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=====Condition1=====
* Dosing Information
:* Dosage
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There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
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<!--FDA-Labeled Indications and Dosage (Pediatric)-->
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=====Condition1=====
* Dosing Information
:* Dosage
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There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.
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=====Condition1=====
* Developed by:
* Class of Recommendation:
* Strength of Evidence:
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
<!--Non–Guideline-Supported Use (Pediatric)-->
|offLabelPedNoGuideSupport=
=====Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
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* Condition1
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|warnings=
* Description
====Precautions====
* Description
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|clinicalTrials=
There is limited information regarding <i>Clinical Trial Experience</i> of {{PAGENAME}} in the drug label.
=====Body as a Whole=====
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|postmarketing=
There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
=====Body as a Whole=====
=====Cardiovascular=====
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=====Endocrine=====
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=====Metabolic and Nutritional=====
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=====Urogenital=====
=====Miscellaneous=====
<!--Drug Interactions-->
|drugInteractions=
* Drug
:* Description
<!--Use in Specific Populations-->
|useInPregnancyFDA=
* '''Pregnancy Category'''
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* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
|useInLaborDelivery=
There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
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There is no FDA guidance on the use of {{PAGENAME}} with respect to nursing mothers.
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There is no FDA guidance on the use of {{PAGENAME}} with respect to pediatric patients.
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There is no FDA guidance on the use of {{PAGENAME}} with respect to geriatric patients.
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There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
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There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
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There is no FDA guidance on the use of {{PAGENAME}} in patients with renal impairment.
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There is no FDA guidance on the use of {{PAGENAME}} in patients with hepatic impairment.
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There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
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There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.
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* Oral
* Intravenous
|monitoring=
There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
* Description
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|IVCompat=
There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
<!--Overdosage-->
==Overview==
|overdose=
'''Progesterone''' is a C-21 [[steroid]] hormone involved in the [[female]] [[menstrual cycle]], [[pregnancy]] (supports ''[[gestation]]'') and [[embryogenesis]] of humans and other species. Progesterone belongs to a class of hormones called [[progestogens]], and is the major naturally occurring human progestogen.
Progesterone should not be confused with [[progestins]], which are synthetically produced [[progestogens]].
===Acute Overdose===
==Chemistry==
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 | issn = }}</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 | pmid = | doi = | issn = }}</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 | pmid = | doi = | issn = }}</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 | pmid = | doi = | issn = }}</ref>
[[Willard Myron Allen]] who 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 PROGEstational STERoidal ketONE.<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> An avid mathematician, Allen recognized that the molecular weight of progesterone is 100 x π = 314 dalt.
====Signs and Symptoms====
Like other [[steroid]]s, progesterone consists of four interconnected [[cyclic hydrocarbon]]s. Progesterone contains [[ketone]] and oxygenated functional groups, as well as two [[methyl]] branches. Like all steroid hormones, it is [[hydrophobic]].
* Description
===Synthesis===
====Management====
[[Image:Reaction-Pregnenolone-Progesterone.png|left|thumb|350px|Conversion of Pregnenolone to Progesterone]]
[[Image:DHEA1.svg|thumb|left|350px|Progesterone is important for [[aldosterone]] ([[mineralocorticoid]]) synthesis, as [[17-hydroxyprogesterone]] is for [[cortisol]] ([[glucocorticoid]]), and [[androstenedione]] for [[sex steroids]].]]
{{clr}}
Progesterone, like all other [[steroid]] [[hormone]]s, is synthesized from [[pregnenolone]], a derivative of [[cholesterol]]. This conversion takes place in two steps. The 3-[[hydroxyl]] group is converted to a [[ketone|keto]] group and the [[double bond]] is moved to C-4, from C-5.
* Description
Progesterone is the precursor of the mineralocorticoid [[aldosterone]], and after conversion to [[17-hydroxyprogesterone]] (another natural progestogen) of [[cortisol]] and [[androstenedione]]. Androstenedione can be converted to [[testosterone]], [[estrone]] and [[estradiol]].
===Chronic Overdose===
==Sources==
There is limited information regarding <i>Chronic Overdose</i> of {{PAGENAME}} in the drug label.
Progesterone is produced in the adrenal glands, the gonads (specifically after ovulation in the [[corpus luteum]]), the brain, and, during pregnancy, in the [[placenta]].
In humans, increasing amounts of progesterone are produced during pregnancy:
<!--Pharmacology-->
* Initially, the source is the corpus luteum that has been "rescued" by the presence of human chorionic gonadotropins ([[hCG]]) from the conceptus.
<!--Drug box 2-->
* However, after the 8th week production of progesterone shifts over 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 is used as substrate for fetal [[corticosteroids]]. At term the placenta produces about 250 mg progesterone per day.
|drugBox=
==Levels==
[[Image:Estradiol Cycle.jpg|right|thumb|300 px|Progesterone levels (black line) during the menstrual cycle]]
In women, progesterone levels are relatively low during the preovulatory phase of the [[menstrual cycle]], rise after [[ovulation]], and are elevated during the luteal phase. In women progesterone levels tend to be < 2 ng/ml prior to ovulation, and > 5 ng/ml after ovulation. If [[pregnancy]] occurs, progesterone levels are maintained at luteal levels initially. With the onset of the luteal-placental shift in progesterone support of the pregnancy levels start to rise further and may reach 100-200 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.
Progesterone levels are relatively low in children and postmenopausal women.<ref>http://cclnprod.cc.nih.gov/dlm/testguide.nsf/Index/CB26894E1EB28DEF85256BA5005B000E?OpenDocument</ref> Adult males have levels similar to those in women during the follicular phase of the menstrual cycle.
==Effects==
<!--Mechanism of Action-->
Progesterone exerts its action primarily through the intracellular [[progesterone receptor]] though a distinct, membrane bound progesterone receptor which has recently been discovered. It has a number of physiological effects, often regulatory, especially of the effects of [[estrogen]]. Estrogen often induces a multiplication of progesterone receptors.
===Reproductive system===
|mechAction=
Progesterone is sometimes called the "hormone of pregnancy"<ref name="colostate">http://www.vivo.colostate.edu/hbooks/pathphys/reprod/placenta/endocrine.html</ref>, and it has many roles relating to the development of the fetus:
* Progesterone converts the [[uterine lining|endometrium]] to its secretory stage to prepare the uterus for implantation. At the same time progesterone affects the vaginal [[epithelium]] and [[cervix|cervical]] [[mucus]]. If pregnancy does not occur, progesterone levels will decrease, leading, in the human, to [[menstruation]]. Normal menstrual bleeding is progesterone withdrawal bleeding.
*
* During implantation and [[gestation]], progesterone appears to decrease the maternal [[immune system|immune]] response to allow for the acceptance of the pregnancy.
<!--Structure-->
* Progesterone decreases contractility of the uterine [[smooth muscle]]. <ref name="colostate"> </ref>
|structure=
* In addition progesterone inhibits [[lactation]] 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 [[labor (childbirth)|labor]].
: [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
The [[fetus]] [[metabolize]]s placental progesterone in the production of [[adrenal]] mineralo- and glucosteroids.
<!--Pharmacodynamics-->
===Nervous system===
|PD=
Progesterone, like [[pregnenolone]] and [[dehydroepiandrosterone]], belongs to the group of [[neurosteroid]]s that are found in high concentrations in certain areas in the brain and are synthesized there.
[[neuroactive steroid|Neurosteroids]] affect [[synapse|synaptic functioning]], are neuroprotective, and affect [[myelin]]ization.<ref>Schumacher M, Guennoun R, Robert F, et al. Local synthesis and dual actions of progesterone in the nervous system: neuroprotection and myelination. Growth Horm IGF Res. 2004 Jun;14 Suppl A:S18-33. PMID 15135772</ref> They are investigated for their potential to improve [[memory]] and [[cognition|cognitive ability]].
There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.
Progesterone as a neuroprotectant affects regulation of [[apoptosis|apoptotic]] genes.
<!--Pharmacokinetics-->
Its effect as a neurosteroid works predominantly through the GSK-3 beta pathway, as an inhibitor. (Other GSK-3 beta inhibitors include [[bipolar disorder|bipolar]] mood stabilizers, [[lithium]] and [[valproic acid]].)
|PK=
===Other systems===
There is limited information regarding <i>Pharmacokinetics</i> of {{PAGENAME}} in the drug label.
* It raises [[epidermal growth factor-1]] levels, a factor often used to induce proliferation, and used to sustain cultures, of [[stem cell]]s.
<!--Nonclinical Toxicology-->
* It increases core temperature (thermogenic function) during ovulation.<ref name="GeorgiaPhysiology">{{GeorgiaPhysiology|5/5ch9/s5ch9_13}}</ref>
|nonClinToxic=
* It reduces [[spasm]] and relaxes [[smooth muscle]]. [[Bronchi]] are widened and [[mucus]] regulated. ([[Progesterone receptor]]s are widely present in [[Mucous membrane|submucosal tissue]].)
There is limited information regarding <i>Nonclinical Toxicology</i> of {{PAGENAME}} in the drug label.
* It acts as an [[Inflammation|antiinflammatory]] agent and regulates the [[immune response]].
<!--Clinical Studies-->
* It reduces [[gall-bladder]] activity.<ref>{{cite journal |author=Hould F, Fried G, Fazekas A, Tremblay S, Mersereau W |title=Progesterone receptors regulate gallbladder motility |journal=J Surg Res |volume=45 |issue=6 |pages=505-12 |year=1988 |pmid=3184927}}</ref>
|clinicalStudies=
* It normalizes [[blood]] clotting and vascular tone, [[zinc]] and [[copper]] levels, [[cell (biology)|cell]] [[oxygen]] levels, and use of fat stores for energy.
There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.
* It assists in [[thyroid]] function, in [[bone]] building by [[osteoblast]]s, in [[bone]], [[teeth]], [[gingiva|gum]]s, [[joint]], [[tendon]], [[ligament]] and [[skin]] resilience and in some cases healing by regulating various types of [[collagen]], and in nerve function and healing by regulating [[myelin]].
<!--How Supplied-->
* It appears to prevent [[endometrial cancer]] (involving the uterine lining) by regulating the effects of estrogen.
|howSupplied=
==Medical applications==
*
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. However, the roles of progesterone may not be fulfilled by the synthetic progestins which in some cases were designed solely to mimic progesterone's [[uterine]] effects.
<!--Patient Counseling Information-->
===[[Bioavailability]]===
|fdaPatientInfo=
Progesterone is poorly absorbed by oral ingestion unless micronised and in oil, or with fatty foods; it does not dissolve in water. Products such as Prometrium, Utrogestan, Minagest and Microgest are therefore capsules containing micronised progesterone in oil - in all three mentioned the oil is peanut oil, which may cause serious [[allergic reactions]] in some people, but compounding [[pharmacies]], which have the facilities and licenses to make their own products, can use alternatives. Vaginal and rectal application is also effective, with products such as CRINONE and PROCHIEVE bioadhesive progesterone vaginal gels (the only progesterone products FDA-approved for use in infertility and during pregnancy) and Cycff, which is progesterone in cocoa butter in the form of [[Pessary|pessaries]]. Progesterone can be given by [[Injection (medicine)|injection]], but because it has a short half-life they need to be daily. Implants, for a longer period, are also available. Marketing of progesterone phamaceutical products, country to country, varies considerably, with many countries having no oral progesterone products marketed, but they can usually be specially imported by pharmacies through international wholesalers.
"Natural progesterone" products derived from yams, do not require a prescription. Wild yams contain a plant steroid called [[diosgenin]], which the human body cannot metabolize into progesterone. Diosgenin can only be chemically processed into progesterone in labs.
There is limited information regarding <i>Patient Counseling Information</i> of {{PAGENAME}} in the drug label.
===Specific uses===
<!--Precautions with Alcohol-->
* Progesterone is used to control anovulatory bleeding. It is also used to prepare uterine lining in [[infertility]] therapy and to support early pregnancy. Patients with [[habitual abortion|recurrent pregnancy loss]] due to inadequate progesterone production may receive progesterone.
* Progesterone is being investigated as potentially beneficial in treating [[multiple sclerosis]], since the characteristic deterioration of nerve [[myelin]] insulation halts during pregnancy, when progesterone levels are raised; deterioration commences again when the levels drop.
|alcohol=
* Progesterone is used in [[hormone therapy]] for [[transsexual woman|transsexual women]], and some [[intersex]] women - especially when synthetic progestins have been ineffective or caused side-effects - since normal [[breast]] tissue cannot develop except in the presence of both progestogen and [[estrogen]]. [[Mammary gland]]ular tissue is otherwise [[fibrosis|fibrotic]], the breast shape conical and the [[areola]] immature. Progesterone can correct those even after years of inadequate hormonal treatment. Research usually cited against such value was conducted using Provera, a synthetic progestin. Progesterone also has a role in skin elasticity and bone strength, in [[Respiration (physiology)|respiration]], in nerve tissue and in [[female sexuality]], and the presence of progesterone receptors in certain muscle and fat tissue may hint at a role in [[Sexual dimorphism|sexually-dimorphic]] proportions of those.
* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
* Progesterone [[receptor antagonist]]s, or [[selective progesterone receptor modulator]]s (SPRM)s, such as [[RU-486]] ([[Mifepristone]]), can be used to prevent conception or induce [[medical abortion]]s.
<!--Brand Names-->
Note that methods of [[hormonal contraception]] do not contain progesterone but a [[progestin]].
|brandNames=
Progesterone may affect male behavior:
* ®<ref>{{Cite web | title = | url = }}</ref>
'Progesterone receptors mediate male aggression toward infants'
PNAS 2003 100: 2951-2956; 10.1073/pnas.0130100100
Lawn chemicals and no-till agricultual practices may disturb both estrogen and progesterone metabolism. [refs required]
<!--Look-Alike Drug Names-->
===Aging===
|lookAlike=
Since most progesterone in males is created during testicular production of [[testosterone]], and most in females by the [[ovaries]], 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 [[progestagen]]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.
* A® — B®<ref name="www.ismp.org">{{Cite web | last = | first = | title = http://www.ismp.org | url = http://www.ismp.org | publisher = | date = }}</ref>
The tendency for progesterone to have a regulatory effect, the presence of progesterone [[receptor (biochemistry)|receptor]]s in many types of body tissue, and the pattern of deterioration (or [[tumor]] 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.
<!--Drug Shortage Status-->
===Brain Damage===
|drugShortage=
}}
Under investigation is the potential for progesterone therapy given within 24 hours of a brain injury to minimize brain damage. Evetually, this could become a standard treatment for the many people suffering traumatic brain injuries annually. This research has been pioneered by Dr. Donald G. Stein at Emory University. Human trials are underway and have shown similar results to the studies he performed years ago where female rats subjected to induced brain injuries recovered with much less permanent damage than males with much lower progesterone levels.
<!--Pill Image-->
==See also==
{{PillImage
*[[Willard Myron Allen]]
|fileName=No image.jpg|This image is provided by the National Library of Medicine.
*[[Bioidentical hormone replacement therapy]]
|drugName=
*[[Prometrium]]
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==References==
<!--Label Display Image-->
{{reflist|2}}
==Additional images==
{{LabelImage
<gallery>
|fileName={{PAGENAME}}11.png|This image is provided by the National Library of Medicine.
Image:Steroidogenesis.gif|[[Steroidogenesis]]
}}
Image:Pregnenolone.png|[[Pregnenolone]]
Image:Doc.gif|[[Deoxycorticosterone]]
</gallery>
{{Hormones}}
{{LabelImage
{{Sex hormones}}
|fileName={{PAGENAME}}11.png|This image is provided by the National Library of Medicine.
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Black Box Warning
Title
See full prescribing information for complete Boxed Warning.
ConditionName:
Content
Overview
Progesterone (oral) is a that is FDA approved for the {{{indicationType}}} of . There is a Black Box Warning for this drug as shown here. Common adverse reactions include .
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Condition1
Dosing Information
Dosage
Condition2
Dosing Information
Dosage
Condition3
Dosing Information
Dosage
Condition4
Dosing Information
Dosage
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
Condition1
Developed by:
Class of Recommendation:
Strength of Evidence:
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Progesterone (oral) in adult patients.
Non–Guideline-Supported Use
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Progesterone (oral) in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding FDA-Labeled Use of Progesterone (oral) in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
Condition1
Developed by:
Class of Recommendation:
Strength of Evidence:
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Progesterone (oral) in pediatric patients.
Non–Guideline-Supported Use
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Progesterone (oral) in pediatric patients.
Contraindications
Condition1
Warnings
Title
See full prescribing information for complete Boxed Warning.
ConditionName:
Content
Description
Precautions
Description
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Clinical Trial Experience of Progesterone (oral) in the drug label.
Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous
Postmarketing Experience
There is limited information regarding Postmarketing Experience of Progesterone (oral) in the drug label.
01.png){kind=link}