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

Abstract

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.

Meningioma in patients exposed to progestin drugs: results from a real-life screening program

“…Our study complements the previous large nationwide cohort study focusing on high dose CPA-associated meningiomas referred for neurosurgical resection or radiation [29]. Despite the small size of CMA and NA groups (with a single case of meningioma in each), the prevalence among CMA (1%) and NA (5%) users is consistent with a lower risk of meningioma under these drugs than in CPA users, as reported in the large epidemiological cohort focusing on surgically-treated meningioma [30].…”

“…The main strength of this study lies in its "real-life" approach. Indeed, numerous retrospective cohorts and one meta-analysis already established the link between progestins and meningioma [29][30][31]. However, the yield of MR screening proposed by the French authorities was unknown, especially regarding the expected detection rate, and imaging characteristics of uncovered meningioma in a pauci/asymptomatic population.…”

“…There were 209 women and one transgender male-to-female. The median (IQR) age was 38 (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46) years. No patient had a history of cranial radiation or type II neuro bromatosis.…”

“…For NA and CMA, further studies are needed to identify patients most likely to bene t from screening.needing an invasive treatment. This risk was higher risk for CPA than CMA and NA, was dose-dependent, and a decreased after progestin discontinuation [29,30]. Recently, a meta-analysis con rmed the association between CPA and meningioma and validated the imaging-requirement before undergoing .…”

Risk of meningioma with medicines containing nomegestrol

“…Data reviewed by PRAC included an observational cohort study and a case–control study that used information from the French national health system 3 4. The studies investigated high-dose nomegestrol used as monotherapy and found an increase in risk of meningioma associated with the cumulative dose and age of the patient 3.…”