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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?
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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.
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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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