General
Preferred name
progesterone
Synonyms
Pregn-4-ene-3,20-dione ()
Progesterone (NSC 9704) ()
NSC 64377, Pregn-4-ene-3,20-dione,NSC 9704 ()
Syngestrone ()
Endometrin ()
Progesterona ()
Prometrium ()
Prochieve ()
Cyclogest ()
Crinone ()
NSC-64377 ()
Utrogestan ()
Gesterol ()
Lutigest ()
U 3672 ()
Progesteronum ()
Progesta-Care ()
Progesterone, micronized ()
NSC-9704 ()
Progestasert ()
Regumate ()
Serenity For Women ()
Milprosa ()
Progesterone-d9 ()
P&D ID
PD002656
CAS
57-83-0
257630-50-5
137940-28-4
15775-74-3
Tags
available
drug
Approved by
FDA
PMDA
First approval
1976
Drug indication
Premature labour
Contraception
Progestin
Drug Status
approved
vet_approved
Max Phase
4.0
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
INDICATION **Gelatinized capsules** The gelatinized capsules are indicated for use in the prevention of endometrial hyperplasia in non-hysterectomized postmenopausal women who are receiving conjugated estrogens tablets. They are also indicated for use in secondary amenorrhea [FDA label]. **Vaginal gel** Progesterone gel (8%) is indicated as progesterone supplementation or replacement as part of an Assisted Reproductive Technology (“ART”) treatment for infertile women with progesterone deficiency. The lower concentration progesterone gel (4%) is used in the treatment of secondary amenorrhea, with the use of the 8% concentration if there is no therapeutic response to the 4% gel [F3898]. **Vaginal insert** This form is indicated to support embryo implantation and early pregnancy by supplementation of corpus luteal function as part of an Assisted Reproductive Technology (ART) treatment program for infertile women [F3901]. **Injection (intramuscular)** This drug is indicated in amenorrhea and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as submucous fibroids or uterine cancer [F3907]. **Tablets, contraceptive** The tablet form of progesterone in contraceptive formulations is indicated for the prevention of pregnancy [F3904].
ROE Progesterone metabolites are excreted mainly by the kidneys. Urinary elimination is observed for 95% of patients in the form of glycuroconjugated metabolites, primarily 3 a, 5 ß–pregnanediol (_pregnandiol_) [F3913]. The glucuronide and sulfate conjugates of pregnanediol and pregnanolone are excreted in the urine and bile. Progesterone metabolites, excreted in the bile, may undergo enterohepatic recycling or may be found excreted in the feces.
TOXICITY Intraperitoneal LD50 (rat): 327 mg/kg [MSDS]. **Use in pregnancy** Only forms of progesterone that are indicated on product labeling for pregnancy should be used. Some forms of progesterone should not be used in pregnancy [FDA label], [F3904]. Refer to individual product monographs for information regarding use in pregnancy. Many studies have found no effects on fetal development associated with long-term use of contraceptive doses of oral progestins. Studies of infant growth and development that have been conducted have not demonstrated significant adverse effects, however, these studies are few in number. It is therefore advisable to rule out suspected pregnancy before starting any hormonal contraceptive [F3904]. **Effects on fertility** Progesterone at high doses is an antifertility drug and high doses would be expected to impair fertility until cessation [F3916]. The progesterone contraceptive should not be used during pregnancy. **Carcinogenicity** Progesterone has been shown to induce or promote the formation of ovarian, uterine, mammary, and genital tract tumors in animals. The clinical relevance of these findings is unknown [F3913]. Certain epidemiological studies of patients using oral contraceptives have reported an increased relative risk of developing breast cancer, especially at a younger age and associated with a longer duration of use. These studies have mainly involved combined oral contraceptives, and therefore, it is unknown whether this risk is attributable to progestins, estrogens, or a combination of both. At this time, there is insufficient data to determine whether the use of progestin-only contraceptives increases the risk in a similar way to combined contraceptives. A meta-analysis of 54 studies showed a small increase in the frequency of breast cancer diagnosis for women who were currently using combined oral contraceptives, or had used them within the past 10 years. There was no increase in the frequency of having breast cancer diagnosed ten or more years after cessation of hormone use. Women with breast cancer should not use oral contraceptives, as there is no sufficient data to fully establish or negate the risk of cancer with hormonal contraceptive use [F3904]. **Use in breastfeeding** Progesterone has been detected in the milk of nursing mothers [F3901], [F3904]. No adverse effects, in general, have been found on breastfeeding ability or on the health, growth, or development of the growing infant. Despite this, isolated post-marketing cases of decreased milk production have been reported [F3904].
METABOLISM Progesterone is mainly metabolized by the liver. After oral administration, the major plasma metabolites found are 20 a hydroxy-Δ4 a-prenolone and 5 a-dihydroprogesterone. Some progesterone metabolites are found excreted in the bile and these metabolites may be deconjugated and subsequently metabolized in the gut by reduction, dehydroxylation, and epimerization [FDA label]. The major plasma and urinary metabolites are comparable to those found during the physiological progesterone secretion of the corpus luteum [F3913].
HALF-LIFE Absorption half-life is approximately 25-50 hours and an elimination half-life of 5-20 minutes (progesterone gel) [F3898]. Progesterone, administered orally, has a short serum half-life (approximately 5 minutes). It is rapidly metabolized to _17-hydroxyprogesterone_ during its first pass through the liver [A175657].
MOA Progesterone binds and activates its nuclear receptor, _PR_, which plays an important part in the signaling of stimuli that maintain the endometrium during its preparation for pregnancy.; ; Progesterone receptor (PR) is a member of the nuclear/steroid hormone receptor (SHR) family of ligand-dependent transcription factors that is expressed primarily in female reproductive tissue as well as the central nervous system. As a result of its binding its associated steroid hormone, progesterone, the progesterone receptor (PR) modulates the expression of genes that regulate the development, differentiation, and proliferation of target tissues [A175666]. In humans, PR is found to be highly expressed in the stromal (connective tissue) cells during the secretory phase and during pregnancy [A175651]. ; ; Progesterone may prevent pregnancy by changing the consistency of cervical mucus to be unfavorable for sperm penetration, and by inhibiting follicle-stimulating hormone (FSH), which normally causes ovulation. With perfect use, the first-year failure rate for progestin-only oral contraceptives is approximately 0.5%. The typical failure rate, however, is estimated to be approximately 5%, due to late or missed pills [F3904].
DESCRIPTION Progesterone is an endogenous steroid and progestogen sex hormone. It is the major progestogen and is required for the production of other endogenous steroids, including the sex hormones and corticosteroids. (GtoPdb)
MOA Progesterone binds and activates its nuclear receptor, _PR_, which plays an important part in the signaling of stimuli that maintain the endometrium during its preparation for pregnancy. Progesterone receptor (PR) is a member of the nuclear/steroid hormone receptor (SHR) family of ligand-dependent transcription factors that is expressed primarily in female reproductive tissue as well as the central nervous system. As a result of its binding its associated steroid hormone, progesterone, the progesterone receptor (PR) modulates the expression of genes that regulate the development, differentiation, and proliferation of target tissues [A175666]. In humans, PR is found to be highly expressed in the stromal (connective tissue) cells during the secretory phase and during pregnancy [A175651]. Progesterone may prevent pregnancy by changing the consistency of cervical mucus to be unfavorable for sperm penetration, and by inhibiting follicle-stimulating hormone (FSH), which normally causes ovulation. With perfect use, the first-year failure rate for progestin-only oral contraceptives is approximately 0.5%. The typical failure rate, however, is estimated to be approximately 5%, due to late or missed pills [F3904].
ABSORPTION **Oral micronized capsules** Following oral administration of progesterone in the micronized soft-gelatin capsule formulation, peak serum concentration was achieved in the first 3 hours. The absolute bioavailability of micronized progesterone is unknown at this time. In postmenopausal women, serum progesterone concentration increased in a dose-proportional and linear fashion after multiple doses of progesterone capsules, ranging from 100 mg/day to 300 mg/day [FDA label]. **IM administration** After intramuscular (IM) administration of 10 mg of progesterone in oil, the maximum plasma concentrations were achieved in about 8 hours post-injection and plasma concentrations stayed above baseline for approximately 24 hours post-injection. Injections of 10, 25, and 50 mg lead to geometric mean values for maximum plasma concentration (CMAX) of 7, 28, and 50 ng/mL, respectively [F3916]. Progesterone administered by the intramuscular (IM) route avoids significant first-pass hepatic metabolism. As a result, endometrial tissue concentrations of progesterone achieved with IM administration are higher when compared with oral administration. Despite this, the highest concentrations of progesterone in endometrial tissue are reached with vaginal administration [A175657]. **Note on oral contraceptive tablet absorption** Serum progestin levels peak about 2 hours after oral administration of progesterone-only contraceptive tablets, followed by rapid distribution and elimination. By 24 hours after drug administration, serum levels remain near the baseline, making efficacy dependent upon strict adherence to the dosing schedule. Large variations in serum progesterone levels occur among individuals. Progestin-only administration leads to lower steady-state serum progestin levels and a shorter elimination half-life than concurrent administration with estrogens [F3904].
INDICATION **Gelatinized capsules**; ; The gelatinized capsules are indicated for use in the prevention of endometrial hyperplasia in non-hysterectomized postmenopausal women who are receiving conjugated estrogens tablets. They are also indicated for use in secondary amenorrhea [FDA label]. ; ; **Vaginal gel**; ; Progesterone gel (8%) is indicated as progesterone supplementation or replacement as part of an Assisted Reproductive Technology (“ART”) treatment for infertile women with progesterone deficiency. The lower concentration progesterone gel (4%) is used in the treatment of secondary amenorrhea, with the use of the 8% concentration if there is no therapeutic response to the 4% gel [F3898].; ; **Vaginal insert**; ; This form is indicated to support embryo implantation and early pregnancy by supplementation of corpus luteal function as part of an Assisted Reproductive Technology (ART) treatment program for infertile women [F3901].; ; **Injection (intramuscular)**; ; This drug is indicated in amenorrhea and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as submucous fibroids or uterine cancer [F3907]. ; ; **Tablets, contraceptive**; ; The tablet form of progesterone in contraceptive formulations is indicated for the prevention of pregnancy [F3904].
TOXICITY Intraperitoneal LD50 (rat): 327 mg/kg [MSDS]. ; ; **Use in pregnancy**; ; Only forms of progesterone that are indicated on product labeling for pregnancy should be used. Some forms of progesterone should not be used in pregnancy [FDA label], [F3904]. Refer to individual product monographs for information regarding use in pregnancy. Many studies have found no effects on fetal development associated with long-term use of contraceptive doses of oral progestins. Studies of infant growth and development that have been conducted have not demonstrated significant adverse effects, however, these studies are few in number. It is therefore advisable to rule out suspected pregnancy before starting any hormonal contraceptive [F3904]. ; ; **Effects on fertility**; ; Progesterone at high doses is an antifertility drug and high doses would be expected to impair fertility until cessation [F3916]. The progesterone contraceptive should not be used during pregnancy. ; ; **Carcinogenicity**; ; Progesterone has been shown to induce or promote the formation of ovarian, uterine, mammary, and genital tract tumors in animals. The clinical relevance of these findings is unknown [F3913]. Certain epidemiological studies of patients using oral contraceptives have reported an increased relative risk of developing breast cancer, especially at a younger age and associated with a longer duration of use. These studies have mainly involved combined oral contraceptives, and therefore, it is unknown whether this risk is attributable to progestins, estrogens, or a combination of both. At this time, there is insufficient data to determine whether the use of progestin-only contraceptives increases the risk in a similar way to combined contraceptives. A meta-analysis of 54 studies showed a small increase in the frequency of breast cancer diagnosis for women who were currently using combined oral contraceptives, or had used them within the past 10 years. There was no increase in the frequency of having breast cancer diagnosed ten or more years after cessation of hormone use. Women with breast cancer should not use oral contraceptives, as there is no sufficient data to fully establish or negate the risk of cancer with hormonal contraceptive use [F3904]. ; ; **Use in breastfeeding**; ; Progesterone has been detected in the milk of nursing mothers [F3901], [F3904]. No adverse effects, in general, have been found on breastfeeding ability or on the health, growth, or development of the growing infant. Despite this, isolated post-marketing cases of decreased milk production have been reported [F3904].
ABSORPTION **Oral micronized capsules**; ; Following oral administration of progesterone in the micronized soft-gelatin capsule formulation, peak serum concentration was achieved in the first 3 hours. The absolute bioavailability of micronized progesterone is unknown at this time. In postmenopausal women, serum progesterone concentration increased in a dose-proportional and linear fashion after multiple doses of progesterone capsules, ranging from 100 mg/day to 300 mg/day [FDA label]. ; ; **IM administration**; ; After intramuscular (IM) administration of 10 mg of progesterone in oil, the maximum plasma concentrations were achieved in about 8 hours post-injection and plasma concentrations stayed above baseline for approximately 24 hours post-injection. Injections of 10, 25, and 50 mg lead to geometric mean values for maximum plasma concentration (CMAX) of 7, 28, and 50 ng/mL, respectively [F3916]. Progesterone administered by the intramuscular (IM) route avoids significant first-pass hepatic metabolism. As a result, endometrial tissue concentrations of progesterone achieved with IM administration are higher when compared with oral administration. Despite this, the highest concentrations of progesterone in endometrial tissue are reached with vaginal administration [A175657]. ; ; **Note on oral contraceptive tablet absorption**; ; Serum progestin levels peak about 2 hours after oral administration of progesterone-only contraceptive tablets, followed by rapid distribution and elimination. By 24 hours after drug administration, serum levels remain near the baseline, making efficacy dependent upon strict adherence to the dosing schedule. Large variations in serum progesterone levels occur among individuals. Progestin-only administration leads to lower steady-state serum progestin levels and a shorter elimination half-life than concurrent administration with estrogens [F3904].
HALF-LIFE Absorption half-life is approximately 25-50 hours and an elimination half-life of 5-20 minutes (progesterone gel) [F3898]. ; ; Progesterone, administered orally, has a short serum half-life (approximately 5 minutes). It is rapidly metabolized to _17-hydroxyprogesterone_ during its first pass through the liver [A175657]. ; ;
DESCRIPTION RARbeta and RARgamma agonist (Tocris Bioactive Compound Library)
DESCRIPTION Suppresses ovulation; induces maturation and secretory activity of the uterine endothelium (LOPAC library)
Cell lines
2
Organisms
2
Compound Sets
33
Cayman Chemical Bioactives
15876
25047
ChEMBL Approved Drugs
CHEMBL103
ChEMBL Drugs
CHEMBL103
Concise Guide to Pharmacology 2017/18
2377
Concise Guide to Pharmacology 2019/20
2377
Concise Guide to Pharmacology 2021/22
2377
Concise Guide to Pharmacology 2023/24
2377
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
DB00396
DrugBank Approved Drugs
DB00396
DrugCentral
2279
DrugCentral Approved Drugs
2279
DrugMAP
DMUY35B
DrugMAP Approved Drugs
DMUY35B
Enamine BioReference Compounds
EU-OPENSCREEN Bioactive Compound Library
EOS101196
Guide to Pharmacology
2377
LOPAC library
LSP-MoA library (Laboratory of Systems Pharmacology)
CHEMBL103
Mcule NIBR MoA Box Subset
MCULE-5238788396
MedChem Express Bioactive Compound Library
HY-N0437
NCATS Inxight Approved Drugs
4G7DS2Q64Y
NIH Clinical Collections (NCC)
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
NURSA ligand set
nursa/index.jsf?doi=10.1621%2FE7EEFRDJA5
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
Progesterone(Prometrium)
TargetMol Bioactive Compound Library
T0478
Tocris Bioactive Compound Library
2835
ZINC Tool Compounds
ZINC000004428529
External IDs
74
Properties
(calculated by RDKit )
Molecular Weight
314.22
Hydrogen Bond Acceptors
2
Hydrogen Bond Donors
0
Rotatable Bonds
1
Ring Count
4
Aromatic Ring Count
0
cLogP
4.72
TPSA
34.14
Fraction CSP3
0.81
Chiral centers
6.0
Largest ring
6.0
QED
0.7
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Selectivity
Progesterone
Pathway
Endocrinology/Hormones
GPCR/G protein
Neuroscience
Metabolic Enzyme/Protease
Vitamin D Related/Nuclear Receptor
Target
ER
??-opioid receptor
CATSPER1, CATSPER2, CATSPER3, CATSPER4, CYP17A1, ESR1, NR3C2, OPRK1, PGR, TRPC5
Endogenous Metabolite
Progesterone Receptor
Estrogen/progestogen Receptor
Primary Target
Progesterone Receptors
MOA
Agonist
Progesterone Receptor Agonists
Progesterone receptor agonist
Member status
member
Disease Area
obstetrics/gynecology, endocrinology
Indication
infertility, amenorrhea
Source data