A woman is at risk for pregnancy and thus a candidate for emergency contraception (EC) within 120 hours following unprotected intercourse. This is based on the estimated life span of sperm in the genital tract. FDAapproved EC pills already available in the United States are effective only up to 72 hours after unprotected intercourse. Ulipristal acetate, a new option for EC with efficacy within 5 days after intercourse, is now available in the United States since December 1, 2010.
Half of all pregnancies in the United States are unintended; data from 2001 reported 3.1 million unintended pregnancies, with half of these ending by elective abortion. 1 Knowledge about EC is especially important for the 4.6 million women not using a regular contraceptive method and the 6.8 million women who rely on condoms for protection against pregnancy.2
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CURRENT EC OPTIONS
The Paragard® Copper T intrauterine contraceptive (IUC) can be used up to 120 hours following sexual intercourse, but this use is off-label. Moreover, the IUC method requires insertion by a trained clinician, is relatively expensive and invasive, and is appropriate only for women seeking to start long-term contraception.
Emergency Contraception Pills
The most currently used EC in the United States is a pill that contains only the progestin levonorgestrel. The original treatment was one 0.75-mg dose within 72 hours after unprotected intercourse, followed by a second 0.75-mg dose 12 hours later. Recent studies have shown that a single dose of 1.5 mg is equally effective as two 0.75-mg divided doses.3
Currently available FDA-approved levonorgestrel formulations are single-dose Plan B One Step™ (approved in July 2009 and manufactured by Teva Pharmaceuticals) and Next Choice®, a 2-pill generic formulation of Plan B (approved in June 2009 and manufactured by Watson Pharmaceuticals). Both can be purchased without a prescription by women and men 17 and older. A prescription is required for females younger than 17, despite evidence of safety in younger women. EC pills are kept behind the pharmacy counter and not on the shelf.
The new EC type, ulipristal acetate, a selective progesterone receptor modulator, was recently approved by the FDA. Ulipristal acetate can be taken up to 5 days following unprotected intercourse, which provides 2 additional days for use in comparison to the current levonorgestrel formulations. It is marketed by Watson Pharmaceuticals under the name of ella® and is available by prescription only.
Mechanism of Action
The primary mechanism of action of EC pills, both levonorgestrel and ulipristal acetate, is inhibition or delay of ovulation. EC pills, by preventing or delaying ovulation to a time past the viability of sperm from unprotected intercourse, prevent fertilization. EC pills will not prevent pregnancy if ovulation and fertilization have already occurred. This is why it is important for women to take EC pills as soon as possible following unprotected intercourse.
Levonorgestrel is approved for use up to 72 hours following unprotected intercourse; there is only limited evidence that levonorgestrel is effective beyond 72 hours.4 Ulipristal acetate is more effective than levonorgestrel in preventing or delaying ovulation, especially during the preovulatory period, which is 1 to 2 days prior to ovulation. Once the preovulatory follicle has reached 18 mm in size, levonorgestrel is no better than placebo at inhibiting ovulation, while ulipristal acetate is still able to inhibit follicular rupture in 59% of cases.5,6
The accepted effectiveness of levonorgestrel up to 72 hours following unprotected intercourse is based on the results of a trial undertaken by the World Health Organization and published in 1998 in which levonorgestrel prevented 95% of expected pregnancies when taken within 24 hours of sexual intercourse, 85% if taken within 25 to 48 hours, and 58% if taken within 49 to 72 hours.7
A large prospective clinical trial conducted in the United States showed that ulipristal acetate was effective and well tolerated as a single 30-mg dose for EC when used 48 to 120 hours following unprotected intercourse.8
Two prospective randomized EC trials compared the efficacy of ulipristal acetate to levonorgestrel. The first included women up to 72 hours following unprotected intercourse and the second up to 120 hours.9,10 When these 2 studies were combined in a meta-analysis, ulipristal acetate was found to have a pregnancy rate 65% lower than levonorgestrel when taken in the first 24 hours following unprotected intercourse and 42% when taken within 72 hours. In the second randomized study, ulipristal acetate prevented significantly more pregnancies than did levonorgestrel in the 72-to-120-hour subgroup, which is consistent with the increased effectiveness of ulipristal acetate in delaying ovulation during the preovulatory period as described previously.
Safety and Side Effects
The most common side effects include headache, nausea, abdominal pain, dysmenorrhea, fatigue, and dizziness.11 These are generally mild and usually resolve within 24 hours.
The incidence of side effects with ulipristal acetate is similar to those seen with levonorgestrel. Cycle length may be slightly shortened after levonorgestrel and slightly prolonged with ulipristal acetate. It is generally recommended that a pregnancy test be performed if menses are more than 1 week late following use of EC. There have been no reports of levonorgestrel or ulipristal acetate causing birth defects or serious complications.
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BARRIERS TO MORE WIDESPREAD USE OF EMERGENCY CONTRACEPTION
Many clinicians do not frequently prescribe EC and rarely provide this information to women during routine visits. Surprisingly, many hospital emergency departments do not routinely provide EC to victims of sexual assault. Unfortunately, many women are unaware that EC is available, effective, and safe.
The introduction of a new, more effective, and safe alternative EC pill may help to improve knowledge about EC by health care providers and thereby help improve access to EC. Additionally, clinicians may have more dialogue about contraception with their patients.
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Emergency contraception is a woman's last chance to prevent unintended pregnancy after unprotected intercourse. Efforts to educate women and men about the availability, safety, and efficacy of EC methods need to be increased. EC should ideally be available in the home medicine cabinet of women who do not wish to become pregnant, for immediate use following unprotected intercourse. Increased use of more effective long-acting contraception should also be encouraged by health care providers.
The increased efficacy of ulipristal acetate, both immediately and up to 5 days following unprotected intercourse, is a distinct advantage over the current approved levonorgestrel- containing products. As a prescription drug, ulipristal acetate should be covered by insurance plans and other thirdparty payers.
The author reports that he is a consultant for HRA Pharma.
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Paul M. Fine, MD, is Professor of Obstetrics and Gynecology, Baylor College of Medicine, and Medical Director, Planned Parenthood Gulf Coast, Houston, TX.