Headache and Combination Estrogen-Progestin Oral Contraceptives: Integrating Evidence, Guidelines, and Clinical Practice

Elizabeth W. Loder; Dawn C. Buse; Joan R. Golub


Headache. 2005;45(3):224-231. 

In This Article

Case 2

A 38-year-old woman consults a new physician 6 months after beginning COC use. Shortly after starting OCs, she began to experience headaches twice a week lasting 12 to 16 hours. The headaches are bilateral, throbbing, and accompanied by nausea and sensitivity to light and sound. They are preceded by a 45-minute visual disturbance consisting of a "bright, shimmering, zigzag line" that enlarges, moves to the periphery of her visual field and then fades away as the headache begins. Upon questioning, she reports occasional similar headaches prior to OC use that were "not as bad." The visual disturbance associated with the headache is new. Her neurologic examination is normal. The patient smokes 1 pack per day of cigarettes.

The prescribing information for combination estrogen-progestin OCs typically lists "migraine with focal neurologic symptoms" as a contraindication to the use of OCs and states that "the onset or exacerbation of migraine or development of headache with a new pattern which is recurrent, persistent, or severe requires discontinuation of OCs and evaluation of the cause."[20]

Safety. Migraine with aura is a statistically independent risk factor for ischemic stroke, as is OC use. The risk of stroke in women who have migraine with aura is increased by a factor of about 6 to 8, and further increased in the presence of other risk factors. Women with migraine who smoke 1 or more packs of cigarettes per day raise their risk by a factor of about 10. If they also use OCs, the odds ratio for stroke is elevated to 34.[8,9,10,21]

Tolerability. There is some evidence that the risk of headache worsening or onset is greater in women who have migraine with aura compared with those who have migraine without aura, with an odds ratio of around 4.[22] There have been suggestions that exogenous estrogen may precipitate aura or cause it to increase in frequency. Evidence also suggests that the risk of developing headache with OC use is higher in patients over 35 years of age.[23,24]

Guidelines. Because of concerns about the interaction of two risk factors for stroke (OC use and migraine with aura), WHO and ACOG guidelines recommend that women who experience migraine with focal neurological symptoms not use OCs (see Table 1 ). These guidelines also suggest that the risks of OC use are "unacceptable" or "outweigh the benefits" if a woman is a smoker, over the age of 35, has uncontrolled hypertension, a history of stroke, or has had breast cancer within the past 5 years. It is not entirely clear why WHO and ACOG guidelines view age 35 as a threshold beyond which OC use is unacceptable. In the case of stroke risk attributable to migraine, it is actually women under 45 whose stroke risk is elevated. There is no evidence that migraine is a risk factor for ischemic stroke in women over 45.[9]

A task force convened by the International Headache Society to assess the use of OCs in women with migraine concluded that "there is a potentially increased risk of ischemic stroke in women with migraine who are using COCs and have additional risk factors which cannot easily be controlled, including migraine with aura. One must individually assess and evaluate these risks. Combined oral contraceptive use may be contraindicated" ( Table 2 ). The task force also concluded that "an increase in attack frequency or severity with OCs is itself an indication for stopping OC, whether or not it is associated with an increased risk of stroke. A change in the character of attacks after starting OC use is possibly of greater concern, but the evidence is conflicting. The thresholds of migraine severity and frequency that represent the contraindication or discontinuation of OCs are still to be determined, and are different for migraine with and without aura... Migraineurs who smoke heavily or have multiple thrombotic risk factors should be advised not to take COCs. When patients with migraine are placed on COCs they should be carefully monitored. If migraines worsen or if there is new-onset migraine related to OC use, one should take into account the patient's age, the type of migraine, the frequency and severity of attacks, and the presence of other vascular risk factors... One must be more restrictive in women with migraine with aura, in smokers, and in older women, as the risk of stroke is higher in these individuals. Any unusual headache that has a sudden onset, a long duration, or is associated with focal neurologic symptoms that differ from typical aura should prompt the immediate discontinuation of OCs, and appropriate neurologic investigations to rule out a cerebrovascular complication should be considered."[18]

This patient has a history of occasional migraine without aura that was not recognized prior to beginning OC use. Migraine without aura by itself is not a contraindication to OC use, but this patient has additional stroke risk factors of age and smoking. Coincident with OC use, her headaches have increased in frequency and are now associated with neurologic accompaniments that meet diagnostic criteria for aura. In general, a worsening of headaches, either in severity or frequency, or the new onset of headaches or neurologic accompaniments to headache requires further evaluation.

For this patient, it would be prudent to use other forms of birth control. A progestin-only pill, subdermal implants, or injectable contraception could also be used. However, this decision must be weighed with care if the patient has factors that might predispose her to a high-risk pregnancy should she use a less-effective contraceptive method and conceive. The patient should be encouraged and assisted to discontinue smoking. If headaches do not improve promptly following OC discontinuation, this patient should be referred to a neurologist or headache specialist for treatment.


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