Oral Contraceptives and Stroke in



Associated Risk Factors Collaborative Group for the Study of Stroke in Young Women

Oral contraceptive use alone, in the absence of smoking, hypertension, migraine, significantly increases the risk of stroke. Regardless of use or nonuse of these agents, hypertension is a risk factor for development of either thrombotic or hemorrhagic stroke. Regular cigarette smoking and a history of symptoms indicative of migraine also increase the likelihood of one or the other type of stroke, but more information is needed before a definite relationship can be established between these clinical factors and cerebroor

vascular disease.

(JAMA 231:718-722, 1975)

OUR first report on the relation be¬ tween oral contraceptives and stroke in young women concluded that the relative risk for cerebral ischemia or infarction was significantly in¬ creased with the use of these hor¬ mones.1 That report also showed that the relative risk of such strokes from oral contraceptives is greater among white women than in blacks and among younger than older women. It did not, however, provide detailed in¬ formation on the influence of other possible risk factors such as hyperten¬ sion, smoking, or migraine. We now report the effect of these factors indi¬ vidually and when combined with the use of oral contraceptives.

used in this case-control study of oral contraceptives and stroke were de¬ scribed in detail in our first report.1 Five hundred ninety-eight nonpregnant young women (15 to 44 years of age) with stroke were selected from the discharge rosters of 91 hospitals located in 12 cities in the United States. For each of these women, a hospital and a neighbor control matched for age, sex, and race were selected. These three groups of


practices, smoking habits, symptoms of headache, and history of other ill¬



material and methods

See also p 731. interviewed at home by trained interviewers of a polling firm. The interviewer requested de¬ tailed information on contraceptive women were

Interview data were obtained from 73% of all the women and in¬ cluded 430 women with various types of stroke, 429 hospital controls, and 451 neighbor controls. The diagnoses of stroke among the respondents con¬ sidered in this report are distributed nesses.

From the Collaborative Group for the Study of Stroke in Young Women, Data Analysis Center, Durham, NC. For a complete list of participants in this study, see page 722. Reprint requests to Box 3203, Duke University Medical Center, Durham, NC 27710 (Dr.


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follows: 140 women had thrombotic stroke (ie, 116 with cerebral infarc¬ tion and 24 with transient ischemia), and 196 women had hemorrhagic stroke (105 with bleeding congenital aneurysms, 21 with intracerebral hematoma, and 70 with unspecified types of intracranial hemorrhage). In this report, we shall frequently employ, as a summary statistic, the relative risk, which is the factor by which the incidence of an illness is in¬ creased because of the presence of a characteristic that is not universal in the population at risk. Relative risk can be estimated in case-control stud¬ ies of illnesses that have a low inci¬ dence.2 We are also concerned with the simultaneous presence of two characteristics (eg, hypertension and oral contraceptive use) and the way in which they react with each other. If the relative risk associated with their simultaneous presence is essentially the product of the relative risks asso¬ ciated with the individual character¬ istics, we conclude that they do not potentiate each other in influencing the development of the illness. In our first publication,1 the esti¬ mates of relative risk for stroke asso¬ ciated with oral contraceptive use were based primarily on a comparison of the interviewed, matched pairs of cases and controls. In the present analysis, it was necessary to divide the case material into groups accord¬ ing to various risk factors, ie, smok¬ ing, degree of hypertension, and mi¬ graine. To ensure adequate sample as

sizes and to make fullest use of the available data, the matching was ig¬ nored and cases were compared with the hospital or neighbor controls as though they were not matched. This procedure is believed to produce a bias in the estimate of relative risk, with the expected value of the esti¬ mates tending to be closer to 1 than the true values.3 As shown in Table 1, the new values for relative risk for all women with thrombotic stroke using oral contraceptives are 4.1 and 4.4 (comparing cases with neighbor and hospital controls, respectively) in¬ stead of 8.8 and 9.5, which were esti¬ mated from matched pairs in our ear¬ lier publication.1 The new estimates of relative risk for hemorrhagic stroke are approximately 2.0 for each control group, the same value ob¬ tained by the matched case-control pairs. The relative risk of stroke re¬ ported here is an age- and race-ad¬ justed estimate, calculated by taking a weighted average of the log relative risks over six age-race strata, a tech¬ nique described by Sheehe" and Fleiss.5

Table 1.—Type of Stroke, Control Subject, and Use of Oral Contraceptive Agents (OCA) Thrombosis

OCA Nonuser OCA User OCA Nonuser OCA User No. of stroke cases Comparison with hospital controls Control subjects Relative risks Confidence limits Comparison with neighbor controls Control subjects Relative risks Confidence limits

Analyses were made of the inter¬ relationships between the occurrence of stroke, the current use of oral con¬ traceptives, and the presence of hy¬ pertension as determined by the max¬ imum blood pressures noted in the hospital records of the cases and hospital controls (Table 2). Among women with normal blood pressure who are currently using oral contra¬ ceptives, the relative risk of throm¬ botic stroke was 3.1 and of hemorrhagic stroke 1.8. In these calculations, a relative risk of 1.0 is assigned to women who neither used the pill nor had elevation of blood pressure recorded in their hospital charts. A strong positive correlation was also observed between increasing blood pressures and relative risk for either thrombotic or hemorrhagic stroke (Figure). This relationship was noted among women using oral contracep¬ tives, as well as among those not using these agents. The trend ap¬ pears quite clear, with a relative risk for thrombotic stroke rising with the degree of hypertension from 1 to 6.9





340 1.0 0.7-1.5

53 4.4 2.8-6.9

340 1.0 0.7-1.4

53 2.0 1.3-3.2

382 1.0 0.7-1.5

69 4.1 2.6-6.6

382 1.0 0.7-1.5

1.9 1.2-2.9

Table 2.—Oral Contraceptive Use and Highest Blood Pressures in Hospital Controls No. of Stroke Cases

No. of Control



Relative Risk

Confidence Limits

26 17

165 25

1.0 3.1

0.6-1.8 1.5-7.2

11 14

68 14

1.3 5.2

0.6-2.6 2.3-12.0

17 12

37 6

3.6 8.9

1.7-7.5 3.5-22.8

26 12

24 3

6.9 13.6

3.3-14.5 4.8-38.6

Nonuser User Borderline

24 6

165 25

1.0 1.8

0.6-1.8 0.8-4.4

Nonuser User

22 5

68 14

2.2 2.8

1.1-4.3 1.0-7.9

26 8

37 6

5.0 8.4

2.5-9.9 3.0-23.1

72 22

24 3

21.6 25.7

11.1-42.3 9.4-70.7

Thrombotic Stroke Normal blood

pressure* Nonuserf

User Borderline


Nonuser User Moderate


Nonuser User Severe





Nonuser User Hemorrhagic Stroke Normal blood pressure




Nonuser User Severe

hypertension Nonuser User

"Normal blood pressure,

Oral contraceptives and stroke in young women. Associated risk factors.

Oral contraceptive use alone, in the absence of smoking, hypertension, or migraine, significantly increases the risk of stroke. Regardless of use or n...
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