Levonorgestrel is a better emergency contraceptive than the combination pill

International Family Planning Perspectives, Mar 1999 by Olenick, I

Women who use a levonorgestrel-only regimen of emergency contraception are about one-third as likely as women using the Yuzpe regimen to become pregnant following treatment; they are also significantly less likely to experience nausea and vomiting. For each method, the pregnancy rate rose with time between unprotected intercourse and treatment, according to a comparative study conducted in 14 countries.l

A total of 1,998 healthy women with regular menstrual cycles were recruited from centers in 21 cities around the world. The women had to have engaged in no more than one act of unprotected intercourse within 72 hours before seeking emergency contraception. Participants were randomized to the levonorgestrel regimen (1,001) or the Yuzpe regimen (997), which uses combined oral contraceptives.

After providing a blood or urine sample, each woman received her first dose of emergency contraception and was given a second dose to be taken at home 12 hours later. Each dose of the levonorgestrel regimen consisted of a 0.75-mg levonogestrel tablet and a placebo; each dose of the Yuzpe regimen contained two 50-mcg tablets of ethinyl estradiol and two 0.25-mg tablets of levonorgestrel.

Women were instructed to record side effects experienced in the week after treatment, resumption of menses and any subsequent acts of intercourse. They returned to the clinic a week after expected resumption of menstruation. At this time, pregnancy tests were administered to women who had not resumed menses.

At the follow-up visit, 42 women were pregnant; among them, 31 had used the Yuzpe method and 11 the levonorgestrel regimen. Analysis of stored urine or blood revealed that four of these women had been pregnant at the time of enrollment into the study; nevertheless, the researchers included these women in the analysis. The pregnancy rate for women using the Yuzpe regimen was higher than that among women taking levonorgestrel (3.2% vs. 1.1%), and women taking levonorgestrel

were about one-third as likely as women using the Yuzpe method to become pregnant (crude risk ratio, 0.36). Analyses adjusting for enrollment center, woman's age, cycle day on which intercourse occurred and reason for seeking treatment produced almost identical results.

The risk of pregnancy increased significantly as the number of hours between unprotected intercourse and use of either method of emergency contraception increased. Among women who took levonorgestrel, failure rates ranged from 0.4% when the treatment was taken within 24 hours of unprotected sex to 2.7% when the treatment was taken 49-72 hours after intercourse. The corresponding rates for users of the Yuzpe method were 2.0% and 4.7%. Thus, the risk of pregnancy at each interval was greater among women who took the Yuzpe regimen than among those who used levonorgestrel.

In a second data analysis, the researchers excluded women who had not followed instructions for using emergency contraception (women who failed to take the first treatment dose within 72 hours of unprotected sex, those who failed to take the second dose within 24 hours of the first dose, those who engaged in further acts of unprotected intercourse, and those who used additional hormonal contraceptives during the cycle). Within this subset of 1,157 women, there were 11 pregnancies among 583 women who had used the Yuzpe regimen and five pregnancies among 574 who had taken levonorgestrel. Women who took levonorgestrel were about half as likely as users of the Yuzpe regimen to become pregnant (crude risk ratio, 0.46).

The frequency of side effects was lower among levonorgestrel users than among women who took the Yuzpe treatment. Nearly one-quarter of women who took levonorgestrel (23%) experienced nausea, compared with 51% of women who used the Yuzpe regimen. The incidence of vomiting was 6% among women who took levonorgestrel and 19% among users of the Yuzpe method. Levonorgestrel was associated with fewer instances of dizziness than the Yuzpe method (11% vs. 17%). Fatigue was also less common among women who took levonorgestrel than among those who used the Yuzpe regimen (17% vs. 29%).

Concluding that levonorgestrel is a more effective and better-tolerated method of postcoital contraception than the Yuzpe regimen, the researchers recommend that levonorgestrel replace the Yuzpe regimen as the standard emergency regimen.

Reference

1. Task Force on Postovulatory Methods of Fertility Regulation, Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception, Lancet, 1998, 352(9126):428433.