Cyproterone acetate (CPA) is a synthetic steroid that does two things at once: it blocks the androgen receptor, and it acts as a potent progestogen (a progesterone-like hormone) that lowers the brain’s signal to the testes to make testosterone. It is sold as Androcur and Cyprostat in the UK and Europe, and at a low 2 mg dose with ethinylestradiol as Dianette and co-cyprindiol.
It has never been licensed in the United States (Kuijpers et al., JCEM 2021; Angus et al., JCEM 2025). In Europe its single most important safety issue is meningioma, a usually benign brain tumor whose risk rises with the total amount of CPA taken. A 2020 EMA review restricted high-dose CPA for that reason (EMA referral, 2020). It is also widely used as the antiandrogen in feminizing hormone therapy for transgender women.
This page summarizes what the UK product labels, the EMA and MHRA reviews and the clinical studies report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Steroidal antiandrogen with progestogenic activity (ATC G03HA01) |
| Brands | Androcur, Cyprostat (CPA alone); Dianette, co-cyprindiol (2 mg CPA + 35 µg ethinylestradiol) |
| Route | Oral tablets; a 300 mg/3 mL depot injection exists in some countries |
| Strengths | 10, 50 and 100 mg tablets alone; 1–2 mg in combination products |
| Half-life (label) | 43.9 ± 12.8 h terminal half-life after a 100 mg oral dose |
| Main mechanism | Blocks androgen receptors and suppresses LH/FSH release |
| Key risks | Dose-dependent meningioma; liver toxicity (fatal cases at 100 mg/day and above) |
| US status | Not FDA-approved; not named in the DEA Schedule III list |
| WADA status | Not named on the 2026 Prohibited List |
What it is
CPA is a chlorinated derivative of progesterone. PubChem lists the formula C₂₄H₂₉ClO₄ and a molecular weight of 416.9 g/mol (PubChem CID 9880). The EMA describes it as “a synthetic progesterone derivative with anti-androgenic properties” (EMA Annex II, 2020).
The Androcur label describes its two actions (Androcur SmPC):
| Action | What it does |
|---|---|
| Androgen receptor blockade | Stops testosterone and DHT from acting on their target tissues, whatever their blood level |
| Progestogenic feedback | Acts on the hypothalamus to reduce gonadotropin (LH and FSH) release, so the testes make less testosterone |
This combination is what sets CPA apart from pure receptor blockers such as bicalutamide. Bicalutamide blocks the receptor but lets testosterone rise. CPA blocks the receptor and lowers testosterone. The label notes that sex drive and potency fall and gonadal function is inhibited. It is also unlike spironolactone, a weaker antiandrogen with no progestogen effect.
Pharmacokinetics
From the Androcur label (Androcur SmPC):
| Parameter | Value |
|---|---|
| Absolute oral bioavailability | 88% of the dose |
| Peak level after 100 mg (two 50 mg tablets) | About 285 ng/mL at about 3 h |
| Terminal half-life | 43.9 ± 12.8 h (≈1.8 days) |
| Clearance | 3.5 ± 1.5 mL/min/kg |
| Protein binding | Almost entirely to albumin; 3.5–4% unbound; not bound to SHBG |
| Metabolism | Hydroxylation and conjugation; main plasma metabolite is 15β-hydroxy-CPA; metabolized by CYP3A4 |
| Excretion | Mostly as metabolites, urine to bile ratio 3:7 |
The long half-life means levels change slowly. The label states that CPA is cleared from the blood over a typical interval of 24–120 h.
Approved medical uses
CPA is authorized through national procedures, so the approved uses differ by country and strength. The EMA summarized them in 2020 (EMA Annex II):
- 10 mg and 50 mg: mainly for signs of androgenization in women (hirsutism, androgenic hair loss, acne, oily skin).
- 50 mg, 100 mg and the 300 mg/3 mL depot: reduction of sex drive in sexual deviation in men, and prostate cancer.
- 1–2 mg with an estrogen: acne (2 mg CPA with 35 µg ethinylestradiol), contraception and menopausal hormone therapy (1–2 mg CPA with estradiol valerate).
In the UK, the labeled uses and doses are:
| Product | Labeled use | Labeled dose |
|---|---|---|
| Androcur 50 mg | Control of libido in severe hypersexuality or sexual deviation in adult men, when other interventions are inappropriate | 50 mg twice daily after meals, then the lowest dose that works |
| Cyprostat 50 mg | Prostate cancer: preventing “flare” when starting an LHRH analogue | 200 mg/day alone for 5–7 days, then 200 mg/day for 3–4 weeks with the LHRH analogue |
| Cyprostat 50 mg | Prostate cancer: long-term palliative treatment when LHRH analogues or surgery are unsuitable | 200–300 mg/day in 2–3 doses; maximum 300 mg/day |
| Cyprostat 50 mg | Hot flushes after orchidectomy or during LHRH analogue treatment | 50 mg/day, titrated within 50–150 mg/day |
Sources: Androcur SmPC; Cyprostat SmPC. The “flare” is the short testosterone surge that LHRH agonists such as leuprolide cause in the first weeks; CPA blocks its effect.
Both labels say CPA must not be given before puberty is complete and is not recommended under 18. The Androcur label adds that it is not a male contraceptive, because sperm production falls only slowly.
Acne and hirsutism (brief)
Dianette and co-cyprindiol (2 mg CPA with 35 µg ethinylestradiol) are licensed in the UK for moderate to severe androgen-related acne and/or hirsutism in women of reproductive age. For acne, they are meant only after topical treatment or oral antibiotics have failed (Dianette SmPC). The product is also a contraceptive. Its label reports a venous blood clot (VTE) risk 1.5–2 times higher than with levonorgestrel-containing pills.
A 2025 Cochrane review of 23 small trials found mostly low- or very-low-certainty evidence. CPA with ethinylestradiol performed similarly to spironolactone, finasteride or ketoconazole on hirsutism scores in single trials (Matjila et al., Cochrane 2025).
Meningioma risk and the 2020 EMA review
What the studies found
A meningioma is a tumor of the membranes around the brain and spinal cord. Most are not cancerous, but they can press on nearby nerves and brain tissue. A link with high-dose CPA was first described in a 2008 case series and added to the labels of products with 10 mg or more per day in 2009 (EMA Annex II; EMA referral).
The key study is a French national cohort of 253,777 girls and women who started high-dose CPA between 2007 and 2014 (Weill et al., BMJ 2021). It compared women exposed to a cumulative dose of at least 3 g in the first six months with women who took less than 3 g. The outcome was meningioma that needed surgery or radiotherapy.
| Cumulative CPA dose | Meningioma rate per 100,000 person-years | Adjusted hazard ratio (95% CI) |
|---|---|---|
| Under 3 g (reference) | 4.5 | 1 (reference) |
| 3 g or more (all exposed) | 23.8 | 6.6 (4.0–11.1) |
| 12–36 g | 26.0 | 6.4 (3.6–11.5) |
| 36–60 g | 54.4 | 11.3 (5.8–22.2) |
| Over 60 g | 129.1 | 21.7 (10.8–43.5) |
Table values from Weill et al., BMJ 2021 and the EMA Annex II. For scale, the Androcur label notes that 12 g corresponds to about one year of 50 mg/day taken 20 days a month. The EMA notes that over 60 g corresponds to about five years of that schedule.
Other findings from the French study:
- Risk falls after stopping. One year after stopping CPA, the risk in the exposed group was 1.8 times that of the control group (95% CI 1.0–3.2), much lower than during use.
- Typical locations. Tumors at the front and middle of the skull base, including the spheno-orbital region, appeared to be specific to CPA.
- Transgender women. An additional analysis of 10,876 transgender women found 3 meningiomas in 14,460 person-years (20.7 per 100,000 person-years).
A later French case-control study of 18,061 women who had meningioma surgery found CPA use in 4.9% of cases vs 0.3% of controls, an odds ratio of 19.21 (95% CI 16.61–22.22). This was the highest of all progestogens studied (Roland et al., BMJ 2024). A 2022 meta-analysis of four observational studies found the excess risk at high doses. Pooling high and low doses together showed no statistically significant increase (Lee et al., Sci Rep 2022).
What regulators decided
On 13 February 2020 the EMA’s safety committee (PRAC) recommended new limits, and the CMDh adopted them on 26 March 2020 (EMA referral):
- Products with 10 mg or more should be used for hirsutism, hair loss, acne and oily skin only after other treatments, including lower-dose CPA, have failed. Once they work, the dose should be reduced to the lowest effective dose.
- All CPA products, including 1–2 mg combinations, are contraindicated in people who have or have had a meningioma.
- If a meningioma is diagnosed, all CPA products must be stopped permanently.
- Use for prostate cancer was not changed.
- The EMA estimated the overall risk as rare, between 1 and 10 in 10,000 people depending on dose and duration.
For 2 mg combination products, the EMA found no evidence of a meningioma risk. It estimated that reaching a 12 g cumulative dose with a 2 mg product would take more than 20 years (EMA Annex II).
The UK MHRA advised that, outside prostate cancer, CPA should be used for libido control in adult men only when other interventions are inappropriate. Up to May 2020 it had received 10 UK reports of meningioma with high-dose CPA, all after 14–36 years of use where duration was known (MHRA Drug Safety Update, 2020).
After French restrictions in 2018–2019, the number of people exposed to CPA in France fell by 85%, from 55,000 in August 2018 to 7,900 high-dose users in December 2021. The yearly rate of CPA-associated meningioma surgery fell by 93% in cisgender women and 86% in men between 2017 and 2021 (Roland et al., Pharmacoepidemiol Drug Saf 2025).
Symptoms listed by regulators include vision changes, hearing loss or ringing in the ears, loss of smell, headaches that worsen over time, memory loss, seizures and weakness in the arms or legs. Meningiomas can also cause no symptoms.
Use in transgender care
CPA is not licensed for gender-affirming care. The MHRA notes off-label use of high-dose CPA in this setting (MHRA, 2020). It is commonly combined with estradiol (for example estradiol valerate) in Europe and Australia (Angus et al., JCEM 2025). The research question has shifted toward the lowest dose that still suppresses testosterone.
Dose studies
| Study | Design and n | CPA doses | Main findings |
|---|---|---|---|
| Kuijpers et al., JCEM 2021 (ENIGI) | Prospective cohort, 882 trans women on estrogen | None, 10, 25, 50 or 100 mg/day | Estrogen alone: testosterone 5.5 nmol/L. All CPA doses: 0.9–1.1 nmol/L, below the 2 nmol/L target. Prolactin rose and HDL fell as the dose increased. No difference in liver enzymes between doses |
| Even Zohar et al., J Sex Med 2021 | Retrospective cohort, 64 trans women | 10–20 vs 50–100 mg/day | Testosterone and gonadotropins suppressed equally. Prolactin at 12 months 398 vs 804 mIU/mL (p = 0.004) |
One limitation of the ENIGI study: only 4 participants started on 10 mg/day, and the authors note that few 10 mg results were available. The 25 mg and 50 mg groups were large (234 and 599 participants).
Randomized trials against spironolactone
| Trial | n and duration | Regimen | Result |
|---|---|---|---|
| Burinkul et al., J Sex Med 2021 | 52 trans women, 12 weeks, single-blind | Estradiol valerate 4 mg/day plus CPA 25 mg/day or spironolactone 100 mg/day | Testosterone in the female range (under 50 ng/dL) in 90% on CPA vs 19% on spironolactone. Drug-induced liver injury and asymptomatic high prolactin were seen with CPA |
| Angus et al., JCEM 2025 | 63 people, 6 months | Estradiol plus CPA 12.5 mg/day or spironolactone 100 mg/day | No difference in breast development (breast–chest distance difference 0.27 cm, 95% CI −0.82 to 1.35). Testosterone under 2 nmol/L in 68.8% vs 45.2% (OR 9.01, 95% CI 1.83–44.44). Prolactin higher with CPA |
In short, CPA suppresses testosterone more reliably than spironolactone, but in the one randomized trial that measured it, that did not translate into more breast growth at 6 months.
Brain tumors in transgender women
A Dutch chart review of 2,555 trans women followed for 23,935 person-years found eight meningiomas. That was 4.1 times the rate in the general female population (95% CI 1.9–7.7) and 11.9 times the male rate (95% CI 5.5–22.7) (Nota et al., Brain 2018). Prolactinomas (prolactin-secreting pituitary tumors) were also more common. Most affected women still used CPA when diagnosed.
A systematic review of 12 published cases in trans women found that the most common doses were 50 or 100 mg/day, used for a median of 9.5 years. Two cases were managed by stopping CPA without surgery (Millward et al., Transgend Health 2022).
Side effects and risks
Liver toxicity
The Androcur label lists direct liver toxicity (jaundice, hepatitis and liver failure) as common. At doses of 100 mg/day and above, fatal cases have been reported, mostly in men with advanced prostate cancer. Toxicity is dose-related and usually appears several months after starting. The label requires liver tests before treatment, regularly during it, and whenever symptoms appear (Androcur SmPC). Benign and malignant liver tumors, which can bleed into the abdomen, are listed as very rare.
A case series of 22 men with CPA-induced liver injury (doses 50–200 mg/day) gives a sense of severity (Bessone et al., Liver Int 2016):
| Feature | Finding |
|---|---|
| Time to onset | 163 ± 97 days |
| Pattern | Hepatocellular injury in 91%, mostly with jaundice |
| Severity | Severe in 50%; fatal in 3 patients (14%) |
| Outcome | 19 recovered after stopping CPA; 3 needed corticosteroids |
In rats, high doses of CPA increased liver tumors, and CPA formed DNA adducts in liver cells from rats, monkeys and human liver cells in the lab. The label states that the clinical relevance is uncertain.
Other labeled side effects
From the Androcur label (Androcur SmPC):
- Very common: reduced sperm count and ejaculate volume. Infertility is usual, and sperm may disappear after 8 weeks. Sperm production usually recovers about 3–5 months after stopping, and in some men up to 20 months.
- Common: lower libido and erectile dysfunction, breast enlargement (gynecomastia), weight change with fluid retention, temporary low mood and restlessness, shortness of breath at high doses, hot flushes, sweating and fatigue.
- Not known: anemia during long-term use, suppression of the adrenal glands, blood clots (a causal link has not been established), and osteoporosis from long-term androgen deprivation.
- Prolactin: levels may rise slightly at higher doses. In the transgender studies above, the rise was dose-dependent.
Who should not use it
The Androcur label lists these contraindications:
- liver disease, past or current liver tumors, or malignant tumors other than prostate cancer;
- past or current meningioma;
- past or current thrombosis or embolism;
- severe diabetes with blood vessel damage, sickle cell anemia, severe chronic depression, or wasting diseases;
- people under 18 or whose bone and testicular development is incomplete.
Interactions
CPA is broken down by CYP3A4. Strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir) are expected to raise its levels, and inducers (rifampicin, phenytoin, St John’s wort) to lower them. At very high doses (100 mg three times a day), it may inhibit several CYP enzymes, raising levels of pioglitazone or rosiglitazone and the risk of muscle damage with CYP3A4-metabolized statins. The label also notes that alcohol appears to reduce its effect (Androcur SmPC). In people with diabetes, blood sugar control should be checked, because CPA can change insulin or tablet needs.
Monitoring
The UK label calls for:
- liver function tests before and during treatment;
- regular checks of adrenal function and red blood count;
- blood sugar checks in people with diabetes;
- a semen analysis before treatment in men who may want children;
- watching for signs of meningioma (Androcur SmPC; EMA referral).
Legal status and use outside medicine
CPA is a prescription-only medicine in the UK (Androcur SmPC) and is not FDA-approved in the US (Angus et al., JCEM 2025). It is not named in the US Schedule III list of anabolic steroids (21 CFR 1308.13). It is not named on the WADA 2026 Prohibited List, which does not include antiandrogens as a class. Because it lowers testosterone and blocks its action, it works against muscle building rather than for it.
Key takeaways
- Two actions in one drug. CPA blocks the androgen receptor and, as a progestogen, lowers LH, FSH and testosterone. Its half-life is about 44 hours.
- Approved in Europe and the UK, never in the US. UK uses are prostate cancer and severe hypersexuality in men. The 2 mg combination with ethinylestradiol is used for acne and hirsutism.
- Meningioma risk rises with total dose. In French data, the hazard ratio reached 21.7 above 60 g cumulative dose. Since 2020, the EMA restricts high-dose use and bans CPA after any meningioma.
- Liver injury can be severe. Fatal cases are reported at 100 mg/day and above, so liver tests are required before and during treatment.
- Lower doses in transgender care. Doses of 10–25 mg/day suppressed testosterone about as well as 50–100 mg/day in cohort studies, with smaller rises in prolactin. In one randomized trial, CPA did not improve breast growth over spironolactone.
Sources
- ADVANZ Pharma. Androcur 50 mg tablets: Summary of Product Characteristics. Revised October 2024. emc.
- ADVANZ Pharma. Cyprostat 50 mg tablet: Summary of Product Characteristics. Revised October 2024. emc.
- Bayer plc. Dianette: Summary of Product Characteristics. emc.
- European Medicines Agency. Cyproterone-containing medicinal products: Article 31 referral. Restrictions in use of cyproterone due to meningioma risk. 2020. EMA.
- European Medicines Agency. Cyproterone Article 31 referral, Annex II: Scientific conclusions. 2020. EMA.
- Medicines and Healthcare products Regulatory Agency. Cyproterone acetate: new advice to minimise risk of meningioma. Drug Safety Update. June 29, 2020. GOV.UK.
- Weill A, Nguyen P, Labidi M, et al. Use of high dose cyproterone acetate and risk of intracranial meningioma in women: cohort study. BMJ. 2021;372:n37. PubMed.
- Roland N, Neumann A, Hoisnard L, et al. Use of progestogens and the risk of intracranial meningioma: national case-control study. BMJ. 2024;384:e078078. PubMed.
- Roland N, Neumann A, Baricault B, et al. High-dose cyproterone acetate and intracranial meningioma: impact of the risk minimisation measures implemented in France in 2018-2019. Pharmacoepidemiol Drug Saf. 2025;34(1):e70078. PubMed.
- Lee KS, Zhang JJY, Kirollos R, et al. A systematic review and meta-analysis of the association between cyproterone acetate and intracranial meningiomas. Sci Rep. 2022;12(1):1942. PubMed.
- Nota NM, Wiepjes CM, de Blok CJM, et al. The occurrence of benign brain tumours in transgender individuals during cross-sex hormone treatment. Brain. 2018;141(7):2047–2054. PubMed.
- Millward CP, Keshwara SM, Islim AI, et al. Development and growth of intracranial meningiomas in transgender women taking cyproterone acetate as gender-affirming progestogen therapy: a systematic review. Transgend Health. 2022;7(6):473–483. PubMed.
- Bessone F, Lucena MI, Roma MG, et al. Cyproterone acetate induces a wide spectrum of acute liver damage including corticosteroid-responsive hepatitis: report of 22 cases. Liver Int. 2016;36(2):302–310. PubMed.
- Kuijpers SME, Wiepjes CM, Conemans EB, et al. Toward a lowest effective dose of cyproterone acetate in trans women: results from the ENIGI study. J Clin Endocrinol Metab. 2021;106(10):e3936–e3945. PubMed.
- Even Zohar N, Sofer Y, Yaish I, et al. Low-dose cyproterone acetate treatment for transgender women. J Sex Med. 2021;18(7):1292–1298. PubMed.
- Burinkul S, Panyakhamlerd K, Suwan A, et al. Anti-androgenic effects comparison between cyproterone acetate and spironolactone in transgender women: a randomized controlled trial. J Sex Med. 2021;18(7):1299–1307. PubMed.
- Angus LM, Leemaqz SY, Kasielska-Trojan AK, et al. Effect of spironolactone and cyproterone acetate on breast growth in transgender people: a randomized clinical trial. J Clin Endocrinol Metab. 2025;110(6):e1874–e1884. PubMed.
- Matjila MJ, Le Roux PA, van der Spuy ZM. Cyproterone acetate for hirsutism. Cochrane Database Syst Rev. 2025;11(11):CD001125. PubMed.
- National Center for Biotechnology Information. Cyproterone acetate, PubChem CID 9880. PubChem.
- World Anti-Doping Agency. The 2026 Prohibited List. WADA.
- Code of Federal Regulations. 21 CFR 1308.13, Schedule III. eCFR.