ACOG Guideline
In 2006, however, the American College of Obstetrics and Gynecology (ACOG) recommended against using combination hormonal contraceptives in patients with migraine with aura. This guideline and some of the studies on which the recommendation was based are problematic, Dr. Calhoun said.
The recommendation stemmed in part from a concern that all women with migraine are at increased risk of stroke if they take combined hormonal contraceptives. That concern was based on a 1996 World Health Organization study that had no US sites. In the study, the majority of stroke cases were smokers and the average age was over 35. In the US, 35 tends to be the age at which physicians—in accordance with ACOG recommendations—no longer prescribe combined hormonal contraceptives for smokers, Dr. Calhoun said. In addition, the majority of the stroke cases were using high-dose pills. The authors concluded that migraine of greater than 12 years’ duration, migraine with aura, and frequent migraine with aura increased the risk of stroke. “But the authors concluded themselves, in no case did corrections for oral contraceptive use alter these observations. It was not a factor,” Dr. Calhoun said.
The ACOG guideline also was based on a Danish population-based case–control study by Lidegaard et al that found a threefold increased risk of ischemic stroke among migraineurs using oral contraceptives. In this study, however, they reported that only 6% of the control group had migraine, whereas 16% to 18% of women in Denmark have migraine—a rate similar to what was seen in the cases. That produced the threefold increased risk reported in the study, Dr. Calhoun said. A similar study in France did not find increased risk among migraineurs using oral contraceptives, but in that study, both controls and migraineurs had the normal frequency of migraine in the population.
Finally, the ACOG recommendation was based on a pooled analysis of two large US case–control studies that found a twofold increased risk of ischemic stroke among migraineurs using oral contraceptives. This finding by Schwartz et al was based on only four cases. The prevalence of migraine was virtually identical among ischemic stroke cases and controls who were using oral contraceptives (7.8% and 7.7%, respectively), but became significant after adjustment for other factors. But a key factor that was not taken into account was use of high-dose (≥ 50 μg EE) pills, Dr. Calhoun said. They were used by only 11 of the 1,564 ischemic and hemorrhagic stroke cases and controls, but accounted for four of the strokes.
Low Doses Appear Safe
Recent studies have had similar findings. A 15-year prospective population-based study by Lidegaard et al in 2012 analyzed 3,300 thrombotic strokes and 1,700 myocardial infarctions in more than 1.6 million women. The overall risk was low, and the absolute risk of thrombotic stroke and myocardial infarction was not increased with 20-μg pills. Pills with doses of 30 μg to 40 μg, however, as much as doubled the risk. “It is still better than the 4.5-times increased risk we had with the 50-μg pills, but we do not want to go there,” Dr. Calhoun said.
A 2013 study by Sidney et al compared a 20-μg oral birth control pill with a 30-μg oral birth control pill, a 20-μg patch birth control product, and a 15-μg ring birth control product. As expected, the 30-μg pill increased risk of thrombotic events, relative to the 20-μg pill, whereas the other products did not, Dr. Calhoun said.
“The argument against using combined hormonal contraceptives in migraine with aura is based on concerns that all women are at increased risk of stroke with oral contraceptives. That is false,” she said. “It is high-dose oral contraceptives that increase the risk.”
—Jake Remaly
Suggested Reading
ACOG Committee on Practice Bulletins-Gynecology. ACOG practice bulletin. No. 73: Use of hormonal contraception in women with coexisting medical conditions. Obstet Gynecol. 2006;107(6):1453-1472.
Calhoun A, Ford S, Pruitt A. The impact of extended-cycle vaginal ring contraception on migraine aura: a retrospective case series. Headache. 2012;52(8):1246-1253.
Hannaford PC, Croft PR, Kay CR. Oral contraception and stroke. Evidence from the Royal College of General Practitioners’ Oral Contraception study. Stroke. 1994;25(5):935-942.
Ischaemic stroke and combined oral contraceptives: results of an international, multicentre, case-control study. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet. 1996;348(9026):498-505.
Lidegaard Ø, Kreiner S. Contraceptives and cerebral thrombosis: a five-year national case-control study. Contraception. 2002;65(3):197-205.
Lidegaard Ø, Løkkegaard E, Jensen A, et al. Thrombotic stroke and myocardial infarction with hormonal contraception. N Engl J Med. 2012;366(24):2257-2266.
MacGregor EA. Contraception and headache. Headache. 2013;53(2):247-276.
Oral contraceptives and stroke in young women. Associated risk factors. JAMA. 1975;231(7):718-722.
Petitti DB, Sidney S, Bernstein A, et al. Stroke in users of low-dose oral contraceptives. N Engl J Med. 1996;335(1):8-15.
Schwartz SM, Petitti DB, Siscovick DS, et al. Stroke and use of low-dose oral contraceptives in young women: a pooled analysis of two US studies. Stroke. 1998;29(11):2277-2284.
Sidney S, Cheetham TC, Connell FA, et al. Recent combined hormonal contraceptives (CHCs) and the risk of thromboembolism and other cardiovascular events in new users. Contraception. 2013;87(1):93-100.
Sulak P, Willis S, Kuehl T, et al. Headaches and oral contraceptives: impact of eliminating the standard 7-day placebo interval. Headache. 2007;47(1):27-37.
Sulak PJ, Scow RD, Preece C, et al. Hormone withdrawal symptoms in oral contraceptive users. Obstet Gynecol. 2000;95(2):261-266.
