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Research eyes EC regimens, timing issues
What is your clinic’s protocol when it comes to emergency contraception (EC)? New research indicates that because the Yuzpe EC regimen of combined oral contraceptives (OCs) is at least partially effective when started up to 120 hours after unprotected intercourse, current protocols may be too restrictive.1
In a separate report, results of a large multicenter randomized trial found that OCs containing the more common norethindrone-ethinyl estradiol combinations of pills work about as well for EC as the standard levonorgestrel-ethinyl estradiol pills used in the Yuzpe regimen.2 The regimen is named after Albert Yuzpe, MD, MSc, who conducted early EC research and now is co-director of the Genesis Fertility Centre in Vancouver, British Columbia.
A wider variation in the regimens and timing of EC could benefit women who are unable to obtain EC within 72 hours or who live in areas where it is difficult to obtain the standard Yuzpe combination of hormones, say the authors of the new research. Recent research showed that levonorgestrel and mifepristone also work well for emergency contraception when used between 72 and 120 hours.3
What’s the next step in EC research?
"The next step in science might be to explore even beyond the (120-hour) time window, depending on where the woman was in her cycle at the time she wanted to start EC," says Charlotte Ellertson, MPA, PhD, president of Ibis Reproductive Health in Cambridge, MA, and lead author of the new research.
Any reason for 72-hour cutoff?
Ellertson says her research group wanted to explore extending the Yuzpe regimen window because members were concerned that women were being turned away after 72 hours without a good reason.
"The 72-hour cutoff was just a guess by Dr. Yuzpe when he first started studying the regimen that later came to bear his name, but it got accepted as a rigid deadline in clinical practice," observes Ellertson. Yuzpe conducted his EC research using a hormone combination he already was using for other investigations, and he selected the 72-hour cutoff based on other regimens used in Europe.4,5
The new research, based on an observational study, included 111 women who requested emergency contraception between 72 and 120 hours after unprotected sex and chose the Yuzpe regimen over insertion of a copper intrauterine device, which is the standard therapy for women seeking EC outside the 72-hour window.
Researchers then compared failure rates for this group with rates among 675 otherwise similar women who started the same therapy within 72 hours.
Perfect use (1.9%) and typical use (3.6%) failure rates were low among women presenting between 72 and 120 hours after unprotected intercourse; these rates did not statistically differ from failure rates for the standard Yuzpe regimen (2.0% during perfect use and 2.5% during typical use).
Researchers note that the small sample size yielded just 25% power to detect a doubling in the failure rates (2% to 4%) and 59% power to detect a tripling in the failure rates (2% to 6%). The results are consistent with similar published work,6,7 says Ellertson.
Look at OC options
When it comes to pill selection for the Yuzpe regimen, results from the new randomized trial may offer support in use of other hormonal combinations outside the original ethinyl estradiol-levonorgestrel dosing. In the Yuzpe regimen, women take one dose within 72 hours after unprotected intercourse and a second dose 12 hours later.
Historically, one-half experience nausea, and one-fifth vomit.2 Researchers set out to determine whether women could use combined OCs other than those containing levonorgestrel and determine whether eliminating the second dose could improve comfort and convenience.
Women presenting at study centers within 72 hours after unprotected intercourse were randomized to receive the standard two-dose Yuzpe regimen, a variant of the regimen substituting norethindrone for levonorgestrel, or only the first dose of the regimen, followed 12 hours later by a placebo.
Perfect-use failure rates are similar
Perfect-use failure rates were low in all groups and did not differ in a statistically significant way; typical-use failure rates were slightly higher, but also did not differ significantly, report investigators. Side effects were similar across groups, except that women taking the single dose reported half the vomiting. Taking the pills with food did not seem to reduce nausea or vomiting, and the pills were not more effective when started sooner after unprotected intercourse.
Combined pills containing norethindrone-ethinyl estradiol work about as well for EC as levonorgestrel-ethinyl estradiol formulations and should be offered when first-line therapies are not available, researchers conclude.
"The implication of the research is that women who don’t have access to a dedicated EC product, or to the exact hormones [ethinyl estradiol and levonorgestrel] that have been so well studied, can go ahead and use these other pills to create their own ECs," says Ellertson.
When reviewing information on the Yuzpe regimen, clinicians should keep in mind that levonorgestrel-only formulations have fewer side effects, says Anita Nelson, MD, professor in the obstetrics and gynecology department at the University of California in Los Angeles (UCLA) and medical director of the women’s health care clinic and nurse practitioner training program at Harbor-UCLA Medical Center in Torrance.
In a randomized controlled trial of levonorgestrel vs. the Yuzpe regimen, the levonorgestrel regimen was better tolerated.8
"Women should still use the tried-and-true methods [levonorgestrel or Yuzpe] if they can get them; but in a pinch, these other [norethindrone-ethinyl estradiol] pills should be better than nothing," says Ellertson.
1. Ellertson C, Evans M, Ferden S, et al. Extending the time limit for starting the Yuzpe regimen of emergency contraception to 120 hours. Obstet Gynecol 2003; 101:1,168-1,171.
2. Ellertson C, Webb A, Blanchard K, et al. Modifying the Yuzpe regimen of emergency contraception: A multicenter randomized controlled trial. Obstet Gynecol 2003; 101:1,160-1,167.
3. Von Hertzen H, Piaggio G, Ding J, et al. Low-dose mifepristone and two regimens of levonorgestrel for emergency contraception: A WHO multicentre randomized trial. Lancet 2002; 360:1,803-1,810.
4. Yuzpe AA, Lancee WJ. Ethinylestradiol and dl-norgestrel as a postcoital contraceptive. Fertil Steril 1977; 28:932-936.
5. Yuzpe AA, Percival Smith R, Rademaker AW. A multicenter clinical investigation employing ethinyl estradiol combined with dl-norgestrel as a postcoital contraceptive agent. Fertil Steril 1982; 37:508-513.
6. Grou F, Rodrigues I. The morning-after pill — how long after? Am J Obstet Gynecol 1994; 171:1,529-1,534.
7. Rodrigues I, Grou F, Joly J. Effectiveness of emergency contraception pills between 72 and 120 hours after unprotected sexual intercourse. Am J Obstet Gynecol 2001; 184:531-537.
8. 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; 352:428-433.