IgG4-related disease: neurologic manifestations
Nov. 29, 2022
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According to the Centers for Disease Control and Prevention in 2022, 14% of women aged 15 to 49 use oral contraception, and 10.4% of women aged 15 to 49 use an intrauterine device or contraceptive implant. The association between hormonal contraception and venous thrombosis and thromboembolism is well established, but the relationship between hormonal contraception and arterial complications is more complicated. Overall, hormonal contraception appears to increase the relative risk of ischemic stroke modestly. Although the risk of ischemic stroke secondary to hormonal contraception on a population level remains low, this risk is accentuated in women with migraine with aura and in women who smoke.
• Most physicians recommend discontinuation of hormonal contraception after ischemic stroke.
• Current guidelines recommend blood pressure measurement prior to initiating hormonal contraception in all women.
• Women with migraine with aura who take hormonal contraception have an increased risk (6 times more likely) of ischemic stroke compared to women without migraine who do not take hormonal contraception.
• Hormonal contraceptives should be avoided in women with additional risk factors for ischemic stroke, such as smoking or a previous personal history of thromboembolism.
• Despite an increased risk of ischemic stroke with hormonal contraception, the risk is still lower than the risk of ischemic stroke associated with pregnancy.
The first oral contraceptive pill was approved by the United States Food and Drug Administration in 1960. Soon thereafter, reports began to emerge in the literature of healthy women on oral contraceptives developing cerebrovascular “instances” and “disturbances” (43; 55). A 1973 case-control study of women aged 15 to 44 in academic hospitals in 12 cities in the United States found that 29% of 429 women with stroke were active users of oral contraception compared to approximately 14% of 843 women without stroke (06).
In 1996, the World Health Organization (WHO) Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception, a case-control study across 17 countries that included 2649 women (697 with ischemic stroke), found that the risk of ischemic stroke was significantly higher in current users of oral contraception compared to nonusers (50).
In 2000, the first meta-analysis of studies that examined the risk between oral contraceptive use and ischemic stroke was published (13). Across the 16 studies included, the relative risk of stroke in contraceptive users was notably higher than in nonusers (RR 2.75; 95% CI: 2.23–3.38). However, the authors concluded that the absolute risk increase attributable to oral contraceptives was likely low given the low incidence of stroke among the relevant age group. Importantly, the dose of estrogen has decreased in most oral contraceptives since the era of the included studies.
In 2001, the American Heart Association endorsed a low risk of stroke with low-dose oral contraceptives in women without additional risk factors but noted that oral contraceptives should be avoided in women with additional risk factors, such as smoking or a previous personal history of thromboembolism (15). This recommendation was reiterated in the 2006 and 2011 editions of the guidelines. In 2014, the first specific guidelines for the prevention of stroke in women were published and included a class 3 recommendation that oral contraceptives may be harmful in women with additional risk factors, such as smoking or prior thromboembolic events (04).
Hormonal contraception is a widely used and effective form of birth control. Despite an increased risk of stroke with hormonal contraception, the risk of stroke is still lower than the risk associated with pregnancy and childbirth. This article will review data on the association between stroke and hormonal contraception. Most studies reviewed include combined oral contraceptives, which are combined formulations of estrogen and progesterones. Doses of estrogen and forms of progestin vary depending on the generation of oral contraceptive and the specific formulation. Many of these studies also include some information on transdermal, injectable, and implantable hormonal contraception. These methods of delivery are also discussed, although to a lesser extent given the paucity of high-quality data.
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