Arthritis Pain Reliever Piroxicam With Emergency Contraceptive Pill Levonorgestrel Increases Latter's Efficacy: Study In Lancet

Consumption of levonorgestrel and piroxicam together prevented 18 out of 19 expected pregnancies, implying that the efficiency of the two drugs together is 95 per cent. Piroxicam targets prostaglandin

While levonorgestrel alone prevented 63 per cent of pregnancies in a particular randomised controlled trial, consuming it together with the anti-inflammatory arthritis analgesic medicine piroxicam prevented 95 per cent of pregnancies, a study published in The Lancet said.

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Consumption of anti-inflammatory arthritis pain relieving drug piroxicam at the same as levonorgestrel, an emergency contraceptive pill, after unprotected sexual intercourse (coitus) increases the efficacy of the latter, and helps prevent more pregnancies than what levonorgestrel had prevented had it been taken alone. While levonorgestrel alone prevented 63 per cent of pregnancies in a particular randomised controlled trial, consuming it together with the anti-inflammatory arthritis analgesic medicine piroxicam prevented 95 per cent of pregnancies, according to a new study published in The Lancet. 

In most countries, emergency contraceptive pills containing either levonorgestrel or ulipristal acetate are the most widely used emergency contraception methods. However, the levonorgestrel drug is available in more countries compared to the ulipristal acetate drug. 

The mechanism of pregnancy prevention of both the drugs is that they prevent or delay ovulation. Also, neither of them are effective post-ovulation. 

A trial conducted in 1998 affixed the accepted effectiveness of levonorgestrel. The trial found that when levonorgestrel is consumed within 24 hours of unprotected coitus, 95 per cent of expected pregnancies are prevented. When taken within 25 to 48 hours, levonorgestrel prevents 85 per cent of expected pregnancies, and when consumed within 49 to 72 hours, the drug prevents 58 per cent of expected pregnancies. However, the efficacy of levonorgestrel might be lower than what the trial found, recent research has suggested. 

How the new study was conducted

As part of the new study published in The Lancet, researchers performed an analysis at a major community sexual and reproductive health service in Hong Kong between August 2018 and August 2022, randomising women who needed levonorgestrel emergency contraception within 72 hours of unprotected coitus to receive a single supervised dose of 1.5-milligram levonorgestrel either with a 40-milligram piroxicam pill, or with a placebo pill. The participants and attending healthcare professionals were not told who was given which drug. 

The authors scheduled a follow-up appointment one to two weeks after the next expected menstrual phase, or period. If women did not have a normal period by the time of the appointment, they were made to undergo a pregnancy test. 

Based on the model established as part of the 1998 trial, the researchers calculated the proportion of pregnancies prevented out of those expected. 

As many as 836 women underwent follow-up tests. Half of these consumed piroxicam and levonorgestrel, and the remaining half consumed a placebo and levonorgestrel. 

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Percentage of pregnancies prevented when taking piroxicam and levonorgestrel together

Among the group of women given piroxicam and levonorgestrel, one pregnancy occurred, while in the other group of women, seven pregnancies occurred. As many as 19 pregnancies were expected to occur in each group had they not been given contraception, or 4.5 per cent of the women in each group were expected to get pregnant. 

Since consumption of levonorgestrel and piroxicam together prevented 18 out of 19 expected pregnancies, the efficiency of the two drugs together is 95 per cent. Meanwhile, consumption of levonorgestrel with a placebo prevented 12 out of 19 expected pregnancies, implying that the efficiency was 63 per cent. 

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No significant differences in rates of side effects between the two groups were observed. 

In a statement released by The Lancet, Dr Raymond Li, the first author on the paper, said the study is the first to suggest that a readily available and safe medication taken at the same time as the levonorgestrel emergency contraceptive pill can prevent more pregnancies than levonorgestrel alone. He also said that the researchers are hopeful that the results will lead to further research and ultimately changes in clinical guidelines to enable women around the world to access more effective emergency contraception.

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How do piroxicam and levonorgestrel prevent pregnancies?

Professor Kristina Gemzell-Danielsson, a co-investigator of the study, said levonorgestrel prevents pregnancy by blocking or postponing the luteinising hormone surge, which disrupts the ovulatory process, and that piroxicam targets a different type of hormone called prostaglandin, which facilitates several reproductive processes such as ovulation, fertilisation, and embryo implantation. 

Therefore, Dr Gemzell-Danielsson said, it is speculated that piroxicam can provide a contraceptive effect both pre-ovulation and post-ovulation. Before ovulation, piroxicam blocks the ovulatory process, and after ovulation, the drug prevents the implantation of the embryo. 

However, the trial does not investigate the mechanism of action of piroxicam, and hence, further research is needed to confirm the mechanism of action. 

Limitations to the study

Some of the limitations to the study acknowledged by the authors include the generalisability of the results to other settings, and the exclusion of women with current or recent use of hormonal contraception and those with more than one episode unprotected coitus before consuming the emergency contraceptive drug. Therefore, the researchers are not sure whether taking piroxicam and levonorgestrel together will be equally effective when women in those circumstances consume them.

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