Cyproterone is an antiandrogen that suppresses the action of testosterone and its metabolite on tissues. Its mechanism of action involves blocking the binding of dihydrotestosterone to specific androgen hormone receptors, particularly those located in prostate cancer cells. The drug exerts negative feedback on the hypothalamic-pituitary axis, thereby inhibiting luteinizing hormone action, which results in reduced testosterone production in the testes.
Cyproterone is virtually 100% absorbed after oral administration. Bioavailability is approximately 88%.
Cyproterone penetrates into plasma, where more than 95% is bound to albumins. It has an affinity for adipose tissue, where it accumulates and is subsequently released gradually.
Cyproterone is metabolized primarily in the liver by the CYP3A4 enzyme, forming the active metabolite 15β-hydroxycyproterone acetate. This metabolite retains its androgenic activity but has reduced progestogenic activity.
Approximately 60% of cyproterone is excreted via bile in faeces and approximately 33% is excreted renally in urine.
⚠️ Warnings
Hepatotoxicity has been reported in patients treated with cyproterone, including jaundice, hepatitis, and hepatic failure. Fatal cases have also been reported in patients receiving cyproterone at doses of 100 mg and above. A higher proportion of fatal cases occurred in men with advanced prostate cancer. The toxicity of the drug is dose-dependent. It is therefore justified to monitor liver function both before initiating therapy and at regular intervals during treatment. If hepatotoxicity is confirmed, the drug should be discontinued, particularly as both benign and malignant liver tumours have been observed following cyproterone treatment, potentially causing life-threatening intra-abdominal haemorrhage.
Long-term cyproterone therapy may cause the development of meningioma. Should this occur, treatment with cyproterone must be terminated.
An increased incidence of thromboembolic disorders has been observed in patients treated with cyproterone; therefore, patients with a positive history of venous or arterial thrombotic or thromboembolic disorders, stroke, or advanced malignancies must exercise particular caution regarding the increased risk of further thromboembolic events.
Cases of anaemia have been reported in men taking cyproterone; therefore, regular monitoring of red blood cell counts is required.
Strict medical monitoring is required in diabetic patients, as cyproterone therapy may necessitate adjustment of the therapeutic dose of oral antidiabetic agents or insulin.
It should be noted that dyspnoea may occur during high-dose cyproterone therapy; however, these symptoms are not considered to require medical intervention.
Adrenal cortex function should be monitored regularly during cyproterone therapy, as preclinical studies suggest possible suppression due to the corticosteroid-like effect of the drug at high doses.
When prescribing cyproterone therapy to women, a thorough general physical examination and gynaecological examination (including breast examination and cervical cytology smear) must be performed, and pregnancy must be ruled out. If persistent spotting or recurrent bleeding occurs during combination therapy, a gynaecological examination is required to exclude organic disease.
