Cyproterone acetate (CPA) is a synthetic steroidal progestogen used as an anti-androgen in a variety of contexts such as Polycystic Ovarian Syndrome (PCOS), Idiopathic Hirsutism, Male-to-Female transgender (as hormone therapy), Prostate cancer, and to suppress sexual drive in men exhibiting sexual deviant behaviour. 

There is a dose-dependent increased risk of meningioma (single or multiple) at CPA doses of  ≥25mg/day. First described in 2008 and highlighted in a population-based French study in 2020, there is a 11-fold higher dose-dependent risk of meningioma with 36g to 60g cumulative CPA dose-exposure compared to <3g. Several large population-based studies in Denmark, Spain, including European Pharmacovigilance Registries, estimate a 6-20 fold risk. It is hypothesised that CPA stimulates progesterone and androgen receptors present in meningioma tumours to trigger growth in skull base, parasagittal & falx-cerebri regions.

Clinical recommendations:

1. CPA at any dose is contraindicated in patients with a history of meningioma.
2. Review current patient cohorts receiving CPA & reassess each case for indication, duration and calculate cumulative dose exposure.
3. Educate patients of long-term CPA exposure with a cumulative dose of ≥10 g about the risk of meningioma (a non-cancerous brain tumour), symptoms to monitor and offer alternative options.
4. Urgent MRI is indicated if vision loss, hearing loss, anosmia, tinnitus, seizures, or limb weakness is noted.
5. Low dose CPA 2 mg in combination with 35 mcg ethinyl oestradiol (e.g., Dianette) has so far not shown to bear the same risk but does possess the theoretical risk & hence should not be used in the context of a history of meningioma.
6. Limiting cumulative exposure is recommended, especially in non-oncology indications.

CPA is a valuable drug in carefully selected indications, but its association with meningioma poses a serious side effect that warrants risk-benefit assessment. Society for Endocrinology will continue to monitor emerging data and collaborate with regulatory bodies to support evidence-based practice.