Efforts to improve emergency contraceptive pills include making them easier to use by eliminating the need for a second dose, reducing side effects and investigating whether the recommended time limit of 72 hours for starting use might be extended.
A progestin-only pill regimen is more effective and better tolerated than combined hormonal pills used for emergency contraception.1 Recent advances in packaging designed for emergency contraceptive use also make progestin-only pills the easier option to use. Progestin-only pills made specifically for emergency contraception consist of a tablet containing 0.75 mg levonorgestrel taken as soon as possible after intercourse, followed 12 hours later by a second tablet containing the same amount of levonorgestrel.
This two-tablet product is a marked improvement over using progestin-only pills intended for daily contraception. To achieve the proper dose needed for emergency contraception, a large number of the low-dose progestin-only pills are needed. For example, a woman must take 20 tablets of daily progestin-only pills (each containing 0.0375 mg levonorgestrel), followed by another dose of 20 tablets 12 hours later.
Yet, the two-dose regimen may be further improved. In a World Health Organization (WHO) study involving some 4,000 women, the contraceptive effectiveness of 1.5 mg levonorgestrel given as a single dose is being compared with a standard regimen of two doses of 0.75 mg levonorgestrel given at a 12-hour interval, and with one dose of 10 mg mifepristone. The study is being conducted in China, Finland, Georgia, Hong Kong, Hungary, India, Mongolia, Slovenia, Sweden, Switzerland and the United Kingdom.
Also under study is whether two doses of 0.75 mg levonorgestrel given 24 hours apart are as effective as two doses given at the standard 12-hour interval. WHO is collaborating with the Family Planning Association of Hong Kong in this study, expected to be completed in 2002.
Meanwhile, a recent study by the New York-based Population Council found a single dose of combined hormonal pills caused fewer side effects than the standard double dose of combined pills. (The study, involving some 2,000 women, also examined how timing of the first dose and use of a different progestin, norethisterone, affected the effectiveness of the combined hormonal regimen.)2
Studying the effectiveness of combined hormonal pills that contain the progestin norethisterone, rather than levonorgestrel, was important because norethisterone-containing oral contraceptives are widely available throughout the world, and might be effective for emergency contraception if the standard combined hormonal regimen or the levonorgestrel-only regimen were unavailable.
The recent Population Council study of modifications of the combined hormonal pill regimen found that the contraceptive failure rate for norethisterone-containing pills was somewhat higher than that for levonorgestrel-containing pills. "The results indicate that if women have the standard combined pills or the levonorgestrel-only pills, they should use them," says Kelly Blanchard, study project director. "But if they do not have access to these pills, norethisterone-containing oral contraceptives clearly are effective for emergency contraception as well. Using them may save women money and time. Many women who need emergency contraception might be able to use the oral contraceptives they already have on hand."
Side effects, timing
Reducing the side effects of nausea and vomiting, which are most commonly experienced by users of combined hormonal pills, is an important goal. A 1998 WHO study involving nearly 2,000 women compared combined hormonal pills with progestin-only pills used for emergency contraception. In the landmark study, half of combined hormonal pill users experienced nausea or vomiting compared to only a quarter of women taking progestin-only pills. Nineteen percent experienced vomiting compared to 6 percent of progestin-only pill users.3
Combined hormonal pills are still the only pill option for emergency contraception in many countries, but a commonly used drug for motion sickness called meclizine may reduce some of the regimen's side effects. In a study conducted by FHI, taking meclizine an hour before starting the combined pill regimen significantly reduced the incidence of nausea (47 percent of women who took meclizine experienced nausea, compared to 64 percent of women who did not take the drug). Severity of nausea and incidence of vomiting were also significantly lower among women who received meclizine before starting the regimen.4
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Extend recommended time limit? |
The 1998 WHO study -- the world's largest randomized, controlled study of emergency contraception -- indicated that the sooner pills are started after unprotected intercourse, the more effective they are.
In the study, progestin-only pills started within 24 hours after unprotected intercourse prevented 95 percent of expected pregnancies. When started between 49 and 72 hours, only 58 percent of expected pregnancies were prevented. A decline in effectiveness as initiation was delayed was even more dramatic for combined hormonal pills, which were less effective than progestin-only pills even when taken soon after unprotected sex. Using combined pills prevented 77 percent of expected pregnancies when started within 24 hours and only 31 percent of expected pregnancies when taken 49 to 72 hours after unprotected intercourse.5
Almost all effectiveness studies have involved only women who took the pills within 72 hours (three days), since current advice is to start taking pills within 72 hours after unprotected intercourse. Women using the method after 72 hours should be informed that effectiveness may be limited.
Yet, some researchers have suggested that, depending on the time of ovulation, the recommended time limit for beginning pills might be extended to four or even five days after unprotected intercourse.6
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A bookmark promotes the Population Council's Spanish-language Web site. |
The recently completed Population Council study found that starting the combined hormonal pill regimen four to five days after unprotected sex reduced the risk of pregnancy by 50 percent among 108 women using the regimen. (The effectiveness of the combined hormonal regimen, regardless of when it was initiated, was higher in this study than in the WHO study.)7
"Our interpretation of data is that the 72-hour recommended cut-off for initiating emergency contraceptive pill therapy is unnecessarily restrictive," says Blanchard, project director of the Population Council study. "Efficacy after 72 hours does drop, but women should be offered the choice of taking the pills up to five days after unprotected sex since the therapy could still halve the risk of pregnancy." One way the pills could still prevent pregnancy up to five days is by inhibiting or delaying ovulation (release of an egg from the ovary) while viable sperm are still present.
In a related study, Canadian researchers recently found that women treated up to five days after unprotected sex had significantly lower pregnancy rates than women who received no emergency contraception. Effectiveness of the method was 72 percent to 87 percent among some 170 women who were treated between three and five days after unprotected sex.8
Existing regimens can safely prevent many unplanned pregnancies. But other products may also provide effective emergency contraception. Foremost among these potential products is the drug mifepristone, which can delay ovulation when administered during the pre-ovulatory phase of the menstrual cycle. When administered after the pre-ovulatory phase of the menstrual cycle, it can also block the hormone progesterone, which is essential for implantation.
In two studies conducted in the United Kingdom that compared one dose of 600 mg mifepristone to the standard combined hormonal regimen taken within 72 hours after unprotected intercourse, no pregnancies occurred among some 550 women who took mifepristone. In contrast, nine pregnancies occurred among some 550 women who took the combined hormonal regimen.9
According to a WHO multicenter, randomized study involving some 1,700 women, pregnancy rates were similar among groups of women taking 600 mg, 50 mg and 10 mg mifepristone within five days of unprotected intercourse.10 The U.S.-based Consortium for Industrial Collaboration in Contraceptive Research is analyzing a pilot study among 400 Chinese women to test the contraceptive effectiveness of 10 mg mifepristone alone or in combination with the anti-estrogen, tamoxifen, used up to five days after unprotected intercourse. Soon to be released are results of the WHO study among some 4,000 women comparing the effectiveness as emergency contraception of 10 mg of mifepristone, a standard regimen of two doses of 0.75 mg levonorgestrel, and 1.5 mg of levonorgestrel given as a single dose.
-- Kim Best
References
- 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):428-33.
- Ellertson C, Webb A, Blanchard K, et al. Three simplifications of the Yuzpe regimen of emergency contraception: results from a randomized, controlled, multicenter clinical trial. Unpublished paper. Population Council, 2000.
- Task Force on Postovulatory Methods of Fertility Regulation.
- Raymond EG, Creinin MD, Barnhart KT, et al. Meclizine for prevention of nausea associated with use of emergency contraceptive pills: a randomized trial. Obstet Gynecol 2000;95(2):271-77.
- Task Force on Postovulatory Methods of Fertility Regulation; Piaggio G, von Hertzen H, Grimes DA, et al. Timing of emergency contraception with levonorgestrel or the Yuzpe regimen. Lancet 1999;353(9154):721.
- Trussell J, Ellertson C, Rodriguez G. The Yuzpe regimen of emergency contraception: how long after the morning after? Obstet Gynecol 1996;88(1):150-54; Grou F, Rodrigues I. The morning-after pill -- how long after? Am J Obstet Gynecol 1994;171(6):1529-34.
- Ellertson.
- Rodrigues I, Grou R, Joly J. Effectiveness of emergency contraceptive pills between 72 and 120 hours after unprotected sexual intercourse. Am J Obstet Gynecol 2001;184(4):531-37.
- Glasier A, Thong KJ, Dewar M, et al. Mifepristone (RU 486) compared with high-dose estrogen and progestogen for emergency postcoital contraception. N Engl J Med 1992;327(15):1041-44; Webb AM, Russell J, Elstein M. Comparison of Yuzpe regimen, danazol and mifepristone (RU 486) in oral postcoital contraception. BMJ 1992;305(6859):927-31.
- Task Force on Postovulatory Methods of Fertility Regulation. Comparison of three single doses of mifepristone as emergency contraception: a randomised trial. Lancet 1999;353(9154):697-702.
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