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    Migraines in Women

    Fluctuating hormones play a role in migraines, making it important to consider hormonal milestones and factors when formulating a treatment plan.

     

    Pregnancy

    Management of migraine in pregnancy remains challenging because the goal is to decrease migraine-related disability and prevent fetal exposure to potentially teratogenic medications. The majority of women, up to 60%, will experience a decrease in migraine frequency during pregnancy.10 The most significant improvement in frequency is seen in women who have menstrual migraine. In some women, migraine frequency increases during the first trimester, but increasing levels of estrogen and absence of hormonal fluctuations are credited for decreased migraine frequency in the second and third trimesters.11, 12 Patients with migraine with aura are less likely to notice a decrease in frequency.10 New-onset migraine in pregnancy – occurring in up to 7% of pregnancies – usually occurs during the first trimester and most often with aura.10,13 Women who continue to experience migraine attacks throughout pregnancy may require treatment but it is important to remember that not all medications used for migraine are safe in pregnancy.

    Acetaminophen, which is FDA category B, is the medication of choice for headache in pregnancy but it’s efficacy in migraine remains limited. NSAIDS can also be used under certain circumstances, though their use in the first and third trimesters is associated with specific risks and contraindications including oligohydramnios, premature closure of the ductus arteriosis, and bleeding complications. Triptans remain FDA category C, meaning that risk to humans has not been ruled out. The Sumatriptan, Naratriptan, and Treximet Pregnancy Registry, which included 528 outcomes of exposure in the first trimester to sumatriptan, detected no signal of teratogenicity associated with major birth defects.15 Although these data are reassuring, no triptan registries with large-scale sample populations are available.

    Opiates carry a category B rating and may be used during pregnancy, but frequent use is associated with concern for rebound headaches and dependence. Antiemetics, diphenhydramine, and corticosteroids are considered safe and may be effective for acute management of migraine. For women with high-frequency migraine who require daily prevention, memantine and cyproheptadine are considered Category B, and amitriptyline and beta blockers are considered Category C (Table 4).15,16 Current standard references such as those available via the FDA, the American Academy of Pediatrics, and Hale’s reference Medications and Mother’s milk should be consulted for current recommendations. (The FDA has determined that use of letter categories for drugs will be abolished and each drug will have a list of known and unknown risk findings. For the purposes of ease of communication in this article these categories were maintained.)

    Migraines should be considered a potential risk factor in obstetrics because there is increasing evidence that migraine is a risk factor for vascular complications during pregnancy, including gestational hypertension and preeclampsia, stroke, myocardial infarction, and venous thromboembolism.16 Further research is warranted to understand the mechanisms underlying increased risk of vascular disease in pregnant migraineurs.

    Menopause

    Fluctuating hormone levels during the transition to menopause can result in an increase in migraine frequency and disability. Research suggests that women who are predisposed to migraine due to fluctuating hormone levels, such as those who have a history of menstrually related migraine, pure menstrual migraine, onset of migraine with pregnancy or contraceptive use, are more likely to have worsening of migraine in perimenopause.17 Unlike perimenopause, during which hormone fluctuations are significant, menopause is characterized by hormonal stability due to decline in production of estrogen and progesterone, which results in a decrease in frequency, intensity, and disability associated with migraine.17 Studies suggest that 62% of prior headache sufferers report a decrease in headache post-menopause and only 14% of menopausal women report having headaches.18 Characteristics of women who experience migraine in menopause are a younger age at menopause, have a history of surgical menopause, and regular use of cigarette or daily use of alcohol.18 Previous use of combined hormonal contraceptives (CHCs) and current use of hormonal therapy also increase risk of postmenopausal migraine.18

    Management of postmenopausal migraine includes use of low-dose hormones. If used continuously, these drugs typically do not increase migraine frequency but the effect of post-menopausal hormone therapy on migraine is unpredictable. In patients who are particularly sensitive to exogenous hormones, postmenopausal hormone therapy may increase migraine frequency. Transdermal preparations have been shown to be less likely to exacerbate migraine.17 Preventative medications such as beta blockers, calcium channel blockers, topiramate, or valproate should be used for women who have frequent migraine episodes whereas acute treatments such as NSAIDs, triptans, and combination analgesics should be optimized with the goal of pain freedom in 2 hours. Comorbid conditions should be considered when using both preventative and acute treatment so that triptans and erogotamines are avoided in patients who have hypertension and heart disease.

    CHCs and stroke

    There remains a clear concern regarding use of CHCs, migraine, and stroke. Although the absolute risk of stroke across the overall migraine population is relatively low, it is well defined and increased in women who have a high frequency of migraine with aura, are older than age 35, or who use OCs and smoke.19 Women with migraine with aura have a 1.5 times higher risk of ischemic stroke; women with migraine with aura who smoke and use OCs have a 7.0 times higher risk of stroke.20

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    The relationship between CHC use and stroke appears to be dose-dependent, with pills containing more than 50 mcg of estrogen conferring the greatest risk.21 The American College of Obstetricians and Gynecologists recommends that clinicians consider use of progestin-only pills (POPs), intrauterine or barrier contraceptives for women who have migraine with aura, those who smoke and who are age 35 or older.22 Use of POPs, implants, depot medroxyprogesterone acetate, and the progestin intrauterine device do not result in an increased risk of stroke and they are considered to be safe in women with migraines.21 The copper intrauterine device also is considered safe for women with migraines.21 Migraine without aura appears to have a minimal effect on ischemic stroke risk so CHCs are a contraceptive option for women with migraine without aura.23

    Summary

    Migraines in women are impacted by the hormonal fluctuations they experience throughout their lives. Menstrual migraines, pregnancy-related headache and the impact of menopause on migraine all support the role of hormonal changes in migraine frequency and explain the increased frequency of migraine in women in general. Management of migraine throughout a woman’s life should consider hormonal milestones and factors, which at times may require hormonal manipulation in addition to optimizing abortive, preventative and alternative treatments. Recognizing hormonal triggers allows for optimizing the treatment plan to more effectively control migraine, which is the ultimate goal of treatment.

    REFERENCES

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    2. Steiner TJ, Stovener LJ, Vos T. GBD 2015: migraine is the third cause of disability in under 50s. Journal of Headache and Pain. (2016) 17:104.

    3. Ward TN. Migraine diagnosis and pathophysiology. Continuum (Minneap Minn). 2012 Aug;18(4):753-63.

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    10. Kvisvik EV, Stovner, LJ, Helde G, Bovim G, Linde M. Headache and migraine during pregnancy and puerperium: the MIGRAstudy. J Headache Pain (2011) 12:443–451.

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    17. Ripa P, Ornello R, Degan D, et al. Migraine in menopausal women: a systematic review. Int J Womens Health. 2015 Aug 20;7:773-82.

    18. Brandes JL. The influence of estrogen on migraine: a systematic review. J Am Med Assoc. 2006; 295(15):1824-1830.

    19. De Falco FA, De Falco A. Migraine with aura: which patients are most at risk of stroke? Neurol Sci. 2015 May;36 Suppl 1:57-60.

    20. MacClellan LR, Giles W, Cole J, et al. Probable migraine with visual aura and risk of ischemic stroke: The Stroke Prevention in Young Women Study. Stroke. 2007;38:2438-2445.

    21. Harris M, Kaneshiro, B. An evidence-based approach to hormonal contraception and headaches. Contraception. 2009; 80: 417-421.

    22. Noncontraceptive use of hormonal contraceptives. Practice Bulletin No 110. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2010;155:206-18.

    23. MacGregor EA. Contraception and Headache. Headache. 2013;53:247-276.

    Kavita Kalidas, MD
    Dr Kalidas is Assistant Professor, Department of Neurology, and Director, Division of Headache Medicine, University of South Florida, ...

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