Epidemiological and clinical data link depot medroxyprogesterone acetate to meningioma

Abstract Meningiomas are among the few intracranial tumors that are more common in females than males. The majority of meningiomas express progesterone receptor (PR), and differences in exposure to progestogens are thought to contribute to sex-based disparity in meningioma. Previous epidemiological and clinical data have demonstrated that multiple progestins, such as cyproterone acetate (CPA), are linked to meningioma. More recently, international epidemiological studies have found a significantly increased risk of meningioma with depot medroxyprogesterone acetate (DMPA), a widely used injectable contraceptive sold under the trade name Depo-Provera. Although the absolute risk of meningioma remains small, exposure to DMPA increases the risk of meningioma by 1.5- to 5.5-fold. DMPA-associated meningiomas are clinically significant, as the risk of craniotomy for tumor resection, not just the risk of tumor diagnosis, is elevated after DMPA exposure. These data suggest that DMPA should be avoided in individuals with a history of meningioma when alternatives are available. The risk of meningioma should be discussed with patients during DMPA counseling, and the utility of screening patients with prolonged DMPA exposure for meningiomas should be investigated. Further work is needed to elucidate the mechanisms of PR signaling in meningioma and to understand the complex interplay of tumor genomics, hormone exposure and signaling, and social and structural drivers of health that may contribute to disparities in meningioma.