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Cyproterone acetate

PubChem CID
9880
Structure
Cyproterone acetate_small.png
Cyproterone acetate_3D_Structure.png
Molecular Formula
Synonyms
  • CYPROTERONE ACETATE
  • 427-51-0
  • Androcur
  • Cyproteroneacetate
  • Cyproterone 17-O-acetate
Molecular Weight
416.9 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-03-26
  • Modify:
    2024-12-27
Description
Cyproterone acetate is a steroid ester resulting from the formal condensation of the carboxy group of acetic acid with the 17-hydroxy group of cyproterone. It is an antiandrogenic drug which has recently been recognized to promote the occurrence and growth of intracranial meningiomas. It has a role as an androgen antagonist, a progestin and a geroprotector. It is a 20-oxo steroid, a 3-oxo-Delta(4) steroid, a chlorinated steroid, a steroid ester and an acetate ester. It is functionally related to a cyproterone.
An anti-androgen that, in the form of its acetate (cyproterone acetate), also has progestational properties. It is used in the treatment of hypersexuality in males, as a palliative in prostatic carcinoma, and, in combination with estrogen, for the therapy of severe acne and hirsutism in females.
Cyproterone Acetate is the acetate salt of a synthetic steroidal antiandrogen with weak progestational and antineoplastic activities. Cyproterone binds the androgen receptor (AR), thereby preventing androgen-induced receptor activation in target tissues and inhibiting the growth of testosterone-sensitive tumor cells. This agent also exerts progestational agonist properties at the level of the pituitary that reduce luteinizing hormone (LH), resulting in reductions in testicular androgen secretion and serum testosterone levels. Treatment with cyproterone alone results in incomplete suppression of serum testosterone levels.

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Cyproterone acetate.png

1.2 3D Conformer

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

[(1S,2S,3S,5R,11R,12S,15R,16S)-15-acetyl-9-chloro-2,16-dimethyl-6-oxo-15-pentacyclo[9.7.0.02,8.03,5.012,16]octadeca-7,9-dienyl] acetate
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C24H29ClO4/c1-12(26)24(29-13(2)27)8-6-16-14-10-20(25)19-11-21(28)15-9-18(15)23(19,4)17(14)5-7-22(16,24)3/h10-11,14-18H,5-9H2,1-4H3/t14-,15+,16-,17-,18-,22-,23-,24-/m0/s1
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

UWFYSQMTEOIJJG-FDTZYFLXSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

CC(=O)[C@]1(CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2C=C(C4=CC(=O)[C@@H]5C[C@@H]5[C@]34C)Cl)C)OC(=O)C
Computed by OEChem 2.3.0 (PubChem release 2021.10.14)

2.2 Molecular Formula

C24H29ClO4
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

2.3.2 European Community (EC) Number

2.3.3 UNII

2.3.4 ChEBI ID

2.3.5 ChEMBL ID

2.3.6 DrugBank ID

2.3.7 DSSTox Substance ID

2.3.8 KEGG ID

2.3.9 Metabolomics Workbench ID

2.3.10 NCI Thesaurus Code

2.3.11 Nikkaji Number

2.3.12 NSC Number

2.3.13 Pharos Ligand ID

2.3.14 Wikidata

2.3.15 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • Androcur
  • Cyproterone Acetate
  • Cyproterone Acetate, (1 alpha,2 alpha)-Isomer
  • Cyproterone Acetate, (1 alpha,2 alpha,9 beta,10 alpha)-Isomer
  • Cyproterone Acetate, (17 alpha)-Isomer

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
416.9 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3-AA
Property Value
3.6
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
0
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
4
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
3
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
416.1754371 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
416.1754371 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
60.4Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
29
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
903
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
8
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Experimental Properties

3.2.1 Color / Form

Crystals from diisopropyl ether
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 466
White crystalline powder
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V72: 585 (1999)

3.2.2 Melting Point

200-201
Wiechert, R.; U S . Patent 3,234,093; February 8, 1966; assigned to Schering AG, Germany.
200-201 °C
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 466

3.2.3 Solubility

Very soluble in dichloromethane and acetone; soluble in methanol; sparingly soluble in ethanol.
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V72: 585 (1999)

3.2.4 Stability / Shelf Life

Stable under recommended storage conditions.
Sigma-Aldrich; Material Safety Data Sheet for Cyproterone acetate. Product Number C3412. Version 4.0 (March 2010). Available from, as of March 3, 2011: https://www.sigmaaldrich.com/safety-center/msds-search.html

3.2.5 Optical Rotation

Specific rotation = +152 deg to +157 deg at 20 °C
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V72: 585 (1999)

3.2.6 Decomposition

When heated to decomposition it emits toxic fumes of /hydrogen chloride/.
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 1058

3.2.7 Collision Cross Section

199.4 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

3.2.8 Other Experimental Properties

Crystals from acetate, mp 237.5-240 °C /Cyproterone/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 466

3.3 Chemical Classes

3.3.1 Drugs

Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749

3.3.2 Endocrine Disruptors

Potential endocrine disrupting compound
S109 | PARCEDC | List of 7074 potential endocrine disrupting compounds (EDCs) by PARC T4.2 | DOI:10.5281/zenodo.10944198

4 Spectral Information

4.1 Mass Spectrometry

4.1.1 GC-MS

1 of 2
Source of Spectrum
JC-529-151-2
Copyright
Copyright © 2020-2024 John Wiley & Sons, Inc. All Rights Reserved.
Thumbnail
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2 of 2
Technique
GC/MS
Source of Spectrum
DigiLab GmbH (C) 2024
Copyright
Copyright © 2024 DigiLab GmbH and Wiley-VCH GmbH. All Rights Reserved.
Thumbnail
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4.1.2 MS-MS

NIST Number
1201289
Instrument Type
IT/ion trap
Collision Energy
0
Spectrum Type
MS2
Precursor Type
[M+H]+
Precursor m/z
417.1827
Total Peaks
114
m/z Top Peak
357.1
m/z 2nd Highest
321.1
m/z 3rd Highest
279.1
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4.1.3 LC-MS

1 of 9
View All
Authors
Elapavalore, A.; Kondić, T.; Singh, R.; Schymanski, E.
Instrument
Q Exactive Orbitrap (Thermo Scientific)
Instrument Type
LC-ESI-QFT
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
15
Fragmentation Mode
HCD
Column Name
Acquity BEH C18 1.7um, 2.1x150mm (Waters)
Retention Time
18.263 min
Precursor m/z
417.1827
Precursor Adduct
[M+H]+
Top 5 Peaks

417.183 999

357.1617 129

321.1851 27

315.1512 15

279.1742 12

Thumbnail
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License
CC BY
Reference
Elapavalore, A.; Kondić, T.; et al., Adding Open Spectral Data to MassBank and PubChem Using Open Source Tools to Support Non-Targeted Exposomics of Mixtures (submitted).
2 of 9
View All
Authors
Elapavalore, A.; Kondić, T.; Singh, R.; Schymanski, E.
Instrument
Q Exactive Orbitrap (Thermo Scientific)
Instrument Type
LC-ESI-QFT
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
30
Fragmentation Mode
HCD
Column Name
Acquity BEH C18 1.7um, 2.1x150mm (Waters)
Retention Time
18.263 min
Precursor m/z
417.1827
Precursor Adduct
[M+H]+
Top 5 Peaks

279.1744 999

313.1355 827

147.1169 779

357.1617 738

321.185 673

Thumbnail
Thumbnail
License
CC BY
Reference
Elapavalore, A.; Kondić, T.; et al., Adding Open Spectral Data to MassBank and PubChem Using Open Source Tools to Support Non-Targeted Exposomics of Mixtures (submitted).

4.2 UV Spectra

UV max (methanol): 281 nm (epsilon 17280)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 466

4.3 IR Spectra

4.3.1 FTIR Spectra

Instrument Name
Bio-Rad FTS
Technique
KBr1 0.70mg
Source of Spectrum
Forensic Spectral Research
Source of Sample
Steraloids
Catalog Number
P0901-000
Lot Number
H431
Copyright
Copyright © 2008-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.3.2 ATR-IR Spectra

1 of 2
Instrument Name
Bio-Rad FTS
Technique
ATR-Neat (DuraSamplIR II)
Source of Spectrum
Forensic Spectral Research
Source of Sample
Steraloids
Catalog Number
P0907-000
Lot Number
B0458
Copyright
Copyright © 2012-2024 John Wiley & Sons, Inc. All Rights Reserved.
Thumbnail
Thumbnail
2 of 2
Instrument Name
Bio-Rad FTS
Technique
ATR-Neat (DuraSamplIR II)
Source of Spectrum
Forensic Spectral Research
Source of Sample
Steraloids Inc.
Catalog Number
P0901-000
Lot Number
H431
Copyright
Copyright © 2009-2024 John Wiley & Sons, Inc. All Rights Reserved.
Thumbnail
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4.4 Raman Spectra

1 of 2
Technique
FT-Raman
Source of Spectrum
Forensic Spectral Research
Source of Sample
Steraloids Inc.
Catalog Number
P0901-000
Lot Number
H431
Copyright
Copyright © 2013-2024 John Wiley & Sons, Inc. All Rights Reserved.
Thumbnail
Thumbnail
2 of 2
Technique
FT-Raman
Source of Spectrum
Forensic Spectral Research
Source of Sample
Steraloids Inc.
Catalog Number
P0907-000
Lot Number
B0458
Copyright
Copyright © 2013-2024 John Wiley & Sons, Inc. All Rights Reserved.
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6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

For the palliative treatment of patients with advanced prostatic carcinoma.

7.2 Clinical Trials

7.2.1 ClinicalTrials.gov

7.2.2 EU Clinical Trials Register

7.3 Therapeutic Uses

Androgen Antagonists; Antineoplastic Agents; Contraceptive Agents, Male; Progestational Hormones, Synthetic
National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)
/Cyproterone is indicated for the/ control of libido in severe hypersexuality and/or sexual deviation in the adult male.
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Androcur (Last updated January 2011). Available from, as of March 23, 2011: https://www.medicines.org.uk/EMC/medicine/1808/SPC/Androcur/
/Cyproterone is indicated for the/ management of patients with prostatic cancer (1) to suppress "flare" with initial LHRH analogue therapy,(2) in long-term palliative treatment where LHRH analogues or surgery are contraindicated, not tolerated, or where oral therapy is preferred, and (3) in the treatment of hot flushes in patients under treatment with LHRH analogues or who have had orchidectomy.
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Cyprostat (Last updated January 2011). Available from, as of March 23, 2011: https://www.medicines.org.uk/EMC/medicine/20815/SPC/Cyprostat+100mg/
Dianette (cyproterone acetate/ethinylestradiol) is recommended for use in women only for the treatment of (a) severe acne, refractory to prolonged oral antibiotic therapy; (b) moderately severe hirsutism.
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Dianette (Last updated November 2010). Available from, as of March 23, 2011: https://www.medicines.org.uk/EMC/medicine/1814/SPC/Dianette/
Although Dianette also acts as an oral contraceptive, it should not be used in women solely for contraception, but should be reserved for those women requiring treatment for the androgen-dependent conditions.
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Dianette (Last updated November 2010). Available from, as of March 23, 2011: https://www.medicines.org.uk/EMC/medicine/1814/SPC/Dianette/

7.4 Drug Warnings

Direct hepatic toxicity, including jaundice, hepatitis and hepatic failure, has been observed in patients treated with Cyprostat. At dosages of 100 mg and above cases with fatal outcome have also been reported. Most reported fatal cases were in men with advanced prostatic cancer. Toxicity is dose-related and develops, usually, several months after treatment has begun. Liver function tests should be performed pre-treatment, regularly during treatment and whenever any symptoms or signs suggestive of hepatotoxicity occur. If hepatotoxicity is confirmed, Cyprostat should be withdrawn, unless the hepatotoxicity can be explained by another cause, eg metastatic disease, in which case Cyprostat should be continued only if the perceived benefit outweighs the risk.
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Cyprostat (Last updated January 2011). Available from, as of March 23, 2011: https://www.medicines.org.uk/EMC/medicine/20815/SPC/Cyprostat+100mg/
In very rare cases benign and malignant liver tumors, which may lead to life-threatening intra-abdominal hemorrhage, have been observed after the use of Cyprostat. If severe upper abdominal complaints, liver enlargement or signs of intra-abdominal hemorrhage occur, a liver tumor should be considered in the differential diagnosis.
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Cyprostat (Last updated January 2011). Available from, as of March 23, 2011: https://www.medicines.org.uk/EMC/medicine/20815/SPC/Cyprostat+100mg/
The occurrence of thromboembolic events has been reported in patients using Cyprostat, although a causal relationship has not been established. Patients with previous arterial or venous thrombotic/thromboembolic events (eg deep vein thrombosis, pulmonary embolism, myocardial infarction), with a history of cerebrovascular accidents or with advanced malignancies are at increased risk of further thromboembolic events, and may be at risk of recurrence of the disease during Cyprostat therapy.
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Cyprostat (Last updated January 2011). Available from, as of March 23, 2011: https://www.medicines.org.uk/EMC/medicine/20815/SPC/Cyprostat+100mg/
In patients with a history of thromboembolic processes or suffering from sickle-cell anemia or severe diabetes with vascular changes, the risk: benefit ratio must be considered carefully in each individual case before Cyprostat is prescribed.
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Cyprostat (Last updated January 2011). Available from, as of March 23, 2011: https://www.medicines.org.uk/EMC/medicine/20815/SPC/Cyprostat+100mg/
For more Drug Warnings (Complete) data for CYPROTERONE ACETATE (17 total), please visit the HSDB record page.

8 Pharmacology and Biochemistry

8.1 Pharmacodynamics

Cyproterone is an antiandrogen. It suppresses the actions of testosterone (and its metabolite dihydrotestosterone) on tissues. It acts by blocking androgen receptors which prevents androgens from binding to them and suppresses luteinizing hormone (which in turn reduces testosterone levels).

8.2 MeSH Pharmacological Classification

Contraceptive Agents, Male
Chemical substances or agents with contraceptive activity in males. Use for male contraceptive agents in general or for which there is no specific heading. (See all compounds classified as Contraceptive Agents, Male.)
Androgen Antagonists
Compounds which inhibit or antagonize the biosynthesis or actions of androgens. (See all compounds classified as Androgen Antagonists.)
Antineoplastic Agents
Substances that inhibit or prevent the proliferation of NEOPLASMS. (See all compounds classified as Antineoplastic Agents.)

8.3 Absorption, Distribution and Excretion

Absorption
Completely absorbed following oral administration.
Route of Elimination
It is excreted approximately 60% in the bile and 33% through the kidneys.
Following oral administration, cyproterone acetate is completely absorbed over a wide dose range. The ingestion of two cyproterone acetate 50 mg tablets gives maximum serum levels of about 285 ng/mL at about 3 hours. Thereafter, drug serum levels declined during a time interval of typically 24 to 120 hr, with a terminal half-life of 43.9 +/- 12.8 hr. The total clearance of cyproterone acetate from serum is 3.5 +/- 1.5 mL/min/kg.
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Androcur (Last updated January 2011). Available from, as of March 23, 2011: https://www.medicines.org.uk/EMC/medicine/1808/SPC/Androcur/
The absolute bioavailability of cyproterone acetate is almost complete (88% of dose).
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Androcur (Last updated January 2011). Available from, as of March 23, 2011: https://www.medicines.org.uk/EMC/medicine/1808/SPC/Androcur/
Some drug is excreted unchanged with bile fluid. Most of the dose is excreted in the form of metabolites at a urinary to biliary ratio of 3:7.
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Androcur (Last updated January 2011). Available from, as of March 23, 2011: https://www.medicines.org.uk/EMC/medicine/1808/SPC/Androcur/
Cyproterone acetate is almost exclusively bound to plasma albumin. About 3.5 - 4% of total drug levels are present unbound. Because protein binding is non-specific, changes in SHBG (sex hormone binding globulin) levels do not affect the pharmacokinetics of cyproterone acetate.
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Androcur (Last updated January 2011). Available from, as of March 23, 2011: https://www.medicines.org.uk/EMC/medicine/1808/SPC/Androcur/
For more Absorption, Distribution and Excretion (Complete) data for CYPROTERONE ACETATE (6 total), please visit the HSDB record page.

8.4 Metabolism / Metabolites

Primarily hepatic. Cyproterone acetate is metabolized by the CYP3A4 enzyme, forming the active metabolite 15beta-hydroxycyproterone acetate, which retains its antiandrogen activity, but has reduced progestational activity.
Cyproterone acetate is metabolized by various pathways, including hydroxylations and conjugations. The main metabolite in human plasma is the 15beta-hydroxy derivative.
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Androcur (Last updated January 2011). Available from, as of March 23, 2011: https://www.medicines.org.uk/EMC/medicine/1808/SPC/Androcur/

8.5 Biological Half-Life

Elimination Following oral or intramuscular administration, the plasma half-life is 38 and 96 hours, respectively.
The renal and biliary excretion proceeds with a half-life of 1.9 days. Metabolites from plasma are eliminated at a similar rate (half-life of 1.7 days).
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Androcur (Last updated January 2011). Available from, as of March 23, 2011: https://www.medicines.org.uk/EMC/medicine/1808/SPC/Androcur/
Terminal half-life of 43.9 +/- 12.8 hr.
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Androcur (Last updated January 2011). Available from, as of March 23, 2011: https://www.medicines.org.uk/EMC/medicine/1808/SPC/Androcur/

8.6 Mechanism of Action

The direct antiandrogenic effect of cyproterone is blockage of the binding of dihydrotestosterone to the specific receptors in the prostatic carcinoma cell. In addition, cyproterone exerts a negative feed-back on the hypothalamo-pituitary axis, by inhibiting the secretion of luteinizing hormone resulting in diminished production of testicular testosterone.
Prostatic carcinoma and its metastases are in general androgen-dependent. Cyproterone acetate exerts a direct anti-androgen action on the tumor and its metastases. It also has progestogenic activity, which exerts a negative feedback effect on the hypothalamic receptors, so leading to a reduction in gonadotrophin release, and hence to diminished production of testicular androgens. Sexual drive and potency are reduced and gonadal function is inhibited.
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Cyprostat (Last updated January 2011). Available from, as of March 23, 2011: https://www.medicines.org.uk/EMC/medicine/20815/SPC/Cyprostat+100mg/
Cell proliferation and cell death appear in several systems as mutually exclusive, which raises the assumption that a same factor or secondary signal(s) might exert opposite control on the two processes. To test this assumption we investigated the time-course evolution of the S phase and apoptotic indices in rat liver during cyproterone acetate (CPA) induced hyperplasia and during the recovery of normal liver mass provoked, respectively, by cyproterone acetate (CPA) treatment and withdrawal. The levels of c-myc and c-ras transcripts were also followed in view of the indications of a positive role of these oncogenes in proliferation. The data showed that proliferation and cell death are not always mutually exclusive and that a high rate of cell death was indifferently associated with high or low c-ras expression. Our data are consistent with a role of this gene in proliferation but exclude that it plays an opposite role in controlling cell death.
Servais P, Galand P; Cell Biol Int Rep 16 (4): 319-28 (1992)
The antigonadotropic effect of cyproterone acetate is also exerted when administered with LHRH analogues. The initial increase of testosterone caused by this class of substances is reduced by cyproterone acetate. An occasional tendency for the prolactin levels to increase slightly has been observed under higher doses of cyproterone acetate.
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Cyprostat (Last updated January 2011). Available from, as of March 23, 2011: https://www.medicines.org.uk/EMC/medicine/20815/SPC/Cyprostat+100mg/
Dianette blocks androgen-receptors. It also reduces androgen synthesis both by negative feedback effect on the hypothalamo-pituitiary-ovarian systems and by the inhibition of androgen-synthesising enzymes.
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Dianette (Last updated November 2010). Available from, as of March 23, 2011: https://www.medicines.org.uk/EMC/medicine/1814/SPC/Dianette/
For more Mechanism of Action (Complete) data for CYPROTERONE ACETATE (8 total), please visit the HSDB record page.

9 Use and Manufacturing

9.1 Uses

MEDICATION

9.2 Impurities

Reported impurities include: 3,20-dioxo-1beta,2beta-dihydro-3'H-cyclopropa[1,2]pregna-1,4,6-trien-17-yl acetate and 6-methoxy-3,20-dioxo-1beta,2beta-dihydro-3'H-cyclopropa[1,2]-pregna-1,4,6-trien-17-yl acetate.
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V91 397 (2007)

9.3 Formulations / Preparations

Mixture of acetate with ethinyl estradiol
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 466
... Commercially available as tablets and as an injectable solution.
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V91 397 (2007)
Oral: Tablet: 50, 100 mg cyproterone acetate, Cyprostat (Bayer plc).
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Cyprostat (Last updated January 2011). Available from, as of March 23, 2011: https://www.medicines.org.uk/EMC/medicine/20815/SPC/Cyprostat+100mg/
Oral: Tablet: 2 mg cyproterone acetate 35 ug ethinylestradiol, Dianette (Bayer plc)
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Dianette (Last updated November 2010).
Oral: Tablet: 50 mg cyproterone acetate, Androcur (Bayer plc).
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Androcur (Last updated January 2011).

10 Identification

10.1 Analytic Laboratory Methods

... Infra-red absorption spectrophotometry and thin-layer chromatography ... /are/ methods for identifying cyproterone acetate; liquid chromatography and ultra-violet absorption spectrophotometry are used to assay its purity.
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V72 585 (1999)

11 Safety and Hazards

11.1 Hazards Identification

11.1.1 GHS Classification

Pictogram(s)
Irritant
Health Hazard
Signal
Danger
GHS Hazard Statements

H312 (64.3%): Harmful in contact with skin [Warning Acute toxicity, dermal]

H332 (64.3%): Harmful if inhaled [Warning Acute toxicity, inhalation]

H351 (97.1%): Suspected of causing cancer [Warning Carcinogenicity]

H360 (32.9%): May damage fertility or the unborn child [Danger Reproductive toxicity]

H373 (27.1%): May causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]

Precautionary Statement Codes

P203, P260, P261, P271, P280, P302+P352, P304+P340, P317, P318, P319, P321, P362+P364, P405, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary

Aggregated GHS information provided per 70 reports by companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

11.1.2 Hazard Classes and Categories

Acute Tox. 4 (64.3%)

Acute Tox. 4 (64.3%)

Carc. 2 (97.1%)

Repr. 1A (32.9%)

STOT RE 2 (27.1%)

11.2 Fire Fighting

11.2.1 Fire Fighting Procedures

Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. ... Wear self contained breathing apparatus for fire fighting if necessary.
Sigma-Aldrich; Material Safety Data Sheet for Cyproterone acetate. Product Number C3412. Version 4.0 (March 2010). Available from, as of March 3, 2011: https://www.sigmaaldrich.com/safety-center/msds-search.html

11.3 Accidental Release Measures

11.3.1 Cleanup Methods

Personal precautions: Use personal protective equipment. Avoid dust formation. Avoid breathing dust. Ensure adequate ventilation. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Keep in suitable, closed containers for disposal.
Sigma-Aldrich; Material Safety Data Sheet for Cyproterone acetate. Product Number C3412. Version 4.0 (March 2010). Available from, as of March 3, 2011: https://www.sigmaaldrich.com/safety-center/msds-search.html

11.3.2 Disposal Methods

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.
SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

11.3.3 Preventive Measures

Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection.
Sigma-Aldrich; Material Safety Data Sheet for Cyproterone acetate. Product Number C3412. Version 4.0 (March 2010). Available from, as of March 3, 2011: https://www.sigmaaldrich.com/safety-center/msds-search.html
Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.
Sigma-Aldrich; Material Safety Data Sheet for Cyproterone acetate. Product Number C3412. Version 4.0 (March 2010). Available from, as of March 3, 2011: https://www.sigmaaldrich.com/safety-center/msds-search.html
SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

11.4 Handling and Storage

11.4.1 Storage Conditions

Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature: 2 - 8 °C
Sigma-Aldrich; Material Safety Data Sheet for Cyproterone acetate. Product Number C3412. Version 4.0 (March 2010). Available from, as of March 3, 2011: https://www.sigmaaldrich.com/safety-center/msds-search.html
Do not store above 25 °C
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Dianette (Last updated November 2010). Available from, as of March 23, 2011: https://www.medicines.org.uk/EMC/medicine/1814/SPC/Dianette/

11.5 Exposure Control and Personal Protection

11.5.1 Personal Protective Equipment (PPE)

Hand protection: For prolonged or repeated contact use protective gloves. Eye protection: Safety glasses with side-shields conforming to EN166. Skin and body protection: Choose body protection according to the amount and concentration of the dangerous substance at the work place.
Sigma-Aldrich; Material Safety Data Sheet for Cyproterone acetate. Product Number C3412. Version 4.0 (March 2010). Available from, as of March 3, 2011: https://www.sigmaaldrich.com/safety-center/msds-search.html
Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).
Sigma-Aldrich; Material Safety Data Sheet for Cyproterone acetate. Product Number C3412. Version 4.0 (March 2010). Available from, as of March 3, 2011: https://www.sigmaaldrich.com/safety-center/msds-search.html

11.6 Regulatory Information

New Zealand EPA Inventory of Chemical Status
Cyproterone acetate: Does not have an individual approval but may be used under an appropriate group standard

11.7 Other Safety Information

11.7.1 Toxic Combustion Products

Hazardous decomposition products formed under fire conditions. - Carbon oxides, Hydrogen chloride gas
Sigma-Aldrich; Material Safety Data Sheet for Cyproterone acetate. Product Number C3412. Version 4.0 (March 2010). Available from, as of March 3, 2011: https://www.sigmaaldrich.com/safety-center/msds-search.html

12 Toxicity

12.1 Toxicological Information

12.1.1 Acute Effects

12.1.2 Interactions

At high therapeutic cyproterone acetate doses of three times 100 mg per day, cyproterone acetate may inhibit CYP2C8. Thiazolidinediones (ie the anti-diabetics pioglitazone and rosiglitazone) are substrates or CYP2C8 (increased blood levels of these anti-diabetics may require dose adjustment).
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Androcur (Last updated January 2011). Available from, as of March 23, 2011: https://www.medicines.org.uk/EMC/medicine/1808/SPC/Androcur/
Alcohol appears to reduce the effect of /cyproterone/ which is of no value in chronic alcoholics.
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Androcur (Last updated January 2011). Available from, as of March 23, 2011: https://www.medicines.org.uk/EMC/medicine/1808/SPC/Androcur/
The risk of statin-associated myopathy or rhabdomyolysis may be increased when those HMG-CoA inhibitors (statins) which are primarily metabolised by CYP3A4 are co-administered with high cyproterone acetate doses, since they share the same metabolic pathway.
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Androcur (Last updated January 2011). Available from, as of March 23, 2011: https://www.medicines.org.uk/EMC/medicine/1808/SPC/Androcur/
Drugs acting on androgen receptors modify opioid transmission in the central nervous system. To investigate a direct interaction, /investigators/ studied whether the binding of [3H]diprenorphine to mouse brain membranes was modified by cyproterone acetate (progesterone derivative with antiandrogen activity), flutamide (non-steroidal antiandrogen), 5alpha-dihydrotestosterone and progesterone. Only cyproterone acetate inhibited [3H]diprenorphine binding (IC50 = (1.62 +/- 0.33) x 10(-6) M) without modifying its association rate. These results suggest that cyproterone acetate binds to opiate receptors independently of its classical androgenic intracellular receptor effect.
Gutierrez M et al; Eur J Pharmacol 328 (1): 99-102 (1997)

12.1.3 Antidote and Emergency Treatment

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160-1

12.1.4 Human Toxicity Excerpts

/HUMAN EXPOSURE STUDIES/ One daily dose of either 5 mg or 10 mg cyproterone acetate (CA) was administered to 2 groups of 4 fertile men for 6 months. The medication was preceded by a 3 months placebo period and followed by a recovery phase of 5 to 8 months. During CA-treatment the sperm count/mL decreased and the percentage of abnormal spermatozoa increased slightly (0.991 less than P less than 0.05). Sperm penetration assessed by the Kremer test did not show any decrease during treatment. Serum levels of testosterone and FSH decreased, but those of LH remained unchanged during treatment. Two pregnancies occurred after 13/4 and 51/2 months of CA-treatment. The serum-CA concentration in these 2 volunteers did not differ from that of the remainder. Three subjects who began the study were withdrawn because of depressive mood changes (2) and weakness combined with dizziness (1). Data from these subjects were not included. The results indicate that daily doses of 5 mg and 10 mg of cyproterone acetate are not effective as a male contraceptive.
Fogh M et al; Acta Endocrinol (Copenh) 91 (3): 545-52 (1979)
/SIGNS AND SYMPTOMS/ Overdose may cause nausea, vomiting and, in females, withdrawal bleeding. There are no specific antidotes and further treatment should be symptomatic.
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Dianette (Last updated November 2010). Available from, as of March 23, 2011: https://www.medicines.org.uk/EMC/medicine/1814/SPC/Dianette/
/CASE REPORTS/ The multiplicity of meningiomas or abrupt lesion growth in patients treated with cyproterone acetate suggests that this progestative treatment may promote lesion growth. /The authors/ report the rapid regression of an incidental meningioma after discontinuation of a 10-year cyproterone acetate treatment. This unique observation suggests that conservative management of meningiomas may be the best option among users of high doses of cyproterone acetate, given that spontaneous regression may occur after hormonal treatment discontinuation.
Goncalves AM et al; AJNR Am J Neuroradiol 31 (8): 1504-5 (2010)
/CASE REPORTS/ ... Three male patients aged 78-83 years are presented, in whom severe hepatotoxic reactions emerged after cyproterone acetate (CPA) administration. Patients were treated with CPA at the doses of 200-300 mg/day for malignant prostate disease for 3-12 months prior to the acute manifestation of the hepatic disease. Clinical features compatible with mixed hepatocellular and cholestatic liver disease including jaundice, white stools and dark urine, manifested in all three cases whereas encephalopathy and ascites were present in two of the patients. Other primary causes of hepatotoxicity (alcohol consumption and viral hepatitis) were also verified in two cases, and in those patients biopsy findings revealed the presence of cirrhotic lesions in liver parenchyma. Discontinuation of the therapeutic agent led to the amelioration of the clinical profile in all the patients whereas a patient died 40 d after hospital admission due to sepsis, despite acute liver disease improvement. ...
Savidou I et al; World J Gastroenterol 12 (46): 7551-5 (2006)
For more Human Toxicity Excerpts (Complete) data for CYPROTERONE ACETATE (20 total), please visit the HSDB record page.

12.1.5 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ ... Male and female C57BL/10J mice were fed 0 or 800 ppm cyproterone acetate (CPA) in the diet for 13 weeks. Body weight was reduced (P > 0.001 at 13 weeks) by approximately 33%. Seminal vesicle weights were reduced (P > 0.001) and showed histological atrophy, changes consistent with the anti-androgenic activity of the compound. Liver weights were increased (P > 0.001) by +90% of control mean weights; hepatocyte hypertrophy and increased fat and glycogen were seen by light microscopy, and hyperplasia of smooth endoplasmic reticulin by transmission electron microscopy. Assessment of liver mixed function oxidase activity demonstrated induction of cytochrome P450 enzymes, and increased isozyme 2B1/2 in males and 3A1 in both sexes was confirmed by immunohistochemical staining of liver sections. An increase in bromodeoxyuridine (BrdU) labelling index of the liver was seen in females only. ...
Tucker MJ, Jones DVet al; Hum Exp Toxicol 15 (1): 64-66 (1996)
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ ... A 52 week CPA study in the mouse strain C57Bl/10J has been reported not to produce liver tumors, although CPA induced significant liver enlargement and induction of the mixed function oxidase CYP3A. The present study is a further investigation of the effects of CPA in mice of the C57Bl/10J strain dosed for 104 weeks. A group of 40 mice/sex were fed 800 ppm CPA in the diet for 104 weeks with a control group of eight/sex. Mortality was high in females after 40 weeks due to hormonal effects in the uterus; no female and only four CPA-dosed males survived to 104 weeks. Liver cell hypertrophy with increased fat and glycogen and single cell or small multifocal areas of hepatocellular necrosis were universal. Proliferating cell nuclear antigen demonstrated an increase in proliferating cells within tumors and within the non-tumor bearing liver of CPA-dosed mice compared with normal livers of control mice. Hepatocellular tumors developed in 44% of males and 22% of females dosed with CPA, compared with none in the controls (the strain has a low, <10%, incidence of spontaneous liver tumors compared with other mouse strains). In addition, over 85% of both sexes dosed with CPA developed adenomatous polyps of the pyloric antrum and pancreatic islet cell hyperplasia, shown by immunostaining to be chiefly of insulin-secreting cells. Adrenocortical atrophy was also observed with other widespread effects in the endocrine system. The results suggest that the liver tumors, as in the rat, are likely to be related to effects on liver growth and mitogenesis. It is suggested that the tumors of the stomach and the pancreatic islet cell hyperplasia are manifestations of the effects of CPA in the endocrine system.
Tucker MJ et al; Carcinogenesis 17 (7): 1473-6 (1996)
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In long-term carcinogenicity studies in rats cyproterone acetate increased the incidence of liver tumors including carcinomas at high doses which concomitantly caused liver toxicity and exceeded the maximum human dose. Further investigations into rodents at lower, non-hepatotoxic doses revealed benign liver proliferations similar to effects described for other steroid hormones. However, it must be borne in mind that sex steroids can promote the growth of certain hormone dependent tissues and tumors.
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Cyprostat (Last updated January 2011). Available from, as of March 23, 2011: https://www.medicines.org.uk/EMC/medicine/20815/SPC/Cyprostat+100mg/
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Cyproterone acetate stimulated the growth of androgen-sensitive mouse mammary carcinoma Shionogi cells in vivo in DD/S mice; the tumor size was increased 11 fold over that in controls after 21 days of treatment with two daily doses of 250 ug/mouse.
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V72 240 (1999)
For more Non-Human Toxicity Excerpts (Complete) data for CYPROTERONE ACETATE (13 total), please visit the HSDB record page.

12.1.6 Non-Human Toxicity Values

LD50 Rat intraperitoneal 565 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 1058
LD50 Mouse intraperitoneal 3300 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 1058

12.1.7 Populations at Special Risk

In patients with a history of thromboembolic processes or suffering from sickle-cell anemia or severe diabetes with vascular changes, the risk: benefit ratio must be considered carefully in each individual case before Cyprostat is prescribed.
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Cyprostat (Last updated January 2011). Available from, as of March 23, 2011: https://www.medicines.org.uk/EMC/medicine/20815/SPC/Cyprostat+100mg/
Cyprostat must not be used in patients with: Meningioma or a history of meningioma; Liver diseases (including Dubin-Johnson syndrome and Rotor syndrome); Malignant tumors (except for carcinoma of the prostate); Previous or existing liver tumors (only if these are not due to metastases from carcinoma of the prostate); Wasting diseases (with the exception of inoperable carcinoma of the prostate); Existing thromboembolic processes; Hypersensitivity to the active substance or any of the excipients.
Datapharm Communications Ltd; Electronic Medicines Compendium (eMC), Summary of Product Characteristics (SPC) for Cyprostat (Last updated January 2011). Available from, as of March 23, 2011: https://www.medicines.org.uk/EMC/medicine/20815/SPC/Cyprostat+100mg/

12.2 Ecological Information

12.2.1 Ecotoxicity Excerpts

/BIRDS and MAMMALS/ To gauge the relative regulative roles of adrenal, gonadal, and thyroid hormones on uropygial gland of male adult pigeons, morphometric, histological, and histochemical observations have been made on a seasonal basis in normal as well as experimentally manipulated birds. Normal birds showed a parallel adrenal-gonadal-uropygial relationship and inverse adrenal-thyroid, thyroid-gonadal, and thyroid-uropygial relationships. Induced hypocorticalism by dexamethasone in the breeding season and hypercorticalism by ACTH or corticosterone treatment in the nonbreeding season were marked by inhibitory and stimulatory changes respectively in the uropygial gland and testis and by inverse thyroid activity. Further, cyproterone acetate treatment in the breeding season completely suppressed testicular functions and increased thyroid activity without affecting either adrenal or uropygial weight, structure, and functions. Based on the observations it is concluded that adrenal steroids are principally involved in regulating the uropygial gland while the gonadal steroids are involved in qualitative aspects of secretion during the breeding phase and thyroid hormones in maintaining the general metabolic profile.
Asnani MV, Ramachandran AV; Gen Comp Endocrinol 92 (2): 213-24 (1993)
/AQUATIC SPECIES/ A short-term gonadal recrudescence bioassay using the mummichog (Fundulus heteroclitus) was employed to examine the consequences of environmentally relevant and pharmacological exposures (1-1000 ng/L) of the androgen, 17alpha-methyl testosterone, and the anti-androgen, cyproterone acetate, on reproductive endocrine endpoints. Recrudescing male (GSI = approx. 2%) and female (GSI = approx. 10%) fish were exposed to graded concentrations of 17alpha-methyl testosterone and cyproterone acetate for 7 or 14 days. In the first experiment (7-day exposure), 17alpha-methyl testosterone concentrations of 250 or 1000 ng/L decreased circulating testosterone and estradiol in female fish, and 11-ketotestosterone in male fish. Plasma T, 11-ketotestosterone and estradiol were decreased following cyproterone acetate exposure (250 and 1000 ng/l). Gonadal steroid biosynthetic capacity was also inhibited in both sexes after exposure to 17alpha-methyl testosterone or cyproterone acetate, as evidenced by decreased in vitro production of testosterone and estradiol. In experiment 2 (14-day exposure), exposures to lower 17alpha-methyl testosterone and cyproterone acetate concentrations (1, 10 and 100 ng/L) resulted in decreased plasma testosterone, with females showing greater sensitivity than males. Both 11-ketotestosterone and estradiol were significantly reduced beginning at 10 ng/L 17alpha-methyl testosterone. In vitro gonadal testosterone production was impaired at 100 ng/L 17alpha-methyl testosterone in both males and females while 1 ng/L cyproterone acetate caused a significant decrease in female fish. In experiment 2, in vitro estradiol production was decreased in females at all concentrations of 17alpha-methyl testosterone and cyproterone acetate, while only 100 ng/L reduced 11-ketotestosterone synthesis in males. Plasma vitellogenin was reduced in females exposed to 1000 ng/L (experiment 1) and 100 ng/L (experiment 2) 17alpha-methyl testosterone, while cyproterone acetate did not alter plasma vitellogenin at any concentration.
Sharpe RL et al; Aquat Toxicol 67 (3): 203-15 (2004)
/AQUATIC SPECIES/ This study was focused on determining the effects of exposure to antiandrogens on the gonadal development of Japanese medaka (Oryzias latipes). Test compounds included the fungicide, vinclozolin and the clinical antiandrogen, cyproterone acetate. Newly hatched medaka were exposed to aqueous solutions of vinclozolin (2500 ug/L) and the vinclozolin fungicide formulation, Ronilan (1000 and 5000 ug/L) and cyproterone acetate (1 and 10 ug/L), for 3 months. Histological evaluation of the gonadal tissues of exposed fish indicated that the 5000 ug/L concentration of the vinclozolin formulation (Ronilan) induced a low incidence of intersex (ie testis-ova) and the 2500 ug/L concentration of vinclozolin-affected spermatogenesis in males. Also, the vinclozolin treatments induced moderate ovarian atresia. Cyproterone acetate also induced a low incidence of testis-ova, but in contrast to the vinclozolin treatment the amount of ovarian tissue in the testis-ova was equal to or greater than the amount of testicular tissue. In the cyproterone acetate treatments, both oogenesis and spermatogenesis were moderately inhibited at all test concentrations. ...
Kiparissis Y et al; Aquat Toxicol. 2003 May 29;63(4):391-403 (2003)
/AQUATIC SPECIES/ The objective of this study was to identify specific physiologic parameters in crustaceans that are targeted by chemicals known to be antiandrogenic in vertebrates. /It was/ hypothesized that chemicals capable of binding to the vertebrate androgen receptor would also elicit toxicity to crustaceans by binding to specific steroid hormone receptors in an antagonistic manner. This hypothesis was tested by evaluating the effects of the antiandrogen cyproterone acetate on growth, molting, sexual differentiation, and reproduction of Daphnia magna. Exposure of daphnids to concentrations of cyproterone acetate appreciably below those that elicited mortality reduced growth but had no effect on molting. These concentrations of cyproterone acetate had no effect on various developmental and maturation parameters. Cyproterone acetate also reduced the number of offspring produced by parthenogenetically reproducing daphnids, but this effect appeared to be a consequence of the reduced size of the daphnids and their inability to accommodate a brood of more than approximately 10 eggs. These results indicate that the antiandrogen cyproterone acetate specifically targets a process critical to growth of daphnids that is independent of molting. Additional studies are warranted to established whether this is an endocrine-related toxicity to crustaceans that is associated with environmental antiandrogens such as some pesticide metabolites.
Leblanc GA, Mclachlan JB; Environ Toxicol Chem 18 (7): 1450-5 (1999)
/AQUATIC SPECIES/ The effects of suspected endocrine disrupting chemicals on freshwater and marine prosobranch species were analysed in laboratory experiments. ... The responses of the fresh water snail Marisa cornuarietis and of two marine prosobranchs (Nucella lapillus, Nassarius (Hinia) reticulatus) to the antiandrogenic model compounds cyproterone acetate and vinclozolin (VZ) are presented. The snails were exposed to nominal cyproterone acetate concentrations of 1.25 mg/L alone and simultaneously to a potent synthetic estrogen (ethinylestradiol), androgen (methyltestosterone) or an indirectly acting xeno-androgen (tributyltin) in experiments with adult specimens and in a life cycle test for 12 months. Marisa and Nucella were furthermore exposed to nominal concentrations of 0.03-1.0 microgram vinclozolin/L for up to 5 months. The antiandrogens induced a number of biological responses in all three species. The length of the penis and of accessory male sex organs (e.g., penis sheath, prostate) were significantly reduced. For Marisa, this effect occurred only in sexually immature specimens and was reversible as the males attained puberty. Typical androgen-mediated responses (imposex development, delayed spermatogenesis, tubulus necrosis of the testis with orchitis and Leydig cell hyperplasia) were partially or totally suppressed by a simultaneous administration of cyproterone acetate. In the two marine species even adult, sexually mature males responded to antiandrogens with a reduction of the male sex organs and an advancement of the sexual repose phase. The results for cyproterone acetate and vinclozolin are compared with the effects of an exposure to xeno-estrogens (bisphenol A, octylphenol) and xeno-androgens (triphenyltin, tributyltin) in the same species. Each group of endocrine disruptors induces a characteristic set of toxicological effects in prosobranch snails which can be used as endpoints in an organismic invertebrate test for the identification of endocrine mimetic test compounds. Estrogens cause primarily an induction of superfemales resulting in an increased female mortality by the enhancement of spawning mass and egg production. The main effects of androgens are a virilization of females by imposex development and a marked decrease of the fecundity. Compared with estrogens and androgens, the antiandrogen responses seem to be less drastic and might have--in contrast to the two other disruptor classes--no biologically significant effects at the population level.
Tillmann MEcotoxicology10 (6):373-88 (2001)

13 Associated Disorders and Diseases

14 Literature

14.1 Consolidated References

14.2 NLM Curated PubMed Citations

14.3 Springer Nature References

14.4 Thieme References

14.5 Chemical Co-Occurrences in Literature

14.6 Chemical-Gene Co-Occurrences in Literature

14.7 Chemical-Disease Co-Occurrences in Literature

15 Patents

15.1 Depositor-Supplied Patent Identifiers

15.2 WIPO PATENTSCOPE

15.3 Chemical Co-Occurrences in Patents

15.4 Chemical-Disease Co-Occurrences in Patents

15.5 Chemical-Gene Co-Occurrences in Patents

16 Interactions and Pathways

16.1 Protein Bound 3D Structures

16.1.1 Ligands from Protein Bound 3D Structures

PDBe Ligand Code
PDBe Conformer

16.2 Chemical-Target Interactions

16.3 Drug-Drug Interactions

16.4 Drug-Food Interactions

  • Avoid alcohol.
  • Take after a meal.

17 Biological Test Results

17.1 BioAssay Results

18 Classification

18.1 MeSH Tree

18.2 NCI Thesaurus Tree

18.3 ChEBI Ontology

18.4 KEGG: ATC

18.5 KEGG: Target-based Classification of Drugs

18.6 KEGG: Drug Groups

18.7 ChemIDplus

18.8 IUPHAR / BPS Guide to PHARMACOLOGY Target Classification

18.9 ChEMBL Target Tree

18.10 UN GHS Classification

18.11 NORMAN Suspect List Exchange Classification

18.12 CCSBase Classification

18.13 EPA DSSTox Classification

18.14 EPA Substance Registry Services Tree

18.15 MolGenie Organic Chemistry Ontology

19 Information Sources

  1. CAS Common Chemistry
    LICENSE
    The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc/4.0/
  2. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  3. DrugBank
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    https://echa.europa.eu/web/guest/legal-notice
    6-chloro-1-β,2-β-dihydro-17-hydroxy-3'H-cyclopropa[1,2]pregna-1,4,6-triene-3,20-dione 17-acetate
    https://echa.europa.eu/substance-information/-/substanceinfo/100.006.409
    6-chloro-1-β,2-β-dihydro-17-hydroxy-3'H-cyclopropa[1,2]pregna-1,4,6-triene-3,20-dione 17-acetate (EC: 207-048-3)
    https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/84752
  7. FDA Global Substance Registration System (GSRS)
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  10. CCSbase
    CCSbase Classification
    https://ccsbase.net/
  11. ChEBI
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  18. ClinicalTrials.gov
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  19. EU Clinical Trials Register
  20. Japan Chemical Substance Dictionary (Nikkaji)
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    Anatomical Therapeutic Chemical (ATC) classification
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    Target-based classification of drugs
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  25. NIST Mass Spectrometry Data Center
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    Cyproterone acetate
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  27. Pharos
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  28. Protein Data Bank in Europe (PDBe)
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  39. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  40. PATENTSCOPE (WIPO)
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CONTENTS