A drug combination that uses emergency contraception and a cyclo-oxygenase-2 (COX-2) inhibitor may effectively disrupt ovulation, making it the first potential candidate for on-demand, pericoital oral contraception, according to an exploratory pilot study.

Among a group of nine patients, six demonstrated ovulation disruption after taking a combination drug of ulipristal acetate (UA) and meloxicam, reported Erica Cahill, MD, of Stanford University in California, and colleagues.

In total, eight of the participants experienced incomplete ovulation, or some signs of ovulatory dysfunction, they wrote in BMJ Sexual & Reproductive Health.

Menstrual cycle length was approximately 3 days longer in the treatment cycle than in the baseline cycle (31.9 days vs 28.6 days, P<0.01), the researchers found, but endometrial stripe thickness and side effects were similar from the baseline to treatment period.

“There’s no specific reason why emergency contraception pills must be taken after intercourse, as their effect is on preventing ovulation or preventing egg release,” Cahill told MedPage Today in an email. “The goal is to prevent egg release while sperm is present, so these medications, taken prior to intercourse, may be more effective.”

Cahill added that “these results suggest that the combination of ulipristal acetate and meloxicam is a great candidate to explore for repeat dosing as an on-demand pericoital contraception.”

Stephanie Teal, MD, MPH, chair of ob/gyn at University Hospitals Cleveland Medical Center, told MedPage Today that there is a potential demand for pericoital contraception, as different patients have a range of preferred methods regarding how to prevent pregnancy.

“Many more women in their teens, 20s, and early 30s are saying ‘I don’t want to be on the pill everyday,’ or ‘I want to have more control in knowing where I am at in my cycle, and then managing my contraception,'” said Teal, who was not involved in the study.

Many women use repeat emergency contraception pills before sex as a method of birth control, although there is limited evidence showing that this is effective, Cahill’s group wrote. The few days leading up to ovulation — also known as the luteal phase — are the most critical for emergency contraception, because this time period is the most difficult to disrupt ovulation, and is when egg fertilization is most likely to occur.

Cahill and colleagues aimed to evaluate UA plus a COX-2 inhibitor on ovulation disruption — defined as an unruptured follicle for at least 5 days — among individuals during their peak fertility. They recruited 10 healthy participants (ages 18-35). Participants included in the analysis had regular menstrual cycles, did not have an exposure to any hormonal medications, and were not pregnant or lactating within the 3 months leading up to the study.

The researchers followed each participant for two cycles between May 2018 and March 2019. During the first baseline cycle, they assessed normal ovulation parameters. The second was a treatment cycle, in which the investigators administered a one-time, 30-mg dose of UA-meloxicam during the fertile window. They conducted ultrasound studies three times a week and collected luteinizing hormone levels to assess ovulation disruption or dysfunction.

Overall, nine participants completed both baseline and treatment cycles and were included in the first analysis. The mean age of patients was 31 and the average BMI was 24.5. All participants demonstrated normal baseline ovulatory function.

Significant differences between the baseline treatment cycles included longer cycle length and lower levels of progesterone, but there were no differences in endometrial stripe thickness or maximum follicle size. All but one of the participants did have an ovulatory luteal progesterone level, suggesting that ovulation occurred at some point during the cycle.

Because this was an exploratory study, it was not powered to detect statistical differences between the baseline and treatment cycles, and could not compare the combination drug to UA alone, Cahill and colleagues noted. Additionally, they said that prospectively determining the luteal phase was difficult, and only two participants received the medication at the peak of the luteal phase as the researchers intended. Finally, this study could not measure true efficacy or side effects, and future research that evaluates repeat dosing is necessary.

Teal said that while this study only measures the pharmacokinetics and pharmacodynamics of this combination drug, it creates opportunities for future research to determine efficacy, identify ideal timing of administration, and compare UA alone to the drug combination.

“This just encourages us to to let patient-interest drive what we are researching,” Teal said. “If this is what patients want, we should keep looking at how to deliver it to them.”

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