Prolonged use of chlormadinone acetate and risk of intracranial meningioma: A population-based cohort study

Abstract

Background and purpose: Chlormadinone acetate (CMA) is a synthetic progestin for which cases of intracranial meningioma have been reported following prolonged exposure.

Method: An observational cohort study was conducted based on the French national health data system. Women aged 10-70 years and who started CMA between 2007 and 2017 were included. Participants were considered to be exposed if they had received a cumulative dose >360 mg of CMA during the first 6 months and very slightly exposed (control group) when they had received a cumulative dose ≤360 mg. The outcome was surgery or radiotherapy for one or more intracranial meningioma(s). Poisson models assessed the relative risk (RR) of meningioma.

Results: In total, 828,499 women were included: 469,976 in the exposed group (mean age 39.1 years, SD 10.1) and 358,523 in the control group (38.3 years, SD 11.0). Surgery or radiotherapy for intracranial meningioma between 2007 and 2017 was recorded for 164 and 104 women in the exposed and control groups, respectively. The incidence of meningioma was 18.5 and 6.8 per 100,000 person-years for the exposed and control groups respectively (crude RR = 2.7, 95% confidence interval [CI] 2.1-3.5; age-adjusted RR = 3.1, 95% CI 2.4-4.0). Meningioma incidence reached almost 47 cases/100,000 person-years in the most exposed group (>8.64 g), giving an age-adjusted RR of 6.9, 95% CI 5.1-9.2, relative to the control group.

Conclusions: A strong dose-effect relationship was observed between prolonged use of CMA and risk of meningiomas. As with other progestogens, meningiomas associated with CMA are more likely to be found at the base of the skull.

Keywords: contraceptive; meningioma; menopause; neurosurgery; progestogen.

FIGURE 1

Associations between chlormadinone acetate use and the risk of intracranial meningioma, by cumulative dose, discontinuation and meningioma location. Poisson models: *adjustment for age; cumulative dose and age considered as time‐dependent variables; **discontinuation of CMA for at least 1 year, depending on prior cumulative CMA dose; ***location was known for a total of 231 meningiomas, remaining unknown for tumours not treated by surgery (radiotherapy only). CI, confidence interval; CMA, chlormadinone acetate; g, grammes; PY, person‐years; aRR, adjusted risk ratio.