BMJ. 2021 Feb 3;372:n37. doi: 10.1136/bmj.n37. PMID: 33536184
This observational cohort study used data from the French administrative healthcare database during 20072015 to assess the risk of meningioma development related to treatment with cyproterone acetate. The cohort comprised 253,777 participants, of whom 54% had high exposure to cyproterone acetate, and 45% had low exposure.
Cyproterone acetate is an effective antiandrogen and is used by women to treat hyperandrogenism of various causes. It is also used for symptom alleviation in trans-women (assigned male at birth). The safety of the drug for the different indications and the respective dose levels used in clinical practice is important to characterise. It has been known since some time that the development of meningioma is related to treatment with cyproterone acetate. The label includes a warning of this risk since 2007, and since 2011 it is formally contraindicated to resume cyproterone acetate after treatment of meningioma. The presence of progesterone receptors on meningiomas provides a possible biological mechanism.
High dose exposure to cyproterone acetate (defined as cumulative dose > 3g in 6 months), was compared to low dose exposure (< 3 g in 6 months). The primary outcome was surgery or radiotherapy for meningioma. Trans-women (male to female) on high dose cyproterone acetate were reported separately.
The relative risk of meningioma was 5.2 (95% confidence interval: 3.28.6) in the high dose group, and there was a cumulative dose-effect. Those with long term high dose exposure had a hazard ratio > 20 (12.835). The location of the meningioma differed between groups. The high dose group had an almost 47-fold increased risk of anterior skull base meningioma. In trans-women, the incidence of meningioma was 20.7 per 100 000 person years, as compared to none in non-exposed trans-men.
This study confirms the risk for high dose long-term use of cyproterone acetate in men, women, and trans individuals. This risk should be remembered in any clinical situation when treatment with cyproterone acetate is considered. However, there was no observed risk for low dose cyproterone acetate use in women.