1. Long-term usage of cyproterone acetate (CPA) at high doses was associated with greater risk of meningioma development in females.
2. Discontinuation of CPA after one year decreased the relative risk associated with treatment.
Evidence Rating Level: 2 (Good)
Cyproterone acetate (CPA) is a hormone therapy treatment classified as as synthetic progestogen with antiandrogen effects. It is indicated for men with inoperable prostate cancer, and for women with hyperandrogenism and related conditions, such as hirsutism. Previously, studies have found a link between meningioma development and use of CPA at high doses (25-100 mg) in the long term (5-30 years). Historically, studies have reported this association in men but not women. The current observational cohort study investigated the association between meningioma and high dose, prolonged use of CPA in girls and women, including the risk after discontinuation of CPA, and the risk of meningioma for transgender female patients. The study based in France compared the incidence of meningioma between an exposed cohort of female patients who received long-term, high dose CPA, and a control cohort consisting of patients who were only slight exposed to CPA and/or discontinued CPA prematurely (less than 3 grams). There were 253,777 patients in the main study (54.9% in the exposed cohort). The incidence was 23.8 per 100,000 person years in the exposed cohort and 4.5 per 100,000 person years in the control: The relative risk was 5.2 (95% CI 3.2-8.6) and the adjusted hazard ratio was 6.6 (95% CI 4.0-11.1). Higher doses were associated with greater risk (HR 11.3, 95% CI 5.8-22.2 for a dose of 36-60 g; HR 21.7, 95% CI 10.8-43.5 for a dose of 60+ g). After stopping CPA treatment for 1 year, the relative risk dropped to 1.8 (95% CI 1.0-3.2). In the analysis of 10,876 transgender patients, three patients in the exposed group developed a meningioma, leading to an incidence of 20.7 per 100,000 person years, whereas zero participants in the control group developed meningioma. Those three patients took high doses of 100-150 mg daily in the short-term, 3-4.5 years. Overall, this study found an increased risk of developing meningiomas in female patients using cyproterone acetate, although the risk is lowered after discontinuing treatment.
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