BLOOD PRESSURE 1994; 3: 319-321

CASE REPORT

Cardiac and Neurologic Complications in Malignant Hypertension
due to Oral Contraceptive Use
LUIZ APARECIDO BORTOLOTTO, HELIO BERNARDES SILVA and FULVIO PILEGGI
From the Hypertension Unit Heart Institute. Srio Puulo, Bruzil

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Bortolotto LA, Silva HB, Pileggi F. Curdiac and Neurologic Complications in Malignant Hypertension due to Oral
Contracrptiiw Use. Blood Pressure 1994; 3: 319-321.

Malignant hypertension is a rare consequence of contraceptive use. We report here on two young women with
malignant hypertension secondary to contraceptive use whose main symptomatology was neurological. Both
patients had renal failure, severe left ventricle hypertrophy, and hemorrhagic stroke, all reversible after control
of blood pressurc and discontinuation of the contraceptive pill. Key words: malignant hypertension, oral
contruceptiiie, left uentricle hypertrophy, stroke.

INTRODUCTION
Arterial hypertension has been described in association
with oral contraceptives since these were introduced in
the 1960s [ 1-51. Malignant hypertension (MH) is a rare
complication occurring among pill users [6-lo], and
terminal renal failure has been reported in a few cases
[7-lO]. Left ventricular hypertrophy in patients with
M H without a previous history of arterial hypertension
has been described as a rare feature [I I]. Neurological
abnormalities such as stroke have been described in
oral contraceptive users due to the thrombogenic effect
of such contraceptives [12]. However, these complications have not been described in pill users as a first
manifestation of MH. We report here on 2 patients who
had taken modern low-dose combined contraceptive
pills presenting with neurological complications as the
first manifestation of MH, both of them with significant left ventricle hypertrophy and renal failure.

C a s e report 1

A 23-year-old white woman was admitted to hospital
with a 3-day history of headache, mental confusion and
aggressiveness. She had been well and normotensive
until 6 months before when she started to have daily
headaches, and severe arterial hypertension ( I80 x 140
mmHg) had been diagnosed. Antihypertensive therapy
was started, and she was instructed to discontinue oral
contraceptives (ethynylestradiol 30 pg, plus levonorgestrel 150 pg) which she had been taking for one year.
However, she complained about the antihypertensive
drugs and continued to take the pill. She remained well
until one day before admission when she presented with
headache and behavioral changes, becoming aggressive
and confused. On admission her blood pressure was

270/180 mmHg, and an eyes fundus examination
showed papilloedema, exudates and mild hypertensive
vessel changes. There were no localized neurological
signs, only behavioral alterations. Blood urea was 39.6
mmol/l and serum creatinine 309 pmol/l. Intensive
therapy with sodium nitroprusside was started, and 24
h later, after furosemide, propranolol and captopril had
been started, her blood pressure was 140/90 mmHg.
Since she remained aggressive despite control of blood
pressure, a cranial computed tomography scan was
performed which revealed a right temporoparietal
intraparenchymal haematoma (Fig. 1). She then
received intravenous dexamethasone, and after one
week her conscious level returned to normal, with
blood pressure under control. Serum creatinine first
increased to 353.6 pmol/l and decreased to 132.6 pmol/l
after 15 days. An electrocardiogram showed sinusal
rhythm, left atrial enlargement and left ventricle hypertrophy, and an echocardiogram demonstrated severe
concentric left ventricular hypertrophy (SWT= 17 mm,
LVEDD =40 mm, E F = 66%, MI = 280 g/m2).
Further investigation showed no evidence of secondary hypertension: urinary vanilmandelic acid was normal as was isotopic renal scintigraphy, and renal
arteriography demonstrated renal arteries of normal
caliber. A cerebral arteriogram did not show any
aneurysms or other vascular malformations. A renal
biopsy performed after clinical stabilization revealed
malignant nephrosclerosis. At the time of discharge
from hospital, blood pressure was I30/80 mmHg, and
she was prescribed furosemide, propranolol and captopril, and the contraceptive agent was discontinued.
Now 4 years later, the patient maintains normotension
by 3-drug antihypertensive treatment, without any
neurological abnormalities and with normal renal
function (serum creatinine = 106 pmol/l). Regression of

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320

L. A . Bortolotto et al.

Fig. 1. A cranial ct scan revealing a right temporoparietal

intraparenchymalhematoma (white area).

left ventricular hypertrophy (SWT = 1 1 mm, LDD = 40
mm, MI = 120 g/m2) was observed.

Case report 2

A 21-year-old woman was admitted to hospital with
accelerating hypertension. Seven months before she
was submitted to a cesarean section after a normal
pregnancy during which the blood pressure was normal. One month after the delivery she began taking oral
contraceptives (ethynylestradiol30 pg and levonorgestrel 150 pg). Three months later she developed headache and fatigue, and on the day of admission she had
intense headache and vomiting followed by generalized
seizures. She was admitted to an intensive care unit in
coma; her blood pressure was 250/180 mmHg and
serum creatinine was 238.7 mmol/l. The fundi showed
exudates and mild arteriolar narrowing. No focal
neurological signs were observed. She remained comatose for 5 days and her conscious level returned to
normal after control of blood pressure with four
antihypertensive drugs, with no further fits. Ten days
later blood pressure was 160/100 mmHg, blood urea

Fig. 2. Computerized cranial tomography scan showing a
right occiptal intraparenchymal hematoma (white area).

was 53.5 mmol/l, serum creatinine 247.5 pmol/l, creatinine clearance 54 ml/min, urinary sediment was normal
and 24 h proteinuria was negative. Both electrocardiogram and echocardiogram revealed left ventricular
hypertrophy (SWT= 13 mm; LEDD=49 mm;
E F = 72%; MI = 190 g/m2). Investigation for a secondary cause of hypertension was negative.
Neurological examination disclosed left temporal
and right nasal hemianopsia and a disordered gait.
Electroencephalographic examination revealed diffuse
sharp-wave activity predominantly in the temporal
area. A computed tomographic scan showed a right
occipital intraparenchymal hematoma (Fig. 2), and
cerebral arteriography showed a mild medial rightward
shift of the right posterior cerebral artery but no further
vascular malformations. At the time of discharge from
hospital her blood pressure was 140/95 mmHg, she was
prescribed furosemide, propranolol and captopril, and
the contraceptive agent was discontinued. Three years
later, the patient is now normotensive on a single
antihypertensive drug, with improvement of renal
function and neurological alterations and regression of
left ventricle hypertrophy (SWT = 10 mm; LEDD = 40
mm; MI = 100 g/m2).

Malignant hypertension due to oral contraceptive use

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DISCUSSION
The association between oral contraceptives and arterial hypertension was first suggested in 1962 by Brownrigget al. [l], but it was well defined only later by Woods
[2] and Weir [3]. Over the following years, many studies
have described a variable incidence of arterial hypertension. In the RCGP-OC Study [4] the prevalence of
hypertension in 1,000 women-years ranged from 8.19 to
13.88% depending on higher doses of progesterone and
fixed doses of estrogens. In another study, Spellacy &
Birk [5] reported an incidence of 0% to 7% according to
the doses of progesterone and estrogen used. In most of
these studies, arterial hypertension was mild to moderate and they demonstrated reversal to normal levels
after 3 months of withdrawal of the pill. However,
severe and malignant hypertension has been described
in a few reports, the first of them published in 1969 by
Harris [6]. The mechanism whereby the contraceptive
pill causes malignant hypertension remains unknown
but some hypotheses have been put forward such as an
extreme example of the varied increase by pressor
effects of estrogens or progestagens or thrombosis of
either the main or intrarenal arteries.
Although the association between malignant hypertension and oral contraceptive is well recognized, the
number of reported cases is small and the clinical
features and prognoses are uncertain. The most recent
study published in 1987 by Lim et al. [lo] reported that
1 I of 34 malignant hypertensive women studied were
taking oral contraceptives. Renal impairment was
infrequent in this group, probably explaining the
excellent prognosis obtained by these investigators
(90% of the subjects surveyed over 10 years). Among
the most common complications of malignant hypertension, terminal renal failure was the only one
reported in the above studies, whereas left ventricular
hypertrophy was not reported. In the present study,
both patients had severe left ventricular hypertrophy
due to malignization of hypertension, and regression
occurred during the follow-up in parallel with blood
pressure control. Neurological complications such as
stroke have been reported [ 121in users of the contraceptive pill, but in most cases the event is associated with
coagulation disturbances more than with hypertensive
complications. These neurological complications have
not been described as a first manifestation of M H in pill
users, although they are well recognized in M H due to
other causes. Both women reported here had a hemorrhagic cerebral accident as a complication of malignant
hypertension and the clinical manifestations were similar to those reported by others. Cerebral tomography

321

was an important complementary examination for a
definitive diagnosis.
In conclusion, despite its low incidence, malignant
hypertension due to oral contraceptive use can be
prevented by effective control of the blood pressure.
Neurological, renal and cardiovascular complications,
although infrequent, d o occur but are reversible after
long term treatment.
REFERENCES
1. Brownrigg GM. Arterial hypertension related to oral
contraceptive use. Can Med Assoc J 1962; 87: 408.
2. Woods JM. Oral contraceptives and hypertension.
Lancet 1967; 2: 653-4.
3. Weir RJ, Briggs E, Mack A, Naismith L, Taylor L,
Wilson E. Blood pressure in women taking oral contraceptives. BMJ 1974; 1: 533-5.
4. Royal College of General Practitioner’s oral contraception study: further analysis of mortality in oral contraceptive users. J Roy Coll Gen Pract 1981; 1: 541-6.
5. Spellacy WN, Birk SA. The effect of intrauterine devices,
oral contraceptives, estrogens, and progestogens on
blood pressure. Am J Obstet Gynecol 1972; 112: 91 2-6.
6. Harris PWR. Malignant hypertension associated with
oral contraceptives. Lancet 1969; 2: 466-7.
7. Zacherle RJ, Richardson JA. Irreversible renal failure
secondary to hypertension induced by oral contraceptives. Ann Intern Med 1972; 77: 83-5.
8. Dunn FG, Jones JV, Fife R. Malignant hypertension
associated with use of oral contraceptives. Br Heart J
1975; 37: 336-8.
9. Zech P, Rifle G, Lindner A, Sassard J, Blanc-Brunat N,
Traeger J. Malignant hypertension with irreversible renal
failure due to oral contraceptives. BMJ 1975; 4: 326-7.
10. Lim G, Isle CG, Hodsman GP, Lever AF, Robertson
JWK. Malignant hypertension in women of childbearing
age and its relation to the contraceptive pill. BMJ 1987;
294: 1057-9.
I I . Shapiro LM, Mackinnon J, Beevers DG. Echocardio-

graphic features of malignant hypertension. Br Heart J
1981; 46: 374-9.
12. Collaborative Group for the Study of Stroke in Young
Women. Oral contraception and increased risk of cerebral ischemia or thrombosis. N Engl J Med 1973; 288:
871-8.
13. Woods JW. Oral contraceptives and hypertension.
Hypertension 1988; 2 (Suppl 2): 11-1 1-15.
14. Beaumont V, Beaumont JL. The vascular risk of oral

contraceptives. Reality and mechanism. Presse Med
1989; 18: 1249-53.
Submitted August 16. 1993: accepted October 20, 1993
Address.for correspondence:
Luiz A Bortolotto
Unidade de Hipertensao lnstituto do Coracao
Av. Dr. Eneas de Carvalho Aguiar 44

SBo Paulo

Brazil CEP 05403-000
Fax: +55 1 I 8815048