Double Dosing Levonorgestrel-Based Emergency Contraception for Individuals With Obesity: A Randomized Controlled Trial

Alison B Edelman, Jon D Hennebold, Kise Bond, Jeong Y Lim, Ganesh Cherala, David F Archer, Jeffrey T Jensen, Alison B Edelman, Jon D Hennebold, Kise Bond, Jeong Y Lim, Ganesh Cherala, David F Archer, Jeffrey T Jensen

Abstract

Objective: To assess whether dose escalation (ie, doubling the dose) of emergency contraception that contains levonorgestrel (LNG) improves pharmacodynamic outcomes in individuals with obesity.

Methods: 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).

Results: 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).

Conclusion: 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.

Clinical trial registration: ClinicalTrials.gov, 02859337.

Conflict of interest statement

Financial Disclosure Alison B. Edelman reports honoraria and travel reimbursement from ACOG, WHO, and Gynuity for committee activities and honoraria for peer review from the Karolinska Institute. She receives royalties from UpToDate, Inc. Oregon Health & Science University receives research funding from OHSU Foundation, Merck, HRA Pharma, and NIH, where she is the principal investigator. Jeffrey T. Jensen has received payments for consulting from AbbVie, Cooper Surgical, Bayer Health care, Merck, Sebela, and TherapeuticsMD. OHSU has received research support from AbbVie, Bayer Health care, Daré, Estetra SPRL, Medicines360, Merck, and Sebela. These companies and organizations may have a commercial or financial interest in the results of this research and technology. These potential conflicts of interest for Alison B. Edelman and Jeffrey T. Jensen have been reviewed and managed by OHSU. None of these have direct conflict with this manuscript. David F. Archer reports DFA grant support to Eastern Virginia Medical School from AbbVie, Bayer Healthcare, Dare, Mithra, Myovant Sciences, and ObsEva; consulting fees from Agile Therapeutics, Mithra, ObsEva and TherapeuticsMD; and stock options for Agile Therapeutics and InnovaGyn, Inc. Ganesh Cherala was involved in this study as a private consultant. He is employed by Gilead Sciences, which was not involved in this research. The other authors did not report any potential conflicts of interest.

Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

Figures

Fig. 1.. CONSORT (Consolidated Standards Reporting Trials)…
Fig. 1.. CONSORT (Consolidated Standards Reporting Trials) flow diagram. *Items not mutually exclusive.
Edelman. Emergency Contraception and BMI. Obstet Gynecol 2022.
Fig. 2.. Kaplan-Meier curves for time to…
Fig. 2.. Kaplan-Meier curves for time to rupture after levonorgestrel (LNG) 1.5 mg (blue line) and LNG 3.0 mg (red line) at time zero. The study groups were no different in their time to follicle rupture (log-rank test P=.2). Time to rupture was censored at day 5.
Edelman. Emergency Contraception and BMI. Obstet Gynecol 2022.

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Source: PubMed

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