Double dosing ulipristal acetate emergency contraception for individuals with obesity: a randomised crossover trial

Abstract

ObjectiveTo determine whether increasing the dose of ulipristal acetate (UPA)-containing emergency contraception (EC) improves pharmacodynamic outcomes in individuals with obesity.Study designWe enrolled healthy, regularly-cycling, confirmed ovulatory, reproductive-age individuals with body mass index (BMI) >30 kg/m2and 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/m2and 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,N-monodemethyl-UPA (NDM-UPA) as an optional substudy.ResultsWe enrolled a total of 52 participants with BMI >30 kg/m2and 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/m2, group 1 37.9 (6.7) kg/m2, and group 2 39.3 (5.4) kg/m2. 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.ConclusionA 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.