The early studies of Longstreth and Swanson and of Vessey and associates indicated that women who take oral contraceptives in the childbearing years—particularly if they are older than 35 years of age and also smoke, are hypertensive, or have migraine—are at increased risk of cerebral infarction. Stroke in these cases is usually a result of arterial occlusion, occurring in both the carotid–middle cerebral and vertebrobasilar territories and sometimes to occlusion of cerebral veins. In most of the reported fatal cases, the thrombosed vessel has been free of atheroma or other disease. The vascular lesion underlying cerebral thrombosis in women taking oral contraceptives was studied by Irey and colleagues. It consists of nodular intimal hyperplasia of eccentric distribution with increased acid mucopolysaccharides and replication of the internal elastic lamina. Similar changes have been found in pregnancy and in humans and animals receiving exogenous steroids, including estrogens. These observations, coupled with evidence that estrogen alters the coagulability of the blood, suggest that a state of hypercoagulability is the important factor in the genesis of contraceptive-associated infarction.
Mainly at increased risk of stroke are women taking high-dose (0.50-mg) estrogen pills; in recent years, lowering the estrogen content has substantially reduced, but not eliminated, this risk. The use of progestin-only pills or of subcutaneously implanted capsules of progestin has not been associated with stroke as far as can be currently determined (Petitti et al). The epidemiologic study reported by Lidegaard and colleagues puts the risk of hormonal contraception in perspective; in a large cohort of Danes, the risks of thrombotic strokes and myocardial infarction over 15 years was very low with estradiol-containing compounds but it increased with age and with the dose of estradiol. It has also become apparent that mutations of the prothrombin gene are more frequent in patients who have cerebral venous thrombosis while on oral contraceptive pills than they are in the general population. Martinelli and associates propose that these genetic abnormalities account for 35 percent of idiopathic cases of cerebral vein thrombosis; and they have contended that contraceptives increase this risk 20-fold.
Stroke in Pregnancy and the Postpartum Period
In addition to the eclamptic-hypertensive state, there is an increased incidence of cerebrovascular events during pregnancy and the postpartum period. The risk of both cerebral infarction and intracerebral hemorrhage appears to be mainly in the 6-week period after delivery rather than during the pregnancy itself (Kittner et al). Fisher (1971) reviewed the literature and analyzed 12 postpartum, 9 puerperal, and 14 contraceptive cases, as well as 9 patients receiving estrogen therapy; arterial thrombosis was demonstrated in half of these cases. Most of the focal vascular lesions during pregnancy were a result of arterial occlusion in the second and third trimesters and in the first week after delivery. Venous occlusion tended to occur 1 to 4 weeks postpartum. In Rochester, New York, the incidence rate of stroke during pregnancy was 6.2 per 100,000, but it doubled with each advance in age from 25 to 29, 30 to 39, and 40 to 49 years (Wiebers et al 1985). Included in most past series are cases with cardiac disease, particularly valve-related embolism. It is perhaps surprising that subarachnoid hemorrhage is not more frequent during the Valsalva activity of childbirth. Carotid artery dissection may also be encountered late in pregnancy or soon after delivery.