Levonorgestrel or ulipristal: Is one a better emergency contraceptive than the other?
Comparison of these two FDA-approved agents should take more into account than just efficacy measured by the crude pregnancy rate
One of the best-kept secrets in women’s health is the availability of effective emergency contraceptives that have few side effects and are inexpensive. Who are candidates for emergency contraception? They include women in whom another method of contraception recently failed; those who recently had unprotected intercourse; and those who have been sexually assaulted.
What are the three most commonly used emergency contraceptive options? They are:
- levonorgestrel, 1.5 mg
- insertion of a copper intrauterine device (IUD)
- ulipristal, 30 mg.
You are likely familiar with protocols for emergency contraceptives using levonorgestrel (Plan B One-Step) (see the FIGURE, panel A) and the copper IUD (ParaGard). You may not be as familiar with ulipristal (sold under the name Ella) (FIGURE, panel B), approved recently by the Food and Drug Administration for use as long as 120 hours after intercourse.
Ulipristal is a selective progesterone-receptor modulator that has predominantly antiprogestin activity. The drug blocks or delays ovulation and suppresses endometrial growth.1 Interestingly, ulipristal can block ovulation for as long as 5 days, even if administered after the onset of the luteinizing hormone (LH) surge.2
Chemical structure of two emergency contraceptives
All have relative advantages, disadvantages
It’s difficult to conclude, with confidence, that any one of the options for emergency contraception is “best” in every circumstance. For example, although generic levonorgestrel is the least expensive of the three options, a copper IUD provides the most cost-effective “emergency” contraception, viewed across a multi-year time frame.
A copper IUD is seldom inserted as emergency contraception, however. In one report, from England, only 3% of 158,000 women who requested emergency contraception received a copper IUD.3
Because levonorgestrel and ulipristal are the most commonly used options for emergency contraception, how do we select which agent to recommend?
The matter of cost-effectiveness
One dose of ulipristal is more expensive than generic levonorgestrel. In the health system in which I work, the cost to the patient of one dose of ulipristal is approximately $45; one dose of brand-name levonorgestrel, 1.5 mg (Plan B One-Step), is priced similarly. A generic prescription for two 0.75-mg levonorgestrel pills (sold under the name Next Choice), however, costs the patient approximately $30.
In an era of cost-conscious health care, some authorities have questioned whether ulipristal is cost-effective because it is more expensive than generic levonorgestrel.6 Investigators who conducted a formal cost-benefit analysis in the United Kingdom, reported that ulipristal was more cost-effective than levonorgestrel.7 In their analysis, one dose of ulipristal was assumed to be 3 times more expensive than generic levonorgestrel. But because ulipristal was more effective than levonorgestrel at reducing the rate of unintended pregnancy, it was more cost effective because it reduced the burden of the costly care associated with unintended pregnancy.
Availability of levonorgestrel and ulipristal
For women who are 17 years or older, levonorgestrel is widely available without a prescription. Such access avoids the cost and delay inherent in a visit to a clinician to obtain a prescription.
Ulipristal is available only with a prescription (TABLE 2). The FDA recommends that
…pregnancy should be excluded before prescribing Ella (ulipristal). If pregnancy cannot be excluded on the basis of history and/or physical examination, pregnancy testing should be performed.
What FDA says about emergency contraception with levonorgestrel and ulipristal
Emergency contraception, as long as 72 h after intercourse
Emergency contraception, as long as 120 h after intercourse
Women 17 y and older
Available without a prescription
Women younger than 17 y
Some physicians interpret this recommendation to mean that a visit to a physician and a pregnancy test are required before they can prescribe ulipristal. Possible alternatives to an office visit before prescribing ulipristal as emergency contraception would be for you to:
- ask the patient to call the office with her menstrual cycle information, and to ensure that office staff reviews that information before you prescribe the drug
- ask the patient to perform a home pregnancy test before you prescribe ulipristal.
For women who lack access to regular health care, levonorgestrel is clearly the best option for emergency contraception. Years of clinical data show that levonorgestrel, if taken accidently by a pregnant woman, is unlikely to harm the pregnancy.
Unlike what we know about levonorgestrel, few data exist about the safety of a 30-mg dose of ulipristal in a woman who is pregnant. Some clinicians clearly view safety data as favoring continued use of levonorgestrel for emergency contraception.
A swift and reliable agent of change for women
The stunningly sudden and irrevocable failure of a barrier contraceptive is quickly followed by dismay and fear. A woman who both knows how to use an emergency contraceptive and has access to highly effective medication can transform a nightmare into calm and successful rescue from the possibility of unintended pregnancy.
We want to hear from you! Tell us what you think.
1. Chabbert-Buffet N, Pintiaux-Kairis A, Bouchard P; VA2914 Study Group. Effects of the progesterone receptor modulator VA2914 in a continuous low-dose on the hypothalamic pituitary ovarian axis and endometrium in normal women: a prospective randomized, placebo-controlled trial. J Clin Endocrinol Metab. 2007;92(9):3582-3589.
2. Brache V, Cochon L, Jesam C, et al. Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture. Hum Reprod. 2010;25(9):2256-2263.
3. National Health Service Contraceptive Services, England: 2006 to 2007. http://www.ic.nhs.uk/ statistics-and-data-collections/health-and-lifestyles/contraception/nhs-contraceptive-services-england:-2006-07.Accessed February 2 2011.
4. Creinin MD, Schlaff W, Archer DF, et al. Progesterone receptor modulator for emergency contraception. Obstet Gynecol. 2006;108(5):1089-1097.
5. Glasier AF, Cameron ST, Fine PM, et al. Ulipristal acetate versus levonorgestrel for emergency contraception: a randomized non-inferiority trial and meta-analysis. Lancet. 2010;375(9714):555-562.
6. Furedi A. New emergency contraceptive method ellaOne—is it worth the price? Reprod Health Matters. 2009;17(34):187-188.
7. Thomas CM, Schmid R, Cameron S. Is it worth paying more for emergency hormonal contraception? The cost-effectiveness of ulipristal acetate versus levonorgestrel 1.5 mg. J Fam Plann Reprod Health Care. 2010;36(4):197-201.