Development and Growth of Intracranial Meningiomas in Transgender Women Taking Cyproterone Acetate as Gender-Affirming Progestogen Therapy: A Systematic Review.

Background: Gender-affirming hormone therapy is critical to the management of transgender persons. Cyproterone acetate (CPA) is a synthetic, progesterone-like compound commonly used in high doses as gender-affirming progestogen therapy in transgender women. An association between high-dose CPA and the development and growth of intracranial meningioma, including case reports in transgender women, has been described. This systematic review summarizes these cases at the patient level and discusses their management.

Methods: This systematic review was registered with PROSPERO (CRD42020191965). A detailed search of the PubMed, EMBASE, and Web of Science electronic bibliographic databases was performed (inception-December 20, 2020). Two review authors independently completed screening, data extraction, and risk of bias assessment in duplicate.

Results: Nine records were included describing (n=12) individual case reports and (n=35) intracranial meningiomas. The median age at presentation was 48 years (interquartile range [IQR], 43-55 years), most frequent daily CPA doses were 50 mg/day (n=5) and 100 mg/day (n=5), and the median duration of CPA use was 9.5 years (IQR, 6.5-17.5 years). Multiple meningiomas were common (n=7). For most cases (n=10), surgical resection was the initial preferred management strategy, but two were successfully managed by CPA cessation.

Conclusions: Transgender women receiving high doses of CPA may be at increased risk of intracranial meningioma development and/or growth, although this remains a rare disease. For presumed CPA-associated meningioma, drug cessation appears to be an appropriate management strategy when surgery is not imminently required to manage raised intracranial pressure or prevent neurological deterioration. Given the importance of gender-affirming hormone therapy to transgender persons, a suitable alternative hormone regimen should be offered, although the use of CPA in both high doses and for prolonged periods of time is now in decline.