American Journal of Obstetrics and Gynecology (2004) 191, 1158e63
Tolerability of levonorgestrel emergency contraceptionin adolescents
Cynthia C. Harper, PhD,a,* Corinne H. Rocca, MPH,a Philip D. Darney, MD, MSc,aHelena von Hertzen, MD, DDS,b Tina R. Raine, MD, MPHa
Center for Reproductive Health Research and Policy, Department of Obstetrics, Gynecology, and ReproductiveSciences, School of Medicine, University of California, San Francisco, Calif, a and Department of Reproductive Healthand Research, World Health Organization, Geneva, Switzerland b
Received for publication December 17, 2003; revised May 1, 2004; accepted May 5, 2004
Objective: We evaluated the tolerability of emergency contraception in adolescents.
Study design: In this descriptive study, 1 0.75 mg levonorgestrel tablet was administered to 52
females aged 13-16 with instructions to take the second tablet 12 hours later (unprotected inter-
course was not an entry requirement). Participants kept diaries of side eﬀects and menstrual pat-
terns. We assessed correct use, side eﬀects caused by treatment, and impact on menstrual cycle.
Results: Virtually all participants used the drug correctly, with no serious adverse events. Minorexpected side eﬀects occurred, including nausea, fatigue, and vomiting. There was no diﬀerence inreporting of side eﬀects by age. Adolescents’ mean duration of menses was comparable pre- andpost-treatment (5.3 vs 5.0 days; P= .146), and onset of menses was within the expected range.
Ninety percent of participants reported they would recommend emergency contraception toa friend or relative if needed.
Conclusion: Adolescents tolerated the medication well, experiencing transient side eﬀects.
Ó 2004 Elsevier Inc. All rights reserved.
In 1999, the United States Food and Drug Adminis-
correct use of the treatmentMoreover, levonorgestrel
tration (FDA) approved 0.75 mg levonorgestrel Plan BÒ
was found to have an acceptable side effect proﬁle, with
(Gedeon Richter, Ltd, Budapest, Hungary) tablets for
23% of participants reporting nausea and 5.6% vomit-
use postcoitally as an emergency contraceptive. The
ing, lower levels than with the standard Yuzpe regimen
safety and efﬁcacy of emergency contraception (EC) is
(ethinyloestradiol 100 m
g plus levonorgestrel 0.5 mg or
well established for adults. In the World Health Organi-
dl-norgestrel 1.0 mg, repeated 12 hours later). Subse-
zation (WHO) Task Force study of levonorgestrel EC,
quent studies of women in various countries also
89% of expected pregnancies were prevented with
showed levonorgestrel EC to be well tolerated.
While young age is associated with greater awareness
of emergency contraception, use of the method is morecommon among adult women than adolescents.We
* Reprint requests: Cynthia C. Harper, PhD, UCSF Box 0744,
have scant data on the tolerability and acceptability of
3333 California Street, Ste. 335, San Francisco, CA, 94143-0744.
the method to adolescents. As with other hormonal
0002-9378/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved.
contraceptives, current FDA labeling of Plan BÒ is not
Research. Procedures were in accordance with the ethical
speciﬁc with respect to use in girls aged 16 years and
standards for human experimentation established by the
younger. If the FDA moves to switch Plan BÒ emer-
Declaration of Helsinki of 1975, revised in 1983.
gency contraception to over-the-counter status, adoles-
Research assistants administered study procedures
cents as well as adults will be able to use it without
at the clinic site. Participants were given the ﬁrst dose
provider supervision. Clinical trials of contraceptives
of emergency contraception in the clinic, and were in-
in the US include adults only, a minority of whom are
structed to take the second dose in 12 hours. They were
between the ages of 18 and 19 years. While enrolling
given diary cards and were asked to record the date and
adolescents in clinical trials is difﬁcult, there is a growing
time of the second dose, and to keep a daily record of
recognition of the need to address the paucity of data in
any bleeding and side effects until the follow-up visit 3
weeks after enrollment. The diary was collected at the
One study on levonorgestrel implants showed that
follow-up visit. The format of the diary card, as well
tolerance of side effects was comparable among adoles-
as the methods, including product, dose, and route of
cents and adults.Studies of low-dose progestin-only
administration were as similar as possible to those in
pills for long-term contraception have shown no differ-
the levonorgestrel arm of the large WHO multicenter
ences in safety or efﬁcacy among adolescents aged 16
that evaluated side effects. Unlike the WHO trial,
years and older compared with adultsHowever, there
which compared the efﬁcacy and safety of different
is no information on the higher doses of progestins used
emergency contraceptive agents and regimens, this trial
examined only the current FDA-approved Plan B regi-
The primary objective of this study was to evaluate
men of 2 doses 12 hours apart. The participants in this
the tolerability of levonorgestrel emergency contracep-
study had not experienced unprotected intercourse dur-
tion (Plan BÒ) in adolescent females. Speciﬁcally, the
ing the present cycle, while the participants in the WHO
study aimed to characterize the side effects proﬁle, assess
trial were seeking emergency contraception because of
correct use of the method, and ascertain the impact on
need after an act of unprotected intercourse.
the menstrual cycle in a sample of young adolescents.
Participants who had not resumed menses at follow-
up returned for an additional visit. The study period wasthus from 3 to 5 weeks, depending on regular menstrual
cycle variation and timing of menses subsequent to dos-ing. Research assistants took medical histories at enroll-
ment, and administered short interviews at enrollmentand follow-up that included items on the participant’s
This study was a single-center, open-label observational
experience using emergency contraception. Participants
trial. Two 0.75 mg Plan BÒ levonorgestrel tablets were ad-
were given $50 at enrollment and $50 at follow-up; if re-
ministered orally to adolescent females recruited at a pub-
quired to return for a second follow-up visit, partici-
licly funded San Francisco family planning clinic and
through ﬂyers at community centers. Inclusion criteriafor the study were: females aged 12 to 16 years who hadreached menarche; good health based on physical exami-nation, medical history, urine analysis, and laboratory
evaluation; normal menstrual cycles for the previous 6cycles, varying in length from 21 to 35 days; no unpro-
Correct use of the medication was measured by self-
tected intercourse during the current cycle (to avoid very
reports of whether participants followed instructions
early pregnancy); willing to abstain from intercourse or to
to ingest the second dose, and whether they had any
use condoms for the study duration; no sex steroid use (in-
problems following directions. We used diary data to
cluding hormonal contraception) in the past 2 months.
measure the frequency (in days) of side effects, including
Exclusion criteria were pregnancy or breastfeeding, hy-
nausea, vomiting, headache, dizziness, fatigue, breast
persensitivity to levonorgestrel or other progestins, use
tenderness, lower abdominal pain, and diarrhea. To as-
of an investigational drug within 30 days, history of emo-
sess impact on menses, we measured the length of men-
tional or psychiatric disorders or use of psychotropic
ses before and after treatment (ie, mean duration of
agents, evidence or admission of illicit drug or alcohol
menstrual ﬂow), and also measured the time until men-
abuse. Research assistants told potential participants
ses after administration of the treatment compared
and their parents that the study was looking at emergency
with the anticipated date (calculated from date of last
contraception and side effects and menstrual bleeding in
menstrual period and cycle length). As a general accept-
girls aged 12 to 16 years. Parental consent was required
ability measure, we also recorded whether participants
for participation. The study was approved by the Univer-
would recommend emergency contraception to a friend
sity of California, San Francisco, Committee on Human
or relative if needed (yes, no, not sure).
. Participants ranged in age from 13 to 16 years,
Summary of sample characteristics (n = 52)
with a mean age of 15.5 years. Most participants were
racial/ethnic minorities; 61% were African American,
19% Latina, 15% multiracial, and 4% white.
Ninety-eight percent of participants (51/52) reported
taking the second dose of Plan BÒ as instructed.
Ninety-four percent (49/52) reported no problems in fol-
lowing directions. Because correct use was uniformly
high, we could not test variation in correct use by age.
In , we compared symptoms reported during the
ﬁrst week (days 1 to 7) with symptoms reported during
the second week (days 8 to 14). Nausea was reported in
the ﬁrst week by 38.5% of participants and vomiting by11.5%. Several other side effects were also commonly re-
* Only participants who have had sexual intercourse (n = 36).
ported. Reports of some symptoms, including nausea(P = .001), fatigue (P = .002), headache (P = .004),
and diarrhea (P = .004) were signiﬁcantly higher duringthe ﬁrst week. However, for others, reports were not sig-
To analyze side effects caused by treatment, we com-
niﬁcantly higher in the ﬁrst week than they were in the
pared side effects reported by participants during
second, including vomiting (P = .160), dizziness (P =
the ﬁrst week (days 1 to 7) after drug administration
.130), breast tenderness (P = .582), and lower abdominal
to those reported during the second week (days 8 to
pain (P = .088). Kruskal-Wallis tests showed no differ-
14), when virtually no levonorgestrel was present in
ence by age in any of the reported side effects ).
the serum; a pharmacokinetic study showed the meanhalf life of levonorgestrel in adolescents to be 21 hours.
We used two-sided t tests to compare the number ofdaily reports of each side effect during the ﬁrst week
There was no difference in the mean duration of
(days 1 to 7) with the number of daily reports of the
menses for the adolescents before and after treatment
same side effect during the second week (days 8 to 14).
In the last menstrual period before enroll-
We used two-sided t tests to assess any difference
ment, the mean duration of menses was 5.0 days, and
in menstrual ﬂow caused by treatment: menstrual ﬂow at
after treatment the mean duration of menses was
last menstrual period (LMP) before enrollment was com-
5.3 days (P = .146). Eight percent experienced a delay
pared with menstrual ﬂow after treatment. Kruskal-
in return to menses over 7 days, 62.5% had a return
Wallis tests were used to detect age differences in return
to menses within 7 days of the anticipated date, and
to menses within the adolescent sample, as well as any
29% an early onset of more than 7 days. Kruskal-Wallis
differences in correct use, side effects, or acceptability.
tests showed no differences by age in return to menses
Signiﬁcance is reported at the .05 level. Stata 6.0
(P = .104) or in duration of ﬂow compared with normal
(College Station, Tex) was used for the analysis.
(P = .313). One participant had unprotected intercourseand had an intrauterine pregnancy.
Recommendation of emergency contraception
A total of 60 participants were enrolled in the study. Six
Ninety percent (47/52) of participants reported that they
participants enrolled were ineligible; 1 was younger than
would recommend emergency contraception to a friend
12 years old (11.6 years), and 5 had taken levonorgestrel
or relative if needed. All others responded that they were
within 2 months of recruitment. Two participants, aged
not sure. Kruskal-Wallis tests showed no difference by
16 years, were lost to follow-up. We analyzed data from
age (P = 0.756) in whether a participant would recom-
the 52 eligible participants who completed the study.
mend EC or was unsure about it. There were no serious
Summary baseline characteristics are presented in
Diary reports of symptoms by week (n = 52)
* Symptoms in days 8 to 14 when levonorgestrel no longer biologically available.
y Paired t test comparing number of days symptom reported in weeks 1 and 2.
z P % .010.
Differences in reports of symptoms (days 1 to 7) by
(n = 48), LMP at follow-up,as compared with expected
* Numbers vary because of the following: 2 participants did not
Concerns about the side effects of hormonal contracep-
begin menses by follow-up visit; 1 became pregnant during study; 2
tion are common among the general public.Beliefs
were still bleeding at follow-up visit; 1 had missing data on menses.
about negative side effects, even when false, can stopadolescents from using hormonal contraception.How-ever, this age group stands to beneﬁt the most from use
levels of vomiting reported. Some of the side effects,
of the product, and to lose the most from misconcep-
such as nausea, headaches, and fatigue are reported at
tions because almost 80% of adolescent pregnancies
higher levels by this adolescent sample, while others, in-
are unintended.This study found that adolescents re-
cluding abdominal pain and breast tenderness, are at
ported minor and transient side effects, similar to those
similar levels. However, comparisons should be inter-
reported in previous adult trials, including nausea
preted with caution because of many differences in the
and vomiting. However, the adolescents tended to re-
samples other than age, including need for emergency
port many symptoms even when they no longer had lev-
contraception at enrollment and different nationalities
onorgestrel in their serum. For nausea or headaches,
and racial/ethnic compositions. International studies on
common and somewhat subjective symptoms, there
emergency contraception as well as other medications
were signiﬁcantly higher reports during the ﬁrst week,
have shown that women of different nationalities and
but for vomiting, the least subjective symptom, there
races/ethnicities experience and report symptoms differ-
were no signiﬁcant differences in levels reported. Vomit-
entlyThere is some evidence that women in deve-
ing is an important symptom because of its potential im-
loped countries report more side effects than women in
developing couHowever, all reported side effects
A comparison between the side effects reported in
were well within the range of what adult trials have
this study with the data from adults in the large inter-
shown and present no serious health risks. A random-
national WHO trialso shows little difference in the
ized, controlled placebo trial would be necessary to
clarify any differences in adolescent users and adults.
Adolescents seeking emergency contraception shouldbe aware, as should adults, that the medication may
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We gratefully acknowledge the William and Flora
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‘Doing family’ in transnational marriages: Second generation women’s attachment to work Marjan Nadim Institute for Social Research Pb 3233 Elisenberg, 0208 Oslo, Norway Work in progress – please do not quote without permission from the author. The children of the 1960s and 70s labour migrants to Europe tend to marry spouses from their parents’ country of origin, a