Emergency Contraception
March 1, 2014
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Emergency Contraception
Special Feature
By Jeffrey T. Jensen, MD, MPH, Editor
Synopsis: We now have three options for emergency contraception — the copper IUD, oral ulipristal acetate, and oral levonorgestrel. One of the most important considerations in using emergency contraception is the initiation of ongoing regular contraception. The special feature will discuss the opportunities and considerations for use of these three different methods of postcoital contraception.
With several options available for emergency contraception (EC), a number of considerations exist for patients and providers. In most practice settings, the health care provider is taken out of the conversation due to the availability of over-the-counter (OTC) products. Overall, having OTC options is a good public health policy. However, since the counseling available from pharmacists will vary widely throughout the country and since there are prescription-only options that offer unique advantages, it is important to be informed about the latest developments. The best time to talk to your patients about EC may be prior to its need. In particular, those women using barrier methods, those with a history of prior contraceptive failure, and those who have infrequent sex deserve a short conversation about the state of the art of EC during routine health check-ups.
Oral levonorgestrel (LNG), a progestin, is now available to all women in the United States without a prescription. It has been well established that a single dose of 1.5 mg LNG is as effective as two 0.75 mg doses taken 12 hours apart.1,2 LNG works by blocking the luteinizing hormone (LH) surge. If the LH surge has initiated, ovulation will proceed normally, and there is no convincing evidence of any pregnancy disruption effect with LNG.3 Although the science is clear on this, it has not reduced the level of public misinformation, and concerns about a post-fertilization effect remain an important barrier to the OTC availability of EC.4 Biologically, pregnancy does not occur until after implantation so abortion cannot occur before this event. Although some individuals have moral objections to any method that might allow fertilization of the oocyte and disrupt implantation, this is not abortion. Some may argue this is just semantics, but I do not think anyone would suggest that an embryo in the freezer of an IVF clinic is the same as a 6-week intrauterine gestation. Family planning methods that allow fertilization but prevent implantation are more correctly termed contragestives (contra-gestation). Since LNG does not have contragestive properties, it needs to be taken as soon after unprotected intercourse as possible to prevent ovulation. Since sperm can remain viable for up to 5 days after ejaculation, the use of LNG EC is done to prevent ovulation during this window. LNG EC is generally recommended for use only within 72 hours of unprotected sex; the product is most effective if taken as soon as possible and efficacy declines as time progresses.5
Ulipristal acetate (UPA) is a selective progesterone receptor modulator. It is available by prescription only. A single dose of 30 mg of UPA will prevent follicle rupture in the 5 days following treatment, even when administered at the initiation of the LH surge.6 Although the available evidence suggests that UPA still relies on suppression of ovulation as the mechanism of action, the drug provides a longer window of activity then LNG. UPA is FDA-approved and marketed for use up to 5 days after unprotected sex, while LNG is recommended for up to 3 days only. Since 5 days covers the window of time that sperm would be viable, it should effectively prevent ovulation throughout the fertile period. Clinical trial results back up these mechanistic details. A large, randomized clinical trial and meta-analysis concluded that UPA was more effective than LNG, preventing more than two-thirds of expected pregnancies compared with 50% for LNG.5 This is an important message that should be communicated to our patients. Another important consideration with UPA is that ovulation is not always prevented or disrupted. It may be just delayed. Follicle rupture typically occurs about 6 days after use of UPA.7 This brings up another important counseling point. EC is not designed to provide regular contraception. Condoms should always be recommended for 7 days, and a regular method of contraception should be started (see below). For both methods of oral EC, the biggest risk of pregnancy occurs with repeated acts of unprotected intercourse in the same cycle.
Recent data have highlighted a number of other important considerations, and these all deserve clear counseling. First, obesity impacts results with LNG. There is convincing evidence that efficacy of LNG is greatly reduced in women weighing > 75 kg, and it appears to be not effective in women weighing > 80 kg.8,9 In contrast, there is no strong evidence of a weight effect with UPA. Although further studies are needed to clarify the upper boundary of this relationship for both drugs, the available data at this point strongly suggest that women weighing ≥ 75 kg should only be offered UPA. Clearly, the fact that LNG is available OTC while UPA is by prescription complicates this recommendation; this is another reason advanced counseling is important.
Although it is tempting to conclude that UPA is a better emergency contraceptive under all circumstances, there are a number of other considerations. Many women are advised to use EC after missing one or two doses of a regular combined oral contraceptive pill. Although EC should be used if the pills are missed at the end of the hormone-free interval, the role of EC after missing one or two pills during the active pill weeks is not clear. There is no evidence that the use of EC in this circumstance is superior to simply following the recommendation of doubling up on the missed pills. However, if EC is to be used in this situation, LNG would be a better recommendation. Adding a high dose of a progestin will not interfere with ongoing contraceptive action of a combined or progestin-only product. Although we have no clear published data, pharmacologic considerations would support that use of a regular contraceptive containing a progestin may interfere with the emergency contraceptive mechanism of UPA, a progestin-receptor antagonist. Furthermore, UPA may interfere with the ongoing contraceptive mechanisms of the progestin.
As mentioned previously, repeated acts of unprotected intercourse in the cycle of EC use provide the biggest risk of unintended pregnancy. Use of condoms and initiation of regular contraception are important and will not be stressed in a pharmacy-only visit. Clinicians need to consider mechanism of action when advising women on starting regular contraception after using EC. Many clinics have been advocating a "quickstart" approach for initiation of regular contraception; starting the pill on the same day of or the day following the EC pill. In my opinion, our enthusiasm for starting a regular method should not compromise our best approach to providing EC. No evidence-based recommendations exist, so it makes sense to consider the biologic plausibility of interaction between progestins and progesterone receptor antagonists as outlined above. With LNG EC, there is no important interference and regular contraception with any method can be initiated without delay. For UPA, the possibility of interference exists, and it is prudent to wait 3 days before starting a combined hormonal method, a progestin-only pill, or inserting a contraceptive implant. Quickstart of the LNG intrauterine system should not present a problem, as the mechanism of action is predominantly local and the low circulating LNG levels are not likely to interfere with UPA activity. Although depot medroxyprogesterone acetate (DMPA) theoretically will interfere with UPA action, the very high dose of this method quite likely provides an emergency contraceptive benefit of its own similar to LNG. Prior to 72 hours, or in non-obese women, use of UPA will not likely offer any additional benefit from DMPA given on the same day. However, if a woman presents 4-5 days following unprotected intercourse or weighs > 75 kg, it would make most sense to use UPA and then administer DMPA 3 days later.
Table 1. Guidance for EC Counseling
| Ulipristal acetate | Levonorgestrel | Copper IUD | |
| Dose/route | 30 mg/oral | 1.5 mg/oral | Intrauterine |
| Accessibility | Prescription only | Over-the-counter | Requires clinic visit |
| Optimal timing | Up to 5 days after UPI | Up to 3 days after UPI | Up to 5 days after UPI |
| Pregnancy risk reduction | 67% | 50% | 98% |
| Mechanism of action | Contraceptive | Contraceptive | Contragestive |
| Impact of obesity |
No evidence of reduced
efficacy up to 80 kg |
Good evidence for reduced
efficacy >75 kg, no efficacy > 80 kg |
No evidence of reduced efficacy with
obesity. No mechanistic concerns. Placement may be more difficult |
Starting regular contraception will be the most important consideration for most women presenting for emergency contraception. Since the rules for starting a combined hormonal method are different for UPA and LNG, office staff and pharmacists need to be educated. In the study by Turok et al,10 there was no reduction in immediate pregnancies when women were randomized to a copper IUD or LNG. However, pregnancy within 6 months was significantly reduced among copper IUD users. This provides strong evidence that ongoing contraception is the most important consideration. Women presenting to a family planning clinic should be offered the copper IUD as a first-line emergency contraceptive treatment. There is solid evidence that supports that the copper IUD is the most effective option and the only option that provides ongoing contraception.11 However, unlike UPA and LNG, the copper IUD does appear to have a contragestive effect. It is important to communicate this as a unique property of the copper IUD and not a general characteristic of EC.
To summarize, the copper IUD represents the best option for most women seeking EC. The disadvantages of the pelvic examination and procedure are far outweighed by efficacy and provision of ongoing contraception. The real-world considerations of clinic access, cost, convenience, and patient preference will likely favor an oral method. Given this, UPA is a clear winner as it has a longer window of activity and higher efficacy. This is particularly important for obese women, as there is no evidence that LNG has any activity in women weighing > 80 kg. Unfortunately, UPA is not available OTC, so obese women should receive counseling and possibly advance prescription for UPA during clinic encounters. One exception to the general preference for UPA is EC use to back up incorrect use of regular hormonal contraception. In most cases, LNG would be preferred to avoid interaction between a progesterone receptor antagonist and agonist. Quickstart initiation of regular hormonal contraception can be offered with LNG EC, but should be delayed for at least 3 days and no more than 7 days after use of UPA.
Table 2. Guidelines for Initiation of Ongoing Contraception
| Ulipristal acetate | Levonorgestrel | Copper IUD | |
| Condoms | Use for 7 days | Use for 7 days | Not needed |
| Combined hormonal methods | Wait at least 3 days | May initiate immediately | |
| Implant | Wait at least 3 days | May initiate immediately | |
| DMPA | Wait at least 3 days | May initiate immediately | |
| LNGIUS | May initiate immediately | May initiate immediately | |
| Copper IUD | May initiate immediately* | May initiate immediately* |
* UPA and LNG provide no additional benefit for EC over copper IUD alone.
References
- von Hertzen H, et al. Low dose mifepristone and two regimens of levonorgestrel for emergency contraception: A WHO multicentre randomised trial. Lancet 2002;360:1803-1810.
- Arowojolu AO, et al. Comparative evaluation of the effectiveness and safety of two regimens of levonorgestrel for emergency contraception in Nigerians. Contraception 2002;66:269-273.
- Gemzell-Danielsson K. Mechanism of action of emergency contraception. Contraception 2010;82:404-409.
- Strong C. Conscientious objection the morning after. Am J Bioeth 2007;7:32-34.
- Glasier AF, et al. Ulipristal acetate versus levonorgestrel for emergency contraception: A randomised non-inferiority trial and meta-analysis. Lancet 2010;375:555-562.
- Brache V, et al. Ulipristal acetate prevents ovulation more effectively than levonorgestrel: Analysis of pooled data from three randomized trials of emergency contraception regimens. Contraception 2013;88:611-618.
- Brache V, et al. Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture. Hum Reprod 2010;25:2256-2263.
- Glasier A. Emergency contraception: Clinical outcomes. Contraception 2013;87:309-313.
- Glasier A, et al. Can we identify women at risk of pregnancy despite using emergency contraception? Data from randomized trials of ulipristal acetate and levonorgestrel. Contraception 2011;84:363-367.
- Turok DK, et al. Emergency contraception with a copper IUD or oral levonorgestrel: An observational study of 1-year pregnancy rates. Contraception 2013 Nov 22. [Epub ahead of print].
- Turok DK, et al. Copper T380 intrauterine device for emergency contraception: Highly effective at any time in the menstrual cycle. Hum Reprod 2013;28:2672-2676.
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