Medroxyprogesterone acetate and risk of intracranial meningioma: a systematic review and meta-analysis

Abstract Objective Medroxyprogesterone acetate (MPA) is widely used for contraception and results in sustained systemic progestin exposure. Observational studies have reported an association between MPA and intracranial meningioma, but effect estimates and exposure definitions vary. Methods We conducted this review in accordance with PRISMA guidelines. PubMed, Embase, Cochrane, and Web of Science were searched on February 7, 2026, without restrictions on date, language, or study design, supplemented by manual searching. We included comparative observational studies evaluating injectable MPA exposure, including intramuscular or subcutaneous depot formulations, and intracranial meningioma outcomes. Random-effects meta-analyses pooled odds ratios (ORs) for any-duration exposure and by duration strata. Results Ten studies met inclusion criteria, of which seven contributed to the primary quantitative synthesis. Injectable MPA exposure was associated with increased odds of intracranial meningioma for any-duration exposure (pooled OR 3.38, 95% CI 1.88 to 6.07), although a wide 95% prediction interval (0.49 to 23.16) reflected substantial between-study heterogeneity. Short-term use (≤ 1 year) was also associated with a statistically significant increase in risk (OR 1.69, 95% CI 1.21 to 2.36). Long-term use (> 1 year) was associated with higher odds of meningioma (OR 2.95, 95% CI 2.08 to 4.19). Leave-one-out sensitivity analyses showed that the any-duration estimate remained statistically significant across study omissions, while duration-stratified estimates, particularly the > 1 year subgroup, were sensitive to omission of individual studies. Conclusion Injectable MPA exposure was associated with increased odds of intracranial meningioma, with a duration-related signal suggesting higher odds with longer use. Given substantial heterogeneity and the observational nature of the evidence, these findings should be interpreted cautiously. They support duration-aware counseling, continued pharmacovigilance, and further comparative studies using standardized exposure definitions.