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含去氧孕烯或左炔诺孕酮的口服避孕药与颅内脑膜瘤风险:全国病例对照研究

Oral contraceptives with progestogens desogestrel or levonorgestrel and risk of intracranial meningioma: national case-control study.

作者信息

Roland Noémie, Kolla Epiphane, Baricault Bérangère, Dayani Pauline, Duranteau Lise, Froelich Sébastien, Zureik Mahmoud, Weill Alain

机构信息

EPI-PHARE Scientific Interest Group, French National Agency for Medicines and Health Products Safety, French National Health Insurance, 93285 Saint-Denis, France.

French National Agency for Medicines and Health Products Safety, Saint-Denis, France.

出版信息

BMJ. 2025 Jun 11;389:e083981. doi: 10.1136/bmj-2024-083981.

Abstract

OBJECTIVE

To assess the risk of intracranial meningioma associated with oral contraceptives containing desogestrel, levonorgestrel, or levonorgestrel combined with oestrogen.

DESIGN

Case-control study.

SETTING

French national health data system (Système National des Données de Santé).

PARTICIPANTS

8391 women living in France who required surgery for intracranial meningioma in 2020-23. Each patient was matched to 10 women without intracranial meningioma (controls) on year of birth and area of residence.

MAIN OUTCOME MEASURE

Risk of intracranial meningioma associated with oral contraceptives containing desogestrel 75µg, levonorgestrel 30µg, or levonorgestrel 50-150 µg combined with oestrogen, and duration of use: short term use was defined by one or more dispensations within the year before the index date only, and prolonged use was defined by continuous use of one year or more (up to seven or more years of continuous use). Conditional logistic regression was used to calculate odds ratios.

RESULTS

92 301 women, mean age 59.7 years (standard deviation 12.9 years), were included. Among 8391women who had undergone surgery for intracranial meningioma, 287 (3.4%) used desogestrel 75µg ( 2769/83 910 (3.3%) controls), 17 (0.2%) used levonorgestrel 30 µg ( 140 (0.2%)), and 157 (1.9%) used levonorgestrel combined with oestrogen ( 1933 (2.3%)). In analyses of desogestrel according to duration of use, the odds ratio for risk of intracranial meningioma for short term use was 1.02 (95% confidence interval 0.77 to 1.34) and for prolonged use was 1.32 (1.14 to 1.53). Risk was driven by more than five continuous years of use: odds ratio 1.51 (1.17 to 1.94) for five to seven years and 2.09 (1.51 to 2.90) for ≥7 years. Excess risk was greater in women with meningiomas located in the middle or anterior part of the skull base (1.90 (1.47 to 2.46) and 1.50 (1.17 to 1.93), respectively) and in those who had previously used a progestogen of known associated increased risk (3.30 (2.64 to 4.11)). Results showed no excess risk of intracranial meningioma for levonorgestrel (alone or combined with oestrogen) regardless of duration of use. The estimated number needed to harm with desogestrel was 67 300 women for one intracranial meningioma requiring surgery. Risk was no longer observed one year after discontinuation of desogestrel.

CONCLUSIONS

The results showed a small increased risk of intracranial meningioma in women who had used desogestrel 75 µg for more than five continuous years, but no risk in users of levonorgestrel (alone or combined with oestrogen).

摘要

目的

评估使用含去氧孕烯、左炔诺孕酮或左炔诺孕酮与雌激素联合的口服避孕药与颅内脑膜瘤的风险。

设计

病例对照研究。

研究背景

法国国家卫生数据系统(Système National des Données de Santé)。

研究对象

2020 - 2023年在法国因颅内脑膜瘤需要手术的8391名女性。每位患者按出生年份和居住地区与10名无颅内脑膜瘤的女性(对照)进行匹配。

主要观察指标

使用含75µg去氧孕烯、30µg左炔诺孕酮或50 - 150µg左炔诺孕酮与雌激素联合的口服避孕药与颅内脑膜瘤的风险,以及使用时长:短期使用定义为仅在索引日期前一年内有一次或多次配药,长期使用定义为连续使用一年或更长时间(最长连续使用七年或更长时间)。采用条件逻辑回归计算比值比。

结果

纳入92301名女性,平均年龄59.7岁(标准差12.9岁)。在8391名接受颅内脑膜瘤手术的女性中,287名(3.4%)使用75µg去氧孕烯(2769/83910名对照(3.3%)),17名(0.2%)使用30µg左炔诺孕酮(140名对照(0.2%)),157名(1.9%)使用左炔诺孕酮与雌激素联合制剂(1933名对照(2.3%))。在根据使用时长对去氧孕烯的分析中,短期使用颅内脑膜瘤风险的比值比为1.02(95%置信区间0.77至1.34),长期使用为1.32(1.14至1.53)。风险由连续使用超过五年驱动:5至7年的比值比为1.51(1.17至1.94),≥7年的比值比为2.09(1.51至2.90)。位于颅底中部或前部的脑膜瘤女性的额外风险更大(分别为1.90(1.47至2.46)和1.50(1.17至1.93)),以及先前使用过已知风险增加的孕激素的女性(3.30(2.64至4.11))。结果显示,无论使用时长如何,左炔诺孕酮(单独或与雌激素联合)均无颅内脑膜瘤额外风险。去氧孕烯导致一例需要手术的颅内脑膜瘤的伤害所需估计人数为67300名女性。停用去氧孕烯一年后未再观察到风险。

结论

结果显示,连续使用75µg去氧孕烯超过五年的女性颅内脑膜瘤风险略有增加,但左炔诺孕酮使用者(单独或与雌激素联合)无风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b1d/12153057/83040a7601de/roln083981.f1.jpg

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