Cyproterone is a synthetic steroidal antiandrogen with progestogenic activity that was developed in the 1960s and later introduced into clinical use for the management of androgen-dependent conditions. It is primarily used in the treatment of prostate cancer, severe hirsutism, acne, and in some gender-affirming hormone therapy regimens due to its ability to block androgen receptors and suppress gonadotropin secretion, leading to reduced testosterone levels. Its clinical development was marked by strong therapeutic efficacy in controlling androgen-driven disease, along with important safety concerns that emerged over time, including risks of hepatotoxicity and an increased incidence of meningioma with long-term or high-dose use, which led to restrictions and updated prescribing guidelines in several countries.
BRAND NAMES
· Androcur – primary and most widely used antiandrogen formulation
· Cyprostat – used mainly in some countries for prostate cancer
· Diane-35 – combined formulation.
MECHANISM OF ACTION
Cyproterone acts as a competitive antagonist at androgen receptors, blocking the action of endogenous androgens such as testosterone and dihydrotestosterone at target tissues. In addition to receptor blockade, it exerts a strong progestogenic effect on the hypothalamic–pituitary axis, leading to suppression of luteinizing hormone (LH) secretion and consequently reduced testicular testosterone production.
PHARMACOKINETICS
Absorption
Cyproterone is well absorbed orally after administration, with peak plasma concentrations typically reached within a few hours. Its bioavailability is relatively high but may vary due to first-pass hepatic metabolism.
Distribution
Cyproterone exhibits a large volume of distribution, reflecting extensive penetration into tissues beyond the bloodstream. Its lipophilic steroid structure allows wide distribution into fatty tissues and highly perfused organs, where it can accumulate and exert prolonged pharmacologic effects.
Metabolism
Cyproterone is extensively metabolized in the liver, primarily through hydroxylation and conjugation pathways. The major metabolite is 15β-hydroxycyproterone acetate, which retains some antiandrogenic activity.
Elimination
Cyproterone is eliminated mainly via biliary excretion into feces, with a smaller fraction excreted in the urine as metabolites. After extensive hepatic metabolism, its conjugated metabolites are secreted into bile and undergo partial enterohepatic recycling, which can prolong its presence in the body.
PHARMACODYNAMICS
Cyproterone exerts its pharmacological effects through dual antiandrogenic and progestogenic actions. It competitively blocks androgen receptors in target tissues, thereby inhibiting the effects of testosterone and dihydrotestosterone and reducing androgen-dependent processes such as sebaceous gland activity, hair growth, and prostate cell proliferation. In addition, its progestogenic activity suppresses the hypothalamic–pituitary–gonadal axis by inhibiting luteinizing hormone (LH) secretion, which leads to decreased endogenous testosterone production.
ADMINISTRATION
Cyproterone is administered orally, usually in tablet form, and is taken once or multiple times daily depending on the indication and dose regimen. It may be given alone (as cyproterone acetate) or in combination products such as ethinylestradiol-containing formulations for acne, hirsutism, or contraception.
DOSAGE AND STRENGTH
Cyproterone (commonly as cyproterone acetate) is available in various strengths depending on indication. Oral tablet strengths commonly include 10 mg, 50 mg, and 100 mg. In the treatment of androgen-dependent conditions such as hirsutism or acne, lower doses (e.g., 2–10 mg daily, often in combination products) are typically used, while higher doses (50–100 mg daily) may be used in prostate cancer or severe hyperandrogenism.
DRUG INTERACTIONS
Cyproterone is primarily metabolized in the liver, so drugs that affect hepatic enzyme activity can significantly alter its levels. Strong CYP3A4 inducers such as rifampicin, phenytoin, carbamazepine, and certain antiepileptics may reduce its plasma concentration and decrease therapeutic efficacy.
FOOD INTERACTIONS
Cyproterone has no clinically significant food interactions. Food does not meaningfully affect its absorption or overall bioavailability, so it can be taken with or without meals based on patient preference and tolerance.
CONTRAINDICATIONS
Cyproterone is contraindicated in patients with known hypersensitivity to cyproterone acetate or any formulation components. It should not be used in individuals with severe liver disease, including active hepatitis, hepatic tumors, or a history of significant hepatic dysfunction, due to the risk of hepatotoxicity.
SIDE EFFECTS
Fatigue and tiredness
Weight gain
Decreased libido
Erectile dysfunction (in males)
Menstrual irregularities (in females)
Breast tenderness or enlargement (gynecomastia)
Nausea
Abdominal discomfort
OVER DOSAGE
Overdosage of Cyproterone is uncommon but may lead to an exaggeration of its known pharmacological effects. Acute ingestion of high doses can result in severe fatigue, dizziness, nausea, vomiting, and marked sedation. In males, excessive antiandrogen activity may cause pronounced suppression of libido and erectile dysfunction, while in females it may lead to menstrual disturbances.
TOXICITY
Toxicity from Cyproterone is mainly associated with dose-dependent hepatic, endocrine, and neurological effects, particularly with long-term or high-dose use. The most clinically important toxic effect is hepatotoxicity, which may present as elevated liver enzymes, cholestatic jaundice, or rarely severe liver injury such as hepatitis or hepatic failure.
