Does Double Dosing Levonorgestrel-Based Emergency Contraception for Obese Patients Affect Clinical Results?

Does Double Dosing Levonorgestrel-Based Emergency Contraception for Obese Patients Affect Clinical Results?
Anna Zhushma, PharmD
Cub Pharmacy

Background: Obesity, defined as a BMI >30 kg/m2, is a risk factor for failure of emergency contraception (EC) containing levonorgestrel (LNG). This is pertinent given the global obesity epidemic. Glasier et al. reanalyzed data from two large randomized control trials and noted risk factors for EC failure. Individuals with BMIs in the obese range who used EC containing LNG had more than a fourfold greater risk of pregnancy compared with individuals with BMI 17-23.9 kg/m2 (OR 4.41, 95% CI 2.05–9.44); individuals with BMIs in the overweight range (25–29.9 kg/m2) were twice as likely as individuals with BMI 17-23.9 kg/m2 to experience failure. EC that contains LNG appears to have a ceiling of efficacy at 70 kg and no EC efficacy for those weighing 80 kg or more.

Purpose or Objective:To assess whether doubling the dose of EC that contains LNG improves pharmacodynamic outcomes in individuals with obesity.

Study Design:  The researchers conducted a randomized controlled trial with participants between 18 and 35 years of age who possessed a regular menstrual cycle lasting from 21 to 35 days, had a BMI of greater than 30 kg/m2, and weighed at least 80 kg (176 lbs). Researchers first confirmed ovulation in the participants by measuring luteal progesterone levels >3 ng/mL. Participants were monitored utilizing transvaginal ultrasonography and blood samples were measured for progesterone, luteinizing hormone, and estradiol every other day until a dominant follicle appeared (minimum 15 mm in width). Upon reaching this point, the participants were randomized into two groups. Group 1 received LNG 1.5 mg and Group 2 received 3 mg LNG. Both groups were then monitored daily for up to seven days. The primary outcome of this study was the difference between groups in the proportion of participants with no follicle rupture for five days following EC dosing. The main secondary outcome compared timing of follicle rupture between the two groups and was assessed using Kaplan-Meier and log-rank tests.

Results: A total of 70 participants enrolled and completed the study procedures. Baseline demographics were similar: mean age 28, mean BMI 38 kg/m2, 77% of participants identified as White non-Hispanic, 50% of participants reported never experiencing a pregnancy. No difference in the intention-to-treat analysis was detected 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=0.14). For the secondary outcome, in the participants with follicle rupture before 5 days, time to rupture also did not differ between groups.

Conclusions: The researchers concluded that individuals who possess a high BMI are at higher risk of failure of EC with LNG. These participants had an altered pharmacokinetic profile, as women with BMIs in the obese range were found to have ~50% reduction in plasma exposure to LNG. Doubling the LNG dose was not an effective intervention to improve outcomes based on the study results. A study limitation was follicle rupture being used as a substitute for ovulation; a more meaningful outcome of interest would be pregnancy rate. 

Key Point: The findings of this study have important clinical relevance for individuals possessing BMIs in the obese range who desire to use EC. The results of this study do not support double dosing of EC with LNG in individuals with BMIs >30 kg/m2 or a weight of ≥80 kg (176 lbs).


  1. Edelman AB, Hennebold JD, Bond K, et al. Double Dosing Levonorgestrel-Based Emergency Contraception for Individuals With Obesity: A Randomized Controlled Trial. Obstet Gynecol. 2022;140(1):48-54. doi: 10.1097/AOG.000000000000471
  2. Glasier A, Cameron ST, Blithe D, et al. Can we identify women at risk of pregnancy despite using emergency contraception? Data from randomized trials of ulipristal acetate and levonorgestrel. Contraception. 2011;84:363–7. doi: