Department of Obstetrics & Gynecology and the Biostatistics Shared Resource, Knight Cancer Institute, Oregon Health & Science University, Portland, and the Division of Reproductive & Developmental Sciences, Oregon Primate National Research Center, Beaverton, Oregon; Clinical Pharmacology, Gilead Sciences, Foster City, California; and the Clinical Research Center, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, Virginia.
Obstet Gynecol. 2022 Jul 1;140(1):48-54. doi: 10.1097/AOG.0000000000004717. Epub 2022 Jun 7.
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.
评估含有左炔诺孕酮（LNG）的紧急避孕药物剂量升级（即加倍剂量）是否能改善肥胖个体的药效学结局。
我们在一项随机药效学研究中招募了月经周期正常、体重指数（BMI）高于 30、体重至少 176 磅的健康、育龄个体。在确认排卵（黄体期孕激素水平大于 3ng/mL）后，我们通过经阴道超声和血样监测孕激素、促黄体生成素和雌二醇，每两天监测一次，直到观察到一个直径大于 15mm 的优势卵泡。此时，参与者服用 LNG 1.5mg 或 3mg（双倍剂量）的口服紧急避孕药，并在接下来的 7 天内每天进行监测。我们的主要结局是两组中，给药后 5 天内无卵泡破裂的参与者比例（是或否）差异。该研究有 80%的效能检测出卵泡破裂至少延迟 5 天的周期比例差异（50%减少）。
共有 70 名参与者完成了研究程序。两组的基线人口统计学特征相似（平均年龄 28 岁，BMI 38）。我们发现两组中没有卵泡破裂超过 5 天的参与者比例差异（LNG 1.5mg：35 名中的 18 名[51.4%]；LNG 3.0mg：35 名中的 24 名[68.6%]，P=.14）。在卵泡破裂发生在 5 天内的参与者中，两组之间的破裂时间没有差异（两组中 75%无破裂概率的日期均为第 2 天）。
BMI 和体重较高的个体使用 LNG 紧急避孕的失败风险更高，表现出改变的药代动力学特征。然而，双倍剂量的简单策略似乎不是改善结局的有效干预措施。
ClinicalTrials.gov，02859337。
