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Taking an Anti-Inflammatory with the Morning-after Pill Increases Effectiveness

Levonorgestrel is a widely used emergency contraceptive pill

Kristoffer Tripplaar / Alamy Stock Photo

A recent clinical trial has discovered that taking an anti-inflammatory drug alongside a widely used morning-after pill can significantly increase its effectiveness in preventing pregnancies.

Levonorgestrel, a popular emergency contraceptive, is known to be less effective when taken after an egg has been released from one of the ovaries. Studies have shown that the drug is only 58% effective in preventing pregnancies when taken between 49 to 72 hours after unprotected sex.

Researchers at the Karolinska Institute in Sweden, led by Kristina Gemzell-Danielsson, suspected that anti-inflammatory drugs could enhance the contraceptive’s efficacy. Anti-inflammatory drugs work by inhibiting prostaglandins, chemical substances that have hormone-like effects and play a role in reproductive processes such as ovulation and fertilization.

To test their hypothesis, Gemzell-Danielsson and her colleagues conducted a randomized trial involving 860 women who sought emergency contraception within 72 hours of unprotected sex at a family planning clinic in Hong Kong between August 2018 and 2022.

Half of the participants were given levonorgestrel and piroxicam, an anti-inflammatory drug used to treat arthritis, while the other half received levonorgestrel and a placebo pill. The treatment allocation was unknown to both the participants and the healthcare professionals involved in the trial.

Results showed that only one woman became pregnant in the group taking the anti-inflammatory drug, compared to seven pregnancies in the placebo group. The two groups showed no significant differences in terms of side effects experienced.

Based on a model analyzing expected pregnancy rates after unprotected sex, the anti-inflammatory drug group prevented 95% of expected pregnancies, while the placebo group only prevented 63%.

It is still unclear how exactly the anti-inflammatory drug helps prevent unwanted pregnancies. More mechanistic studies need to be conducted to determine the underlying mechanisms, according to Gemzell-Danielsson.

The researchers believe that the findings from this trial should lead to changes in how emergency contraceptives are prescribed worldwide. Piroxicam, the anti-inflammatory drug used in the study, is low-cost and widely available, making it easy to incorporate with levonorgestrel.

Gemzell-Danielsson also suggests that combining piroxicam with another commonly used emergency contraceptive, ulipristal, could be effective as both contraceptives work similarly to levonorgestrel. However, no studies have been conducted on this combination yet.

Judith Stephenson, a researcher at University College London, acknowledges the potential impact of these findings on clinical practice but suggests that further studies should be conducted to confirm the results. “Though well designed, it is only one trial, so it would be reassuring to have the findings confirmed in another study,” says Stephenson.

She also highlights the importance of investigating if the combination of these drugs would work in individuals who have missed one of their daily contraceptive pills.

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