Taking a Painkiller Can Make Emergency Contraception More Effective

Scientists have found that adding a pain killer to an emergency contraceptive pill can improve the latter’s effectiveness.

In a study published Aug. 16 in the journal Lancet, researchers from Hong Kong and Sweden report that women taking piroxicam, an anti-inflammatory available by prescription only, together with the oral emergency contraceptive levonorgestrel (sold under various brand names including Plan B One-Step, Take Action, and My Way), had a significantly lowered chance of getting pregnant compared to women taking the same contraceptive pill and a placebo. The study involved 860 women seeking emergency morning-after contraceptive pills following unprotected sex at the Family Planning Association of Hong Kong. Half were randomly assigned to take a single 40 mg pill of piroxicam with their single levonorgestrel pill, while the other half were given a placebo pill with their contraceptive medication.

Among those taking piroxicam, one became pregnant compared to seven in the placebo group. After calculating the likelihood of pregnancy among women taking levonorgestrel, the scientists estimated that the combination of levonorgestrel and piroxicam prevented 94.7% of expected pregnancies, while levonorgestrel alone prevented 63.4% of pregnancies.

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Piroxicam is a non-steroidal anti-inflammatory drug (NSAID), a category that includes well-known pain killers like aspirin, ibuprofen, and naproxen. All of them work by inhibiting the activity of ​​cyclooxygenase (COX) enzymes in the body, which generate prostaglandins. It’s the prostaglandins, a group of lipid compounds, that connects the seemingly unrelated drugs: Prostaglandins are involved both in reducing inflammation and triggering ovulation, which releases the egg from the ovaries during each menstrual cycle. Levonorgestrel, a synthetic version of the natural hormone progesterone, is only effective in preventing pregnancy if women take it before ovulation. Because NSAIDs suppress prostaglandins, they can also suppress ovulation and therefore enhance the effectiveness of an emergency contraceptive.

Currently, doctors do not routinely prescribe an NSAID along with emergency contraception in the way that the women in the study took them, says Dr. Erica Cahill, assistant professor in obstetrics and gynecology at Stanford University, who wrote an accompanying commentary to the study. “This study was the first to demonstrate improved pregnancy prevention.”

Based on the results, however, Dr. Raymond Li, from the department of obstetrics and gynecology at the University of Hong Kong and Queen Mary Hospital and the study’s first author, says “We think it is worth considering this piroxicam-levonorgestrel combination to be put into routine clinical use.” Before that can happen, international health bodies like the World Health Organization and European health agencies would have to evaluate the evidence and weigh the benefits and risks. Prolonged use of NSAIDs can cause stomach and gastrointestinal ulcers, but, Li says, “we did not observe any increased incidence of stomachache among our study participants who used just a single dose of piroxicam for emergency contraception purposes.”

The researchers chose to include piroxicam in the study because it is one the longer-acting COX inhibitors available. Whether the improvement applies to other NSAIDs isn’t clear, says Cahill, since they work in similar ways but have differing potency and lengths of time in which they remain active in the body. More research is also needed to understand if anti-inflammatory drugs would have the same pregnancy-preventing effect when taken with other emergency contraceptives besides levonorgestrel, such as ulipristal acetate (Ella), a progestin that prevents pregnancy by delaying the release of the egg from the ovaries and making the uterus less hospitable for pregnancy. So far, the study is the first randomized trial to investigate the combination of an NSAID with an emergency contraceptive.