What is cyproterone?

Cyproterone: A Steroidal Antiandrogen with Multiple Clinical Applications

Cyproterone acetate is a steroidal antiandrogen with progestational properties that inhibits androgen binding to receptors and suppresses testosterone production through pituitary feedback inhibition. 1

Mechanism of Action

• Cyproterone acetate (CPA) acts through dual mechanisms: direct competitive inhibition of androgen receptor binding and negative feedback on the hypothalamic-pituitary axis to suppress testosterone production 1, 2
• It has strong progestational activity in addition to its antiandrogenic effects, making it different from non-steroidal antiandrogens 3, 2
• CPA creates feedback inhibition of pituitary LHRH (luteinizing hormone-releasing hormone) release, thereby suppressing testosterone production 1, 4

Clinical Applications

Prostate Cancer

• CPA is available in Canada and Europe (not FDA-approved in the US) for treatment of androgen-sensitive metastatic prostate cancer 1
• In prostate cancer treatment, CPA shows no significant survival difference compared to diethylstilbestrol (DES), but with fewer cardiovascular side effects 1
• When used alone, CPA is less effective than goserelin (an LHRH agonist) in delaying progression of metastatic prostate cancer (median time to progression: 225 days for cyproterone vs. 346 days for goserelin) 1
• CPA can reduce tumor flare when initiating LHRH agonist therapy for prostate cancer 1

Transgender Healthcare

• Used as an antiandrogen component in gender-affirming hormone therapy for transgender women/transfeminine individuals 1
• Lower doses (10 mg daily) are equally effective as higher doses (25-100 mg) in suppressing testosterone levels below 2 nmol/L when combined with estrogen therapy 5
• Higher doses are associated with more side effects, particularly elevated prolactin levels 5

Dermatological and Endocrine Conditions

• Effective for treating androgen-mediated skin disorders including acne, seborrhea, and hirsutism 6, 2
• Used in combination with ethinylestradiol (EE/CPA) for women with facial acne, with 82.8% of patients showing good or very good response after six treatment cycles 6
• Component in hormone replacement therapy preparations for menopausal women 3

Other Applications

• Treatment of sexual disorders in men, including hypersexuality 2, 4
• Management of precocious puberty 2

Side Effects and Monitoring

• Generally well tolerated, but liver toxicity has been recognized as a complication of long-term use 1
• Other potential side effects include edema, weight gain, shortness of breath (rarely seen) 1
• Can cause tiredness, lack of drive, listlessness and depressive moods 4
• Gynecomastia occurs in approximately 20% of male patients 4
• Higher doses are associated with increased prolactin levels and lower high-density lipoprotein concentrations 5
• Should be avoided in patients with hereditary angioedema as it may worsen the condition 1

Dosing Considerations

• For transgender women, lower doses (10 mg daily) are as effective as higher doses (25-100 mg) for testosterone suppression when combined with estrogen therapy 5
• For acne treatment in women, typically used at 2 mg in combination with 0.035 mg ethinylestradiol 6
• For sexual disorders in men, doses of 100-200 mg daily orally or 300 mg weekly intramuscularly have been used 4

Contraindications

• Should not be used in patients with hereditary angioedema as it may worsen the condition 1
• Caution in patients with liver disease due to potential hepatotoxicity 1
• Not recommended for patients with a history of thromboembolic disorders when used in combination with estrogens 7

Cyproterone acetate represents an important therapeutic option in various clinical scenarios, particularly in prostate cancer, transgender healthcare, and androgen-mediated dermatological conditions, though careful monitoring for side effects is essential during treatment.