September 25, 2023

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Lancet: A more effective emergency contraception is born!

Lancet: A more effective emergency contraception is born!



Lancet: A more effective emergency contraception is born!

A team from the University of Hong Kong has found for the first time that levonorgestrel combined with piroxicam can prevent 94.7% of unprotected intercourse pregnancies. 

Emergency contraception is a remedial measure after unprotected intercourse, sexual assault or contraceptive failure, to avoid unintended pregnancy.

Oral hormonal emergency contraceptives are the most widely used in most countries or regions, such as levonorgestrel tablets.

Levonorgestrel is more effective before ovulation, because its mechanism is to block or delay the peak of luteinizing hormone, that is, to disrupt the ovulation process and prevent conception.

The later the follicular phase, the worse the contraceptive effect of levonorgestrel. Once the ovulation process occurs, levonorgestrel will not work. Ulipristal acetate, which has a higher efficacy rate than levonorgestrel, also works by inhibiting ovulation . Clinical studies have shown that its effectiveness in preventing pregnancy after ovulation is insufficient .

In order to find a more effective oral emergency contraceptive, especially one that can work after ovulation, a research team from the University of Hong Kong conducted a new attempt.

In their randomized double-blind placebo-controlled trial, a single dose of levonorgestrel (1.5mg) + piroxicam (40mg) compared with levonorgestrel + placebo, reduced the risk of contraceptive failure by 80%, and prevented 94.7% of expected pregnancies, while the latter only prevented 63.4%. The trial results were published in The Lancet .

Lancet: A more effective emergency contraception is born!

The inspiration for this combination came from the role of prostaglandins in promoting multiple reproductive processes such as ovulation, fertilization and embryo implantation, which means that using inhibitors of the key enzyme involved in prostaglandin production – cyclooxygenase (COX) – may have a synergistic effect with oral emergency contraceptives and improve the effectiveness of contraception during and after ovulation.

Some previous clinical trials have explored several COX inhibitors, including rofecoxib, meloxicam and celecoxib, but the sample size was small. The researchers chose piroxicam, one of the longest-used COX inhibitors.

The trial included women who sought oral emergency contraceptives from the Hong Kong Family Planning Association and chose levonorgestrel. The inclusion criteria included being over 18 years old and healthy, having unprotected intercourse within 72 hours in the current menstrual cycle, having a menstrual cycle between 24 and 42 days, agreeing to avoid unprotected intercourse again, and being followed up for 6 weeks.

Lancet: A more effective emergency contraception is born!

A total of 860 women were assigned to the trial group and placebo group at a ratio of 1:1. Both groups had 12 participants lost to follow-up, and the remaining 418 were included in the efficacy analysis.

A total of 8 participants became pregnant, of which 1 (0.2%) in the trial group and 7 (1.7%) in the placebo group.

The number of expected pregnancies within both groups (based on the time of unprotected intercourse in the menstrual cycle, calculated by the Trussell model) were 19.0 (4.5%) and 19.1 (4.6%), respectively.

That is to say, the trial group (18.0/19.0, 94.7%) prevented significantly more expected pregnancies than the placebo group (12.1/19.1, 63.4%) (p<0.0001). The risk of contraceptive failure in the trial group was reduced by 80% compared with the placebo group (OR=0.20, p=0.036).

Lancet: A more effective emergency contraception is born!

The subsequent menstrual cycle recovery time in advance for the trial group and placebo group were median 1 day and 0 days respectively, with no significant difference in range and distribution. In both groups, 39% of participants reported non-menstrual spotting or bleeding within six days after taking the drug. Compared with the placebo group, the trial group had a significant reduction in menstrual blood volume during the subsequent menstrual period.

The most common adverse events (>5%) were fatigue or weakness, nausea, lower abdominal pain, dizziness and headache. Three percent of participants in both groups reported stomach pain. There was no significant difference in adverse event rates between the two groups.

Overall, the results of this clinical trial showed that levonorgestrel combined with piroxicam was more effective than levonorgestrel alone for emergency contraception.

The first author of the study Dr Raymond Li pointed out that this trial was the first to show that a readily available and safe drug taken with levonorgestrel can prevent more pregnancies. They hope that these results will stimulate further research and ultimately change clinical guidelines to provide women around the world with more effective emergency contraception.

In a commentary article published at the same time, the commentators affirmed the results of the study and also reminded that most of the participants in this trial were non-obese Asian women (only 81 of the participants included in the efficacy analysis had a BMI>26kg/m2 or weight>70kg).

Given that levonorgestrel for emergency contraception is less effective for obese people, the results of this trial may not be generalizable to women with higher BMI .

 

 

 

 

Lancet: A more effective emergency contraception is born!

References:

[1] Glasier A F, Cameron S T, Fine P M, et al. Ulipristal acetate versus levonorgestrel for emergency contraception: a randomised non-inferiority trial and meta-analysis[J]. Lancet, 2010, 375(9714): 555-562.

[2] Li HWR, Lo SST, Ng E H Y, Ho PC. Efficacy of ulipristal acetate for emergency contraception and its effect on the subsequent bleeding pattern when administered before or after ovulation[J]. Human Reproduction, 2016, 31(6): 1200-1207.

[3] https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01240-0/fulltext

[4] https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01612-4/fulltext

(source:internet, reference only)


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