Progestogen use and the risk of intracranial meningioma: a systematic review and meta-analysis.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational epidemiological studies
PubMed 41732194 · doi:10.1016/j.eclinm.2026.103791
What was done
Authors conducted a systematic review and random-effects meta-analysis searching PubMed/MEDLINE, Embase, Cochrane Library, EPI-PHARE, and pharmacovigilance reports up to November 1, 2025. They included English and French epidemiological studies assessing associations between specific progestogens and intracranial meningiomas. Risk of bias was evaluated using the Newcastle-Ottawa Scale (NOS) and certainty was assessed with GRADE. Primary outcome was intracranial meningioma; secondary outcomes included malignancy, anatomical location, and post-withdrawal regression.
What was found
From 542 screened records, 78 studies were included in the systematic review and 14 high-quality observational studies in the meta-analysis. Cyproterone acetate (CPA) was associated with increased meningioma risk (5 studies, 1,047 exposed; pooled OR 12.36, 95% CI: 7.47–20.45; I² = 73.8%; GRADE: moderate). Depot medroxyprogesterone acetate was also associated with increased risk (6 studies, 842 exposed; pooled OR 2.68, 95% CI: 1.72–4.19; I² = 92.7%; GRADE: low). Increased risk signals were observed without meta-analytic pooling for chlormadinone acetate (3 studies, 164–683 exposed), nomegestrol acetate (3 studies, 171–969 exposed), promegestone (1 study, 83 exposed), medrogestone (1 study, 42 exposed), and desogestrel (2 studies, 115–287 exposed). No signal was found for norgestrel, levonorgestrel, progesterone, dydrogesterone, or spironolactone; evidence was insufficient for dienogest and hydroxyprogesterone. Tumour regression after withdrawal was documented for CPA and nomegestrol acetate.
Why it matters
This study provides molecule-specific risk profiles for intracranial meningioma, identifying elevated risks for high-dose macroprogestogens while finding no signal of harm for common alternatives such as levonorgestrel and natural progesterone.
Limits
All meta-analyzed evidence came from observational studies subject to potential residual confounding and outcome misclassification. Between-study heterogeneity was high (I² = 73.8% to 92.7%), and evidence for several individual progestogens was too sparse to allow quantitative pooling.
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