A dose-dependent association between the use of cyproterone acetate and intracranial meningioma has been identified but data for other potent progestogens are scarce. We assessed the association between intracranial meningioma surgery and exposure to three potent progestogens: cyproterone acetate (CPA; ≥25 mg/day), nomegestrol acetate (NOMAC; 3.75-5 mg/day), and chlormadinone acetate (CMA; 2-10 mg/day).
In this nationwide population-based case-control study, cases underwent surgery for intracranial meningioma in France from 2009-2018. 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.
In total, 25,216 cases were included (75% women, median age 58 years). Progestogen exposure was noted for 9.9% of cases (2,497/25,216) and 1.9% (2,382/126,080) of controls, with an odds ratio of 6.7 [95% CI, 6.3-7.1]. The odds ratio was 1.2 [1.0-1.4] for short-term use (< one year) and 9.5 [8.8-10.2] for prolonged use. A strong association was identified for prolonged use of CPA (OR=22.7 [19.5-26.4]), NOMAC (OR=6.5 [5.8-7.2]), and CMA (OR=4.7 [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 [26.5-48.2] and 23.9 [17.8-32.2] for CPA. The estimated number of attributable cases was 2,124[2028-2220] (212/year).
We observed a strong association between prolonged exposure to potent progestogens and surgery for meningioma. The risk increased from chlormadinone to nomegestrol to cyproterone acetate. Individuals should be informed of this risk.