ArticlesHaemorrhagic stroke, overall stroke risk, and combined oral contraceptives: results of an international, multicentre, case-control study
Introduction
Although the association between use of oral contraceptives (OCs) and cerebral infarction was established in case-control1, 2, 3, 4, 5, 6, 7, 8, 9, 10 and cohort studies11, 12, 13, 14, 15 during the 1960s and 1970s, the effect of OC use on risk of haemorrhagic stroke—the most common type of stroke in women of reproductive age—was less well established in these studies. Most studies of haemorrhagic stroke have focused on subarachnoid haemorrhage (the most common type of haemorrhagic stroke in these women), but these data are controversial9, 12, 16, 17 and there is no consensus about the association between risks of fatal and non-fatal subarachnoid haemorrhage and current and past use of OCs.
The findings of previous studies of the effect of OC use on risks of haemorrhagic stroke are limited because of the small numbers of participants and inadequate differentiation of stroke type. The aim of the WHO collaborative, case-control study was to assess the association between current use of combined OCs and haemorrhagic stroke and to provide an overall assessment of current OC use and risk of all types of stroke.18
Section snippets
Patients and methods
Details of study methods have been published elsewhere.18, 19, 20 Haemorrhagic strokes were classified as subarachnoid, intracerebral, or undifferentiated. A diagnosis of subarachnoid haemorrhage was made when computed tomography (CT) or magnetic resonance imaging (MRI) showed blood in the subarachnoid space. When a CT or MRI scan was not done or reported as normal, the diagnosis could be made if the clinical presentation was compatible with a diffuse neurological disorder with typical signs of
Results
1083 (48·3%) of the 2242 strokes studied were haemorrhagic (table 1). One case from Europe and nine from the developing countries were excluded from all subsequent analyses, because their OC status was not known. Five further cases were excluded because no matched controls had been recruited. 2910 controls were matched to the 1068 cases—an average of 2·6 controls per case in Europe and 2·8 controls per case in the developing countries.
Cases and controls had similar mean body-mass index, number
Discussion
Overall, current use of combined OCs was associated with a slightly increased risk of haemorrhagic stroke; this increased risk was significant in the developing countries but not in Europe. There was no increase in risk of haemorrhagic stroke in younger women in either group of countries, whereas for older women the odds ratios were above 2. The major risk factors for haemorrhagic stroke were a history of high blood pressure (detected outside pregnancy), hypertension during pregnancy, a family
Overall risk of stroke
The separate assessment of the risks of haemorrhagic and ischaemic strokes associated with use of combined OCs is of scientific and clinical importance. However, for women using or contemplating the use of OCs, the overall risk of stroke of any type is a more important consideration. Based on analyses of 2198 cases of any kind of stroke and 6086 matched controls whose OC use was known, and for whom complete information was available on confounding variables (a history of hypertension and
References (31)
- et al.
Oral contraceptives and stroke: a preliminary report on an epidemiologic study in Taiwan, China
Int J Gynecol Obstet
(1986) Epidemiology of stroke
Lancet
(1992)- et al.
Investigation of deaths from pulmonary, coronary and cerebral thrombosis and embolism in women of child-bearing age
BMJ
(1968) - et al.
Investigation of relation between use of oral contraceptives and thromboembolic disease: a further report
BMJ
(1969) - et al.
Thromboembolism and oral contraceptives: an epidemiological case control study
Am J Epidemiol
(1969) - et al.
Ischaemic cerebrovascular disease in young adults
Acta Neurol Scand
(1973) Oral contraceptives and stroke in young women
JAMA
(1975)- et al.
Oral contraceptives and non-fatal stroke in healthy young women
Ann Intern Med
(1978) - et al.
Stroke before 55 years of age at Karolinska Hospital 1973–77: a study of 388 well-defined cases
Acta Neurol Scand
(1984) - et al.
Fatal stroke and use of oral contraceptives: findings from a case-control study
Am J Epidemiol
(1992)
Oral contraception and risk of a cerebral thromboembolic attack: results of a case-control study
BMJ
The Walnut Creek contraceptive study. Centre for Population Research Monograph Number 81–564
Further analysis of mortality in oral contraceptive users
Lancet
Incidence of arterial disease among oral contraceptive users
J R Coll Gen Practitioners
Oral contraceptives and stroke: findings in a large prospective study
BMJ
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Writing committee given at end of article