [[estrogen]]s, progestogens have little or no role in [[feminization (biology)|feminization]].<ref>{{Cite web|title=Progesterone|url=https://www.hormone.org/your-health-and-hormones/glands-and-hormones-a-to-z/hormones/progesterone|access-date=2021-12-11|website=www.hormone.org}}</ref>

==Biochemistry==

===Biosynthesis===
{{Main|Progesterone#Biosynthesis}}
[[File:Steroidogenesis.svg|thumb|450px|class=skin-invert-image|[[Steroidogenesis]], with progestogens and their precursors inside the yellow box.<ref name="HäggströmRichfield2014">{{cite journal|last2=Richfield|first2=David|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|last1=Häggström|first1=Mikael|doi-access=free}}</ref>]]

Progesterone is produced from [[cholesterol]] with [[pregnenolone]] as a [[metabolic intermediate]]. In the first step in the [[steroidogenic pathway]], cholesterol is converted into pregnenolone, which serves as the [[precursor (chemistry)|precursor]] to the progestogens progesterone and 17α-hydroxyprogesterone. These progestogens, along with another steroid, [[17α-hydroxypregnenolone]], are the precursors of all other endogenous steroids, including the androgens, estrogens, glucocorticoids, mineralocorticoids, and neurosteroids. Thus, many tissues producing steroids, including the [[adrenal gland]]s, [[testicle|testes]], and [[ovary|ovaries]], produce progestogens.

In some tissues, the [[enzyme]]s required for the final product are not all located in a single cell. For example, in [[ovarian follicle]]s, cholesterol is converted to [[androstenedione]], an androgen, in the [[theca cell]]s, which is then further converted into estrogen in the [[granulosa cell]]s. Fetal adrenal glands also produce pregnenolone in some species, which is converted into progesterone and estrogens by the placenta (see below). In the human, the fetal adrenals produce [[dehydroepiandrosterone]] (DHEA) via the pregnenolone pathway.

{{Production rates, secretion rates, clearance rates, and blood levels of major sex hormones}}

====Ovarian production====
Progesterone is the major progestogen produced by the [[corpus luteum]] of the [[ovary]] in all mammalian species. [[Luteal cell]]s possess the necessary enzymes to convert cholesterol to pregnenolone, which is subsequently converted into progesterone. Progesterone is highest in the diestrus phase of the estrous cycle.

====Placental production====
The role of the placenta in progestogen production varies by species. In the sheep, horse, and human, the [[placenta]] takes over the majority of progestogen production, whereas in other species the corpus luteum remains the primary source of progestogens. In the sheep and human, progesterone is the major placental progestogen.

The equine placenta produces a variety of progestogens, primarily [[5α-dihydroprogesterone]] and [[5α,20α-tetrahydroprogesterone]], beginning on day 60. A complete luteo-placental shift occurs by day 120–150.

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

The endogenous progestogens are [[natural product|naturally occurring]] [[pregnane]] [[steroid]]s with [[ketone]] and/or [[hydroxyl group]]s at the C3 and C20 positions.

==Medical use==
{{Main|Progestogen (medication)|Progesterone (medication)|Pharmacodynamics of progesterone|Pharmacokinetics of progesterone}}

[[Progestogen (medication)|Progestogen]]s, including both [[progesterone (medication)|progesterone]] and [[progestin]]s, are used medically in [[hormonal contraception|hormonal birth control]], [[hormone replacement therapy|hormone therapy]], to treat [[gynecological disorder]]s, to suppress [[sex hormone]] levels for various purposes, and for other indications.

==References==
{{Reflist}}

==Further reading==
* {{cite journal |author=[[Wulf H. Utian|Utian WH]], Shoupe D, Bachmann G, Pinkerton JV, Pickar JH |title=Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate |journal=Fertil. Steril. |volume=75 |issue=6 |pages=1065–79 |date=June 2001 |pmid=11384629 |doi=10.1016/S0015-0282(01)01791-5|doi-access=free }} (the Women's Health, Osteoporosis, Progestin, Estrogen study)
* {{cite journal  |vauthors=Hulley S, Grady D, Bush T, etal |title=Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group |journal=JAMA |volume=280 |issue=7 |pages=605–13 |date=August 1998 |pmid=9718051 |doi=10.1001/jama.280.7.605 |doi-access=free }}

==External links==
* {{MeSH name|Progestins}}
* [http://www.ergogenics.org/anabolenboek/index5en.html The Nomenclature of Steroids]
* [http://www.millionwomenstudy.org/index2.html The Million Women Study]


{{Progesterone}}
{{Hormones}}
{{Endogenous steroids}}
{{Progestogens and antiprogestogens}}
{{Progesterone receptor modulators}}

[[Category:Hormones of the hypothalamus-pituitary-gonad axis]]
[[Category:Hormones of the hypothalamic-pituitary-prolactin axis]]
[[Category:Hormones of the pregnant female]]
[[Category:Progestogens| ]]
[[Category:Prolactin releasers]]
[[Category:Sex hormones]]