Reproductive considerations and hormonal fluctuations throughout a woman’s life require careful consideration when treating migraine.
Jessica Ailani, MD, FAHS
Migraine has a cumulative lifetime incidence of 43% in women and 18% in men,1 is ranked seventh in global disease burden,2 and is the top cause of disability in people aged 15 to 49 years.2,3 Migraine peaks during reproductive years, so understanding the link between the condition and hormones and how to treat migraine throughout pregnancy, lactation, perimenopause, and menopause is essential for medical providers.
Migraine occurs more frequently in women than in men because of the effects of female sex hormones on migraine pathophysiology.4 In children, the prevalence of migraine is similar in boys and girls, with an increase occurring in women only after puberty and peaking in the fourth decade.5 Changes in estrogen levels have a direct effect on migraine, with menstrual migraine triggered by falling levels of estrogen in the late luteal phase of the menstrual cycle. This fall in estrogen can also cause migraine with use of oral contraceptives with a hormone-free (placebo) interval. During pregnancy, with a rise in estrogen levels, many women with migraine experience an improvement in migraine severity and frequency.6 They will feel this improvement, if it occurs, by the second trimester. During lactation, some notice continued protection from migraine because of the stability of female hormones. However, women may see an increase in migraines during perimenopause because of hormone irregularity,7 and in menopause, many will have a reduction of migraine severity and frequency because of lower levels of female sex hormones.4,8
Unlike migraine without aura, migraine with aura may increase or occur for the first time in pregnancy, as aura can increase with a rise in estrogen.6 Migraine with aura does not generally change during menopause, and historically, aura symptoms become more predominant with age.4 Migraine with aura may also respond differently to exogenous hormones, occasionally being triggered by higher levels of estrogen seen in older formulations of oral contraceptive hormones.
The treatment of migraine during vulnerable time periods, such as pregnancy and lactation, requires an important tool set. Treatment considerations are especially important because medications used for migraine may need to be stopped or changed when the patient becomes pregnant and may need to change again when the patient is lactating. A discussion about pregnancy and lactation and migraine treatment is best prior to a patient’s desire to become pregnant so the physician can put a treatment plan in place for this time.
The safest treatment of migraine in pregnancy and lactation is with lifestyle modifications and behavioral therapy.9 Mild to moderate daily exercise and yoga have been shown to reduce the frequency of migraine attacks. Biofeedback, meditation, and mindfulness all have evidence supporting the prevention of migraine and are safe to learn and use during pregnancy. A discussion on adequate nutrition, hydration, and sleep hygiene during pregnancy is also encouraged prepregnancy.
Lifestyle changes and biofeedback may not be enough to treat an acute migraine attack, so a discussion about acute options is necessary prepregnancy and during lactation. Clinicians need to balance consideration of the use of acetaminophen, metoclopramide, ibuprofen (during lactation), and sumatriptan (or eletriptan in lactation) with potential risks. Newer data indicate that magnesium and compounds containing butalbital may not be safe to use during pregnancy.9
Clinicians may consider neuromodulation devices, particularly the transcutaneous supraorbital stimulator, for both acute treatment and prevention of migraine during pregnancy. While there are no studies of safety in pregnancy for these devices, the relative risk to the fetus is theoretically low.
A small case series is evaluating the safety of peripheral nerve blocks with lidocaine only as treatment of migraine in pregnancy.10 In the 13 cases reported, no adverse outcomes of pregnancy were observed. Clinicians may consider greater occipital block with lidocaine only to treat migraine during pregnancy.10
Preventive medications are generally stopped prior to pregnancy for patients with migraine because, as with most medications, the potential risk of continuing them may outweigh the benefit. In general, women should wait 5.5 half-lives after cessation of medication to become pregnant. If a patient is considering continuing her preventive medication during pregnancy or needs to be started on preventive medication during pregnancy, she should consider a maternal fetal medicine consult for a complete review of safety of medication use throughout pregnancy.
Although migraine can improve in menopause for many women, it may worsen during perimenopause. With rapid fluctuations in hormones during this time, patients may see a rise in the frequency and severity of migraine attacks. Many patients are started on preventive treatments at this time to attempt to reduce migraine frequency. Because hormone irregularity is the cause of more frequent attacks, stabilizing hormones may help migraines. If menses are irregular, use of continuous combined hormonal contraceptives is an option, depending on the patient’s health and smoking status.4 If menses are regular, patients may consider perimenstrual estrogen supplementation.
Hormone replacement therapy (HRT) in patients with migraine may potentially worsen migraine, though study results are inconsistent.4 The goal post menopause in women who have worsening migraine or who need to be on HRT for other reasons is to stabilize estrogen; this lessens the risk of migraine from HRT. For patients who decide to use HRT, nonoral routes of estradiol are less likely to have a negative impact on migraine.4
Migraines throughout a woman’s life can vary and present different challenges in treatment. An ongoing dialogue with your patients throughout life’s stages can help ensure that their needs and concerns are met and addressed.
Jessica Ailani, MD, FAHS, is the director of the MedStar Georgetown Headache Center, and an associate professor of neurology at MedStar Georgetown University Hospital.
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