ArticlePDF Available
Venous thrombosis in users of non-oral hormonal
contraception: follow-up study, Denmark 2001-10
OPEN ACCESS
Øjvind Lidegaard professor 1, Lars Hougaard Nielsen statistician 1, Charlotte Wessel Skovlund data
manager 1, Ellen Løkkegaard senior registrar 2
1Gynaecological Clinic 4232, Blegdamsvej 9, DK-2100 Copehagen Ø, Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Denmark;
2Department of Obstetrics and Gynaecology, Hillerød Hospital, University of Copenhagen, Denmark
Abstract
Objective To assess the risk of venous thrombosis in current users of
non-oral hormonal contraception.
Design Historical national registry based cohort study.
Setting Four national registries in Denmark.
Participants All Danish non-pregnant women aged 15-49 (n=1 626
158), free of previous thrombotic disease or cancer, were followed from
2001 to 2010.
Main outcome measures Incidence rate of venous thrombosis in users
of transdermal, vaginal, intrauterine, or subcutaneous hormonal
contraception, relative risk of venous thrombosis compared with
non-users, and rate ratios of venous thrombosis in current users of
non-oral products compared with the standard reference oral
contraceptive with levonorgestrel and 30-40 µg oestrogen. Diagnoses
were confirmed by at least four weeks of anticoagulation therapy after
the diagnosis.
Results Within 9 429 128 woman years of observation, 5287 first ever
venous thrombosis events were recorded, of which 3434 were confirmed.
In non-users of hormonal contraception the incidence rate of confirmed
events was 2.1 per 10 000 woman years. Compared with non-users of
hormonal contraception, and after adjustment for age, calendar year,
and education, the relative risk of confirmed venous thrombosis in users
of transdermal combined contraceptive patches was 7.9 (95% confidence
interval 3.5 to 17.7) and of the vaginal ring was 6.5 (4.7 to 8.9). The
corresponding incidences per 10 000 exposure years were 9.7 and 7.8
events. The relative risk was increased in women who used
subcutaneous implants (1.4, 0.6 to 3.4) but not in those who used the
levonorgestrel intrauterine system (0.6, 0.4 to 0.8). Compared with users
of combined oral contraceptives containing levonorgestrel, the adjusted
relative risk of venous thrombosis in users of transdermal patches was
2.3 (1.0 to 5.2) and of the vaginal ring was 1.9 (1.3 to 2.7).
Conclusion Women who use transdermal patches or vaginal rings for
contraception have a 7.9 and 6.5 times increased risk of confirmed
venous thrombosis compared with non-users of hormonal contraception
of the same age, corresponding to 9.7 and 7.8 events per 10 000
exposure years. The risk was slightly increased in women using
subcutaneous implants but not in those using the levonorgestrel
intrauterine system.
Introduction
Several studies have assessed the risk of venous thrombosis in
women using oral contraceptives.1-10 However, none has assessed
the risk in women using subcutaneous hormonal implants. A
recent study reported a 48% higher risk of venous thrombosis
in women using a vaginal ring compared with those using
combined oral contraceptives containing levonorgestrel,11 and
a few studies have reported the risk in women using a
transdermal combined contraceptive patch, although the results
were conflicting.12-16
Using a historical national registry based cohort study design,
we assessed the absolute and relative risk of venous thrombosis
in Danish women using non-oral hormonal contraception.
Methods
Information on the four national data sources that provided
information for the study is provided in detail elsewhere.10
Briefly, from Statistics Denmark we obtained data on length of
schooling, ongoing or finished education, vital status, and
emigration of all Danish women aged 15-49 from 1 January
2001 to 31 December 2010. We censored women in cases of
death or emigration.
Since 1977 the national registry of patients has collected
discharge diagnoses from all public and private hospitals in
Denmark (see appendix for a list of the relevant diagnoses and
Correspondence to: Ø Lidegaard Lidegaard@rh.regionh.dk
Extra material supplied by the author (see http://www.bmj.com/content/344/bmj.e2990?tab=related#webextra)
Disease codes (international classification of diseases, 10th revision)
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Research
RESEARCH
codes used in this study). To include only first ever events, we
excluded women with any type of venous or arterial thrombotic
event before the study period (1977-2000), those with cancer,
those who had undergone bilateral oophorectomy or
hysterectomy, and those who had been sterilised. From study
follow-up we censored a woman’s risk time during pregnancy,
calculated from conception to three months after delivery, and
women with a coagulation disorder from the first time such a
diagnosis was recorded (appendix). The registry records only
women admitted alive to hospital. Lethal events from venous
thrombosis were captured in the national cause of death registry.
A diagnosis of venous thrombosis was confirmed through
prescribed anticoagulation therapy recorded in the national
registry of medicinal products for at least four weeks after the
diagnosis. Since 1 January 1994, and validated from 1995,
information on filled prescriptions, including hormonal
contraception, collected by the national registry of medicinal
products has been complete. From this database we obtained
information that had been updated daily on redeemed
prescriptions of hormonal contraception from 1995 to 2010.
We categorised the products in use according to progestogen
type, oestrogen dose, and route of being administered. Duration
of use was estimated from the prescribed defined daily doses
from the date of prescription until the end date of defined daily
doses of the last redeemed prescription or date of a study event.
When hormonal contraception was switched without pause, we
calculated duration as the sum of use before switch and current
use of the new preparation. If a pause lasted for more than four
weeks, we reset the length of use. To account for use before
study start (left censoring bias), we allocated continuous users
of hormonal contraception to the relevant duration of use
category on 1 January 2001 by assessing use before the study
period back to 1995.
Women who used the levonorgestrel intrauterine system were
censored after three years and included again when a new
prescription of a hormonal contraceptive product was recorded.
This was done owing to missing information on removal of
these devices.
Length of schooling and level of education were used as proxies
for social class. Four strata were applied: elementary school
education only, ongoing or completed high school education,
high school and ongoing or ended middle length education, and
high school and ongoing or ended long education. A fifth
category included women without information on education,
typically the youngest women.
We controlled for calendar year to deal with potential secular
confounding of increasing adiposity by time.
Data on smoking were not available. Smoking is a weak risk
factor for venous thrombosis in young women. However, we
have no reason to believe in preferential prescribing of specific
types of hormonal contraception among smokers. In Denmark
the correlation between smoking and length of education is
strong. Thus, controlling for years of schooling and length of
education may have captured most confounding (if any)
influenced by smoking.
As women treated for infertility with ovarian stimulation drugs
(Anatomical Therapeutic Chemical code G03G) are anticipated
to be at an increased risk of venous thrombosis, we censored
these women during such treatment.
Statistical analysis
Using multiple Poisson regression we analysed data in five year
age groups: 15-19, 20-24, and 45-49 years. The non-oral
contraceptive products included transdermal patches containing
norelgestromin (the active metabolite of norgestimate) and
ethinylestradiol, a vaginal ring with etonogestrel (third
generation progestogen) and ethinylestradiol, subcutaneous
implants containing etonogestrel only, and the levonorgestrel
intrauterine system (hormone intrauterine device). Two reference
oral contraceptives with levonorgestrel and norgestimate,
respectively, were assessed for comparison.
We stratified the estimates into three categories according to
length of contraceptive use (<1 year, 1-4 years, >4 years).
Absolute as well as relative risk estimates were calculated. The
reference group for the relative risk estimates was non-users of
all types of hormonal contraception (never users+former users).
We calculated rate ratios for the different product types, with
users of oral contraceptives containing 30-40 µg oestrogen and
levonorgestrel as reference. Tests for interaction with age and
year were carried out.
Relative risk estimates were adjusted for age, calendar year,
length of schooling and education, and eventually for length of
contraceptive use. For all relative risk estimates and incidence
rate ratios we calculated 95% confidence limits. We set the level
of significance at P<0.05.
Results
After exclusions and censoring, 1 626 158 non-pregnant women
free of previous thrombotic diseases or cancer contributed 9
429 128 woman years of observation. During this time 5287
diagnoses of first ever venous thrombosis events were recorded,
corresponding to 8.1 per 10 000 woman years. Current users of
hormonal contraception contributed 3 536 946 woman years
and of these, 325 849 concerned non-oral products. Non-users
of hormonal contraception contributed 5 892 182 woman years,
with an overall incidence of confirmed venous thrombosis of
2.1 per 10 000 woman years. The incidence of venous
thrombosis increased by 42.9% during the 10 year study period,
or by 4.3% per year (table 1). After adjustment for calendar
year and use of hormonal contraception, the incidence increased
by 6.3-fold with increasing age and decreased by 51.2% with
increasing length of education.
Hormonal contraception and venous
thrombosis
Current use of combined oral contraceptives with 30-40 µg
oestrogen and levonorgestrel increased the risk of confirmed
venous thrombosis by 3.2 (2.7 to 3.8), corresponding to an
incidence of 6.2 events per 10 000 exposure years (table 2).
During 6178 woman years, six confirmed events of venous
thrombosis were observed in association with transdermal
combined contraceptive patches, corresponding to an incidence
of 9.7 per 10 000 exposure years. Compared with non-users of
hormonal contraception, the adjusted relative risk was 7.9 (3.5
to 17.7) and compared with users of oral contraceptives
containing levonorgestrel the rate ratio was 2.5 (1.1 to 5.6, tables
2 and 3). After adjustment for length of use, the rate ratio was
reduced to 2.3 (1.0 to 5.2). When compared with oral
contraceptives containing the corresponding progestogen
(norgestimate), the adjusted rate ratio was 2.2 (1.0 to 5.0).
During 50 334 woman years, 39 confirmed venous thrombosis
events were observed with the combined contraceptive vaginal
ring, corresponding to an incidence of 7.8 per 10 000 exposure
years and an adjusted relative risk of 6.5 (4.7 to 8.9) compared
with non-users of hormonal contraception. Compared with users
of combined oral contraceptives with levonorgestrel, the rate
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RESEARCH
ratio was 2.0 (1.4 to 2.9), which after adjustment for length of
use was reduced to 1.9 (1.3 to 2.7, tables 2 and 3).
During 29 497 woman years, five confirmed venous thrombosis
events were observed with progestogen only subcutaneous
implants, corresponding to an incidence rate of 1.7 per 10 000
exposure years and an adjusted relative risk of 1.4 (0.6 to 3.4,
table 2) compared with non-users of hormonal contraception.
Compared with users of combined oral contraceptives with
levonorgestrel, the rate ratio was 0.4 (0.2 to 1.1, table 3).
The adjusted relative risk of confirmed venous thrombosis with
the levonorgestrel intrauterine system was 0.6 (0.4 to 0.8, table
2). Compared with users of combined oral contraceptives with
levonorgestrel, the rate ratio was 0.2 (0.1 to 0.3, table 3).
After stratification according to length of use, the relative risk
of venous thrombosis in women using combined oral
contraceptives was reduced with increasing length of use (table
4). No reduction by time was seen in users of transdermal
combined contraceptive patches or progestogen only
contraception, and no consistent changes were seen for women
who used the vaginal ring.
Discussion
Women who use combined hormonal transdermal patches or
vaginal rings for contraception have a 7.9 or 6.5 times increased
risk of venous thrombosis compared with non-users of hormonal
contraception of the same age, corresponding to 9.7 and 7.8
events per 10 000 exposure years. The risk was slightly
increased in women using subcutaneous implants but not in
those using the levonorgestrel intrauterine system.
An incidence rate of confirmed venous thrombosis in users of
transdermal patches of 1 in 1000 exposure years was found in
a recent American study,11 and a relative risk of 7.9 compared
with non-users of hormonal contraception or twice the risk with
use of the corresponding combined oral contraceptive containing
norgestimate in several previous studies11 14-16 although not all12 13
(table 5). These results are supported by pharmacokinetic
studies showing 60% higher plasma levels of oestrogen in
women who use transdermal patches compared with those using
the corresponding combined oral contraceptive.17
With an incidence of 7.8 confirmed events per 10 000 exposure
years, the vaginal ring conferred a 90% higher risk of venous
thrombosis than did combined oral contraceptives containing
levonorgestrel, bringing the risk to the same level as that of
combined oral contraceptives with third and fourth generation
progestogens, and compatible with the Food and Drug
Administration study.11 Supporting our and the FDA results is
the three18 and five times19 increase in sex hormone binding
globulin in users of vaginal ring contraception compared with
users of combined oral contraceptives containing levonorgestrel,
and the activated protein C sensitivity ratio 3.75 times higher
than with oral contraceptives,19 both considered as surrogate
markers for the risk of venous thrombosis.
The modest non-significant 40% increased relative risk of
venous thrombosis in women using subcutaneous implants is
not surprising, as other types of progestogen only contraception
do not confer an increased risk,10 and it is less than half the risk
found in users of combined oral contraceptives containing
levonorgestrel.
The low risk of venous thrombosis in users of the levonorgestrel
intrauterine system has been shown in previous studies.7 10 In
the present study this product actually significantly decreased
the risk of venous thrombosis, suggesting that the influence of
progestogen only contraception on risk of venous thrombosis
may depend on dose.
The inconsistent changes with length of use for the non-oral
products could be influenced by the low power in some of the
length of use categories. Another possibility, however, is that
the non-oral route influences the coagulation system and liver
differentially compared with the oral route. Nor did the FDA
report show any consistent change in risk with length of use of
either the patch or the vaginal ring.
The clinical implications of the findings can be expressed in
terms of the number of women who should change their
hormonal contraceptive from the transdermal patch or the
vaginal ring to combined oral contraceptives containing
levonorgestrel to prevent one event of venous thrombosis in a
year. If the incidence rate of venous thrombosis in women using
combined oral contraceptives containing levonorgestrel is 6 per
10 000 exposure years, the vaginal ring is 11 per 10 exposure
years, and the transdermal patch is 14 per 10 000 exposure years,
then 2000 women using the vaginal ring and 1250 using the
transdermal patch should shift to combined oral contraceptives
with levonorgestrel to prevent one event of venous thrombosis
in one year. A risk of 10 per 10 000 woman years implies a risk
of venous thrombosis of more than 1% over a 10 year user
period. Therefore women are generally advised to use combined
oral contraceptives with levonorgestrel or norgestimate, rather
than to use transdermal patches or vaginal rings.
Strengths and limitations of the study
The inclusion of all Danish non-pregnant women over a decade
ensures outstanding external validity. Information on use of
hormonal contraception from a prescription database is the most
reliable data on exposure available today for four reasons.
Firstly, each pharmacy transfers data electronically by bar codes,
eliminating typing errors. Secondly, the collection of these data
in a central national database is done primarily for
reimbursement purposes and therefore should not be biased by
the pursuit of pharmacoepidemiological studies. Thirdly, the
continued daily update of information on use eliminates recall
bias, as we know from case-control studies, and the problems
of continuous updating of data on exposure in cohort studies.
Fourthly, we eliminated the problem of left censoring bias by
assessing exposure to hormonal contraception over a six year
period before our study started. And we were able to validate
each venous thrombosis event by linking individual data on
diagnosis to succeeding anticoagulation therapy.
We could not control for family disposition or for body mass
index. Adiposity is a well documented risk factor for venous
thrombosis. So far no study has shown any confounding
influence from adiposity, as the rate ratio between hormonal
contraception with different progestogens was not changed in
studies adjusting for this information.6 8 20
Conclusion
Use of transdermal patches and vaginal rings conferred incidence
rates of 9.7 and 7.8 confirmed venous thromboses per 10 000
exposure years, and relative risks of 7.9 and 6.5 compared with
non-use of hormonal contraception, respectively. A
subcutaneous progestogen only implant may increase the risk
by 40%, whereas the levonorgestrel intrauterine system did not
confer any increased risk, but perhaps even protection.
This study was approved by the Danish Data Protection Agency (J No
2010-41-4778).
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RESEARCH
What is already known on this topic
Combined oral contraceptives with levonorgestrel or norgestimate confer half the risk of venous thrombosis than oral contraceptives
containing desogestrel, gestodene, or drospirenone
Progestogen only pills do not confer an increased risk of venous thrombosis
What this study adds
Women who use combined contraceptive transdermal patches are at an increased risk of venous thrombosis about eight times that of
non-users of hormonal contraception, corresponding to 9.7 events per 10 000 exposure years
Vaginal rings increased the risk of venous thrombosis 6.5 times compared with non-use of hormonal contraception, corresponding to
7.8 events per 10 000 exposure years
The risk of venous thrombosis was not significantly increased with use of subcutaneous implants or the levonorgestrel intrauterine
system compared with non-use of hormonal contraception
Contributors: ØL planned the study, supervised the analysis, interpreted
the results, and wrote the manuscript. He is guarantor of the study. EL
planned the study, interpreted the results, and revised the manuscript.
LHN made the statistical analyses and interpreted the results. CWS
prepared all data from the national registry of patients and national
death registry. All authors discussed and approved the final manuscript.
ØL decided when and where to attempt publication.
Funding: The expenses were covered by the Gynaecological Clinic,
Juliane Marie Centre, Rigshospitalet.
Competing interests: All authors have completed the ICMJE uniform
disclosure form at www.icmje.org/coi_disclosure.pdf (available on
request from the corresponding author) and declare: no support from
any organisation for the submitted work. The primary investigator has
within the last three years received honorariums for speeches in
pharmacoepidemiological issues, including fees from Bayer Pharma
Denmark, MSD Denmark, and Theramex, Monaco, and has been expert
witness for plaintiff in a legal US case in 2011. EL has within the last
three years participated in two congresses the expenses of which were
covered by pharmaceutical companies. LHN and CWS declared no
financial relationships with any organisations that might have an interest
in the submitted work in the previous three years, and no other
relationships or activities that could appear to have influenced the
submitted work.
Ethical approval: Ethical approval is not requested for registry based
studies in Denmark, and consent from participating patients is not
required.
Data sharing: No additional data available.
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Accepted: 30 March 2012
Cite this as: BMJ 2012;344:e2990
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RESEARCH
Tables
Table 1| Crude incidence rate and adjusted relative risk of confirmed venous thrombosis according to age, calendar year, and length of
education
P valueAdjusted relative risk* (95% CI)Incidence per 10 000 woman years
Venous thrombosis
Woman yearsVariables ConfirmedAll
Age:
<0.0010.16 (0.13 to 0.19)1.792513651 403 92515-19
<0.0010.19 (0.16 to 0.22)2.723264791 198 09820-24
<0.0010.30 (0.27 to 0.33)3.383875941 145 72925-29
<0.0010.44 (0.40 to 0.48)3.454487151 299 64530-34
<0.0010.60 (0.55 to 0.66)3.986019301 509 44735-39
<0.0010.82 (0.75 to 0.89)4.6770511051 510 04240-44
1.00 (reference)5.2671610991 362 24245-49
Year:
<0.0010.70 (0.61 to 0.79)3.17315444994 0952001
<0.0010.72 (0.64 to 0.82)3.38331466979 7152002
<0.0010.68 (0.60 to 0.77)3.16304438963 4702003
<0.0010.79 (0.70 to 0.89)3.35319512953 6042004
0.00050.81 (0.72 to 0.91)3.85362525939 9352005
0.00280.84 (0.74 to 0.94)3.90363537929 9752006
0.65310.97 (0.87 to 1.09)4.24391615921 7132007
0.01710.87 (0.77 to 0.98)3.78347538918 3492008
0.65970.98 (0.87 to 1.09)4.00365599911 8252009
1.00 (reference)3.68337613916 4492010
Education:
0.00041.25 (1.11 to 1.42)5.35115918192 164 6351 (low)
<0.0010.72 (0.62 to 0.83)3.063144751 026 5252
0.00870.83 (0.73 to 0.95)4.3597414562 236 9723
<0.0010.61 (0.53 to 0.71)2.763826021 385 2144 (high)
1.00 (reference)2.316059352 615 782Not available
*Adjusted for age, calendar year, education, and use of hormonal contraception.
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BMJ 2012;344:e2990 doi: 10.1136/bmj.e2990 (Published 10 May 2012) Page 5 of 9
RESEARCH
Table 2| Crude incidence rate and adjusted relative risk of venous thrombosis in current users of non-oral hormonal contraception and
combined oral contraceptives (COC) with non-users as reference
P valueAdjusted relative risk* (95% CI)
Incidence per 10 000
exposure years
No with venous
thrombosisWoman yearsOutcome, contraception type
All venous thromboses:
1.00 (reference)3.8422625 892 182Non-use
<0.0012.37 (2.05 to 2.74)8.68201231 675COC with levonorgestrel and
30-40 µg oestrogen
<0.0012.63 (2.27 to 3.05)6.63198298 566COC with norgestimate
<0.0014.40 (2.09 to 9.24)11.3376178Patch
<0.0014.29 (3.27 to 5.62)10.935550 334Vaginal ring
0.0052.08 (1.25 to 3.46)5.091529 497Implant
0.0400.80 (0.65 to 0.99)3.6788239 841Levonorgestrel IUS
Confirmed events:
1.00 (reference)2.0512095 892 182Non-use
<0.0013.21 (2.70 to 3.81)6.22144231 675COC with levonorgestrel and
30-40 µg oestrogen
<0.0013.57 (2.98 to 4.27)4.52135298 566COC with norgestimate
<0.0017.90 (3.54 to 17.65)9.7166178Patch
<0.0016.48 (4.69 to 8.94)7.753950 334Vaginal ring
0.4501.40 (0.58 to 3.38)1.70529 497Implant
0.0020.57 (0.41 to 0.81)1.3833239 841Levonorgestrel IUS
Patch=transdermal contraceptive patch (EVRA; Johnson & Johnson, NJ, USA); implant=subcutaneous implant (Implanon; MSD; NJ, USA); vaginal ring=combined
hormonal vaginal ring (NuvaRing; MSD, NJ, USA); levonorgestrel IUS=levonorgestrel intrauterine system (Mirena: Bayer Pharma, Berlin, Germany).
*Adjusted for age, calendar year, and education.
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BMJ 2012;344:e2990 doi: 10.1136/bmj.e2990 (Published 10 May 2012) Page 6 of 9
RESEARCH
Table 3| Rate ratio estimates of venous thrombosis between users of different types of non-oral hormonal contraception and users of
combined oral contraceptives (COC) with levonorgestrel and 30-40 µg oestrogen (reference group)
P valueAdjusted rate ratio (95% CI)*
No with venous
thrombosisWoman yearsOutcome, contraception type
All venous thrombosis:
1.00 (reference)201231 675COC with levonorgestrel and 30-40 µg
oestrogen
0.3051.11 (0.91 to 1.35)198298 566COC with norgestimate
0.1091.85 (0.87 to 3.94)76178Patch
0.00011.81 (1.34 to 2.44)5550 334Vaginal ring
0.6230.88 (0.52 to 1.48)1529 497Implant
<0.0010.34 (0.26 to 0.43)88239 841Levonorgestrel IUS
Confirmed events:
1.00 (reference)144231 675COC with levonorgestrel and 30-40 µg
oestrogen
0.3781.11 (0.88 to 1.41)135298 566COC with norgestimate
0.0312.46 (1.09 to 5.58)66178Patch
0.00012.02 (1.41 to 2.89)3950 334Vaginal ring
0.0700.44 (0.18 to 1.07)529 497Implant
<0.0010.18 (0.12 to 0.26)33239 841Levonorgestrel IUS
Confirmed events adjusted for length of use:
1.00 (reference)144231 675COC with levonorgestrel and 30-40 µg
oestrogen
0.4651.09 (0.86 to 1.38)135298 566COC with norgestimate
0.0452.31 (1.02 to 5.23)66178Patch
0.0011.90 (1.33 to 2.71)3950 334Vaginal ring
0.0640.43 (0.18 to 1.05)529 497Implant
<0.0010.18 (0.12 to 0.26)33239 841Levonorgestrel IUS
Patch=transdermal contraceptive patch (EVRA; Johnson & Johnson, NJ, USA); implant=subcutaneous implant (Implanon; MSD; NJ, USA); vaginal ring=combined
hormonal vaginal ring (NuvaRing; MSD, NJ, USA); levonorgestrel IUS=levonorgestrel intrauterine system (Mirena; Bayer Pharma, Berlin, Germany).
*Adjusted for age, calendar year, and education.
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BMJ 2012;344:e2990 doi: 10.1136/bmj.e2990 (Published 10 May 2012) Page 7 of 9
RESEARCH
Table 4| Relative risk of confirmed venous thrombosis in current users of different types of hormonal contraception according to length
of use
Adjusted relative risk (95% CI)*
No with confirmed
venous thrombosisHormonal contraception >4 years1-4 years<1 year
1 (reference)1 (reference)1 (reference)1209Non-use
2.71 (2.06 to 3.58)3.07 (2.28 to 4.13)4.25 (3.17 to 5.69)144COC with levonorgestrel and
30-40 µg oestrogen
2.67 (1.82 to 3.92)2.97 (2.19 to 4.03)4.97 (3.86 to 6.39)135COC with norgestimate
NA11.9 (3.82 to 36.9)6.89 (2.22 to 21.4)6Patch
5.37 (1.73 to 16.7)3.83 (1.91 to 7.69)8.36 (5.73 to 12.2)39Vaginal ring
NA1.43 (0.46 to 4.45)1.63 (0.41 to 6.52)5Implant
NA0.61 (0.39 to 0.94)0.59 (0.34 to 1.05)33Levonorgestrel IUS
COC=combined oral contraceptive; patch=transdermal contraceptive patch (EVRA; Johnson & Johnson, NJ, USA); implant=subcutaneous implant (Implanon;
MSD, NJ, USA); vaginal ring=combined hormonal vaginal ring (NuvaRing; MSD; NJ, USA); levonorgestrel IUS=levonorgestrel intrauterine system (Mirena; Bayer
Pharma, Berlin, Germany); NA=not available.
*Adjusted for age, calendar year, and education.
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BMJ 2012;344:e2990 doi: 10.1136/bmj.e2990 (Published 10 May 2012) Page 8 of 9
RESEARCH
Table 5| Incidence of venous thrombosis in users of transdermal contraceptive patch and corresponding combined oral contraceptive
(COC) with norgestimate, and rate ratio of venous thrombosis in users of patch versus users of combined oral contraceptives with
norgestimate
Rate ratio (95% CI)
Incidence per 10 000 exposure years
No with venous thrombosisSampling periodStudy COC with norgestimatePatch
1.1 (0.7 to 1.8)4.25.3682002-05Jick 200612
1.1 (0.6 to 2.1)NANA562002-06Jick 200713
2.4 (1.2 to 5.0)NANA382002-07Jick 201014
2.2 (1.3 to 3.8)1.84.1572002-04Cole 200715
2.0 (1.2 to 3.3)NANA2012002-06Dore 201016
1.3* (0.9 to 1.7)6.6*9.66252001-07FDA 201111
2.2 (1.0 to 5.0)4.59.734342001-10Lidegaard 201110
NA=not available; FDA=Food and Drug Administration.
*Reference group was users of combined oral contraceptives with levonorgestrel and 30-40 µg oestrogen.
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RESEARCH
ResearchGate has not been able to resolve any citations for this publication.
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