By Rebecca H. Allen, MD, MPH, Editor
SYNOPSIS: In this randomized controlled trial of 70 obese women, double dosing levonorgestrel emergency contraception (3 mg vs. 1.5 mg) did not prevent more follicle ruptures and, therefore, is unlikely to improve emergency contraception performance in this population.
SOURCE: Edelman AB, et al. Double dosing levonorgestrel-based emergency contraception for individuals with obesity. Obstet Gynecol 2022;140:48-54.
Levonorgestrel oral emergency contraception normally is dosed at 1.5 mg. However, studies have shown higher failure rates in women with a body mass index (BMI)
> 30 and likely no effect at all at weights of 80 kg or more.1 Some experts have recommended doubling the dose in obese women, but there are no clinical data proving that this strategy would be effective.2 Therefore, the authors of this study sought to evaluate the effects of 3 mg of levonorgestrel on preventing ovulation.
This was a randomized controlled trial conducted in Oregon and Virginia between June 2017 and February 2021. Women ages 18 to 35 years with regular menstrual cycles, BMI > 30, weight ≥ 176 pounds, and who were not at risk of pregnancy (abstinent or using nonhormonal contraception) were recruited. Exclusion criteria included thyroid dysfunction, polycystic ovarian syndrome, impaired liver or renal function, actively in a weight loss program, pregnancy, breastfeeding, recent use (past eight weeks) of hormonal contraception, current use of drugs that interfere with hormone metabolism, smoking, vaping, or chronic marijuana use. A serum progesterone level in the luteal phase to confirm ovulatory status was obtained prior to enrollment. After the onset of menses, starting on days 6-8 of the cycle, follicular activity was monitored every other day with transvaginal ultrasound and blood sampling for progesterone, estradiol, and luteinizing hormone (LH) levels until a dominant follicle measuring 15 mm or greater in at least one dimension was confirmed. Participants then were randomized to 1.5 mg vs. 3.0 mg of levonorgestrel (LNG), and ingestion was directly observed.
Post-dosing, individuals were monitored daily with transvaginal ultrasounds and blood sampling until evidence of follicle rupture (more than 50% reduction in the size of the follicle or complete disappearance of the follicle) or for up to seven days if no rupture occurred. The sample size was calculated to detect a 30% difference, with a 5% significance level and 80% power, in the proportion of cycles with at least a five-day delay in follicle rupture. A total of 70 women were recruited and completed all study procedures; 35 were randomized to each arm. The mean age was 28 years, the mean BMI was 38, and half were nulligravid. At the time of study drug dosing, the mean largest follicle measurement was similar in both groups (LNG 1.5 mg: 16.3 mm vs. LNG 3.0 mg: 15.9 mm). There was no difference between the two groups in the proportion of participants who achieved at least five days without evidence of follicle rupture after LNG dosing (LNG 1.5 mg: 51.4% vs. LNG 3.0 mg: 68.6%; P = 0.14). The time to follicle rupture also was no different between the two groups.
COMMENTARY
Emergency contraception can be used to prevent pregnancy after unprotected or inadequately protected intercourse when taken within three to five days, depending on the regimen.3 The mechanism of action of oral emergency contraception is to inhibit or delay ovulation during that cycle. It does not cause abortion. Current oral regimens available in the United States are LNG 1.5 mg, which is available over the counter (approved for up to three days after unprotected intercourse) and ulipristal acetate 30 mg, which requires a prescription (approved for up to five days after unprotected intercourse). Obesity is a risk factor for oral emergency contraception failure for both drugs. The risk of pregnancy after taking LNG 1.5 mg in women with a BMI > 30 is four times greater than in women with a BMI in the normal range.1
Oral emergency contraception in a one-time dose ideally will achieve high enough peak serum levels of the drug to delay or block the LH surge that provokes ovulation. The study investigators previously demonstrated that increasing the LNG dose to 3 mg maintained this peak serum drug level among obese women when 1.5 mg did not. Therefore, with this study they were aiming to show that this would translate into improved ovulation delay and inhibition but failed to demonstrate that result. These findings are important because they do not support the expert opinion that obese individuals be given a double dose of LNG for emergency contraception. The limitation of this study is that follicle rupture is a surrogate for ovulation, and the study did not evaluate the clinical pregnancy rate, which is the true outcome of interest after emergency contraception.
Nevertheless, the results emphasize that obese women should be steered toward ulipristal acetate if they desire oral emergency contraception. Otherwise, the copper or LNG intrauterine device (IUD) can be used as emergency contraception if the patient would like to use the device as an ongoing method of contraception.3 Both of these options are more effective than oral emergency contraception, and their efficacy is not affected by weight. A recent landmark study showed that the 52 mg LNG IUD was noninferior to the copper IUD for emergency contraception.5 Our emphasis should be placed on ramping up capabilities for placing IUDs for emergency contraception as soon as possible when patients call for emergency contraception needs.
REFERENCES
- Glasier A, 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;84:363-367.
- The Faculty of Sexual & Reproductive Healthcare. FSRH clinical guideline: Emergency contraception. Amended December 2020. https://www.fsrh.org/documents/ceu-clinical-guidance-emergency-contraception-march-2017/
- American College of Obstetricians and Gynecologists. Emergency contraception. Practice Bulletin Number 152. Published September 2015. https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2015/09/emergency-contraception
- Edelman AB, et al. Impact of obesity on the pharmacokinetics of levonorgestrel-based emergency contraception: Single and double dosing. Contraception 2016;94:52-57.
- Turok DK, et al. Levonorgestrel vs. copper intrauterine devices for emergency contraception. N Engl J Med 2021;384:335-344.
