PDF(Pubmed)
Abstract：
To assess the risk of intracranial meningioma associated with the use of selected progestogens.
National case-control study.
French National Health Data System (ie, Système National des Données de Santé).
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).
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.
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.
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.
National case-control study.
French National Health Data System (ie, Système National des Données de Santé).
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).
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.
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.
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.
摘要：
评估与使用选定的孕激素相关的颅内脑膜瘤的风险。
全国病例对照研究。
法国国家健康数据系统（即，SantésNationaldesDonnéesdeSanté).
总共108366名女性中,在2009年1月1日至2018年12月31日期间（宫内系统限制纳入期）接受脑膜瘤颅内手术的18061名居住在法国的妇女被视为病例组。每个病例与出生年份和居住地区的五个对照相匹配（90305个对照）。
使用了一些孕激素：孕酮，羟孕酮,地屈孕酮，medrogestone,醋酸甲羟孕酮，普美孕酮,Dienogest,和宫内注射左炔诺孕酮.对于每种孕激素，使用定义为在索引日期前一年内至少一次给药(对于13.5mg左炔诺孕酮宫内节育系统,3年内,对于52mg,5年内).使用条件逻辑回归计算每种孕激素脑膜瘤关联的比值比。
平均年龄为57.6岁（标准偏差12.8）。分析显示，使用medrogestone会增加脑膜瘤的风险（42例暴露病例/18061例（0.2％）v79例暴露对照/90305例对照（0.1％），优势比3.49(95%置信区间2.38至5.10))，醋酸甲羟孕酮（可注射，9/18061（0.05%）v11/90305（0.01%），5.55（2.27至13.56）），和普美司通(83/18061(0.5%)v225/90305(0.2%)，2.39（1.85至3.09））。这种超额风险是由长期使用（≥一年）驱动的。结果显示孕酮没有颅内脑膜瘤的额外风险，地屈孕酮，或左炔诺孕酮宫内系统。由于接受这些药物的人数很少，因此无法得出有关孕酮或羟孕酮的结论。醋酸环丙孕酮（891/18061（4.9％）v256/90305（0.3％）观察到脑膜瘤的风险高度增加，优势比19.21（95%置信区间16.61至22.22）），醋酸诺美孕酮（925/18061（5.1％）v1121/90305（1.2％），4.93（4.50至5.41）），和醋酸氯丁酮(628/18061(3.5%)v946/90305(1.0%)，3.87（3.48至4.30）），用作阳性对照。
延长使用medrogestone,醋酸甲羟孕酮，发现普美孕酮会增加颅内脑膜瘤的风险。与使用可注射的醋酸甲羟孕酮相关的风险增加，一种广泛使用的避孕药，左炔诺孕酮宫内系统的安全性是重要的新发现。
全国病例对照研究。
法国国家健康数据系统（即，SantésNationaldesDonnéesdeSanté).
总共108366名女性中,在2009年1月1日至2018年12月31日期间（宫内系统限制纳入期）接受脑膜瘤颅内手术的18061名居住在法国的妇女被视为病例组。每个病例与出生年份和居住地区的五个对照相匹配（90305个对照）。
使用了一些孕激素：孕酮，羟孕酮,地屈孕酮，medrogestone,醋酸甲羟孕酮，普美孕酮,Dienogest,和宫内注射左炔诺孕酮.对于每种孕激素，使用定义为在索引日期前一年内至少一次给药(对于13.5mg左炔诺孕酮宫内节育系统,3年内,对于52mg,5年内).使用条件逻辑回归计算每种孕激素脑膜瘤关联的比值比。
平均年龄为57.6岁（标准偏差12.8）。分析显示，使用medrogestone会增加脑膜瘤的风险（42例暴露病例/18061例（0.2％）v79例暴露对照/90305例对照（0.1％），优势比3.49(95%置信区间2.38至5.10))，醋酸甲羟孕酮（可注射，9/18061（0.05%）v11/90305（0.01%），5.55（2.27至13.56）），和普美司通(83/18061(0.5%)v225/90305(0.2%)，2.39（1.85至3.09））。这种超额风险是由长期使用（≥一年）驱动的。结果显示孕酮没有颅内脑膜瘤的额外风险，地屈孕酮，或左炔诺孕酮宫内系统。由于接受这些药物的人数很少，因此无法得出有关孕酮或羟孕酮的结论。醋酸环丙孕酮（891/18061（4.9％）v256/90305（0.3％）观察到脑膜瘤的风险高度增加，优势比19.21（95%置信区间16.61至22.22）），醋酸诺美孕酮（925/18061（5.1％）v1121/90305（1.2％），4.93（4.50至5.41）），和醋酸氯丁酮(628/18061(3.5%)v946/90305(1.0%)，3.87（3.48至4.30）），用作阳性对照。
延长使用medrogestone,醋酸甲羟孕酮，发现普美孕酮会增加颅内脑膜瘤的风险。与使用可注射的醋酸甲羟孕酮相关的风险增加，一种广泛使用的避孕药，左炔诺孕酮宫内系统的安全性是重要的新发现。
