Can I prescribe cyproterone acetate (CA) in the US?

Cyproterone Acetate Availability in the United States

No, you cannot prescribe cyproterone acetate (CPA) in the United States because it is not FDA-approved and remains unavailable for clinical use in this country, despite its established efficacy and availability in Europe and Canada. 1, 2

Regulatory Status

• CPA is only available in Canada and Europe for treatment of androgen-sensitive metastatic prostate cancer and other androgen-related conditions. 1, 2
• The medication has no FDA approval for any indication in the United States, making it inaccessible through standard prescribing channels. 1
• This represents a significant therapeutic gap, as CPA is recognized by European and Canadian medical communities as a second-line hormonal therapy for prostate cancer. 1

Clinical Context and Evidence

Despite its unavailability in the US, the evidence base for CPA is substantial:

Established Indications Elsewhere

• Prostate cancer management: CPA functions as monotherapy providing complete androgen blockade through dual mechanisms—competitive androgen receptor inhibition and suppression of testosterone production via negative feedback on the hypothalamic-pituitary axis. 2, 3
• Prevention of tumor flare: When initiating LHRH agonist therapy, CPA effectively prevents acute disease exacerbation. 1, 3
• Transgender healthcare: The World Professional Association for Transgender Health recommends CPA as an antiandrogen component in hormone therapy for transgender women. 1
• Other applications: CPA is used for recurrent ischemic priapism prevention and vasomotor symptoms in cancer patients in countries where it is available. 4

Comparative Effectiveness

• CPA shows no significant survival difference compared to diethylstilbestrol in prostate cancer, but demonstrates fewer cardiovascular side effects. 1, 2
• When used alone, CPA is less effective than goserelin in delaying metastatic prostate cancer progression. 1, 2
• In transgender care, doses as low as 10 mg daily effectively suppress testosterone below 2 nmol/L when combined with estrogens, with fewer side effects than higher doses. 5

Alternative Approaches in the US

Since CPA is unavailable, US clinicians must use FDA-approved alternatives:

For Prostate Cancer

• First-generation antiandrogens: Flutamide, nilutamide, or bicalutamide in combined androgen blockade regimens (though these lack CPA's dual mechanism). 4
• Second-generation antiandrogens: Enzalutamide, apalutamide, or darolutamide for more potent androgen receptor blockade.
• LHRH agonists/antagonists: Without the benefit of CPA for flare prevention, requiring alternative strategies for managing initial testosterone surge.

For Transgender Care

• Spironolactone: The most commonly used antiandrogen in US transgender medicine, though less potent than CPA.
• GnRH agonists: More expensive but highly effective for testosterone suppression.
• Bicalutamide: Off-label use as an alternative antiandrogen, though with different side effect profile.

Important Caveats

• The lack of US availability does not reflect concerns about efficacy, but rather regulatory and market factors. 1, 2
• Hepatotoxicity remains a recognized complication of long-term CPA use, requiring regular liver function monitoring in countries where it is prescribed. 1, 2
• CPA is contraindicated in hereditary angioedema and requires caution in pre-existing liver disease. 1