Depot Medroxyprogesterone Acetate and Risk of Meningioma in the US.
Level 3 - non-randomized controlled study
Retrospective propensity score-matched cohort study using electronic health record database
PubMed 40892397 · doi:10.1001/jamaneurol.2025.3011
What was done
This retrospective population-based cohort study analyzed electronic health record data from the US TriNetX database (68 healthcare organizations) between December 2004 and December 2024. Researchers evaluated females who used only one specific hormonal contraceptive or progestin modality (depot medroxyprogesterone acetate [DMPA], oral medroxyprogesterone acetate, combined oral contraceptives, intrauterine devices, progestin-only pills, or subdermal implants) and compared them with non-hormone user controls using propensity score matching. Diagnoses were tracked via ICD, CPT, and RxNorm codes to calculate relative risk (RR) and number needed to harm (NNH) for subsequent meningioma diagnosis.
What was found
From 10,425,438 eligible females (mean age 33.4 years), the propensity-matched DMPA cohort included 88,667 patients (mean age 26.2 years). DMPA use was associated with an elevated risk of meningioma (RR 2.43, 95% CI 1.77–3.33; NNH = 1,152), with the risk confined to individuals with >4 years of exposure or those initiating use after age 31 years. Oral medroxyprogesterone acetate showed a smaller increase in risk (RR 1.18, 95% CI 1.10–1.27; NNH = 3,020). No elevated risk of meningioma was found with combined oral contraceptives, intrauterine devices, progestin-only pills, or subdermal implants.
Why it matters
This study provides large-scale US data linking prolonged or older-age use of DMPA to increased relative meningioma risk, while reassuringly finding no elevated risk across other common contraceptive options. The high number needed to harm indicates that absolute risk for individual patients remains low.
Limits
The study is observational and retrospective, depending on billing and coding data that may contain diagnostic or exposure misclassifications. Despite propensity score matching, residual confounding and differences in indications for progestin use cannot be fully ruled out. The abstract does not report adherence, precise cumulative lifetime dosing, or potential surveillance bias from differential head imaging across groups.
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