Low-dose OCs not linked with stroke risk

Findings from a new Australian study indicate that use of modern, low-dose oral contraceptives (OCs) containing 50 mcg estrogen or less do not appear to appreciably raise the risk of ischemic stroke in healthy women.1

Early evidence in the mid-1970s linked OC use to increased risk for stroke; however, studies with low-dose pills in the 1980s and 1990s have suggested less overall risk.2 Despite the data, uncertainly about stroke risk associated with pill use has remained, says Sasitorn Siritho, MD, who served as a stroke research fellow at the National Stroke Research Institute in Melbourne, Australia, where the current research was conducted. Ischemic stroke is the type of stroke in which a blood clot blocks an artery supplying the brain.

"This study is important as another piece of data about low-dose oral contraceptives and ischemic stroke," observes Diana Petitti, MD, MPH, director of research and evaluation for Pasadena-based Kaiser Permanente Southern California, a group-practice health maintenance organization. "Data from U.S. studies3,4 found no increase in the risk of ischemic stroke in current OC users; whereas studies done by the World Health Organization (WHO), the Transnational Study and, more recently, the Risk of Arterial Thrombosis in Relation to Oral Contraceptives (RATIO) study5,6,7 all reported increases in the risk of ischemic stroke in current OC users." (Review research highlights in previous Contraceptive Technology Update articles: "Ischemic stroke risk low for OC users," April 1998, p. 47; "Low-dose OCs don’t increase stroke risk," December 1996, p. 148.)

Petitti, who has conducted research on the subject, says her assessment of the literature now leads her to believe that use of low-estrogen dose oral contraceptive in women without hypertension does not increase the risk of ischemic stroke, with the risk slightly elevated in women who are heavy smokers. She also sees no documented differences in the risk of stroke between users of low-estrogen formulations with different progestins.

Look at the study

In the new study, researchers at four large Melbourne, Australia, hospitals matched 234 women ages 15-55 who had a stroke between 1984 and 1996 to 234 women recruited from the same geographic areas as the stroke patients. Detailed personal interviews were conducted, including family medical histories and lists of previous and current medications.

Researchers found that women who reported currently using pills with fewer than 50 mcg of estrogen seemed to be at no greater risk of ischemic stroke. In addition, there was no association between the number of years a woman had taken OCs and the risk of stroke. Although the odds ratio of stroke was 1.76 for women who used low-estrogen pills, that number did not reach the level of statistical significance, researchers report.

Factors associated with an increased risk of ischemic stroke were a history of hypertension, transient ischemic attack, previous myocardial infarction, or diabetes mellitus; family history of stroke; and smoking more than 20 cigarettes per day.

What’s the next step?

The next step in research should focus on the risk of stroke in women using newer generation of pills, says Siritho. Researchers in the Australian study were unable to describe which of the drugs that contained 50 mcg ethinyl estradiol also contained varying doses of norethindrone, lynestrenol, and ethynodiol diacetate.

The question of differences in stroke risk between low-estrogen OCs containing different progestins is an important one, Petitti agrees.

"A possible reason for the difference between the WHO/European studies and the U.S. studies is that there is a difference in the risk of stroke between low-estrogen OCs with levonorgestrel compared with those containing progestins that are in the estrane class," observes Petitti. "In the WHO and European studies, the use of low-estrogen OCs with an estrane was very infrequent, whereas these OCs are commonly used in the U.S."

Further research is needed to examine stroke risks in women with migraines, says Siritho. Several studies have found that OC users with a history of migraine are two to four times more likely to have an ischemic stroke than nonusers with a similar medical history.3,8

The increased risks involved with combined pill use and migraines with focal neurologic symptoms led the WHO in 2000 to revise its medical eligibility criteria to state that combined oral contraceptives should not be initiated in women of any age with the medical condition.9

According to the www.managingcontraception.com web site organized by Tiger, GA-based Bridging the Gap Foundation, focal neurologic symptoms include spots in front of one’s eyes, blurred vision, loss of vision (or partial loss of vision), weakness in an arm or a leg, slurred speech or an aura (sense) before headache onset that such pain is oncoming.10 Alternative contraceptive options for these women include progestin-only methods such as the mini-pill and quarterly contraceptive injection.10

References

1. Siritho S, Thrift AG, McNeil JJ, et al. Risk of ischemic stroke among users of the oral contraceptive pill: The Melbourne Risk Factor Study (MERFS) Group. Stroke 2003; 34:1,575-1,580.

2. Thorogood M. Stroke and steroid hormonal contraception. Contraception 1998; 57:157-167.

3. Schwartz SM, Petitti DB, Siscovick DS, et al. Stroke and use of low-dose oral contraceptives in young women: A pooled analysis of two U.S. studies. Stroke 1998; 29:2,277–2,284.

4. Petitti DB, Sidney S, Bernstein A, et al. Stroke in users of low-dose oral contraceptives. N Engl J Med 1996; 335:8-15.

5. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Ischaemic stroke and combined oral contraceptives: Results of an international, multicentre, case-control study. Lancet 1996; 348:498-505.

6. Heinemann LA, Lewis MA, Spitzer WO, et al. Thromboembolic stroke in young women: A European case-control study on oral contraceptives: Transnational Research Group on Oral Contraceptives and the Health of Young Women. Contraception 1998; 57:29-37.

7. Kemmeren JM, Tanis BC, van den Bosch MA, et al. Risk of Arterial Thrombosis in Relation to Oral Contraceptives (RATIO) study: Oral contraceptives and the risk of ischemic stroke. Stroke 2002; 33:1,202-1,208.

8. Chang CL, Donaghy M, Poulter N, et al. Migraine and stroke in young women: Case-control study. BMJ 1999; 318:13-18.

9. World Health Organization, Department of Reproduc-tive Health and Research. Medical Eligibility Criteria for Contraceptive Use. Second ed. 2000. Accessed at www.who.int/reproductive-health/publications/RHR_00_2_ medical_eligibility_criteria_second_edition/rhr_00_2_acknowledgments.html.

10. Hatcher RA. "I stopped pills because of migraine headaches — what next?" Questions and Answers. Accessed at www.managingcontraception.com.