法国国民健康保险Alain Weill研究了大剂量使用醋酸环丙孕酮与女性颅内脑膜瘤风险的相关性。2021年2月3日，该研究成果发表在《英国医学杂志》上。
为了探讨大剂量醋酸环丙孕酮（一种孕激素，用于临床治疗高雄激素血症）治疗后发生脑膜瘤的风险，研究组对2007-2015年间法国行政保健数据库SNDS中的数据进行了一项观察性队列研究。
研究对象包括253 777名居住在法国的7-70岁女性，她们在2007-2014年间开始使用醋酸环丙孕酮。这些参与者至少有一次大剂量使用醋酸环丙孕酮，没有脑膜瘤或良性脑瘤的历史，没有长期的疾病状态。当受试者在前六个月内接受了至少3g的累积剂量（139 222名受试者）时被视为暴露（暴露组）；当她们接受了小于3g的累积剂量（114 555名受试者）时被视为轻微暴露（对照组）。另外一项分析包括10876名跨性别参与者（从男性转变为女性）。主要结局为一个或多个颅内脑膜瘤的手术（切除或减压）或放射治疗。
总体来说，暴露组中有69例脑膜瘤（289 544人-年随访），对照组中有20例脑膜瘤（439 949人-年随访）患者接受了手术或放疗治疗。暴露组和对照组中脑膜瘤的发病率分别为23.8/10万人年和4.5/10万人年，粗相对风险为5.2，校正风险比为6.6。累积剂量大于60g的醋酸环丙孕酮的校正风险比为21.7。
停用醋酸环丙孕酮一年后，暴露组患脑膜瘤的风险仅比对照组高1.8倍。在一项补充分析中，2006年已经使用醋酸环丙孕酮的123 997名妇女中，共有463名女性患有脑膜瘤（即累积剂量方面暴露最高的组，风险为383/10万人-年）。脑膜瘤位于前颅底和中颅底，特别是中颅底内侧三分之一，累及蝶眶区，似乎为醋酸环丙孕酮所特异。变性参与者在醋酸环丙孕酮暴露后患脑膜瘤的风险也显著升高（每14 460人-年3例；每10万人-年20.7例）。
研究结果表明，醋酸环丙孕酮的使用与颅内脑膜瘤风险有很强的量效关系。在停止治疗后，风险显著降低。
附：英文原文
Title: Use of high dose cyproterone acetate and risk of intracranial meningioma in women: cohort study
Author: Alain Weill, Pierre Nguyen, Moujahed Labidi, Benjamin Cadier, Thibault Passeri, Lise Duranteau, Anne-Laure Bernat, Isabelle Yoldjian, Sylvie Fontanel, Sébastien Froelich, Jol Coste
Issue&Volume: 2021/02/03
Abstract:
Objective To assess the risk of meningioma associated with use of high dose cyproterone acetate, a progestogen indicated for clinical hyperandrogenism.
Design Observational cohort study.
Setting Data from SNDS, the French administrative healthcare database, between 2007 and 2015.
Participants 253777 girls and women aged 7-70 years living in France who started cyproterone acetate between 2007 and 2014. Participants had at least one reimbursement for high dose cyproterone acetate and no history of meningioma or benign brain tumour, or long term disease status. Participants were considered to be exposed when they had received a cumulative dose of at least 3 g during the first six months (139222 participants) and very slightly exposed (control group) when they had received a cumulative dose of less than 3 g (114555 participants). 10876 transgender participants (male to female) were included in an additional analysis.
Main outcome measure Surgery (resection or decompression) or radiotherapy for one or more intracranial meningiomas.
Results Overall, 69 meningiomas in the exposed group (during 289544 person years of follow-up) and 20 meningiomas in the control group (during 439949 person years of follow-up) were treated by surgery or radiotherapy. The incidence of meningioma in the two groups was 23.8 and 4.5 per 100000 person years, respectively (crude relative risk 5.2, 95% confidence interval 3.2 to 8.6; adjusted hazard ratio 6.6, 95% confidence interval 4.0 to 11.1). The adjusted hazard ratio for a cumulative dose of cyproterone acetate of more than 60 g was 21.7 (10.8 to 43.5). After discontinuation of cyproterone acetate for one year, the risk of meningioma in the exposed group was 1.8-fold higher (1.0 to 3.2) than in the control group. In a complementary analysis, 463 women with meningioma were observed among 123997 already using cyproterone acetate in 2006 (risk of 383 per 100000 person years in the group with the highest exposure in terms of cumulative dose). Meningiomas located in the anterior skull base and middle skull base, particularly the medial third of the middle skull base, involving the spheno-orbital region, appeared to be specific to cyproterone acetate. An additional analysis of transgender participants showed a high risk of meningioma (three per 14460 person years; 20.7 per 100000 person years).
Conclusions A strong dose-effect relation was observed between use of cyproterone acetate and risk of intracranial meningiomas. A noticeable reduction in risk was observed after discontinuation of treatment.
DOI: 10.1136/bmj.n37
Source: https://www.bmj.com/content/372/bmj.n37
BMJ-British Medical Journal:《英国医学杂志》，创刊于1840年。隶属于BMJ出版集团，最新IF：93.333
官方网址：http://www.bmj.com/
投稿链接：https://mc.manuscriptcentral.com/bmj
本期文章：《英国医学杂志》：Online/在线发表
