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

Abstract

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