Cyproterone Acetate (CPA)
Overview
Cyproterone acetate is a progestogen with potent anti-androgenic effects. It suppresses testosterone production by acting on the HPG axis (similar to how progesterone signals the body to reduce gonadotropins). It is widely used in Europe, Australia, Canada, and parts of Asia.
| Property | Details |
|---|---|
| Drug class | Progestogen; anti-androgen |
| Mechanism | Suppresses LH/FSH → reduced T production; weak androgen receptor blocker |
| Half-life | 38 hours |
| Typical dose | 10–12.5 mg/day |
| Frequency | Once daily |
Dosing
Dose-dependent meningioma risk
CPA carries a dose-dependent risk of meningioma (a usually benign brain tumour). Higher cumulative doses significantly increase risk. Do not exceed 12.5 mg/day — historic doses of 50–100 mg/day are no longer considered safe. Note that the European Medicines Agency (EMA) formally restricts all medicines with CPA doses ≥10 mg/day (2020 PRAC ruling), so 12.5 mg/day is within the restricted range — discuss cumulative dose monitoring with your provider.
| Level | Dose | Notes |
|---|---|---|
| Starting | 6.25–12.5 mg/day | Quarter to half a 50 mg tablet |
| Typical | 10–12.5 mg/day | Sufficient for most |
| Maximum recommended | 12.5 mg/day | Higher doses increase meningioma risk |
| Reduction attempt | Try 6.25 mg/day after 6–12 months | Some can reduce CPA once E2 is stable |
Cumulative Dose Monitoring
If you take CPA long-term, track your total lifetime dose. Meningioma risk increases significantly after 3+ years of use, even at 10–12.5 mg/day. Consider switching to another anti-androgen (bicalutamide or estrogen monotherapy) once your T has been suppressed for 1–2 years.
How It Works
- Progestogenic activity — CPA acts on progesterone receptors in the hypothalamus/pituitary, reducing GnRH, LH, and FSH output
- Androgen receptor blockade — weak competitive inhibition of androgen receptors
- Direct T suppression — reduces testicular testosterone production via reduced LH stimulation
Because of its progestogenic effects, CPA is more potent at suppressing T than spironolactone or bicalutamide, but carries additional risks.
Side Effects
| Side Effect | Frequency | Notes |
|---|---|---|
| Meningioma | Rare (dose-dependent) | Risk increases with cumulative dose >25 mg/day over years |
| Depression | Common (up to 20%) | Can be significant; monitor mental health |
| Fatigue | Common | Especially at higher doses |
| Weight gain | Some | Due to progestogenic effects |
| Increased prolactin | Common | Monitor prolactin levels |
| Liver enzyme elevation | Occasional | Usually mild |
| Vitamin B12 deficiency | Long-term use | Consider supplementation |
Depression Risk
CPA can cause or worsen depression in some individuals. If you have a history of depression, monitor closely. If mood significantly declines in the first weeks, consider switching to bicalutamide or spironolactone.
Monitoring
| Test | Frequency | Rationale |
|---|---|---|
| T (testosterone) | Every 3 months | Confirm suppression |
| Prolactin | Annually | CPA can raise prolactin |
| Liver function | Annually | ALT, AST |
| Mental health | Ongoing | Monitor for depression |
| Meningioma symptoms | Ongoing | Headaches, vision changes, seizures |
Meningioma Risk — Detailed Information
What Is Meningioma?
A meningioma is a tumour of the meninges (the membranes covering the brain and spinal cord). The vast majority (>90%) are benign, but they can cause symptoms and require surgical removal.
Risk Factors
- Cumulative CPA dose — risk increases with total lifetime exposure
- Dose > 25 mg/day — significantly higher risk than low doses
- Duration of use — longer use increases cumulative dose
- History of meningioma — absolute contraindication
Symptoms
- Persistent headaches
- Vision changes (blurring, double vision)
- Seizures
- Hearing loss or tinnitus
- Memory problems
- Personality changes
Stop CPA and seek medical attention if you develop any of these symptoms
Risk Mitigation
- Use the lowest effective dose — 10–12.5 mg/day, never more (note: the EMA restricts all doses ≥10 mg/day)
- Consider reducing dose after 6–12 months — once E2 is stable, some people can lower CPA or switch to monotherapy
- Consider switching to bicalutamide or spironolactone if you have risk factors
- Do not use CPA if you have a personal or family history of meningioma
Comparison
| Aspect | CPA | Spironolactone | Bicalutamide |
|---|---|---|---|
| T suppression | Strong | Mild | Does not lower T |
| Meningioma risk | Yes | No | No |
| Depression risk | Yes | Low | Low |
| Potassium issues | No | Yes | No |
| Prolactin elevation | Yes | No | No |
References
Weill A, et al. (2021). Use of high-dose cyproterone acetate and risk of intracranial meningioma in women: a nested case-control study. BMJ. https://www.bmj.com/content/372/bmj.n37
Nota NM, et al. (2018). Prolactin levels in transgender women receiving cyproterone acetate. Journal of Clinical Medicine.
WPATH (2022). Standards of Care, Version 8. https://www.tandfonline.com/doi/full/10.1080/26895269.2022.2100644