Cyproterone Acetate (DB04839): A Comprehensive Pharmacological and Clinical Monograph

Executive Summary

Cyproterone acetate (CPA) is a potent, synthetic, steroidal agent characterized by a dual mechanism of action, functioning as both a competitive antiandrogen and a powerful progestin.[1] Its primary pharmacodynamic effects are achieved through two synergistic pathways: direct competitive antagonism of the androgen receptor (AR) at peripheral target tissues and central antigonadotropic activity mediated by its progestogenic properties, which suppress the hypothalamic-pituitary-gonadal axis and reduce endogenous testosterone production.[3] This dual action underpins its clinical utility across a wide, dose-dependent spectrum of indications. In low-dose formulations, typically combined with an estrogen, it is used to treat severe acne, hirsutism, and other signs of androgenization in women. In high-dose monotherapy, it serves as a palliative treatment for advanced, inoperable prostate cancer and is used for the reduction of sex drive in men with sexual deviations.[3]

Despite its therapeutic efficacy, the clinical application of cyproterone acetate is constrained by significant safety concerns that have shaped its regulatory status and prescribing guidelines globally. The most critical of these is a dose- and duration-dependent risk of developing intracranial meningiomas, a finding from long-term pharmacovigilance that has prompted major regulatory restrictions, particularly in Europe.[6] Furthermore, CPA is associated with a risk of hepatotoxicity, including rare but potentially fatal cases of liver failure, necessitating rigorous monitoring of hepatic function.[8] The risk of thromboembolic events, especially when used in combination with estrogens, also represents a serious adverse effect.[9]