U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS
This repository is under review for potential modification in compliance with Administration directives.

Details

Stereochemistry ABSOLUTE
Molecular Formula C21H30O2
Molecular Weight 314.4617
Optical Activity UNSPECIFIED
Defined Stereocenters 6 / 6
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of Progesterone

SMILES

CC(=O)[C@H]1CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(C)[C@H]3CC[C@]12C

InChI

InChIKey=RJKFOVLPORLFTN-LEKSSAKUSA-N
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

HIDE SMILES / InChI

Molecular Formula C21H30O2
Molecular Weight 314.4617
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 6 / 6
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/8282004 http://www.rxlist.com/endometrin-drug/clinical-pharmacology.htm

Progesterone is indicated in amenorrhea and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as submucous fibroids of uterine cancer. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Progesterone is a naturally occurring steroid that is secreted by the ovary, placenta, and adrenal gland. In the presence of adequate estrogen, progesterone transforms a proliferative endometrium into a secretory endometrium. Progesterone is necessary to increase endometrial receptivity for implantation of an embryo. Once an embryo is implanted, progesterone acts to maintain a pregnancy. Progesterone shares the pharmacological actions of the progestins. Progesterone binds to the progesterone and estrogen receptors. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Once bound to the receptor, progesterone will slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing hormone) surge. In women who have adequate endogenous estrogen, progesterone transforms a proliferative endometrium into a secretory one. Progesterone is metabolized primarily by the liver largely to pregnanediols and pregnanolones. Pregnanediols and pregnanolones are conjugated in the liver to glucuronide and sulfate metabolites. Progesterone metabolites that are excreted in the bile may be deconjugated and may be further metabolized in the gut via reduction, dehydroxylation, and epimerization. Common progesterone side effects may include: drowsiness, dizziness; breast pain; mood changes; headache; constipation, diarrhea, heartburn; bloating, swelling in your hands or feet; joint pain; hot flashes; or vaginal discharge.

CNS Activity

Curator's Comment: Progesterone readily cross the blood brain barrier (BBB) reducing oedema to barely measurable levels.

Originator

Sources: DOI:10.1159/000301641
Curator's Comment: Using a test based upon Fraenkel and Ancel/ Bouin, Corner and W.M. Allen isolated the hormone progesterone (1929) and first maintained pregnancy with corpus luteum extracts after early ablation of the ovaries rabbit, 1930).

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
PROGESTERONE

Approved Use

Is indicated in amenorrhea and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as submucous fibroids of uterine cancer.

Launch Date

2007
Primary
PROGESTERONE

Approved Use

Is indicated in amenorrhea and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as submucous fibroids of uterine cancer.

Launch Date

2007
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
60.6 ng/mL
300 mg 1 times / day multiple, oral
dose: 300 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PROGESTERONE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: FEMALE
food status: UNKNOWN
14.87 ng/mL
90 mg single, vaginal
dose: 90 mg
route of administration: Vaginal
experiment type: SINGLE
co-administered:
PROGESTERONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
15.97 ng/mL
90 mg 1 times / day steady-state, vaginal
dose: 90 mg
route of administration: Vaginal
experiment type: STEADY-STATE
co-administered:
PROGESTERONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
175.7 ng × h/mL
300 mg 1 times / day multiple, oral
dose: 300 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PROGESTERONE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: FEMALE
food status: UNKNOWN
296.78 ng × h/mL
90 mg single, vaginal
dose: 90 mg
route of administration: Vaginal
experiment type: SINGLE
co-administered:
PROGESTERONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
391.98 ng × h/mL
90 mg 1 times / day steady-state, vaginal
dose: 90 mg
route of administration: Vaginal
experiment type: STEADY-STATE
co-administered:
PROGESTERONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
34.8 h
90 mg single, vaginal
dose: 90 mg
route of administration: Vaginal
experiment type: SINGLE
co-administered:
PROGESTERONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
45 h
90 mg 1 times / day steady-state, vaginal
dose: 90 mg
route of administration: Vaginal
experiment type: STEADY-STATE
co-administered:
PROGESTERONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
OverviewDrug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
yes
yes
yes
yes
likely (co-administration study)
Comment: Ketoconazole is a known inhibitor of cytochrome P450 3A4, hence these data suggest that ketoconazole or other known inhibitors of this enzyme may increase the bioavailability of progesterone
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Thrombospondin-1 and -2 in node-negative breast cancer: correlation with angiogenic factors, p53, cathepsin D, hormone receptors and prognosis.
2001
The rate-determining step in P450 C21-catalyzing reactions in a membrane-reconstituted system.
2001 Apr 6
Dexamethasone up-regulates type II IL-1 receptor in mouse primary activated astrocytes.
2001 Feb
Human types 1 and 3 3 alpha-hydroxysteroid dehydrogenases: differential lability and tissue distribution.
2001 Feb
Endothelins enhance prostaglandin (PGE(2) and PGF(2alpha)) biosynthesis and release by human luteal cells: evidence of a new paracrine/autocrine regulation of luteal function.
2001 Feb
Action of chicken II GnRH on the human placenta.
2001 Feb
Adenosine triphosphate-evoked cytosolic calcium oscillations in human granulosa-luteal cells: role of protein kinase C.
2001 Feb
Short-term administration of antivascular endothelial growth factor antibody in the late follicular phase delays follicular development in the rhesus monkey.
2001 Feb
Follow-up examination at the age of 15 months of extremely preterm infants after postnatal estradiol and progesterone replacement.
2001 Feb
Fertility and body composition after laparoscopic bilateral adrenalectomy in a 30-year-old female with congenital adrenal hyperplasia.
2001 Feb
Progesterone, but not medroxyprogesterone, inhibits vascular cell adhesion molecule-1 expression in human vascular endothelial cells.
2001 Feb
Enhanced verbal memory in nondemented elderly women receiving hormone-replacement therapy.
2001 Feb
Menstrual history and risk of hip fractures in postmenopausal women. The Iowa Women's Health Study.
2001 Feb 1
Prognostic and predictive significance of ErbB-2 breast tumor levels measured by enzyme immunoassay.
2001 Feb 1
Estrogen prevents oxidative stress-induced endothelial cell apoptosis in rats.
2001 Feb 6
Re: Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer.
2001 Feb 7
Lp(a) lipoprotein--an independent risk factor for coronary heart disease after menopause.
2001 Jan
Reliability of ovulation tests in infertile women.
2001 Jan
Serum allopregnanolone in women with postpartum "blues".
2001 Jan
Sex steroids and bone.
2001 Jan
Net amino acid flux across the fetal liver and placenta during spontaneous ovine parturition.
2001 Jan
Concordance in judgments among c-erbB-2 (HER2/neu) overexpression detected by two immunohistochemical tests and gene amplification detected by Southern blot hybridization in breast carcinoma.
2001 Jan
The APC is dispensable for first meiotic anaphase in Xenopus oocytes.
2001 Jan
The octadecaneuropeptide ODN stimulates neurosteroid biosynthesis through activation of central-type benzodiazepine receptors.
2001 Jan
Targeted disruption of luteinizing hormone/human chorionic gonadotropin receptor gene.
2001 Jan
Mutations at the boundary of the hinge and ligand binding domain of the androgen receptor confer increased transactivation function.
2001 Jan
Separable features of the ligand-binding domain determine the differential subcellular localization and ligand-binding specificity of glucocorticoid receptor and progesterone receptor.
2001 Jan
Estrogen receptor beta regulates sexually dimorphic neural responses to estradiol.
2001 Jan
Establishment and characterization of a steroidogenic human granulosa-like tumor cell line, KGN, that expresses functional follicle-stimulating hormone receptor.
2001 Jan
Glucocorticoids regulate plasma membrane potential during rat thymocyte apoptosis in vivo and in vitro.
2001 Jan
Assessment of mechanisms of thyroid hormone action in mouse Leydig cells: regulation of the steroidogenic acute regulatory protein, steroidogenesis, and luteinizing hormone receptor function.
2001 Jan
Biphasic action of prolactin in the regulation of murine Leydig tumor cell functions.
2001 Jan
Differential regulation of two forms of gonadotropin-releasing hormone messenger ribonucleic acid in human granulosa-luteal cells.
2001 Jan
Molecular cytogenetic comparison of apocrine hyperplasia and apocrine carcinoma of the breast.
2001 Jan
Prostaglandin receptors and role of G protein-activated pathways on corpora lutea of pseudopregnant rabbit in vitro.
2001 Jan
In vitro regulation of local secretion and contraction of the bovine oviduct: stimulation by luteinizing hormone, endothelin-1 and prostaglandins, and inhibition by oxytocin.
2001 Jan
Granulosa-luteal cell function in vitro and ovarian stimulation protocols.
2001 Jan
Charcoal treatment and risk of escape ovulation in oral contraceptive users.
2001 Jan
Reproductive hormones and blood pressure during pregnancy.
2001 Jan
Hormones and the brain: more studies.
2001 Jan
Low peripheral blood levels of the immunosuppressive cytokine interleukin 10 (IL-10) at the start of gonadotrophin stimulation indicates increased risk for development of ovarian hyperstimulation syndrome (OHSS).
2001 Jan
Effect of endogenous estrogen on blood flow through carotid arteries.
2001 Jan
The influence of menstrual cycle phase on skeletal muscle contractile characteristics in humans.
2001 Jan 1
17beta-oestradiol acutely regulates Cl- secretion in rat distal colonic epithelium.
2001 Jan 1
Effect of medroxyprogesterone acetate plus estradiol on endothelium-dependent vasodilation in postmenopausal women.
2001 Jan 15
Functional involvement of Xenopus LIM kinases in progression of oocyte maturation.
2001 Jan 15
Evidence that epithelial and mesenchymal estrogen receptor-alpha mediates effects of estrogen on prostatic epithelium.
2001 Jan 15
Evaluation of in vitro methods for detecting the effects of various chemicals on the human progesterone receptor, with a focus on pyrethroid insecticides.
2001 Jan 3
Estrogen, selective estrogen receptor modulation, and coronary heart disease: something or nothing.
2001 Jan 3
Effects of low-frequency magnetic fields on implantation in rats.
2001 Jan-Feb
Patents

Sample Use Guides

5 to 10 mg during 8 consecutive days
Route of Administration: Intramuscular
In Vitro Use Guide
Curator's Comment: As a resule 34% reduction in cell proliferation was observed in the MB468 cells with treatment of P4, as compared with the cells with treatment of vehicle alone. As expected, P4 had no effects on cell proliferation of the parental MB231. However, the treatment of the mPRα stably-expressing MB231 cells with P4 induced a significant reduction of cell proliferation (28.1%). These data suggest that mPRα is also involved in regulating cell proliferation of BPBC cells.
To test whether the female sex hormone controls cell proliferation of MB468 (basal phenotype breast cancers) cells, cell were incubated the with progesterone (P4) (30 ng/ml) for 24 hours.
Substance Class Chemical
Created
by admin
on Mon Mar 31 17:52:48 GMT 2025
Edited
by admin
on Mon Mar 31 17:52:48 GMT 2025
Record UNII
4G7DS2Q64Y
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CRINONE
Preferred Name English
Progesterone
EP   GREEN BOOK   HSDB   INCI   INN   MART.   MI   ORANGE BOOK   USP   USP-RS   VANDF   WHO-DD   WHO-IP  
INCI   INN  
Official Name English
PREGN-4-ENE-3,20-DIONE
Systematic Name English
PROGESTERONE [EP MONOGRAPH]
Common Name English
PROGESTERONE [JAN]
Common Name English
U 3672
Code English
PROGESTERONE [MI]
Common Name English
PROGESTERONE [HSDB]
Common Name English
PROGESTERONE [GREEN BOOK]
Common Name English
PROGESTERONE [VANDF]
Common Name English
Progesterone [WHO-DD]
Common Name English
PROGESTERONE [WHO-IP]
Common Name English
PROGESTERONE [ORANGE BOOK]
Common Name English
NSC-9704
Code English
BIJUVA COMPONENT PROGESTERONE
Common Name English
PROGESTERONUM [WHO-IP LATIN]
Common Name English
UTROGESTAN
Brand Name English
ENDOMETRIN
Brand Name English
PROGESTERONE, MICRONIZED
Common Name English
MILPROSA
Brand Name English
PROGESTERONE [USP-RS]
Common Name English
PROMETRIUM
Brand Name English
PROGESTERONE [USP MONOGRAPH]
Common Name English
NSC-64377
Code English
PROGESTERONE [MART.]
Common Name English
PROGESTASERT
Brand Name English
progesterone [INN]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 664818
Created by admin on Mon Mar 31 17:52:48 GMT 2025 , Edited by admin on Mon Mar 31 17:52:48 GMT 2025
WHO-VATC QG03FA04
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NDF-RT N0000005934
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LIVERTOX 803
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LOINC 83109-9
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FDA ORPHAN DRUG 82694
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CFR 21 CFR 556.540
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LOINC 83110-7
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DSLD 4218 (Number of products:3)
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LOINC 12820-7
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LOINC 44729-2
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CFR 21 CFR 522.1940
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LOINC 24109-1
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CFR 21 CFR 862.1430
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WHO-ATC G03FA04
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LOINC 14890-8
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EU-Orphan Drug EU/3/13/1101
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LOINC 17483-9
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WHO-VATC QG03DA04
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CFR 21 CFR 310.530
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NDF-RT N0000005934
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LOINC 44730-0
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LOINC 35223-7
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CFR 21 CFR 862.1620
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NCI_THESAURUS C2296
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NDF-RT N0000175601
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NDF-RT N0000005934
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LOINC 2838-1
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LOINC 2839-9
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WHO-ATC G03DA04
Created by admin on Mon Mar 31 17:52:48 GMT 2025 , Edited by admin on Mon Mar 31 17:52:48 GMT 2025
FDA ORPHAN DRUG 284809
Created by admin on Mon Mar 31 17:52:48 GMT 2025 , Edited by admin on Mon Mar 31 17:52:48 GMT 2025
Code System Code Type Description
IUPHAR
2377
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PRIMARY
CHEBI
17026
Created by admin on Mon Mar 31 17:52:48 GMT 2025 , Edited by admin on Mon Mar 31 17:52:48 GMT 2025
PRIMARY
RS_ITEM_NUM
1568007
Created by admin on Mon Mar 31 17:52:48 GMT 2025 , Edited by admin on Mon Mar 31 17:52:48 GMT 2025
PRIMARY
NSC
64377
Created by admin on Mon Mar 31 17:52:48 GMT 2025 , Edited by admin on Mon Mar 31 17:52:48 GMT 2025
PRIMARY
WIKIPEDIA
PROGESTERONE
Created by admin on Mon Mar 31 17:52:48 GMT 2025 , Edited by admin on Mon Mar 31 17:52:48 GMT 2025
PRIMARY
CAS
57-83-0
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PRIMARY
ChEMBL
CHEMBL103
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PRIMARY
EPA CompTox
DTXSID3022370
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PRIMARY
FDA UNII
4G7DS2Q64Y
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PRIMARY
PUBCHEM
5994
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PRIMARY
DRUG BANK
DB00396
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PRIMARY
MESH
D011374
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PRIMARY
SMS_ID
100000090354
Created by admin on Mon Mar 31 17:52:48 GMT 2025 , Edited by admin on Mon Mar 31 17:52:48 GMT 2025
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
PROGESTERONE
Created by admin on Mon Mar 31 17:52:48 GMT 2025 , Edited by admin on Mon Mar 31 17:52:48 GMT 2025
PRIMARY Description: Colourless crystals or a white to slightly yellowish white, crystalline powder; odourless. Solubility: Practically insoluble in water; soluble in 8 parts of ethanol (~750 g/l) TS. Category: Progestational steroid. Storage: Progesterone should be kept in a well-closed container, protected from light. Additional information: Progesterone may exist in 2 polymorphic forms, one of which melts at about 130?C, the other at about 121?C. Definition: Progesterone contains not less than 97.0% and not more than 102.0% of C21H30O2, calculated with reference to the dried substance.
MERCK INDEX
m9159
Created by admin on Mon Mar 31 17:52:48 GMT 2025 , Edited by admin on Mon Mar 31 17:52:48 GMT 2025
PRIMARY Merck Index
EVMPD
SUB10076MIG
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PRIMARY
DRUG CENTRAL
2279
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PRIMARY
ECHA (EC/EINECS)
200-350-6
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PRIMARY
LACTMED
Progesterone
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PRIMARY
NCI_THESAURUS
C777
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PRIMARY
DAILYMED
4G7DS2Q64Y
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PRIMARY
INN
417
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PRIMARY
HSDB
3389
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PRIMARY
NSC
9704
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PRIMARY
RXCUI
8727
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PRIMARY
MESH
C400424
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PRIMARY
RXCUI
259409
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ALTERNATIVE
WIKIPEDIA
Progesterone (medication)
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PRIMARY
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