Risk of intracranial meningioma with three potent progestogens: A population‐based case–control study

BACKGROUND AND PURPOSE: A dose‐dependent association between the use of cyproterone acetate (CPA) and intracranial meningioma has been identified but data for other potent progestogens are scarce. The association was assessed between intracranial meningioma surgery and exposure to three potent progestogens: CPA (≥25 mg/day), nomegestrol acetate (NOMAC) (3.75–5 mg/day) and chlormadinone acetate (CMA) (2–10 mg/day). METHODS: In this nationwide population‐based case–control study, cases underwent surgery for intracranial meningioma in France from 2009 to 2018. They were matched to five control subjects for sex, year of birth and area of residence. Progestogen exposure was defined as progestogen use within the year before surgery for cases or the same date for their controls. RESULTS: In total, 25,216 cases were included (75% women, median age 58 years). Progestogen exposure was noted for 9.9% of cases (2497/25,216) and 1.9% (2382/126,080) of controls, with an odds ratio (OR) of 6.7 (95% confidence interval [CI] 6.3–7.1). The OR was 1.2 (1.0–1.4) for short‐term use (<1 year) and 9.5 (8.8–10.2) for prolonged use. A strong association was identified for prolonged use of CPA (OR = 22.7, 95% CI 19.5–26.4), NOMAC (OR = 6.5, 95% CI 5.8–7.2) and CMA (OR = 4.7, 95% CI 4.5–5.3). Progestogen exposure increased the risk of meningioma for all histological grades and anatomical sites, particularly for the anterior and middle skull base: OR = 35.7 (95% CI 26.5–48.2) and 23.9 (95% CI 17.8–32.2) for CPA. The estimated number of attributable cases was 2124 (95% CI 2028–2220) (212/year). CONCLUSION: A strong association between prolonged exposure to potent progestogens and surgery for meningioma was observed. The risk increased from CMA to NOMAC to CPA. Individuals should be informed of this risk.