Edelman Alison, Hennebold Jon D, Bond Kise, Lim Jeong Y, Cherala Ganesh, Blue Steven W, Kraft Shawn P, Erikson David W, Archer David, Jensen Jeffery
Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, Oregon, USA
Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, Oregon, USA.
BMJ Sex Reprod Health. 2025 Jan 6;51(1):27-35. doi: 10.1136/bmjsrh-2024-202401.
To determine whether increasing the dose of ulipristal acetate (UPA)-containing emergency contraception (EC) improves pharmacodynamic outcomes in individuals with obesity.
We enrolled healthy, regularly-cycling, confirmed ovulatory, reproductive-age individuals with body mass index (BMI) >30 kg/m and weight >80 kg in a randomised crossover study. We monitored participants with transvaginal ultrasound and blood sampling for progesterone, luteinising hormone (LH), and estradiol every other day until a dominant follicle measuring >15 mm was visualised. At that point, participants received either oral UPA EC 30 mg or 60 mg and returned for daily monitoring up to 7 days. After a no treatment washout cycle, participants returned for a second monitored cycle and received the other UPA dose. Our primary outcome was the proportion of subjects with no follicle rupture 5 days post-dosing (yes/no). For reference, we also enrolled a control group with BMI <25 kg/m and weight <80 kg who received UPA EC 30 mg during a single cycle. We also obtained blood samples for pharmacokinetic parameters for UPA and its active metabolite, -monodemethyl-UPA (NDM-UPA) as an optional substudy.
We enrolled a total of 52 participants with BMI >30 kg/m and 12 controls, with the following cycles completed: 12 controls, 49 UPA 30 mg, and 46 UPA 60 mg. The entire cohort demographics were a mean (SD) age of 29.8 (3.4) years and BMI by group: controls 22.5 (1.4) kg/m, group 1 37.9 (6.7) kg/m, and group 2 39.3 (5.4) kg/m. All 12 (100%) of controls had a delay of at least 5 days for follicle rupture. Among the high BMI group, dosing groups (UPA EC 30 mg vs 60 mg) were similar in the proportion of cycles without follicle rupture over 5 days post-UPA dosing (UPA 30 mg: 47/49 (96%), UPA 60 mg: 42/46 (91%), Fisher's exact test p=0.43). However, after excluding cycles where dosing occurred too late (after LH surge), a delay of at least 5 days occurred in all participants at both doses. The 60 mg UPA dose resulted in a twofold increase in maximum observed concentration and the area under the curve of both UPA and NDM-UPA levels compared with 30 mg.
A standard 30 mg dose of UPA is sufficient to delay ovulation regardless of BMI or weight. Results of our study do not support dose adjustment for body size.
确定增加含醋酸乌利司他（UPA）的紧急避孕药（EC）剂量是否能改善肥胖个体的药效学结果。
我们在一项随机交叉研究中纳入了健康、月经周期规律、已确认排卵的育龄个体，其体重指数（BMI）>30 kg/m²且体重>80 kg。我们每隔一天用经阴道超声和采集血液样本监测参与者的孕酮、促黄体生成素（LH）和雌二醇，直到观察到一个直径>15 mm的优势卵泡。此时，参与者口服30 mg或60 mg的UPA紧急避孕药，并返回进行长达7天的每日监测。在一个无治疗的洗脱期后，参与者返回进行第二个监测周期，并接受另一种UPA剂量。我们的主要结局是给药后5天无卵泡破裂的受试者比例（是/否）。作为对照参考，我们还纳入了一个BMI<25 kg/m²且体重<80 kg的对照组，他们在一个周期内接受30 mg的UPA紧急避孕药。作为一项可选的子研究，我们还采集了血液样本以测定UPA及其活性代谢物单去甲基-UPA（NDM-UPA）的药代动力学参数。
我们共纳入了52名BMI>30 kg/m²的参与者和12名对照组，完成了以下周期：12名对照组、49个30 mg UPA周期和46个60 mg UPA周期。整个队列的人口统计学特征为平均（标准差）年龄29.8（3.4）岁，按组划分的BMI：对照组22.5（1.4）kg/m²，第1组37.9（6.7）kg/m²，第2组39.3（5.4）kg/m²。所有12名（100%）对照组的卵泡破裂至少延迟了5天。在高BMI组中，给药组（30 mg UPA紧急避孕药与60 mg UPA紧急避孕药）在UPA给药后5天无卵泡破裂的周期比例相似（30 mg UPA：47/49（96%），60 mg UPA：42/46（91%），Fisher精确检验p=0.43）。然而，在排除给药时间过晚（促黄体生成素高峰后）的周期后，两种剂量的所有参与者卵泡破裂均至少延迟了5天。与30 mg相比，60 mg UPA剂量使UPA和NDM-UPA水平的最大观察浓度和曲线下面积增加了两倍。
无论BMI或体重如何标准剂量30 mg的UPA足以延迟排卵。我们的研究结果不支持根据体型调整剂量。
