Abstract
Progestin-associated meningioma is a rare complication of cyproterone acetate (CPA), an anti-androgen commonly prescribed in feminizing hormone therapy regimens for transgender and gender-diverse individuals. A dose-response association has been observed, particularly with longer-term exposure to doses ≥ 50 mg daily; however, the dose below which CPA use is safe remains unclear. We herein report the cases of 2 transgender women using CPA who developed meningioma. Novel aspects of our cases include: (i) the presence of symptomatic giant meningiomas (> 5 cm), including multiple meningiomas in one patient, requiring urgent surgical intervention; (ii) meningioma development with both high-dose, long duration and low-dose, shorter duration CPA; and (iii) the presence of a PIK3CA missense variant in one patient, which may play a role in the pathogenesis of progestin-associated meningioma. Our cases highlight the real-world risk of this likely underreported adverse effect and underscore the importance of clinician vigilance for neurological sequelae. We suggest using the lowest dose of CPA that maintains adequate androgen suppression, with consideration of alternative anti-androgens where appropriate.