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A drug commonly used to treat arthritis pain can boost the effectiveness of the morning-after pill. Image credit: Aitor Diago/Getty Images.
  • Between 2017 and 2019, 28% of women aged 15-44 in the United States report having used emergency contraceptive pills at least once in their lives.
  • Although emergency contraception is effective at halting unwanted pregnancies, sometimes pregnancies can occur.
  • Researchers from The University of Hong Kong have found taking an emergency contraceptive pill with an anti-inflammatory medication helps prevent significantly more pregnancies compared to when the morning-after pill was taken alone.

In survey data from 2017–2019, 28% of female respondents in the United States aged 15 to 44 reported having used emergency contraceptive pills — such as the morning-after pill, also known as “plan B” — at least once in their lives.

Emergency contraceptive pills are most effective when taken as close to the time of intercourse as possible, although the Centers for Disease Control and Prevention (CDC) advise they can all be used within 5 days of unprotected sexual intercourse.

Nevertheless, some preparations have notably reduced effectiveness beyond 3 days.

Even with emergency contraception, pregnancy can still occur. And the longer a person waits to take it after intercourse, the more their pregnancy risk increases.

Now, researchers from The University of Hong Kong have found that taking an emergency contraceptive pill with an anti-inflammatory medication commonly used for arthritis pain helps prevent significantly more pregnancies compared to when the morning-after pill was taken alone.

This study was recently published in the journal The Lancet.

The morning-after pill is a medication that, in the U.S., women can take up to 5 days after unprotected sexual intercourse to help prevent pregnancy.

The pill is mainly intended for people assigned female at birth who have unprotected penetrative sex or whose method of birth control has failed, for instance, by forgetting to take a birth control pill or when a condom breaks.

Morning-after pills mainly use either the hormone levonorgestrel or ulipristal acetate. Levonorgestrel is available as an over-the-counter medication without a prescription.

The American Association of Obstetricians and Gynaecologists (ACOG) advises that levonorgestrel is most effective when taken within 3 days of penetrative sexual intercourse, but remains moderately effective for up to 5 days.

Ulipristal acetate requires a prescription in the U.S., but it is a more effective emergency contraceptive than levonorgestrel, and the ACOG advises it can be taken up to 5 days after sex with no decrease in efficacy.

Both types of morning-after pills work by delaying or halting ovulation so an egg cannot be fertilized by sperm. That is why it is important to take the morning-after pill after unprotected sexual intercourse as soon as possible.

Taking the morning-after pill may also cause some side effects, including:

For this study, Dr. Raymond Li — clinical associate professor in the Department of Obstetrics and Gynecology at The University of Hong Kong, and first author of the study — and his team conducted a study at a major community sexual and reproductive health service in Hong Kong between August 2018 and August 2022.

Women who needed to take a morning-after pill containing levonorgestrel either received both the morning-after pill and an anti-inflammatory medication or the morning-after pill and a placebo pill.

Scientists used a drug called piroxicam, commonly used to treat arthritis pain, as the anti-inflammatory medication in this study.

“Piroxicam is one of the longest-acting anti-inflammatory drugs and hence may theoretically cover a wider window of the ‘fertile period’ of a woman,” Dr. Li explained.

Of the 836 women the scientists followed up on, there was one pregnancy reported among the 418 women who took piroxicam and levonorgestrel, compared to seven pregnancies among the 418 women who had the placebo and levonorgestrel.

That means the piroxicam-levonorgestrel combo was 95% effective in preventing pregnancy compared to the levonorgestrel-placebo combo, which was 63% effective.

Scientists also reported no significant differences in the side effects between the two study groups.

How could an anti-inflammatory medication — such as one taken for arthritis — help a morning-after pill be more effective?

According to Dr. Li, it is all about prostaglandins. He explained to Medical News Today:

“The essential role of prostaglandins in ovulation, fertilization, and embryo implantation has been appreciated for many years. That formed the basis of our postulation that an anti-inflammatory drug [that] inhibits prostaglandin synthesis may have synergistic effects in emergency contraception.”

Prostaglandins are a type of lipid that acts like a hormone in the body. The body makes prostaglandins where there might be an infection or wound. Prostaglandins cause the inflammation, fever, and/or pain associated with healing.

Prostaglandins also help facilitate certain reproductive processes, including fertilization, ovulation, and they kickstart the labor process.

Because anti-inflammatory drugs target prostaglandins, scientists theorized they would provide a contraceptive effect, aiding the effects of the morning-after pill.

“The exact mechanisms by which it works as a contraceptive, however, [are] yet to be studied in further research,” Dr. Li added.

When asked about the next steps in this research, Dr. Li said: “We will plan further research studies to explore its effectiveness compared to other current options of emergency contraception and to investigate the mechanisms of action of this combination regimen.”

MNT also spoke with Dr. Laura MacIsaac, clinical professor and associate director of the Complex Family Planning Fellowship Program in the Raquel and Jaime Gilinski Department of Obstetrics, Gynecology and Reproductive Science at the Icahn School of Medicine at Mount Sinai, about this study, in which she was not involved.

She commented that her first reaction to the study was excitement to see that a simple and safe addition to a levonorgestrel morning-after pill could lower pregnancy risk.

“There was an overall very low rate of pregnancy overall in this trial, but the addition of the piroxicam had a big impact to make pregnancy even less likely,” Dr. MacIsaac pointed out.

She did caution that while episodic use of piroxicam was not thought to have any safety problems, chronic continuous high-dose use of these medications can damage the lining of the stomach and gastrointestinal tract and cause bleeding or ulcers.

When it comes to further research on this topic, Dr. MacIsaac said the investigators should focus on replicating this protocol in a more diverse patient population, as well as using the prostaglandin inhibitor alone for effectiveness in blocking pregnancy.

“Knowing the effectiveness both alone and in combination with levonorgestrel would add to the information women need to make choices around how to prevent pregnancy at the time of intercourse, if they choose not to be on a continuous or long-acting method,” she added.