Double Dosing Levonorgestrel-Based Emergency Contraception for Individuals With Obesity: A Randomized Controlled Trial.
Double Dosing Levonorgestrel-Based Emergency Contraception for Individuals With Obesity: A Randomized Controlled Trial.
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DOI：
10.1097/aog.0000000000004717
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发表时间：
2022-07-01
影响因子：
7.2
通讯作者：
Jensen, Jeffrey T.
中科院分区：
文献类型：
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作者：
Edelman, Alison B.;Hennebold, Jon D.;Bond, Kise;Lim, Jeong Y.;Cherala, Ganesh;Archer, David F.;Jensen, Jeffrey T.
将含有左炔诺孕酮的紧急避孕药的剂量从1.5毫克增加到3毫克并不能改善肥胖者的排卵延迟发生率。评估包含左旋诺孕酮(LNG)的紧急避孕药物剂量增加(即增加一倍剂量)是否改善肥胖者的药效学结果。在一项随机的药效学研究中，我们招募了月经周期规律、体重指数(BMI)大于30、体重至少176磅的健康、生育年龄的个体。在确认排卵(黄体孕酮水平大于3 ng/mL)后，我们每隔一天经阴道超声和采血监测黄体酮、黄体生成素和雌二醇，直到观察到15 mm或更大的优势卵泡。在这一点上，参与者接受了口服紧急避孕药LNG 1.5毫克或3毫克(双倍剂量)，然后返回进行每日监测，最长可达7天。我们的主要结果是在给药后5天(是或否)没有卵泡破裂的参与者所占比例的差异。这项研究有80%的能力来检测卵泡破裂至少延迟5天的周期比例的30%的差异(减少50%)。共有70人参加并完成了学习程序。两组的基线人口统计数据相似(平均年龄28岁，体重指数38)。两组患者服药后5天内未出现卵泡破裂的比例无差异(LNG 1.5 mg：18/35[51.4%]；LNG 3.0 mg：24/35[68.6%]，P=0.14)。在卵泡破裂5天前的参与者中，卵泡破裂的时间在两组之间没有差异(两组中无破裂概率为75%的那一天是第二天)。BMI和体重较高的个体使用LNG紧急避孕失败的风险更高，并显示出改变的药代动力学特征。然而，将剂量增加一倍的简单策略似乎不是改善结果的有效干预措施。临床试验网站，02859337。
Increasing the dose of levonorgestrel-containing emergency contraception from 1.5 mg to 3 mg did not improve rates of ovulation delay in individuals with obesity. To assess whether dose escalation (ie, doubling the dose) of emergency contraception that contains levonorgestrel (LNG) improves pharmacodynamic outcomes in individuals with obesity. We enrolled healthy, reproductive-age individuals with regular menstrual cycles, body mass index (BMI) higher than 30, and weight at least 176 lbs in a randomized pharmacodynamic study. After confirming ovulation (luteal progesterone level greater than 3 ng/mL), we monitored participants with transvaginal ultrasonography and blood sampling for progesterone, luteinizing hormone, and estradiol every other day until a dominant follicle measuring 15 mm or greater was visualized. At that point, participants received either oral emergency contraception with LNG 1.5 mg or 3 mg (double dose) and returned for daily monitoring for up to 7 days. Our primary outcome was the difference in the proportion of participants with no follicle rupture 5 days postdosing (yes or no) between groups. The study had 80% power to detect a 30% difference in the proportion of cycles with at least a 5-day delay in follicle rupture (50% decrease). A total of 70 enrolled and completed study procedures. The two groups had similar baseline demographics (mean age 28 years, BMI 38). We found no difference between groups in the proportion of participants without follicle rupture more than 5 days post–LNG dosing (LNG 1.5 mg: 18/35 [51.4%]; LNG 3.0 mg: 24/35 [68.6%], P=.14). Among participants with follicle rupture before 5 days, the time to rupture did not differ between groups (day at 75% probability of no rupture is day 2 for both groups). Individuals with higher BMIs and weights experience a higher risk of failure of emergency contraception with LNG and exhibit an altered pharmacokinetic profile. However, the simple strategy of doubling the dose does not appear to be an effective intervention to improve outcomes. ClinicalTrials.gov, 02859337.