Pattern of Intracranial Meningiomas Associated With Prolonged DMPA Use: Systematic Review of Synthetic Progestins and Case Series of DMPA-Associated Intracranial Meningiomas

BACKGROUND AND OBJECTIVES: In recent years, reports have demonstrated a unique set of features shared among meningioma patients with a history of prolonged progestin use. This has not yet been described for patients with prolonged use of depot medroxyprogesterone acetate (DMPA), commonly used in the United States. To characterize the clinical, radiological, and pathological features of DMPA-associated meningiomas and compare them with a matched, nonexposed control cohort. METHODS: A preferred reporting items for systematic reviews and meta-analysis-based systematic review of progestin-associated meningiomas was performed followed by a single-center retrospective case-control study (2014-2024). Women with ≥2 years of uninterrupted DMPA use and histologically confirmed intracranial meningioma were included. Age-matched and sex-matched surgical meningioma cases without DMPA exposure served as controls. Outcomes included tumor multiplicity, location, osseous invasion, progesterone-receptor (PR) status, and histopathology. Multivariable logistic regression assessed independent associations with DMPA use. RESULTS: The systematic review identified 32 studies showing that high-dose progestins were associated with significant increased meningioma risk and reported tumor regression after drug withdrawal. Institutional analysis included 95 patients: 38 DMPA-exposed (median age 44.6 years; median exposure 129 months) harboring 85 tumors and 57 controls. DMPA-associated meningiomas showed markedly higher rate of osseous invasion (50.0% vs 17.5%; P < .001), were located in the cavernous sinus (39.5% vs 15.8%, P = .01) and planum sphenoidale (21.1% vs 7.0%, P = .04), and higher number of meningiomas per patient (P < .001). PR expression was universal in DMPA tumors (100% vs 61.8%; P < .001). On multivariable analysis, tumor multiplicity (odds ratio 12.2; P = .0057) and PR positivity (odds ratio 69.6; P < .001) independently predicted DMPA exposure. CONCLUSION: Long-term DMPA use is associated with a distinct pattern of multiple, bone-invasive, PR-positive meningiomas. Based on established patterns with other progestins, drug discontinuation and observation before surgical intervention should be considered for asymptomatic lesions, although prospective validation is warranted.