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British Journal of Family Planning. 2000 Apr; 26(2):67-8.This editorial comments on the superior efficacy of levonorgestrel as an emergency contraceptive. A comparative trial between levonorgestrel and the Yuzpe regimen conducted by the WHO indicated that levonorgestrel has a pregnancy rate one-third that of the comparison group. The result, however, has been questioned in several accounts. First, the Yuzpe regimen did not appear to perform particularly well in the trial, which might have influenced the comparison. Second, the method used to measure the true efficacy of emergency contraception, or proportion of pregnancies prevented, has limitations. Nevertheless, an interesting result of the WHO trial was the correlation between interval to treatment and pregnancy rate, where the shorter the coitus-to-treatment interval, the lower the pregnancy rate. With levonorgestrel, rates of unwanted pregnancies are expected to decrease. However, there are obstacles to the wholesale switch to levonorgestrel; namely, cost, difficulty in distribution relating to its new drug status, and resistance to change. The speed with which levonorgestrel has been introduced in the UK following a high quality randomized trial is impressive. However, the implementation of research findings remains a challenge. The use of levonorgestrel for emergency contraception may be an appropriate service standard for family planning in the future.
JOURNAL OF THE AMERICAN MEDICAL WOMEN S ASSOCIATION. 1998; 53(5 Suppl 2):222-4, 232.During the last decade, the UNDP/UNFPA/WHO/World Bank Special Program of Research, Development, and Research Training in Human Reproduction has been in the forefront of research on new methods of emergency contraception. This research has focused on both levonorgestrel and mifepristone. The results of large clinical studies suggest that both these compounds are better tolerated and even more effective than the Yuzpe regimen. This article, intended for purposes of continuing medical education, summarizes the findings of studies that have compared these three approaches to emergency contraception.
Lancet. 1999 Feb 27; 353(9154):721.A World Health Organization (WHO) study of combined oral contraceptives (Yuzpe regimen) and levonorgestrel alone for emergency contraception found that the effectiveness of both treatments declined with increasing time since unprotected intercourse. An earlier review of primarily observational studies found no such timing effect, however. The authors' reanalysis of the WHO data revealed a consistent linear relationship between efficacy and time from intercourse to treatment. The pregnancy rate rose from 0.5% when treatment was given within 12 hours of treatment to 4.1% when 61-72 hours had elapsed. The odds ratio of pregnancy associated with either treatment at a given time compared with treatment 12 hours earlier was 1.46 (95% confidence interval, 1.20-1.77). This estimate was not affected by adjustment for confounding factors such as age, weight, cycle length, or cycle day in which unprotected intercourse took place. The consistency between the WHO trial and an earlier randomized controlled trial, the statistically significant temporal effect observed with both treatment regimens, and biologic plausibility all suggest that the effect of timing on emergency contraception efficacy is real.
JOURNAL OF FAMILY PRACTICE. 1998 Dec; 47(6):417.A study supported by the World Health Organization's Task Force on Postovulatory Methods of Fertility Control compared the efficacy of the Yuzpe and levonorgestrel-only methods of emergency contraception (EC). Enrolled in this double-blind, randomized trial were 1998 women from 21 centers around the world who requested EC within 72 hours of unprotected intercourse. The pregnancy rate was 1.1% for levonorgestrel alone and 3.2% for the combined ethinyl estradiol-levonorgestrel regimen. The crude relative risk of pregnancy was 0.36 (95% confidence interval, 0.18-0.70) for levonorgestrel compared with the Yuzpe regimen. The former method prevented 85% of expected pregnancies, while the latter prevented only 57%. Finally, side effects such as nausea, vomiting, dizziness, and fatigue were significantly less common in the levonorgestrel group. Although these findings document the superiority of the levonorgestrel regimen for EC, the 0.75 mg tablets are not currently manufactured in the US.
Lancet. 1998 Aug 8; 352(9126):416-7.The World Health Organization (WHO) multicenter, randomized trial reported in this issue of "The Lancet" confirms that levonorgestrel-only (two 750-mcg doses) is significantly more effective in preventing pregnancy after unprotected intercourse than the standard Yuzpe regimen (two doses of 500 mcg levonorgestrel and 100 mcg ethinyl estradiol) and is further associated with significantly less nausea and vomiting. When initiated within 24 hours of coitus, the failure rate was only 0.4% for levonorgestrel compared with 2.0% for the combined hormonal method. A further advantage of a progestogen-only emergency contraceptive method is avoidance of contraindications in women with past proven arterial or venous thrombosis or a current attack of migraine with focal aura. Although only one pharmaceutical company (Gedeon Richter in Budapest, Hungary) currently manufactures 750 mcg of levonorgestrel in a single tablet, others are likely to follow this example given the findings of the WHO study. Strong pressure exists to increase availability of postcoital contraception through trained nurses and retail pharmacists. However, potential users will still require counseling on the importance of selecting a long-term method of contraception and a family planning provider.
Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception.
Lancet. 1998 Aug 8; 352(9126):428-33.A previous study suggested that provision of two 0.75 mg doses of levonorgestrel for emergency contraception caused less nausea and vomiting and was more effective than the Yuzpe regimen of combined oral contraceptives (two doses of 100 mcg of ethinyl estradiol and 0.5 mg of levonorgestrel). These two regimens were evaluated further in a double-blind, randomized World Health Organization study of 1998 women recruited from 21 centers worldwide who requested emergency contraception within 72 hours of unprotected intercourse. Among the 1955 women for whom the outcome was known, the crude pregnancy rate was 1.1% (11/976) in the levonorgestrel group and 3.2% (31/979) in the Yuzpe group. The crude relative risk of pregnancy for levonorgestrel compared with the Yuzpe regimen was 0.36 (95% confidence interval, 0.18-0.70). The proportion of pregnancies prevented was 85% in the former group and 57% in the latter group. Nausea and vomiting occurred significantly less frequently in the levonorgestrel group (23.1% and 5.6%, respectively) than in the Yuzpe regimen group (50.5% and 18.8%, respectively). The efficacy of both treatments declined significantly (p = 0.01) with increasing time since unprotected intercourse. These findings confirm that the levonorgestrel regimen may be more effective and is better tolerated than the current standard in emergency contraception.