Emergency contraception is more likely to fail in women with obesity, but simply doubling the dose of levonorgestrel (LNG)-based contraception does not appear to be effective according to the results of a randomized, controlled trial.
Alison B. Edelman, MD, MPH, of the department of obstetrics & gynecology at Oregon Health & Science University, Portland, led the study published online in Obstetrics & Gynecology.
The researchers included healthy women ages 18-35 with regular menstrual cycles, body mass index (BMI) higher than 30 kg/m2, and weight at least 176 pounds in a randomized study.
After confirming ovulation, researchers monitored participants with transvaginal ultrasonography and blood sampling for progesterone, luteinizing hormone, and estradiol every other day until a dominant follicle 15 mm or greater was seen.
At that point the women received either LNG 1.5 mg or 3 mg and returned for daily monitoring up to 7 days.
Emergency contraception with LNG works by preventing the luteinizing hormone surge, blocking follicle rupture. The researchers had hypothesized that women with obesity might not be getting enough LNG to block the surge after oral dosing.
Previous trials had shown women with obesity had a fourfold higher risk of pregnancy, compared with women with normal BMI taking emergency contraception.
The primary outcome in this trial was whether women had follicle rupture 5 days after dosing.
The authors wrote: “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).”
A total of 70 women completed study procedures. The two groups (35 women in each) had similar demographics (mean age, 28 years; BMI, 38).
No differences found between groups
“We found no difference between groups in the proportion of participants without follicle rupture,” the researchers wrote.
More than 5 days after dosing, 51.4% in the lower-dose group did not experience follicle rupture. In the double-dose group 68.6% did not experience rupture but the difference was not significant (P = .14).
Among participants with follicle rupture before 5 days, the time to rupture – the secondary endpoint – also did not differ between groups.
The researchers concluded that more research on the failures of hormonal emergency contraception in women with obesity is needed.
Dr. Eve Espey
Eve Espey, MD, MPH, distinguished professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque, said in an interview that the study was well designed and the results “form a strong basis for clinical recommendations.”
“Providers should not recommend a higher dose of LNG emergency contraception for patients who are overweight or obese, but rather should counsel patients on the superior effectiveness of ulipristal acetate for those seeking oral emergency contraception as well as the longer time period after unprotected sex – 5 days – that ulipristal maintains its effectiveness.”
“Providers should also counsel patients on the most effective emergency contraception methods, the copper or LNG intrauterine device,” she said.
She said the unique study design of a pharmacodynamic randomized controlled trial adds weight to the findings.
She and the authors noted a limitation is the use of a surrogate outcome, ovulation delay, for ethical and feasibility reasons, instead of the outcome of interest, pregnancy.
The trial was conducted at Oregon Health & Science University and Eastern Virginia Medical School, Norfolk, from June 2017 to February 2021.
Study enrollees were compensated for their time. They were required not to be at risk for pregnancy (abstinent or using a nonhormonal method of contraception).
Dr. Edelman reported receiving honoraria and travel reimbursement from the American College of Obstetricians and Gynecologists, the World Health Organization, and Gynuity for committee activities and honoraria for peer review from the Karolinska Institute. She receives royalties from UpToDate. Several coauthors have received payments for consulting from multiple pharmaceutical companies. These companies and organizations may have a commercial or financial interest in the results of this research and technology. Another was involved in this study as a private consultant and is employed by Gilead Sciences, which was not involved in this research.