A randomized clinical trial of two emergency contraceptive pill regimens in a Ugandan population.

BACKGROUND: Recent trials on emergency contraception (EC) have indicated that levonorgestrel (LNG) used alone has fewer side-effects and is more efficacious than the Yuzpe regimen (high dose combined oral contraceptive pills). However, the experienced side-effects and acceptability may vary between different groups or societies. OBJECTIVE: The primary objective of this study was to determine side-effects and acceptability of two emergency contraceptive pill (ECP) regimens among users in Kampala, Uganda. STUDY DESIGN: Randomized clinical trial. METHODS: A total of 337 women were enrolled in a double blind randomized clinical trial. Women requesting ECPs within 72 hours after unprotected sexual intercourse received either LNG or the Yuzpe regimen. The women returned for follow-up after three days and a follow-up interview was performed after one year. RESULTS: Levonorgestrel had significantly fewer side-effects than the Yuzpe regimen (p < 0.001). There was a significant association between having worries about the method and experiencing side-effects (p < 0.001). Most women (81%) were prime users of EC. The majority would recommend ECP to other clients. CONCLUSIONS: Levonorgestrel is a superior option to the Yuzpe regimen and should be promoted as the recommended ECP. Having worries about ECP may influence experience of the side-effects. Correct information is critical in promotion of ECP use.

Ulipristal acetate versus levonorgestrel for emergency contraception: a randomised non-inferiority trial and meta-analysis.

BACKGROUND: Emergency contraception can prevent unintended pregnancies, but current methods are only effective if used as soon as possible after sexual intercourse and before ovulation. We compared the efficacy and safety of ulipristal acetate with levonorgestrel for emergency contraception. METHODS: Women with regular menstrual cycles who presented to a participating family planning clinic requesting emergency contraception within 5 days of unprotected sexual intercourse were eligible for enrolment in this randomised, multicentre, non-inferiority trial. 2221 women were randomly assigned to receive a single, supervised dose of 30 mg ulipristal acetate (n=1104) or 1.5 mg levonorgestrel (n=1117) orally. Allocation was by block randomisation stratified by centre and time from unprotected sexual intercourse to treatment, with allocation concealment by identical opaque boxes labelled with a unique treatment number. Participants were masked to treatment assignment whereas investigators were not. Follow-up was done 5-7 days after expected onset of next menses. The primary endpoint was pregnancy rate in women who received emergency contraception within 72 h of unprotected sexual intercourse, with a non-inferiority margin of 1% point difference between groups (limit of 1.6 for odds ratio). Analysis was done on the efficacy-evaluable population, which excluded women lost to follow-up, those aged over 35 years, women with unknown follow-up pregnancy status, and those who had re-enrolled in the study. Additionally, we undertook a meta-analysis of our trial and an earlier study to assess the efficacy of ulipristal acetate compared with levonorgestrel. This trial is registered with ClinicalTrials.gov, number NCT00551616. FINDINGS: In the efficacy-evaluable population, 1696 women received emergency contraception within 72 h of sexual intercourse (ulipristal acetate, n=844; levonorgestrel, n=852). There were 15 pregnancies in the ulipristal acetate group (1.8%, 95% CI 1.0-3.0) and 22 in the levonorgestrel group (2.6%, 1.7-3.9; odds ratio [OR] 0.68, 95% CI 0.35-1.31). In 203 women who received emergency contraception between 72 h and 120 h after sexual intercourse, there were three pregnancies, all of which were in the levonorgestrel group. The most frequent adverse event was headache (ulipristal acetate, 213 events [19.3%] in 1104 women; levonorgestrel, 211 events [18.9%] in 1117 women). Two serious adverse events were judged possibly related to use of emergency contraception; a case of dizziness in the ulipristal acetate group and a molar pregnancy in the levonorgestrel group. In the meta-analysis (0-72 h), there were 22 (1.4%) pregnancies in 1617 women in the ulipristal acetate group and 35 (2.2%) in 1625 women in the levonorgestrel group (OR 0.58, 0.33-0.99; p=0.046). INTERPRETATION: Ulipristal acetate provides women and health-care providers with an effective alternative for emergency contraception that can be used up to 5 days after unprotected sexual intercourse. FUNDING: HRA Pharma.

Ulipristal acetate taken 48-120 hours after intercourse for emergency contraception.

OBJECTIVE: To evaluate the efficacy and safety of ulipristal acetate as emergency contraception in women presenting 48-120 hours after receiving ulipristal acetate for unprotected intercourse. METHODS: Women aged 18 years or older with regular cycles who presented for emergency contraception 48 to 120 hours after unprotected intercourse were enrolled in 45 Planned Parenthood clinics and treated with a single dose of 30 mg ulipristal acetate. Pregnancy status was determined by high-sensitivity urinary human chorionic gonadotropin testing and return of menses. RESULTS: A total of 1,241 women were evaluated for efficacy. Twenty-six were pregnant at follow-up, for a pregnancy rate of 2.1% (95% confidence interval 1.4-3.1%). These results satisfy the protocol-defined statistical criteria for success because the pregnancy rate was lower than both the estimated expected pregnancy rate and a predefined clinical irrelevance threshold. In addition, efficacy did not decrease over time: pregnancy rates were 2.3% (1.4-3.8%), 2.1% (1.0-4.1%), and 1.3% (0.1-4.8%) for intervals of 48 to 72 hours, more than 72 to 96 hours, and more than 96 to 120 hours, respectively. Adverse events were mainly mild or moderate, the most frequent being headache, nausea, and abdominal pain. Cycle length increased a mean of 2.8 days, whereas the duration of menstrual bleeding did not change. CONCLUSION: Ulipristal acetate is effective and well-tolerated for emergency contraception 48-120 hours after unprotected intercourse. LEVEL OF EVIDENCE: II.

Comparing continuation rates and side effects of hormonal contraceptives in East Asian and Caucasian women after abortion.

BACKGROUND: The purpose of this study was to determine whether East Asian women had more side effects and a higher discontinuation rate than Caucasian women when choosing to use hormonal contraceptives. STUDY DESIGN: This was an observational cohort study of usual care using questionnaires for 2 months after being given hormonal contraceptives following an abortion in Vancouver, Canada. RESULTS: In the first month, 73 (64.4%) of the 110 East Asian and 86 (80.4%) of the 107 Caucasian women took any of the sample provided (p=.020). In the second month, 52 (47.3%) of the East Asian and 62 (57%) of the Caucasian women used the prescription to buy and take their hormonal contraception (p=.12). Total side effects were similar, but there was more nausea in the East Asian women (23.3% vs. 8.1%) (p=.03) and more acne in the Caucasian women (8.2% vs. 20.9%) (p=.05). CONCLUSIONS: There may be both physiological and cultural differences leading East Asian women to use less hormonal contraception.

Hormonal emergency contraception: a clinical primer.

Unintended and teenage pregnancies are major public health concerns in the United States. Emergency contraception is used to prevent pregnancy after failure of a contraceptive method or after unprotected intercourse. Expanded use of emergency contraception has the potential to reduce unintended pregnancy and induced abortions, while reducing state and federal healthcare expenditures. The recent approval of Plan B as an over-the-counter medication for individuals over 18 years of age should improve access to this medication. However, there are still widespread misconceptions about the mechanisms and implications of emergency contraception. Expanded access to emergency contraception is associated with increased use, but not associated with decreased efficacy, increased sexual risk-taking behavior, or less consistent use of traditional birth control methods. This review is designed to provide clinicians with information regarding the use of emergency contraception for reproductive age patients. It includes a brief description of methods of use, mechanisms of action, and side effect profiles of the most commonly used methods of emergency contraception, levonorgestrel and the Yuzpe method.

Emergency contraception.

Teen birth rates in the United States have declined during the last decade but remain much higher than rates in other developed countries. Reduction of unintended pregnancy during adolescence and the associated negative consequences of early pregnancy and early childbearing remain public health concerns. Emergency contraception has the potential to significantly reduce teen-pregnancy rates. This policy statement provides pediatricians with a review of emergency contraception, including a definition of emergency contraception, formulations and potential adverse effects, efficacy and mechanisms of action, typical use, and safety issues, including contraindications. This review includes teens' and young adults' reported knowledge and attitudes about hormonal emergency contraception and issues of access and availability. The American Academy of Pediatrics, as well as other professional organizations, supports over-the-counter availability of emergency contraception. In previous publications, the American Academy of Pediatrics has addressed the issues of adolescent pregnancy and other methods of contraception.

Differences between emergency contraception users in the United States and the United Kingdom.

OBJECTIVES: to characterize emergency contraception (EC) users and clinical trial participants in the United States and the United Kingdom, comparing previous EC use and awareness, contraceptive history, and experience with EC. METHODS: We collected data from all EC seekers (n=5383) at 1 US and 2 UK clinics (9/97-8/98). We also collected detailed information from women (n=2157) enrolling in an EC trial at the first 3 clinics and 2 additional UK sites (9/97-2/00). RESULTS: More US (16%) than UK (4%) women reported additional acts (other than in the last 5 days) of unprotected sex during the cycle in which they sought EC. Fifty-eight percent of UK trial participants had used EC previously compared to 18% in the United States. Most participants in both groups used contraception regularly and reported needing EC because of condom breaks (67% and 56%). More UK than US participants used an ongoing method of contraception (38% v 28%). US women reported more side effects at follow-up than UK women did (76% v 59%), although similar proportions would take EC again or recommend it. CONCLUSIONS: US and UK women in our trial experienced different side effects. Researchers should use caution when presenting aggregate results from international multicenter trials. In addition, readers should be aware that such aggregate results might mask important geographical differences. More research on experience with EC and barriers to contraceptive use in the United States is needed.

Emergency contraception.

Emergency contraception is used to prevent pregnancy after a coital act not adequately protected by a regular method of contraception. In contrast to early medical abortion, emergency contraception prevents a pregnancy from starting and does not disrupt an established pregnancy. The most commonly used approaches consist of two oral doses of contraceptive steroids. The levonorgestrel-only regimen (levonorgestrel, 0.75 mg, repeated in 12 hours) appears to be more effective and better tolerated than the Yuzpe regimen (ethinyl estradiol, 100 microg, and levonorgestrel, 0.5 mg, repeated in 12 hours). In the largest randomized, controlled trial to date, levonorgestrel prevented about 85% of pregnancies that would have occurred without its use. Hormonal emergency contraception has no known medical contraindications, although it is not indicated for suspected or confirmed pregnancy. However, if hormonal emergency contraception is inadvertently taken in early pregnancy, neither the woman nor the fetus will be harmed. Nausea and vomiting associated with the Yuzpe regimen can be reduced by prophylactic use of meclizine. A strong medical and legal case exists for making hormonal emergency contraception available over the counter, as has happened in countries other than the United States. Easier access to and wider use of emergency contraception could dramatically lower the high rates of unintended pregnancy and induced abortion in the United States.

Hormonal emergency contraception.

In the 1960s, high-dose estrogen was identified as a highly effective emergency contraceptive but was associated with a high frequency of nausea and vomiting. The combination of low-dose estrogen and a progestin (the Yuzpe regimen) is highly effective and much better tolerated. Recently, a progestin-only regimen containing levonorgestrel was found to be more effective than the Yuzpe regimen and caused significantly less nausea and vomiting. Danazol, an antigonadotropin, is well tolerated but has questionable efficacy Mifepristone has several pharmacologic actions that make it highly effective with an adverse-effect profile similar to that of the Yuzpe regimen. Progress has been made in the last 3 years toward increasing the number of emergency contraceptives that are accessible to women in the United States, and several highly effective options are available. The most effective and well-tolerated regimen available is levonorgestrel. However, the barriers to access and low patient and provider awareness limit the impact of emergency contraception on the rate of unintended pregnancies.

Emergency hormonal contraception: the community pharmacy perspective.

OBJECTIVE: To explore the views of community pharmacists in the North West of England towards the deregulation of emergency hormonal contraception (EHC) and to examine their support and training needs. DESIGN: Two focus group discussions. SUBJECTS: Fourteen community pharmacists, of whom eight were currently participating in a scheme to supply EHC free of charge through a patient group direction (PGD). RESULTS: A number of themes emerged from the discussions, which appeared to influence participants' views towards the use of EHC and towards deregulation. A number of participants appeared to lack detailed knowledge about the mode of action of EHC and misunderstandings about this, coupled with erroneously held beliefs about the adverse effects of the drug, appeared to influence their attitudes to deregulation. Participants identified risks associated with pharmacy supply of EHC, both to women and to themselves, in the form of litigation. EHC was accorded a special status which seemed to go beyond its pharmacological properties and risk-benefit profile. A key and recurring theme was abuse, an ill-defined concept which appeared to refer to multiple or repeated use. It is interesting to note that none of those participants supplying EHC under a PGD could provide any examples of such abuse from their own experience. CONCLUSIONS: This small-scale study provides useful insights into the attitudes of these pharmacists towards EHC, the impact of increased availability of the drug, and the type of women who they believed would use EHC.

[Emergency contraception: a simple, safe, effective and economical method for preventing undesired pregnancy]. / Anticoncepción de emergencia: un método simple, seguro, efectivo y económico para prevenir embarazos no deseados.

In the following article, the most recent knowledge on emergency contraception (EC) is reviewed. EC is defined as those contraceptive methods that may be used to prevent an unwanted pregnancy up to 3 days after unprotected intercourse, contraceptive failure or rape. In case of non-hormonal methods (IUD), the time window for pregnancy prevention goes up to 5 days after intercourse. The different regimens now available, hormonal and non-hormonal methods, indications, contraceptive effectiveness, side effects and safety profile, possible mechanisms of action and counseling strategies will be reviewed. The potential benefits on reproductive health of wide-spread knowledge and easy, non-restrictive access to this methodology are emphasized. An extensive list of recent references is enclosed.

Emergency contraception: is it time to change method?

PIP: The Yuzpe method of using combined oral contraceptives for emergency contraception has been available for 25 years; prevents 75% of pregnancies that would have occurred if no treatment were used; has an excellent safety record; and is contraindicated only in patients with a history of thromboembolism, migraine at presentation, or a history of migraine with aura. However, this method has side effects of nausea and vomiting, and the World Health Organization recently reported that use of levonorgestrel alone is effective and associated with fewer side effects. No additional research has been conducted on the timing or dosage of the estrogen-progestogen method, but some dose-effectiveness studies have been performed on mifepristone. Mifepristone, however, is not widely available. The levonorgestrel studies found a negative correlation between the interval from unprotected intercourse to treatment and effectiveness but concluded that levonorgestrel was more effective than the combined method (this study found a lower effectiveness for the combined method than previously reported). Given that each method is effective, consideration of whether the new one should be adopted must take into account the fact that the levonorgestrel is currently not licensed for this use, is not prepared in convenient dosages, and is more expensive and less available. Introduction of new methods of emergency contraception should augment choices rather than replace other methods.^ieng

The effects of self-administering emergency contraception.

BACKGROUND: Emergency postcoital contraception prevents pregnancy, but it must be prescribed by a doctor and taken within 72 hours of intercourse. It has been proposed that emergency contraception be made available without a prescription. We undertook a study to learn how women might behave if given a supply of emergency contraceptive pills to keep at home. METHODS: We assigned 553 women to be given a replaceable supply of hormonal emergency contraceptive pills to take home (the treatment group) and 530 women to use emergency contraception obtained by visiting a doctor (the control group). The frequency of use of emergency contraception, the use of other contraceptives, and the incidence of unwanted pregnancy were determined in both groups of women one year later. RESULTS: The results for 549 women in the treatment group and 522 women in the control group were available for analysis. Three hundred seventy-nine of the women in the treatment group (69 percent) and 326 of the women in the control group (62 percent) contributed detailed information at follow-up. One hundred eighty of the women in the treatment group (47 percent) used emergency contraception at least once. Among those who returned the study questionnaire, 98 percent used emergency contraception correctly. There were no serious adverse effects. Eighty-seven women in the control group (27 percent) used emergency contraception at least once (P<0.001 for the comparison with the treatment group). The women in the treatment group were not more likely to use emergency contraception repeatedly. Their use of other methods of contraception was no different from that of the women in the control group. There were 18 unintended pregnancies in the treatment group and 25 in the control group (relative risk, 0.7; 95 percent confidence interval, 0.4 to 1.2). CONCLUSIONS: Making emergency contraception more easily obtainable does no harm and may reduce the rate of unwanted pregnancies.

PIP: The feasibility of providing women with a supply of emergency contraception to keep on hand in the event of unprotected intercourse was investigated in a comparative study involving 1071 women 16-44 years of age recruited from a family planning clinic and hospital in Edinburgh, Scotland, in 1994-96. 549 women (treatment group) were given a replaceable supply of hormonal emergency contraceptive pills to take home and 522 women (controls) were counseled about the method and instructed to call their physician if it was needed. Emergency contraception was used on a total of 387 occasions during the 4-month study period (248 times by women in the treatment group and 139 times by controls). The women in the treatment group were significantly more likely to use emergency contraception on only one occasion during the study period than those in the control group (36% vs. 14%, p 0.001), but not more likely to use it more than once (12% vs. 13%). Use of other fertility control methods did not differ between study groups. There were 18 unintended pregnancies in the treatment group and 25 in the control group (relative risk, 0.7; 95% confidence interval, 0.4-1.2). 79% of women in the treatment group and 61% of controls believed emergency contraception should be available without a prescription. Support for this strategy was highest among women with a history of an induced abortion prior to study entry. These findings suggest that making emergency contraception more available has the potential to reduce the rate of unintended pregnancies.

Hormonal postcoital contraception.

Wide availability of hormonal postcoital contraception (HPC) is likely to reduce the incidence of unplanned pregnancies. The two most common indications for HPC are unprotected intercourse and 'condom accidents'. The combined estrogen/progestogen HPC described by Yuzpe is the most widely used method. It is given within 72 h of unprotected intercourse. The efficacy of combined HPC is high. The crude failure rate is 1-5 per 100 woman-months while the true reduction in pregnancy risk is over 75%. Efficacy is not influenced by the exposure-treatment interval within the 72-h 'window'. The mechanisms of action is multifocal and depends on the cycle phase at which treatment is instituted. Data are presented suggesting a consistent endometrial effect. None of the side-effects of HPC are serious. When HPC fails, there is so far no evidence of an adverse effect of the treatment on the outcome of pregnancy. Counselling should include all the above together with discussion of possible side-effects such as nausea and vomiting. The clinician should ensure that the woman uses an effective contraceptive thereafter. There is renewed interest in progestogen-only postcoital contraception. Varying doses of levonorgestrel have been used. The efficacy of some regimens is similar to that of the combined HPC. Danazol has not proved to be as effective. Antiprogestins hold the greatest promise of emergency contraception with high efficacy and low side-effects.