Cyproterone: antiandrogen with progestogenic activity
Cyproterone is a steroid drug with antiandrogenic and progestogenic properties. Clinically it is used as cyproterone acetate, the ester prodrug with longer duration and better oral bioavailability. Use since the 1970s includes treatment of androgen related conditions in women (hirsutism, severe acne, alopecia) and advanced prostate cancer in men.
Cyproterone differs from pure antiandrogens such as bicalutamide by additional progestogenic activity. This can be used therapeutically, e.g. to suppress gonadotropin secretion. It also causes typical progestogenic adverse effects such as fatigue, breast tension or mood changes. A specific safety concern is the increased risk of meningioma with high dose long term use.
Mechanism of action
Cyproterone acts on several hormone receptors:
- Competitive inhibition of the androgen receptor in target tissues (prostate, sebaceous glands, hair follicles, hypothalamus)
- Agonist at the progesterone receptor with progestogenic effect
- Inhibition of gonadotropin release through negative feedback at the hypothalamus, reducing testicular testosterone production
The combination of receptor block and endogenous testosterone suppression produces marked reduction of androgen effects. In men testosterone production drops to levels similar to chemical castration with GnRH analogues.
Cyproterone acetate is metabolised hepatically via CYP3A4. The half life is 1 to 3 days, allowing once or twice daily dosing.
Indications
- Severe hirsutism in women: when other therapies are insufficient, often combined with ethinylestradiol (Diane 35)
- Severe acne and androgenetic alopecia: in women with androgen component
- Prostate cancer: monotherapy or combined with GnRH analogues to avoid flare phenomenon
- Gender affirming hormone therapy in trans women: as antiandrogen, often combined with oestrogen
- Precocious puberty in boys: in selected cases under specialist care
- Severe sexual deviation: after strict indication
Dosing and administration
Hirsutism, acne, alopecia in women: 50 to 100 mg cyproterone acetate per day on cycle days 1 to 10, combined with an oral contraceptive or ethinylestradiol. Diane 35 contains 2 mg cyproterone acetate per tablet, taken continuously with ethinylestradiol.
Prostate cancer: 100 to 300 mg per day, often in combination with other agents.
Gender affirming hormone therapy: 25 to 100 mg per day orally, individual adjustment to testosterone levels.
Take with meals, since cyproterone is lipophilic and absorbs better with fatty food.
Monitoring: regular liver enzymes, clinical evaluation, and with high dose use cranial imaging after longer therapy because of meningioma risk.
Adverse effects
Common: fatigue, depressive mood, libido loss, weight changes, breast tension, galactorrhoea, hyperprolactinaemia, rash, pruritus.
Uncommon: erectile dysfunction, testicular hypoplasia in men, fluid retention, hyperglycaemia, raised liver transaminases.
Rare and very rare: hepatotoxic reactions up to fulminant hepatitis, liver tumours, thromboembolic events, meningiomas (particularly with long term high dose), anaphylaxis.
Meningioma risk:
- Increased risk with high dose use over several years, particularly in women over 35
- Cumulative dose of more than 10 g per year or treatment duration over 5 years markedly increases risk
- Signs of meningioma (headache, visual disturbance, neurological deficit) require immediate imaging and discontinuation
- Since 2021 the EMA recommends using cyproterone acetate at high doses only with strict indication and after failure of other options
Interactions
- Strong CYP3A4 inhibitors (itraconazole, ritonavir, erythromycin): raised levels
- Strong CYP3A4 inducers (rifampicin, phenytoin, carbamazepine, St John's wort): reduced levels, possible loss of effect
- Antidiabetics: hyperglycaemia possible, adjust diabetes therapy
- Anticoagulants: possible INR changes
- Other hormonal substances: complex interactions, individual assessment
Special considerations
Pregnancy: contraindicated.
Breastfeeding: contraindicated.
Before therapy:
- History and laboratory (liver, blood count, lipids, glucose)
- In women rule out pregnancy
- Counselling on contraception (also between contraceptive cover and therapy)
- For high dose indications: information about meningioma risk
During therapy: regular liver tests, clinical assessment of efficacy and tolerability. Discuss annual cranial imaging with long term high dose use.
Gender affirming hormone therapy: should be supervised in specialised endocrinology centres with individual titration to testosterone level and clinical effect.
Patient communication: honest information about effect, adverse events and the specific meningioma risk is essential. Patients should take new neurological symptoms seriously and seek medical assessment.
Related substances
- Cyproterone acetate, clinically used ester prodrug
- Dienogest, modern progestogen with antiandrogenic effect
- Dutasteride, 5 alpha reductase inhibitor
- Estradiol valerate, oestrogen component in HRT and pill
- Norethisterone, progestogen with residual androgenic effect
Frequently asked questions
How does cyproterone differ from cyproterone acetate?
Cyproterone is the free substance, cyproterone acetate the ester prodrug. Clinically cyproterone acetate is generally used because it is more orally bioavailable with longer duration. Pharmacologically the action is identical.
Why is meningioma risk relevant?
With longer high dose use of cyproterone acetate (several years, cumulative dose over 10 g per year) the risk of meningiomas rises markedly. These benign tumours can cause neurological symptoms depending on location. With strict indication and careful monitoring use is possible; close observation is recommended.
Does cyproterone help in women with acne?
In women with marked androgenic component and acne, cyproterone acetate combined with ethinylestradiol (Diane 35) is an established option. Mild to moderate acne should first be treated with topical therapy and possibly oral antibiotics.
Is cyproterone standard in prostate cancer?
Today GnRH analogues (leuprorelin, goserelin) or GnRH antagonists (degarelix) and modern non steroidal antiandrogens (enzalutamide, apalutamide) are preferred. Cyproterone remains a reserve option or is initially combined with GnRH analogues to avoid the flare phenomenon.
Sources
- EMA European Medicines Agency
- BfArM German Federal Institute for Drugs and Medical Devices
- AWMF guidelines hirsutism, prostate cancer, gender affirming therapy
- Gelbe Liste cyproterone monograph
Legal notice and disclaimer
The information on this page is provided for general information only and does not constitute medical advice, diagnosis or treatment recommendation. It does not replace advice from a qualified physician or pharmacist. Medicines should only be used on prescription or after dispensing by a pharmacist. All information is based on the product information available at the time of writing and on recognised scientific sources; the manufacturer's current product information always prevails. Sanoliste assumes no liability for completeness, timeliness or accuracy of the information presented. In a medical emergency call the European emergency number 112.