Hormonal Emergency Contraception

Melissa Sanders Wanner, Pharm.D., Rachel L. Couchenour, Pharm.D.

Disclosures

Pharmacotherapy. 2002;22(1) 

In This Article

Efficacy

The probability of conceiving after one act of unprotected intercourse is relatively low and varies based on when during the menstrual cycle intercourse occurs.[17] There is a possibility of conception when intercourse takes place within the 5 days before or on the estimated date of ovulation. Probabilities of conception after a single act of unprotected intercourse range from 10% when intercourse occurs 5 days before ovulation to 33% when it occurs on the day of ovulation.[17] In addition, a recent study found that these 6 fertile days are highly variable, and more than 70% of women ovulate before day 10 or after day 17 of their menstrual cycles.[18] Thus, when evaluating clinical studies of the efficacy of emergency contraception, it is important to recognize that not all women who have unprotected intercourse become pregnant. Studies should assess the expected number of pregnancies. This is calculated by identifying the day during a woman's cycle on which intercourse occurred and multiplying it by the probability of conception on that cycle day. This number then should be compared with the number of observed pregnancies that occurred despite the use of emergency contraception.[4] Table 2 summarizes the clinical trials assessing the efficacy and tolerability of the various forms of hormonal emergency contraception.

In 1972, a study was conducted to evaluate the combination of ethinyl estradiol 100 µg and d,l-norgestrel 1.0 mg as a single dose for emergency contraception.[19] Since that time, many trials have been conducted, and the regimen has been modified to what is seen in practice today: two doses of ethinyl estradiol 100 µg and norgestrel 1.0 mg separated by 12 hours, with the first dose taken within 72 hours of unprotected intercourse.[7,20]

The most recent estimate of the effectiveness of the Yuzpe regimen was reported in a meta-analysis.[21] Only studies that reported results based on the cycle day of unprotected intercourse relative to the expected day of ovulation were included. To assess the regimen's effectiveness, the authors compared the combined outcomes from eight studies to five sets of external conception probabilities. The expected conception probabilities were derived from two studies that examined women who were not using contraception. The authors determined the likelihood of pregnancy from unprotected intercourse on each menstrual cycle day relative to the day of ovulation. Comparisons were made between the expected number of pregnancies and the actual conception rates. Forty-five estimates of effectiveness were determined and ranged from 56.4-89.3%. The authors' preferred point estimate was that the Yuzpe regimen decreased the risk of pregnancy by 74.1% (95% confidence interval [CI] 62.9-79.2%).[21]

A progestin-only regimen, two doses of levonorgestrel 0.75 mg taken at 12-hour intervals, is another option for emergency contraception when taken within 72 hours of unprotected intercourse. The first evidence of effectiveness came from a prospective randomized study comparing levonorgestrel alone with the Yuzpe regimen in 834 women.[22] Women had to present within 48 hours of unprotected intercourse, have had normal menstrual cycles for the previous 3 months, and agree to no further acts of intercourse during the study. After excluding patients who had further acts of unprotected intercourse, failure rates were similar between the two regimens. In the Yuzpe group, 2.6% of women became pregnant compared with 2.4% in the levonorgestrel group (difference was not statistically significant). Pregnancy rates appeared to increase in women who began either regimen more than 24 hours after intercourse, although these results were not significant. The frequency rates of nausea (46.5% vs 16.1%), vomiting (22.4% vs 2.7%), and fatigue (36.8% vs 23.9%) were significantly higher in the Yuzpe group than in the levonorgestrel group (p<0.001). The rates of dizziness, breast tenderness, and intermenstrual spotting or bleeding were similar between the groups.

Another larger double-blind randomized study compared levonorgestrel with the Yuzpe regimen.[10] This study enrolled 1998 healthy women with regular menstrual cycles who had only one act of unprotected intercourse within 72 hours before treatment. The pregnancy rates were 3.2% (95% CI 2.2-4.5%) and 1.1% (95% CI 0.6-2.0%) for the Yuzpe and levonorgestrel regimens, respectively. The crude relative risk of pregnancy was 0.36 (95% CI 0.18-0.70) for levonorgestrel compared with the Yuzpe regimen. The authors also compared the number of observed pregnancies with the number of expected pregnancies and found that the levonorgestrel regimen prevented 85% (95% CI 74-93%) of expected pregnancies, whereas the Yuzpe regimen prevented 57% (95% CI 39-71%). They also reported that the earlier either emergency contraceptive treatment was given during the 72-hour interval, the greater the efficacy.[25] Women who took their first dose within 24 hours of unprotected intercourse had the lowest pregnancy rates: 0.4% (95% CI 0.1-1.6%) and 2.0% (95% CI 0.9-3.7%) for levonorgestrel and Yuzpe regimens, respectively. Pregnancy rates increased to 1.2% (95% CI 0.3-3.0%) and 4.1% (95% CI 2.3-6.6%) as time after unprotected intercourse increased to 24-48 hours before the first dose and to 2.7% (95% CI 0.9-6.1%) and 4.7% (95% CI 1.9-9.4%) for 49-72 hours after intercourse for levonorgestrel and Yuzpe regimens, respectively.[10]

High-dose ethinyl estradiol 5 mg/day alone was introduced in the 1960s and has been shown to be effective as an emergency contraceptive.[6,23] The regimen is given for 5 consecutive days after unprotected intercourse but leads to a high frequency of nausea and vomiting. In an early study of this regimen,[6] only 17 pregnancies occurred among 3016 women who were given this regimen after unprotected intercourse. However, 54% experienced nausea; 24%, vomiting; and 23%, breast tenderness.[6] In another study,23 high-dose ethinyl estradiol was compared with the Yuzpe regimen. The observed pregnancy rates in the high-dose ethinyl estradiol group and the Yuzpe regimen group were found to be significantly less than the expected pregnancy rates: 6.5% versus 1.1% and 5.5% versus 0.5%, respectively (p<0.0005). Adverse effects such as nausea and vomiting occurred more frequently in the high-dose ethinyl estradiol group.[23]

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