Repeated use of pre- and postcoital hormonal contraception for prevention of pregnancy.

Abstract

Repeated use of postcoital hormonal contraception is not currently recommended due to the higher risk of side effects and lower contraceptive effectiveness compared to other modern methods of contraception. However, emerging evidence indicates renewed interest in a regular coitally-dependent method of oral contraception. We re-evaluated the existing data on safety and effectiveness of pericoital use of levonorgestrel and other hormonal drugs to prevent pregnancy.
To determine the effectiveness and safety of repeated use of pre- and postcoital hormonal contraception for pregnancy prevention
We searched the computerized databases MEDLINE, POPLINE, CINAHL, LILACS, EMBASE and CENTRAL for trials that tested repeated pre- and postcoital use of hormonal drugs for pregnancy prevention. We also searched for current trials via ClinicalTrials.gov and ICTRP.
Published and unpublished studies in any language of repeated postcoital or immediately precoital use of hormonal drugs for contraception with pregnancy as an outcome
Two authors independently confirmed the eligibility and extracted data from the included studies. We calculated confidence intervals (CI) around individual study Pearl indices using a Poisson distribution. We presented individual study estimates and pooled estimates and their 95% CI, where appropriate.
We found 21 trials that evaluated pericoital use of LNG and other hormonal drugs on a regular basis to prevent pregnancy. Pericoital levonorgestrel (LNG) was reasonably efficacious and safe. The pooled Pearl Index for the 0.75 mg dose of LNG was 5.1 per 100 woman-years (WY) (95% CI 3.8 to 6.7). The pooled Pearl Index for all doses of LNG was 4.9 per 100 WY (95% CI 4.3 to 5.5). Other hormonal drugs appeared promising but most of them were not studied extensively. Most women liked the pericoital method in spite of frequent menstrual irregularities.
The studies of pericoital LNG regimens provided promising results but had a number of serious methodological limitations. A pressing need exits to conduct a rigorous research to confirm the efficacy and safety of pericoital use of LNG as a primary means of contraception among women with infrequent intercourse. If the method is shown to be efficacious, safe and acceptable, the results may warrant revision of the current WHO recommendations and marketing strategies.

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Repeated use of pre- and postcoital hormonal contraception
for prevention of pregnancy (Review)
Halpern V, Raymond EG, Lopez LM
Thisisareprintof aCochrane review, preparedandmaintained byThe Cochrane Collaboration andpublishedin TheCochrane Library
2010, Issue 5
http://www.thecochranelibrary.com
Repeated use of pre- and postcoital hormonal contraception for prevention of pregnancy (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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T A B L E O F C O N T E N T S
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HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
ABSTRACT. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
BACKGROUND. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
OBJECTIVES. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
METHODS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DISCUSSION. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
AUTHORS’ CONCLUSIONS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
ACKNOWLEDGEMENTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
REFERENCES. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CHARACTERISTICS OF STUDIES. . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
CONTRIBUTIONS OF AUTHORS. . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
SOURCES OF SUPPORT. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
DIFFERENCES BETWEEN PROTOCOL AND REVIEW
INDEX TERMS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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iRepeated use of pre- and postcoital hormonal contraception for prevention of pregnancy (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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[Intervention Review]
Repeated use of pre- and postcoital hormonal contraception
for prevention of pregnancy
Vera Halpern1, Elizabeth G. Raymond1, Laureen M Lopez1
1Behavioral and Biomedical Research, Family Health International, Research Triangle Park, North Carolina, USA
Contact address: Vera Halpern, Behavioral and Biomedical Research, Family Health International, PO Box 13950, Research Triangle
Park, North Carolina, NC 27709, USA. vhalpern@fhi.org.
Editorial group: Cochrane Fertility Regulation Group.
Publication status and date: Edited (no change to conclusions), published in Issue 5, 2010.
Review content assessed as up-to-date: 9 February 2009.
Citation: Halpern V, Raymond EG, Lopez LM. Repeated use of pre- and postcoital hormonal contraception for prevention of
pregnancy. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD007595. DOI: 10.1002/14651858.CD007595.pub2.
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
A B S T R A C T
Background
Repeated use of postcoital hormonal contraception is not currently recommended due to the higher risk of side effects and lower
contraceptive effectiveness compared to other modern methods of contraception. However, emerging evidence indicates renewed
interest in a regular coitally-dependent method of oral contraception. We re-evaluated the existing data on safety and effectiveness of
pericoital use of levonorgestrel and other hormonal drugs to prevent pregnancy.
Objectives
To determine the effectiveness and safety of repeated use of pre- and postcoital hormonal contraception for pregnancy prevention
Search strategy
We searched the computerized databases MEDLINE, POPLINE, CINAHL, LILACS, EMBASE and CENTRAL for trials that tested
repeated pre- and postcoital use of hormonal drugs for pregnancy prevention. We also searched for current trials via ClinicalTrials.gov
and ICTRP.
Selection criteria
Published and unpublished studies in any language of repeated postcoital or immediately precoital use of hormonal drugs for contra-
ception with pregnancy as an outcome
Data collection and analysis
Two authors independently confirmed the eligibility and extracted data from the included studies. We calculated confidence intervals
(CI) around individual study Pearl indices using a Poisson distribution. We presented individual study estimates and pooled estimates
and their 95% CI, where appropriate.
Main results
We found 21 trials that evaluated pericoital use of LNG and other hormonal drugs on a regular basis to prevent pregnancy. Pericoital
levonorgestrel (LNG) was reasonably efficacious and safe. The pooled Pearl Index for the 0.75 mg dose of LNG was 5.1 per 100
woman-years (WY) (95% CI 3.8 to 6.7). The pooled Pearl Index for all doses of LNG was 4.9 per 100 WY (95% CI 4.3 to 5.5). Other
hormonal drugs appeared promising but most of them were not studied extensively. Most women liked the pericoital method in spite
of frequent menstrual irregularities.
1 Repeated use of pre- and postcoital hormonal contraception for prevention of pregnancy (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Authors’ conclusions
The studies of pericoital LNG regimens provided promising results but had a number of serious methodological limitations. A pressing
needexitstoconduct arigorous researchtoconfirm theefficacyandsafety of pericoital use of LNGasaprimary meansof contraception
among women with infrequent intercourse. If the method is shown to be efficacious, safe and acceptable, the results may warrant
revision of the current WHO recommendations and marketing strategies.
P L A I N L A N G U A G E S U M M A R Y
Repeated use of hormonal drugs right before or after sex to prevent pregnancy
Currently, no oral birth control method is approved for using only when needed, i.e., at the time of sex. However, many women may
want to use such a method. Our review looked at studies of different drugs taken around the sex act to find out how well the drugs
worked to prevent pregnancy. We also assessed the safety of the drugs and whether women liked them.
We did computer searches to find relevant studies in all languages. We also wrote to researchers to find other trials. We assessed the
quality of the research methods used in the studies. We entered the data into RevMan. The data were entered into RevMan and the
Pearl Index was used to estimate effect.
We found 21 studies conducted over the past 40 years. These studies found that using some hormones right before or after sex did
prevent pregnancy. In particular, levonorgestrel seemed to work well and was safe and accepted by thousands of women in several large
trials. However, mostof thestudies wereold and incomplete. More high quality researchis neededbefore we can know for sure whether
using levonorgestrel repeatedly around the time of sex is a good and safe method of birth control.
B A C K G R O U N D
A coitally-dependent oral contraceptive may provide important
advantages for women with infrequent sex as itreduces the dosing
frequency,maybeconvenientandprivate.Inaddition,becausepill
ingestion is triggered by a coital event, its use may be more consis-
tent than use of daily contraceptive pills. Postcoital contraception
withorallevonorgestrel(LNG)wasevaluatedinnumerousclinical
studies and had been registered for decades in Eastern European
and Asian countries (Seregely 1977; Farkas 1981). Currently, its
repeated use as a regular contraceptive is not recommended due
to the higher risk of side effects and lower contraceptive effective-
nesscomparedtoothermodernmethodsofcontraception (WHO
2000). The approved emergency contraceptive regimens are not
intended for repeated use (ACOG 2005). However, repeated use
of different drugs or other substances immediately before or af-
ter coitus as a primary method of contraception has been docu-
mented in several reports (Arowojolu 2000; Lerkiatbundit 2000;
Britwum 2006). Although many of the reported methods are ei-
ther untested drugs marketed for other purposes (e.g., norethin-
drone tablets) or are traditional preparations that are known to be
ineffective, these data indicates an existing interest among women
worldwide in pericoital oral method of contraception. Given the
potential benefits and renewed interest in an oral coitally-depen-
dentmethodofcontraception, re-examination oftheexisting data
on safety and effectiveness of pericoital use of hormonal drugs to
prevent pregnancy is warranted. The results may help inform ex-
isting recommendations or provide guidance for future research.
Description of the intervention
Hormonal drug taken immediately before or after each act of in-
tercourse for pregnancy prevention.
How the intervention might work
The main mechanism of action of a single use of emergency con-
traception appears to be prevention of ovulation. Effects on the
endometrium, cervical mucus, embryo transfer and other compo-
nents that contribute to the establishment of a viable pregnancy,
areplausiblebutlesswelldemonstrated(Croxatto2003;Novikova
2007). Extrapolation of these data to the repeated use of pre- and
postcoital hormonal contraception shouldbemadeonly withcau-
tion.
2Repeated use of pre- and postcoital hormonal contraception for prevention of pregnancy (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Why it is important to do this review
Several non-comparative studies indicated that postcoital hor-
monal contraception is safe and effective when used repeatedly
(WHO 1987;WHO 2000).Although randomizedcontrolledtri-
als may not have been conducted to date, a systematic review of
the available observational clinical data may provide important
guidance about whether the existing recommendation that warns
againstrepeateduseofthemethodshouldbereconsidered.Asum-
mary of the data may also be useful in planning future research.
O B J E C T I V E S
To determine the effectiveness and safety of repeated use of pre-
and postcoital hormonal contraception for pregnancy prevention
M E T H O D S
Criteria for considering studies for this review
Types of studies
We included all published and unpublished studies of repeated
postcoital orimmediatelyprecoitaluseofhormonaldrugsforcon-
traception with pregnancy as an outcome. To be included in this
review, written reports had to contain information on time of fol-
low up, regimen and dose of the drug. Although we did not antic-
ipate finding any comparative trials we searched and included all
study designs. We followed the Cochrane guidance for inclusion
of non-randomized trials (Higgins 2008). All languages of publi-
cation were eligible for inclusion.
Types of participants
We included all women who repeatedly used hormonal methods
immediately before or after coitus to prevent pregnancy and who
provided data in the eligible trials.
Types of interventions
Hormonal drug by mouth after or immediately before each act of
intercourse and taken repeatedly during one or more menstrual
cycles for contraception
Types of outcome measures
Primary outcomes
Pregnancy as defined by the researchers was the primary outcome
of interest.
Secondary outcomes
All related side effects, including bleeding patterns, and discon-
tinuation rates (if available) were the secondary outcomes.
Search methods for identification of studies
Electronic searches
We searchedthe computerized databases MEDLINE, POPLINE,
CINAHL, LILACS, and EMBASE and Cochrane Central Regis-
terofControlledTrials(CENTRAL) for trialsthattestedrepeated
pre- or postcoital use of hormonal drugs for pregnancy preven-
tion. In addition, we searched for recent clinical trials through
ClinicalTrials.gov (NIH 2008) and the International Clinical Tri-
als Registry Platform (ICTRP) (WHO 2008).The strategies are
given below.
MEDLINE via PubMed - two searches
1. (contraception, postcoital OR contraceptive agents, postcoital
OR contraceptives, postcoital OR emergency contracept* OR
postinor* OR “morning after pill” OR “morning after pills” OR
vacation pills OR precoital OR pericoital OR (contracept* AND
“plan b” ) OR hormone* OR hormonal OR (contracept* AND
(postcoital OR LNG))) AND (repeat* OR routine OR occasion*
OR contraception behavior)
AND (clinical trial OR clinical trials OR randomized controlled
trial OR randomized controlled trials OR controlled clinical trial
OR controlled clinical trials OR random* OR evaluation studies
OR comparative study OR follow-up study)
limited to female, human
2. (contraception, postcoital OR contraceptive agents, postcoital
OR contraceptives, postcoital OR emergency contracept* OR
postinor* OR “morning after pill” OR “morning after pills” OR
vacation pills OR precoital OR pre-coital OR (contracept* AND
“plan b”) OR ((contracept* OR hormone* OR hormonal) AND
(postcoital OR post-coital OR post coital OR levonorgestrel OR
norgestrel OR progestins OR d-norgestrol))) AND (repeat* OR
routine OR occasion* OR continuous OR contraception behav-
ior) AND (clinical trial OR clinical trials OR randomized con-
trolledtrial OR randomized controlled trials OR controlled clini-
cal trial OR controlled clinical trials OR random* OR evaluation
studies OR comparative study OR follow-up study)
3Repeated use of pre- and postcoital hormonal contraception for prevention of pregnancy (Review)
Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.