Chlormadinone acetate

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. 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. It is taken by mouth.

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
Drug classProgestogen; Progestin; Progestogen ester; Antigonadotropin; Steroidal antiandrogen
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability100%
Protein binding96.6–99.4% (to albumin and not to SHBGTooltip sex hormone-binding globulin or CBGTooltip corticosteroid-binding globulin)
MetabolismLiver (reduction, hydroxylation, deacetylation, conjugation)
Metabolites3α-Hydroxy-CMA
3β-Hydroxy-CMA
• Others
Elimination half-life25–89 hours
ExcretionUrine: 33–45%
Feces: 24–41%
Identifiers
  • [(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=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

Side effects of the combination of an estrogen and CMA include menstrual irregularities, headaches, nausea, breast tenderness, vaginal discharge, and others. At high dosages, CMA can cause sexual dysfunction, demasculinization, adrenal insufficiency, and changes in carbohydrate metabolism among other adverse effects. 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. It is also an antiandrogen, and hence is an antagonist of the androgen receptor, the biological target of androgens like testosterone and dihydrotestosterone. Due to its progestogenic activity, CMA has antigonadotropic effects. The medication has weak glucocorticoid activity and no other important hormonal activity.

CMA was discovered in 1959 and was introduced for medical use in 1965. It may be considered a "first-generation" progestin. 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. CMA is available widely throughout the world in birth control pills, but is notably not marketed in any predominantly English-speaking countries. It is available alone in only a few countries, including France, Mexico, Japan, and South Korea.

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