Chlormadinone acetate

Chlormadinone acetate
Clinical data
Trade namesBelara, Lutéran, Prostal, others
Other namesCMA; RS-1280; ICI-39575; STG-155; NSC-92338; 17α-Acetoxy-6-chloro-6-dehydroprogesterone; 17α-Acetoxy-6-chloropregna-4,6-diene-3,20-dione
Routes of
administration		By mouth[1]
Drug classProgestogen; Progestin; Progestogen ester; Antigonadotropin; Steroidal antiandrogen
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability100%[1][2][3]
Protein binding96.6–99.4% (to albumin and not to SHBGTooltip sex hormone-binding globulin or CBGTooltip corticosteroid-binding globulin)[1][2]
MetabolismLiver (reduction, hydroxylation, deacetylation, conjugation)[1][3]
Metabolites• 3α-Hydroxy-CMA[4][1]
• 3β-Hydroxy-CMA[4][1]
• Others[1]
Elimination half-life25–89 hours[5][1][2][6]
ExcretionUrine: 33–45%[6][2]
Feces: 24–41%[6][2]
Identifiers
IUPAC name
  • [(8R,9S,10R,13S,14S,17R)-17-acetyl-6-chloro-10,13-dimethyl-3-oxo-2,8,9,11,12,14,15,16-octahydro-1H-cyclopenta[a]phenanthren-17-yl] acetate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.005.563
Chemical and physical data
FormulaC23H29ClO4
Molar mass404.93 g·mol−1
3D model (JSmol)
SMILES
  • CC(=O)[C@]1(CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2C=C(C4=CC(=O)CC[C@]34C)Cl)C)OC(=O)C
InChI
  • InChI=1S/C23H29ClO4/c1-13(25)23(28-14(2)26)10-7-18-16-12-20(24)19-11-15(27)5-8-21(19,3)17(16)6-9-22(18,23)4/h11-12,16-18H,5-10H2,1-4H3/t16-,17+,18+,21-,22+,23+/m1/s1
  • Key:QMBJSIBWORFWQT-DFXBJWIESA-N

Chlormadinone acetate (CMA), sold under the brand names Belara, Gynorelle, Lutéran, and Prostal among others, is a progestin and antiandrogen medication which is used in birth control pills to prevent pregnancy, as a component of menopausal hormone therapy, in the treatment of gynecological disorders, and in the treatment of androgen-dependent conditions like enlarged prostate and prostate cancer in men and acne and hirsutism in women.[1][5][7][2][8][9][10] It is available both at a low dose in combination with an estrogen in birth control pills and, in a few countries like France and Japan, at low, moderate, and high doses alone for various indications.[11] It is taken by mouth.[1]

Side effects of the combination of an estrogen and CMA include menstrual irregularities, headaches, nausea, breast tenderness, vaginal discharge, and others.[2] At high dosages, CMA can cause sexual dysfunction, demasculinization, adrenal insufficiency, and changes in carbohydrate metabolism among other adverse effects.[12][13] The drug is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone.[1] It is also an antiandrogen, and hence is an antagonist of the androgen receptor, the biological target of androgens like testosterone and dihydrotestosterone.[1] Due to its progestogenic activity, CMA has antigonadotropic effects.[1][14][15] The medication has weak glucocorticoid activity and no other important hormonal activity.[1]

CMA was discovered in 1959 and was introduced for medical use in 1965.[16][17][18] It may be considered a "first-generation" progestin.[19] The medication was withdrawn in some countries in 1970 due to concerns about mammary toxicity observed in dogs, but this turned out not to apply to humans.[7][20][21][22][23] CMA is available widely throughout the world in birth control pills, but is notably not marketed in any predominantly English-speaking countries.[24][11] It is available alone in only a few countries, including France, Mexico, Japan, and South Korea.[24][11]

  1. ^ a b c d e f g h i j k l m n Kuhl H (2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration" (PDF). Climacteric. 8 (Suppl 1): 3–63. doi:10.1080/13697130500148875. PMID 16112947. S2CID 24616324.
  2. ^ a b c d e f g Raudrant D, Rabe T (2003). "Progestogens with antiandrogenic properties". Drugs. 63 (5): 463–92. doi:10.2165/00003495-200363050-00003. PMID 12600226. S2CID 28436828.
  3. ^ a b Lobo R, Crosignani PG, Paoletti R (31 October 2002). Women's Health and Menopause: New Strategies - Improved Quality of Life. Springer Science & Business Media. pp. 94–. ISBN 978-1-4020-7149-2.
  4. ^ a b Cite error: The named reference pmid19590256 was invoked but never defined (see the help page).
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  8. ^ Mydlo JH, Godec CJ (11 July 2003). Prostate Cancer: Science and Clinical Practice. Academic Press. pp. 437–. ISBN 978-0-08-049789-1.
  9. ^ Kanimoto Y, Okada K (November 1991). "[Antiandrogen therapy of benign prostatic hyperplasia--review of the agents evaluation of the clinical results]". Hinyokika Kiyo (in Japanese). 37 (11): 1423–8. PMID 1722627.
  10. ^ Ishizuka O, Nishizawa O, Hirao Y, Ohshima S (November 2002). "Evidence-based meta-analysis of pharmacotherapy for benign prostatic hypertrophy". Int. J. Urol. 9 (11): 607–12. doi:10.1046/j.1442-2042.2002.00539.x. PMID 12534901. S2CID 8249363.
  11. ^ a b c Cite error: The named reference Drugs.com was invoked but never defined (see the help page).
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  15. ^ Chassard D, Schatz B (2005). "[The antigonadrotropic activity of chlormadinone acetate in reproductive women]". Gynécologie, Obstétrique & Fertilité (in French). 33 (1–2): 29–34. doi:10.1016/j.gyobfe.2004.12.002. PMID 15752663.
  16. ^ Cite error: The named reference Carp2015 was invoked but never defined (see the help page).
  17. ^ Patterson R (21 December 2012). Drugs in Litigation: Damage Awards Involving Prescription and Nonprescription Drugs. LexisNexis. pp. 184–. ISBN 978-0-327-18698-4.
  18. ^ Bud R, Finn BS, Trischler H (1999). Manifesting Medicine: Bodies and Machines. Taylor & Francis. pp. 113–. ISBN 978-90-5702-408-5.
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  20. ^ Cite error: The named reference Lingeman2012 was invoked but never defined (see the help page).
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  22. ^ Cite error: The named reference Dallenbach-Hellweg2013 was invoked but never defined (see the help page).
  23. ^ Cite error: The named reference Gangolli2007 was invoked but never defined (see the help page).
  24. ^ a b Cite error: The named reference Martindale was invoked but never defined (see the help page).
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