Objective To assess the risk of intracranial meningioma associated with the use of selected progestogens. Design National case-control study. Setting French National Health Data System (ie, Système National des Données de Santé ). Participants Of 108 366 women overall, 18 061 women living in France who had intracranial surgery for meningioma between 1 January 2009 and 31 December 2018 (restricted inclusion periods for intrauterine systems) were deemed to be in the case group. Each case was matched to five controls for year of birth and area of residence (90 305 controls). Main outcome measures Selected progestogens were used: progesterone, hydroxyprogesterone, dydrogesterone, medrogestone, medroxyprogesterone acetate, promegestone, dienogest, and intrauterine levonorgestrel. For each progestogen, use was defined by at least one dispensation within the year before the index date (within three years for 13.5 mg levonorgestrel intrauterine systems and five years for 52 mg). Conditional logistic regression was used to calculate odds ratio for each progestogen meningioma association. Results Mean age was 57.6 years (standard deviation 12.8). Analyses showed excess risk of meningioma with use of medrogestone (42 exposed cases/18 061 cases (0.2%) v 79 exposed controls/90 305 controls (0.1%), odds ratio 3.49 (95% confidence interval 2.38 to 5.10)), medroxyprogesterone acetate (injectable, 9/18 061 (0.05%) v 11/90 305 (0.01%), 5.55 (2.27 to 13.56)), and promegestone (83/18 061 (0.5%) v 225/90 305 (0.2 %), 2.39 (1.85 to 3.09)). This excess risk was driven by prolonged use (≥one year). Results showed no excess risk of intracranial meningioma for progesterone, dydrogesterone, or levonorgestrel intrauterine systems. No conclusions could be drawn concerning dienogest or hydroxyprogesterone because of the small number of individuals who received these drugs. A highly increased risk of meningioma was observed for cyproterone acetate (891/18 061 (4.9%) v 256/90 305 (0.3%), odds ratio 19.21 (95% confidence interval 16.61 to 22.22)), nomegestrol acetate (925/18 061 (5.1%) v 1121/90 305 (1.2%), 4.93 (4.50 to 5.41)), and chlormadinone acetate (628/18 061 (3.5%) v 946/90 305 (1.0%), 3.87 (3.48 to 4.30)), which were used as positive controls for use. Conclusions Prolonged use of medrogestone, medroxyprogesterone acetate, and promegestone was found to increase the risk of intracranial meningioma. The increased risk associated with the use of injectable medroxyprogesterone acetate, a widely used contraceptive, and the safety of levonorgestrel intrauterine systems are important new findings. Under the terms of the SNDS data use agreement, the complete study data cannot be shared with other investigators (). However, the authors try to share publication related data as much as possible: algorithms and other additional information are provided in the supplemental data; aggregated data can be supplied upon request by contacting the corresponding author at noemie.roland{at}assurance-maladie.fr.

中文翻译：

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孕激素的使用和颅内脑膜瘤的风险：国家病例对照研究

目的 评估与使用选定孕激素相关的颅内脑膜瘤风险。设计国家病例对照研究。建立法国国家健康数据系统（即Système National des Données de Santé）。参与者 在总共 108 366 名女性中，有 18 061 名居住在法国的女性在 2009 年 1 月 1 日至 2018 年 12 月 31 日（宫内系统的纳入限制期）期间接受过颅内脑膜瘤手术，被视为病例组。每个病例与出生年份和居住地区的五个对照相匹配（90 305 个对照）。主要结果指标 使用选定的孕激素：孕酮、羟孕酮、地屈孕酮、甲孕酮、醋酸甲羟孕酮、普罗孕酮、地诺孕素和宫内左炔诺孕酮。对于每种孕激素，使用的定义是在索引日期之前的一年内至少进行一次配药（13.5 mg 左炔诺孕酮宫内节育系统在三年内，52 mg 左炔诺孕酮宫内节育系统在五年内）。使用条件逻辑回归来计算每个孕激素脑膜瘤关联的比值比。结果 平均年龄为 57.6 岁（标准差 12.8）。分析显示，使用甲孕酮会增加脑膜瘤的风险（42 例暴露病例/18 061 例（0.2%）v 79 例暴露对照/90 305 例对照（0.1%），比值比 3.49（95% 置信区间 2.38 至 5.10））、甲羟孕酮醋酸盐（注射剂，9/18 061 (0.05%) v 11/90 305 (0.01%)、5.55（2.27 至 13.56））和普孕酮 (83/18 061 (0.5%) v 225/90 305 (0.2 %) ，2.39（1.85 至 3.09））。这种超额风险是由于长期使用（≥一年）造成的。结果显示，黄体酮、地屈孕酮或左炔诺孕酮宫内节育系统不会增加颅内脑膜瘤的风险。由于服用地诺孕酮或羟孕酮的人数很少，因此无法得出有关这些药物的结论。观察到醋酸环丙孕酮（891/18 061 (4.9%) vs 256/90 305 (0.3%)，比值比 19.21（95% 置信区间 16.61 至 22.22））、醋酸诺美地孕酮（925/18）的脑膜瘤风险显着增加061 (5.1%) vs 1121/90 305 (1.2%)、4.93 (4.50 至 5.41)) 和醋酸氯地孕酮 (628/18 061 (3.5%) vs 946/90 305 (1.0%)、3.87 (3.48 至 4.30) ))，用作阳性对照。结论 长期使用甲孕酮、醋酸甲羟孕酮和普罗孕酮会增加颅内脑膜瘤的风险。与注射醋酸甲羟孕酮（一种广泛使用的避孕药）的使用相关的风险增加以及左炔诺孕酮宫内节育系统的安全性是重要的新发现。根据SNDS数据使用协议的条款，完整的研究数据不能与其他研究者共享（）。然而，作者尝试尽可能多地共享与出版物相关的数据：补充数据中提供了算法和其他附加信息；可以根据要求通过联系 noemie.roland{at}assurance-maladie.fr 上的相应作者来提供汇总数据。