Use of progestogens and the risk of intracranial meningioma: national case-control study.
Level 4 - case-series / case-control
Nationwide matched case-control study
PubMed 38537944 · doi:10.1136/bmj-2023-078078
What was done
A national matched case-control study was conducted using the French National Health Data System (SNDS). Cases were 18,061 women who underwent intracranial surgery for meningioma between 2009 and 2018. Each case was matched by birth year and residence area to five controls (n = 90,305; total N = 108,366). Progestogen exposure was defined by dispensation within 1 year before the index date (3–5 years for levonorgestrel IUDs). Odds ratios were calculated using conditional logistic regression, with cyproterone, nomegestrol, and chlormadinone acetates evaluated as positive controls.
What was found
Mean participant age was 57.6 years (SD 12.8). Prolonged use (≥1 year) was associated with increased risk of meningioma requiring surgery for: - Medrogestone: 42/18,061 cases (0.2%) vs 79/90,305 controls (0.1%), OR 3.49 (95% CI 2.38 to 5.10) - Injectable medroxyprogesterone acetate: 9/18,061 cases (0.05%) vs 11/90,305 controls (0.01%), OR 5.55 (95% CI 2.27 to 13.56) - Promegestone: 83/18,061 cases (0.5%) vs 225/90,305 controls (0.2%), OR 2.39 (95% CI 1.85 to 3.09) Positive controls showed elevated risks: cyproterone acetate OR 19.21 (95% CI 16.61 to 22.22), nomegestrol acetate OR 4.93 (95% CI 4.50 to 5.41), and chlormadinone acetate OR 3.87 (95% CI 3.48 to 4.30). No excess risk was found for progesterone, dydrogesterone, or levonorgestrel IUDs. Data were insufficient to draw conclusions for dienogest or hydroxyprogesterone.
Why it matters
This nationwide study identifies prolonged use of injectable medroxyprogesterone acetate, medrogestone, and promegestone as risk factors for surgical meningioma, while providing reassurance regarding the safety of levonorgestrel intrauterine systems.
Limits
The study included only surgically treated meningiomas, excluding conservatively managed or asymptomatic cases. Exposure was derived from dispensation claims rather than verified adherence. Exposed case counts were very small for certain agents (e.g., 9 cases for injectable medroxyprogesterone acetate), and statistical power was insufficient to evaluate dienogest or hydroxyprogesterone.
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