Doubling Levonorgestrel Dose Fails to Prevent Pregnancy in Women with Obesity

Women with higher body mass indexes (BMI) and weights are significantly more likely to experience failure with levonorgestrel as emergency contraception than women with lower BMIs and weights.

That is the main finding of a randomized controlled trial published in the journal Obstetrics & Gynecology, which also found that the morning-after pill exhibits an altered pharmacokinetic profile in overweight women.

However, the simple step of doubling the dose does not appear to be an effective intervention to improve outcomes.

“Emergency contraception is a critical therapy for our patients,” said principal investigator Alison Edelman, MD, MPH, a professor of obstetrics and gynecology at Oregon Health & Science University (OHUS) School of Medicine, in Portland, in an OHUS statement. “We need to ensure that it works effectively for everyone, no matter their BMI or weight.”

The study was conducted at OHUS and Eastern Virginia Medical School, in Norfolk, between June 2017and February 2021.

A total of 70 healthy, reproductive-age women with regular menstrual cycles, BMI >30 kg/m², and a weight of at least 176 lbs enrolled and completed study procedures.

After confirming ovulation, which was defined as a luteal progesterone level >3 ng/mL, subjects were monitored every other day via transvaginal ultrasonography and blood sampling for progesterone, luteinizing hormone and estradiol, until the visualization of a dominant follicle measuring ≥15 mm.

At that point, participants received oral emergency contraception, being randomly assigned to either levonorgestrel 1.5 mg (n = 35) or levonorgestrel 3 mg (double dose) (n = 35), then returned for daily monitoring for up to 7 days.

Baseline demographics were similar between groups, with a mean age of 28 years and a BMI of 38.

The primary outcome was the difference in the percentage of participants with no follicle rupture 5 days postdosing between the two 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 or a 50% decrease.

FINDINGS

There was no difference between the groups in the percentage of women without follicle rupture more than 5 days postdosing: 51.4% for levonorgestrel 1.5 mg and 68.6% for the double dose (P =.14).

Similarly, among participants with follicle rupture before day 5, the time to rupture did not vary between the two groups: 75% probability of no rupture at day 2 for both groups.

Women with BMI 30 experienced a failure of the morning-after pill 4 times as often as those with a BMI of <25.

“Although our results showed no difference in effectiveness between the group that took the single dose or double dose of levonorgestrel, the study will help guide research to find the most effective strategy,” Edelman told Contemporary OB/GYN®. “The more we understand about why the pill does not work and how to correct it, the better care we can provide for patients.”

There is no harm in double-dosing the pill, according to Edelman, but study results demonstrate that it could still fail to prevent pregnancy.

Effective alternatives to double dosing to prevent pregnancy in the study population are non-hormonal forms of contraception, such as copper IUDs.

Reference: Edelman AB, Hennebold JD, Bond K, et al. Double dosing levonorgestrel-based emergency contraception for individuals with obesity. Obstet Gynecol. 2022;140:48-54.