低剂量米非司酮与两种左炔诺孕酮方案用于紧急避孕：一项世界卫生组织多中心随机试验

Low dose mifepristone and two regimens of levonorgestrel for emergency contraception: a WHO multicentre randomised trial.

作者信息

von Hertzen Helena, Piaggio Gilda, Ding Juhong, Chen Junling, Song Si, Bártfai György, Ng Ernest, Gemzell-Danielsson Kristina, Oyunbileg Amindavaa, Wu Shangchun, Cheng Weiyu, Lüdicke Frank, Pretnar-Darovec Alenka, Kirkman Rosemary, Mittal Suneeta, Khomassuridze Archil, Apter Dan, Peregoudov Alexandre

机构信息

Department of Reproductive Health and Research, WHO, Geneva, Switzerland.

出版信息

Lancet. 2002 Dec 7;360(9348):1803-10. doi: 10.1016/S0140-6736(02)11767-3.

DOI:10.1016/S0140-6736(02)11767-3

PMID:12480356

Abstract

BACKGROUND

A single 10 mg dose of mifepristone, and two 0.75 mg doses of levonorgestrel 12 h apart, are effective for emergency contraception. Because no studies had compared the efficacies of both compounds, or investigated a single dose of 1.5 mg levonorgestrel, we undertook this three-arm trial.

METHODS

We did a randomised, double-blind trial in 15 family-planning clinics in 10 countries. We randomly assigned 4136 healthy women with regular menstrual cycles, who requested emergency contraception within 120 h of one unprotected coitus, to one of three regimens: 10 mg single-dose mifepristone; 1.5 mg single-dose levonorgestrel; or two doses of 0.75 mg levonorgestrel given 12 h apart. The primary outcome was unintended pregnancy; other outcomes were side-effects and timing of next menstruation. Analysis was by intention to treat, but we did exclude some patients from the final analyses.

FINDINGS

Of 4071 women with known outcome, pregnancy rates were 1.5% (21/1359) in those given mifepristone, 1.5% (20/1356) in those assigned single-dose levonorgestrel, and 1.8% (24/1356) in women assigned two-dose levonorgestrel. These proportions did not differ significantly (p=0.83). The relative risk of pregnancy for single-dose levonorgestrel compared with two-dose levonorgestrel was 0.83 (95% CI 0.46-1.50), and that for levonorgestrel (the two regimens combined) compared with mifepristone, 1.05 (0.63-1.76). Side-effects were mild and did not differ greatly between groups, and most women menstruated within 2 days of the expected date. Women who took levonorgestrel had earlier menses than did those who took mifepristone.

INTERPRETATION

The three regimens studied are very efficacious for emergency contraception and prevent a high proportion of pregnancies if taken within 5 days of unprotected coitus. Mifepristone and levonorgestrel do not differ in efficacy. A 1.5 mg single levonorgestrel dose can substitute two 0.75 mg doses 12 h apart.

摘要

背景

单次服用10毫克米非司酮以及间隔12小时分两次服用0.75毫克左炔诺孕酮均为有效的紧急避孕方法。由于此前尚无研究比较这两种药物的疗效，也未对单次服用1.5毫克左炔诺孕酮进行研究，我们开展了这项三臂试验。

方法

我们在10个国家的15家计划生育诊所进行了一项随机双盲试验。将4136名月经周期规律、在无保护性交后120小时内要求紧急避孕的健康女性随机分配至三种治疗方案之一：单次服用10毫克米非司酮；单次服用1.5毫克左炔诺孕酮；或间隔12小时分两次服用0.75毫克左炔诺孕酮。主要结局为意外妊娠；其他结局为副作用及下次月经时间。分析采用意向性分析，但我们在最终分析中排除了部分患者。

结果

在4071名结局已知的女性中，服用米非司酮者的妊娠率为1.5%（21/1359），单次服用左炔诺孕酮者为1.5%（20/1356），分两次服用左炔诺孕酮者为1.8%（24/1356）。这些比例无显著差异（p=0.83）。单次服用左炔诺孕酮与分两次服用左炔诺孕酮相比，妊娠的相对风险为0.83（95%可信区间0.46 - 1.50），左炔诺孕酮（两种方案合并）与米非司酮相比为1.05（0.63 - 1.76）。副作用较轻，组间差异不大，大多数女性在预期日期的2天内月经来潮。服用左炔诺孕酮的女性月经来潮时间早于服用米非司酮的女性。