Prolonged Depot Medroxyprogesterone Acetate Use and Intracranial Meningiomas: Insights From a Systematic Review and Institutional Case Series

Background: Recent studies have identified distinctive features in meningioma patients with long-term progestin exposure, but these patterns have not been described in those using depot medroxyprogesterone acetate (DMPA), a contraceptive commonly prescribed in the United States. Objective: To define the clinical, imaging, and pathological characteristics of DMPA-related meningiomas and compare them to a matched cohort without progestin exposure. Methods: A PRISMA-guided systematic review of progestin-associated meningiomas was conducted, followed by a retrospective case–control study at a single institution (2014–2024). Women with ≥2 years of uninterrupted DMPA use and pathologically confirmed intracranial meningiomas were included. Age- and sex-matched patients with surgically treated meningiomas but no history of progestin use served as controls. Outcomes included tumor multiplicity, anatomical distribution, bone invasion, progesterone receptor (PR) status, and histopathology. Independent predictors of DMPA exposure were assessed with multivariable logistic regression. Results: The literature review identified 24 studies linking high dose progestins with elevated meningioma risk and demonstrating tumor regression after drug withdrawal. The institutional cohort comprised 95 patients: 38 DMPA-exposed (median age 44.6 years; median exposure 129 months) with 85 tumors, and 57 controls with 60 tumors. Compared with controls, DMPA-related tumors more frequently invaded bone (50.0% vs. 17.5%; p