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ORIGINAL ARTICLE
Stopping oral contraceptives: an effective
blood pressure-lowering intervention
in women with hypertension
JN Lubianca
1
, LB Moreira
1,2
, M Gus
1,3
and FD Fuchs
1,3
1
Programa de Po
´
s-Graduac¸a˜o em Medicina:Cie
ˆ
ncias Me
´
dicas, Hospital de Clı
´
nicas de Porto Alegre,
Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil;
2
Division of Clinical Pharmacology,
Hospital de Clı
´
nicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil;
3
Division of Cardiology, Hospital de Clı
´
nicas de Porto Alegre, Universidade Federal do Rio Grande do Sul,
Porto Alegre, RS, Brazil
The association of combined oral contraceptives (OC)
with higher blood pressure (BP) may be attenuated with
pills with smaller doses of oestrogen. The effect of
stopping OC on BP of patients with hypertension
was not described to date. In a cohort study of patients
with hypertension, we identified 72 women using OC
among 2112 patients seen from 1989 to 2002. Stopping
hormonal contraception was recommended to all. The
main outcome measurement was BP change in women
who stopped (n ¼ 44) and who did not stop (n ¼ 28) OC,
adjusting for baseline BP and age. Odds ratio for having
a reduction of at least 20 mmHg in systolic blood
pressure (SBP) or 10 mmHg in diastolic blood pressure
(DBP), adjusting for age, change in weight and prescrip-
tion of BP-lowering drugs, were calculated. The mean
follow-up time was 6.677.5 months. Participants who
stopped and did not stop OC had similar baseline
characteristics. The deltas of SBP (adjusted) were
15.172.6 mmHg in patients who stopped and
2.873.2 mmHg in patients who did not stop OC
(P ¼ 0.004). The corresponding values for DBP were
10.471.8 and 2.772.2 mmHg (P ¼ 0.008), respectively.
The odds ratio (adjusted) for having a decrease of at
least 20 mmHg in SBP or 10 mmHg in DBP was 0.28 (95%
CI 0.08–0.90) in patients who stopped OC. Stopping OC
is an effective antihypertensive intervention in a clinical
setting.
Journal of Human Hypertension (2005) 19, 451–455.
doi:10.1038/sj.jhh.1001841
Published online 10 March 2005
Keywords:
oral contraceptives; blood pressure
Introduction
Oral contraception remains as one of the contra-
ceptive methods mostly used worldwide. In the
United States, approximately 34.5 million women
were using contraception in the last decade.
1
Oral
contraceptives (OC) and tubal ligation correspond to
85% of the contraceptive methods used in Brazil.
2
In
a population-based survey in Porto Alegre, 81.8% of
the women in the reproductive age were using OC.
3
Despite several attempts to reducing the rate
of undesirable effects of OC, many are unlikely
to be fully eliminated. Higher blood pressure
levels are among their usual adverse effects,
4,5
and
uncontrolled hypertension has been acknow-
ledged as a relative contraindication for the use
of combined OC.
6
Most studies documenting the association be-
tween hypertension and use of contraceptives
involved compounds of first generation, with at
least 50 mg of oestrogen. It was postulated that the
incidence of hypertension would be lower if smaller
doses of oestrogen were used.
7,8
However, higher
blood pressure (BP) levels were found even in
patients using monophasic pills containing 30 mg
of oestrogen.
9
In a cohort study, a two-fold increase in risk for
hypertension was detected in current OC users, as
compared to nonusers.
10
Recently, we found that
among hypertensive patients referred to a hyperten-
sion clinic, those using OC presented the highest
probability of having uncontrolled BP, mainly at the
expense of diastolic pressure.
11
Thus, the use of OC may worsen the prognosis of
hypertensive women. An effective measure to low-
ering BP and consequent morbidity might be to
substitute the contraceptive method, but as far as we
Received 26 October 2004; revised and accepted 29 December
2004; published online 10 March 2005
Correspondence: Professor FD Fuchs, Servic¸o de Cardiologia, sala
2061, Hospital de Clı
´
nicas de Porto Alegre, Ramiro Barcelos 2350,
90035-903, Porto Alegre RS, Brazil.
E-mail: ffuchs@hcpa.ufrgs.br
Journal of Human Hypertension (2005) 19, 451–455
&
2005 Nature Publishing Group All rights reserved 0950-9240/05
$30.00
www.nature.com/jhh
know there are no studies showing the effectiveness
of this measure. In this report, we demonstrate that
stopping the use of OC is an effective antihyperten-
sive intervention in a clinical setting.
Methods
Our data come from a prospectively planned cohort
study of hypertensive patients that is on way since
1989 in the Hypertensive Outpatient Clinic of
Hospital de Clinicas de Porto Alegre. A more
detailed description and results of this study may
be seen elsewhere.
11–15
In brief, the study was
planned to investigate several aspects related to
the diagnosis and management of hypertension in a
clinical setting. The influence of hormonal contra-
ceptives on the control of BP was one of the specific
objectives established a priori. Patients enrolled in
the original cohort represented the whole spectrum
of patients with hypertension, since our outpatient
clinic was open to the referral of patients with
uncomplicated, resistant, and potentially secondary
hypertension. In a register of 2112 patients seen
from 1989 to 2002, 72 hypertensive women using
combined OC were identified and constituted the
sample for this study.
All participants were evaluated according to
the protocol used in the main study, which inclu-
ded an extensive collection of data concerning
medical history, physical examination, and labora-
tory testing.
BP was measured according to standard techni-
ques at three consecutive visits. During each visit,
BP was measured twice at 5-min interval. The mean
of six BP measurements — usual BP — was used to
diagnose and classify hypertension. Blood pressure
diagnosis and classification for this analysis fol-
lowed the recommendations from 7th report of the
Joint National Committee (JNC).
16
Detailed questions were asked about the use of
contraceptive methods (at the time of the visit or
in the past) and method employed (Ogino-Knaus,
condoms, pill, IUD, or diaphragm). Almost all
women under oral contraception were using pills
with 30 mg of oestrogen.
All patients using hormonal contraception were
advised to change their method under the orienta-
tion of a gynaecologist, explaining the reasons for
the measure. In the follow-up visits, the protocol
included the questioning if the patient had stopped
using the contraceptive. The groups for comparison
consisted of patients who had stopped and
patients who were still using them at the time of
the follow-up visit.
The main outcome measure was the BP variation
between the initial evaluation and the follow-up
visit. A dummy variable was computed correspond-
ing to the reduction of at least 20 mmHg in systolic
pressure or 10 mmHg in diastolic pressure between
the two visits.
The baseline prognostic characteristics were com-
pared using the Student’s t-test or the w
2
test when
appropriate. The deltas of systolic and diastolic BP
between baseline and follow-up visits were calcu-
lated and tested by a Student’s t-test for indepen-
dent samples. In a multivariate model, the deltas
between the groups were adjusted for the baseline
BP and age.
The rate of patients with improved prognosis (at
least 20 mmHg decreasing in systolic pressure or
10 mmHg in diastolic pressure) in the two groups
was evaluated using the w
2
test. Improved prognosis
was also included as a dependent variable in a
logistic regression model, controlling for age, anti-
hypertensive drug prescription, and body weight
variation. All statistical analyses were performed
with SPSS version 10.0.
The project was approved by the Ethics Commit-
tee of our Institution. Since the participants were
under usual medical care, a signed written consent
was waived.
Results
The mean age of the patients was 37.776.2 years.
The follow-up was 6.677.5 months (range ¼ 1–33
months). There was no difference in baseline
characteristics between participants who stopped
and did not stop the use of OC (Table 1). The
antihypertensive treatment did not differ among
groups. The reasons for not having stopped the use
of OC were not systematically registered, but mostly
comprised difficulties in getting the assistance of
a gynaecologist or fear to use a less efficacious
method.
The severity of hypertension was reclassified
according to JNC 7 and did not differ among groups.
In the group of patients who stopped combined OC,
9.1% were at the prehypertensive stage, 45.5% at
stage 1, and 45.5% were classified at stage 2. Among
those who did not stop using the contraceptive
during the follow-up, there were 17.9% of patients
classified as prehypertension, 25% classified as stage
1, and 57.1% as stage 2 hypertension (P ¼ 0.18 for
comparison between groups). The antihyper-
tensive drug and nondrug treatment did not differ
among groups.
Systolic blood pressure (SBP) tended to be lower
at follow-up visit in patients who stopped using OC,
while the variation in diastolic pressure was not
significantly different between groups (Table 2).
After adjustment for initial BP and age, the deltas
of SBP and diastolic blood pressure (DBP) were
significantly higher in the patients who stopped
using OC (Table 2).
There was a trend towards improved prognosis,
defined as a reduction of at least 20 mmHg in SBP or
10 mmHg in DBP, in patients who stopped using the
OC (Table 3). After adjustment for age, variation in
weight, and drug prescription at the initial visit, the
Blood pressure lowering after stopping oral contraceptives
JN Lubianca et al
452
Journal of Human Hypertension
association between stopping hormonal OC and
improvement in prognosis turned significant
(Figure 1). Controlling for other potential confoun-
ders, such as baseline BP, informed compliance with
drug prescription and with adhesion to the hypoca-
loric diet did not change the estimates substantially.
Since the period of observation was too long, we
looked at the association between OC suspension
and BP changing in blocks or three periods of
4 years. Despite the wide confidence intervals,
the associations were similar to the observed in
the entire cohort.
Table 1 Baseline characteristics of the women who stopped and did not stop using hormonal contraception (mean7s.d. or n (%), when
appropriate)
Characteristics Stopped n ¼ 44 Did not stop n ¼ 28 P*
Age (years) 38.375.8 37.076.97 0.404
White (n, %) 36 (81.8%) 22 (78.6%) 0.734
Income (minimum wages) 2.970.6 2.870.5 0.678
Years at school 7.173.4 7.673.3 0.548
Body mass index (kg/m
2
) 29.175.3 27.075.1 0.125
Duration of hypertension (years) 3.071.9 2.871.4 0.562
Drugs in initial evaluation (n,%)
None 27 (65.9%) 12 (42.9%) 0.138
One 11 (26.8%) 11 (39.3%)
Two or more 3 (7.3%) 5 (17.9%)
Systolic blood pressure (mmHg) 152.7720.3 159728 0.274
Diastolic blood pressure (mmHg) 98.7710.8 103.0720.5 0.242
Drugs in follow-up (n,%)
None 23 (57.5%) 10 (37%) 0.05
One 12 (30%) 7 (25.9%)
Two or more 5 (12.5%) 10 (37%)
Follow-up time (months) 6.9 (8.5) 5.8 (5.3) 0.543
*Student’s t-test for continuous variables; w
2
test for categorical variables.
Table 2 BP (mmHg) at baseline and follow-up (means7s.d.), with the corresponding deltas (means7s.e.), in women who stopped and
did not stop using OC
Blood pressure Stopped OC Baseline Follow-up Delta*P*Delta** adjusted P**
SBP Yes 152.7720.3 139.3718 13.773.1 0.09 15.172.6 0.004
No 159.0728.0 154.0721.8 5.074.1 2.873.2
DBP Yes 98.7710.8 89.7711.2 9.371.9 0.22 10.471.8 0.008
No 103.0720.5 98.7714 4.373.7 2.772.2
SBP, systolic blood pressure; DBP, diastolic blood pressure; OC, oral contraceptives.
*Student’s t-test for independent samples.
**Adjusted for the respective baseline BP and age.
Table 3 Proportion of participants who had a reduction of at
least 20 mmHg in systolic blood pressure (SBP) or 10 mmHg in
diastolic blood pressure (DBP) (n and (%))
Followed the
recommendation to
stopping OC
Had a reduction of 20 mmHg in
SBP or 10 mmHg in DBP
*
Yes No
Yes 22 (73.3) 22 (52.4)
No 8 (26.7) 20 (47.6)
Total 30 (100) 42 (100)
*
Exact Fisher test–P ¼ 0.089; odds ratio (95% CI): 0.40 (0.15–1.10).
Age (10 years)
1.39 (0.89–2.16)
1.35 (0.61–2.97)
0.66 (0.22–1.97)
Improvement
Weight variation (10 Kg)
Drug prescription
Stopping OC 0.27 (0.08– 0.90)
0.0
1.0
Worsening
OR
Exposure
2.0
Figure 1 Association between stopping OC and improved prog-
nosis (reduction of at least 10 mmHg in DBP or 20 mmHg in SBP)
adjusted to other variables of exposure.
Blood pressure lowering after stopping oral contraceptives
JN Lubianca et al
453
Journal of Human Hypertension
Discussion
The detailed recording of information in this cohort
allowed to identifying a clinically significant BP
lowering effect in hypertensive women who stopped
using oestrogen-based hormonal contraceptives. We
are not aware of other studies that have addressed
this clinical question through this design. In the
same cohort, we found that compliance with a
hypocaloric diet and with the use of antihyper-
tensive drugs was accompanied by a significant
reduction in BP, but not compliance with the
recommendation to increase physical activity and
to follow a low sodium diet.
13
Compliance with the
recommendation to stop using OC may be another
effective antihypertensive measure. The magnitude
of the effect, in average of 12.3 mmHg for SBP and
7.7 mmHg for DBP, is higher than the effect of other
nondrug interventions accepted as effective.
16
The present findings were expected to a certain
extent. The association between the use of OC and BP
elevation has been repeatedly demonstrated.
11,17–19
In
the last Joint National Committee, JNC 7 report, it is
emphasized that OC raise BP and that the risk
of hypertension increases with length of use. They
recommend that OC users should get their pressure
levels checked regularly during the period when
they are taking OC and that the onset of hyper-
tension is a reason to consider other forms of
contraception.
16
Most studies, however, have focused on the
development of hypertension in women who were
previously normotensive. There are only two
studies
11,20
on patients with a previous diagnosis
of hypertension, in whom a positive association
was observed between BP and the use of OC, anti-
cipating that the withdrawal of OC could be an
appropriate measure to improve BP control in
hypertensive women.
The relationship between higher BP and risk for
cardiovascular and renal diseases was demonstrated
in a large series of cohort studies,
21,22
showing that
risks are directly proportional to the usual BP levels
of individuals. Pooling 61 cohort studies, with
approximately 1 million of individuals (12.7 million
person-years at risk), the investigators from the
Prospective Studies Collaboration demonstrated
that the incidence of stroke and coronary heart
disease increased two-fold at each difference of
20 mmHg in usual SBP or 10 mmHg in usual DBP.
23
Accordingly, our findings show that stopping
OC may lead to a reduction of almost 50% in
cardiovascular risk.
The present study has some limitations. Despite
the large size of the original cohort, just a few
patients fulfilled the inclusion criteria. Owing to the
relatively low statistical power, an alpha error may
not be fully discarded (chance finding), but the
differences in BP behaviour between participants
who stopped and did not stop using OC seem to be
consistent. Because of the non-experimental design,
it cannot be ruled out that part of the BP lowering
effect in patients who followed the recommendation
of stopping the OC is due to other prognostic
characteristics of these women. The most likely
confounders, however, were controlled in the multi-
variate analysis and showed to be in the conser-
vative side. This observation was made among
a population attending to a hypertension clinic
of a hospital offering secondary and tertiary care
in Brazil, thus limiting generalizability to other
populations.
In conclusion, we demonstrated that when wo-
men with hypertension treated in an outpatient
setting stop using hormonal contraceptives, there is
a clinically relevant reduction of BP and presumably
an improvement in prognosis. The replacement of
the contraceptive method is required in women with
hypertension.
Acknowledgements
This work was supported by the grants CAPES,
CNPq, and FAPERGS, Brazil.
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