November 2023
Adding a COX inhibitor might improve the efficacy of emergency contraception

A single 40-mg dose of piroxicam added to levonorgestrel resulted in a lower pregnancy rate than did levonorgestrel alone.

The most commonly used form of oral emergency contraception is a single 1.5-mg dose of levonorgestrel, which disrupts ovulation and must be taken within 72 hours after unprotected sexual intercourse. Cyclo-oxygenase (COX) inhibitors – generally used as nonsteroidal anti-inflammatory drugs (NSAIDs) – also disrupt ovulation, but their ability to prevent pregnancy has not been studied previously.

Researchers in Hong Kong randomised 860 healthy women who requested emergency contraception to 1.5-mg levonorgestrel plus 40-mg piroxicam (a COX inhibitor with a half-life of about 50 hours) or to levonorgestrel plus placebo. Mean time between unprotected sexual intercourse and emergency contraception use was 18 hours. Women using hormonal contraception were excluded from this study.

Key results were as follows:

  • seven pregnancies occurred in the levonorgestrel-alone group (1.7%), and one occurred in the combined levonorgestrel/piroxicam group (0.2%)
  • compared with the number of pregnancies expected without emergency contraception (19 in each group), 63% fewer pregnancies occurred with levonorgestrel alone, and 95% fewer occurred with levonorgestrel/piroxicam
  • side effects (e.g. nausea, fatigue) were similar between groups.

Comment: When levonorgestrel is the preferred option for emergency contraception, the additional prescrip­tion of a long­-acting COX inhibitor should be considered as a safe option to improve efficacy. However, because levonorgestrel for emergency contra­ception is available over the counter in the USA, informing women about the option of adding a COX inhibitor will be challenging. Whether over-the­-counter NSAIDs can offer similar benefits is unclear.

Marie Claire O’Dwyer, MB BCh BAO, MPH, Clinical Assistant Professor in Family Medicine, University of Michigan Medical School, Ann Arbor, USA.

Li RHW, et al. Oral emergency contra­ ception with levonorgestrel plus piroxicam: a randomised double­blind placebo­ controlled trial. Lancet 2023; 402: 851­-858.

This summary is taken from the following Journal Watch titles: General Medicine, Women’s Health, Ambulatory Medicine.