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Migraine Throughout the Female Reproductive Life Cycle

      Abstract

      By the end of their reproductive life cycle, roughly 40% of women have experienced migraine. Women have certain times of vulnerability for migraine that relate to abrupt declines in estrogen levels. Specifically, the prevalence of migraine is higher after menarche, during menstruation, during the postpartum period, and during perimenopause, but it is commonly lower during the second and third trimesters of pregnancy and the postmenopausal years. Therapeutic strategies for migraine management include hormonal manipulation aimed at eliminating or minimizing the decreases in estrogen that trigger the especially severe menstrual-related attacks. This article reviews special considerations for triptan use in pregnant and lactating women and in women with high risk for cardiovascular disease. Health care professionals caring for women throughout their life span should be aware of these important sex-based differences in migraine and migraine management.

      Abbreviations and Acronyms:

      CHC (combined hormonal contraception), EE (ethinyl estradiol), HCP (health care professional), MRM (menstrual-related migraine)
      CME Activity
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      Learning Objectives: On completion of this article, you should be able to (1) describe the epidemiology of migraine in women, (2) describe the reproductive factors that influence the course of migraine in women, and (3) effectively treat migraine in women, including menstrual-related migraine, migraine during pregnancy and lactation, and migraine that worsens in the menopausal transition.
      Disclosures: As a provider accredited by ACCME, Mayo Clinic College of Medicine and Science (Mayo School of Continuous Professional Development) must ensure balance, independence, objectivity, and scientific rigor in its educational activities. Course Director(s), Planning Committee members, Faculty, and all others who are in a position to control the content of this educational activity are required to disclose all relevant financial relationships with any commercial interest related to the subject matter of the educational activity. Safeguards against commercial bias have been put in place. Faculty also will disclose any off-label and/or investigational use of pharmaceuticals or instruments discussed in their presentation. Disclosure of this information will be published in course materials so that those participants in the activity may formulate their own judgments regarding the presentation.
      In their editorial and administrative roles, Karl A. Nath, MBChB, Terry L. Jopke, Kimberly D. Sankey, and Jenna M. Pederson, have control of the content of this program but have no relevant financial relationship(s) with industry.
      Dr Faubion is a consultant for Mithra Pharmaceuticals and Procter & Gamble Co. Dr Calhoun is a consultant for Amgen, Depomed, and electroCore; is on the speaker's bureaus for Avanir, Depomed, Promius Pharma, Supernus and Teva and has received research support from Allergan, Autonomic Technologies, Capnia, and Scion NeuroStim.
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      By the end of their reproductive life cycle, roughly 40% of women have experienced migraine. Migraine is 3 times more common in women than in men, and worldwide, roughly one-fourth of reproductive-aged women have migraine. Of those who seek headache treatment from their health care professional (HCP), more than 90% meet diagnostic criteria for migraine,
      • Tepper S.J.
      • Dahlöf C.G.
      • Dowson A.
      • et al.
      Prevalence and diagnosis of migraine in patients consulting their physician with a complaint of headache: data from the Landmark Study.
      yet the majority do not receive a correct diagnosis. In one review, 46% of persons with migraine in the United States thought they had a sinus headache, and 32% thought they had a tension headache.
      • Lipton R.B.
      • Stewart W.F.
      • Diamond S.
      • Diamond M.L.
      • Reed M.
      Prevalence and burden of migraine in the United States: data from the American Migraine Study II.
      When patients with chronic migraine consult an HCP who is not a headache specialist, only 16% receive a correct diagnosis.
      • Adams A.M.
      • Serrano D.
      • Buse D.C.
      • et al.
      The impact of chronic migraine: the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study methods and baseline results.
      The International Classification of Headache Disorders criteria for diagnosis of migraine are summarized in Table 1.
      Headache Classification Committee of the International Headache Society (IHS)
      The International Classification of Headache Disorders, 3rd edition (beta version).
      Table 1International Classification of Headache Disorders Criteria for Migraine
      Data from Cephalalgia.
      Headache Classification Committee of the International Headache Society (IHS)
      The International Classification of Headache Disorders, 3rd edition (beta version).
      Migraine is an episodic, recurring headache that lasts 4 to 72 hours and meets the following criteria:
      • 1.
        Any 2 of these 4 pain qualities:
        • Moderate to severe intensity
        • Pulsatile
          But 50% are steady.
        • Unilateral
          But 59% are bilateral.
        • Exacerbated by or causing avoidance of routine physical activity
      • 2.
        Either or both of these associated symptoms:
        • Nausea or vomiting (or both)
          But almost 70% are not associated with vomiting.
        • Photophobia and phonophobia
      a But 50% are steady.
      b But 59% are bilateral.
      c But almost 70% are not associated with vomiting.
      The prevalence of migraine steadily increases through childhood, and the male to female ratio shifts with puberty, when migraine becomes markedly more prevalent in females and remains so throughout the rest of their lives. Most headache centers report that roughly 85% of their patients with migraine are women, and up to 70% of female migraineurs report a menstrual association with their attacks and changes in headaches related to hormonal contraception, pregnancy, and menopause. Thus, patients with menstrual-related migraine (MRM) account for about half of all migraineurs.
      Which HCP a woman selects can greatly influence her course of treatment. Traditionally, neurologists are not trained in the hormonal management of MRM or catamenial epilepsy, and most training in gynecology, family medicine, and internal medicine does not delve into the hormonal management of neurologic disorders. A serious need exists to educate HCPs about sex-based differences in migraine and strategies for management of hormonally related headaches.

      Menstrual-Related Migraine

      Menstruation is a potent migraine trigger. By the end of their reproductive years, 40.9% of women have had migraine,
      • Launer L.J.
      • Terwindt G.M.
      • Ferrari M.D.
      The prevalence and characteristics of migraine in a population-based cohort: the GEM study.
      and menstrual attacks are up to 4 times more likely to be severe, to be associated with nausea and vomiting,
      • MacGregor E.A.
      • Hackshaw A.
      Prevalence of migraine on each day of the natural menstrual cycle.
      or to be resistant to abortive treatments.
      • Silberstein S.D.
      • Massiou H.
      • Le Jeunne C.
      • Johnson-Pratt L.
      • McCarroll K.A.
      • Lines C.R.
      Rizatriptan in the treatment of menstrual migraine.
      Although a review of conventional strategies for management of migraine is beyond the scope of this concise review, prophylactic strategies often include antihypertensives, anticonvulsants, and antidepressants.
      • Starling A.J.
      • Dodick D.W.
      Best practices for patients with chronic migraine: burden, diagnosis, and management in primary care.
      Hormonal prophylaxis may be helpful for hormonally triggered migraines that do not respond to these treatments and can be used in conjunction with them. Targeted strategies can often be used in which a hormonal agent is prescribed for only a few days in each cycle. A prospective, randomized clinical trial confirmed the efficacy of 1.5 mg of transdermal estradiol gel applied for 7 days, beginning 10 days after ovulation and continued through the second day of menstrual bleeding.
      • MacGregor E.A.
      • Frith A.
      • Ellis J.
      • Aspinall L.
      • Hackshaw A.
      Prevention of menstrual attacks of migraine: a double-blind placebo-controlled crossover study.
      In a similar study, 1.5 mg of estradiol gel was effective, whereas lower doses were ineffective.
      • de Lignières B.
      • Vincens M.
      • Mauvais-Jarvis P.
      • Mas J.L.
      • Touboul P.J.
      • Bousser M.G.
      Prevention of menstrual migraine by percutaneous oestradiol.
      This therapy provides serum estradiol levels of approximately 75 pg/mL (to convert to pmol/L, multiply by 3.671), but efficacy requires correct timing of the intervention.
      Some women have noncontraceptive indications that support the use of combined hormonal contraception (CHC), including irregular menstrual cycles, dysmenorrhea, heavy menstrual bleeding, acne, hirsutism, and endometriosis, all of which are commonly managed with CHC. This therapy can be judiciously tailored to prevent the sudden declines in estrogen that trigger MRM.
      • Calhoun A.H.
      Hormonal contraceptives and migraine with aura—is there still a risk?.
      One approach is the use of extended-cycle CHC (for ≥12 weeks).
      • Calhoun A.H.
      Menstrual migraine: update on pathophysiology and approach to therapy and management.
      Oral CHC at doses of 20 to 35 μg of ethinyl estradiol (EE) can be used with continuous dosing of the active pills, eliminating the placebo week for months or years.
      • Calhoun A.H.
      Hormonal contraceptives and migraine with aura—is there still a risk?.
      • Sulak P.
      • Willis S.
      • Kuehl T.
      • Coffee A.
      • Clark J.
      Headaches and oral contraceptives: impact of eliminating the standard 7-day placebo interval.
      Although some CHC formulations are marketed for extended or continuous use, it is possible to use all monophasic CHC formulations (oral or parenteral) in this manner. Sulak et al
      • Sulak P.
      • Willis S.
      • Kuehl T.
      • Coffee A.
      • Clark J.
      Headaches and oral contraceptives: impact of eliminating the standard 7-day placebo interval.
      reported that MRM was reduced when CHC containing 30 μg of EE was taken in an extended fashion (as opposed to a regimen of 21 days of active drug and 7 days of placebo). If withdrawal bleeding is scheduled, adequate estrogen supplementation (estrogen add-back therapy) can be given with estradiol-17β during the pill-free week to limit the decrease in EE to an equivalent of 10 μg of EE or less; this level has been found to prevent MRM (Table 2).
      • Calhoun A.H.
      Menstrual migraine: update on pathophysiology and approach to therapy and management.
      A CHC vaginal ring that contains 15 μg of EE can also be used with extended-cycle dosing by replacing the ring every 3 to 4 weeks continuously while maintaining contraceptive efficacy.
      • Timmer C.J.
      • Mulders T.M.
      Pharmacokinetics of etonogestrel and ethinylestradiol released from a combined contraceptive vaginal ring.
      If a withdrawal week is scheduled, a 0.075-mg transdermal estradiol-17β patch can be used during the scheduled week without the CHC ring to limit the decrease in estradiol and prevent MRM.
      • Calhoun A.H.
      • Hutchinson S.
      Hormonal therapies for menstrual migraine.
      Table 2Hormonal Regimens for Preventing Menstrual Migraine
      CHC = combined hormonal contraception; EE = ethinyl estradiol.
      Brand nameGeneric alternativeDosageClinical pearlEstrogen add-back during hormone-free interval
      Estrogen add-back is used only if CHC is not continuous. The goal is to prevent EE from decreasing to 10 μg or less.
      Continuous formulations
       Lybrel
      No longer on the market in the United States.
      Ashlyna, Amethyst 28
      No longer on the market in the United States.
      20 μg EE and 0.09 mg levonorgestrel once daily for 365 dCan substitute any generic 20-μg EE pill and use continuously without hormone-free intervalAdd transdermal estradiol, 0.1 mg, daily

      or

      Add conjugated equine estrogens, 0.9 mg daily
       NuvaRingNone (although many insurance plans will cover this drug)Vaginal ring (delivering 15 μg EE and 0.12 mg etonogestrel daily) can be inserted once every 3-4 wk to be used in a continuous fashionWomen who are sensitive to the decrease in estrogen in the last week may need to replace the ring every 3 wkAdd transdermal estradiol, 0.075 mg daily
      Extended formulations
       LoSeasoniqueAmethia Lo, Camrese Lo20 μg EE and 0.1 mg levonorgestrel for 84 d, followed by 7 d of 10 μg EE
       Any 20-μg EE CHC used in an extended manner20 μg EE used ≥2 mo without placeboAdd transdermal estradiol, 0.1 mg daily

      or

      Add conjugated equine estrogens, 0.9 mg daily
       Any 30-μg EE CHC used in an extended manner30 μg EE used ≥2 mo without placeboAdd conjugated equine estrogens, 0.9 mg twice daily
      Monthly formulations
       Lo Loestrin Fe 1/10None10 μg EE and 1 mg norethindrone for 24 d, followed by 10 μg EE for 2 d and then placebo for 2 dUltralow doses may be associated with increased breakthrough bleeding, which may improve with time
       NataziaNoneGradually decrease estradiol valerate dose from 3 to 2 to 1 mg

      Increase dienogest dose from 2 to 3 mg
      Pill pack has a different missed-pill algorithm; refer to package insert
      a CHC = combined hormonal contraception; EE = ethinyl estradiol.
      b Estrogen add-back is used only if CHC is not continuous. The goal is to prevent EE from decreasing to 10 μg or less.
      c No longer on the market in the United States.
      In women who have migraine with aura, the use of CHC is contraindicated according to the Centers for Disease Control and Prevention US medical eligibility criteria for contraceptive use.
      • Curtis K.M.
      • Tepper N.K.
      • Jatlaoui T.C.
      • et al.
      U.S. medical eligibility criteria for contraceptive use, 2016.
      This concern first arose in the era of high-dose and ultrahigh-dose CHC (50-150 μg of different estrogens). Those extremely high estrogen doses far exceed today’s commonly used 20- to 30-μg EE products, and one product has only 10 μg of EE. The controversy is maintained by international studies, including one study that found a small but significantly increased risk of stroke associated with CHC.
      WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception
      Ischaemic stroke and combined oral contraceptives: results of an international, multicentre, case-control study.
      However, in that study, the women tended to be older (mean age, >35 years) and smokers, and most of the women with stroke had been treated with 50-μg EE CHC.
      WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception
      Ischaemic stroke and combined oral contraceptives: results of an international, multicentre, case-control study.
      In contrast, large US studies have found that CHC does not increase stroke risk
      • Petitti D.B.
      • Sidney S.
      • Bernstein A.
      • Wolf S.
      • Quesenberry C.
      • Ziel H.K.
      Stroke in users of low-dose oral contraceptives.
      because the doses are lower and CHC is contraindicated in smokers, especially those older than 35 years. Chan et al
      • Chan W.S.
      • Ray J.
      • Wai E.K.
      • et al.
      Risk of stroke in women exposed to low-dose oral contraceptives: a critical evaluation of the evidence.
      concluded that the risk of stroke among women taking low-dose oral CHC was “tenuous at best and perhaps nonexistent.”
      Higher estrogen levels increase the prevalence of aura,
      • Calhoun A.H.
      Hormonal contraceptives and migraine with aura—is there still a risk?.
      and a higher prevalence of aura is associated with higher stroke risk.
      WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception
      Ischaemic stroke and combined oral contraceptives: results of an international, multicentre, case-control study.
      To reduce peak estrogen levels throughout the menstrual cycle, extended-cycle dosing of an ultralow-dose contraceptive ring (15 μg of EE) can be used in women who have migraine with aura and MRM.
      • Calhoun A.H.
      Hormonal contraceptives and migraine with aura—is there still a risk?.
      A retrospective study of 28 patients found that this treatment strategy decreased aura frequency from 3.2 to 0.2 times a month, and MRM was prevented in 91.3% of users. If a woman does not want to use a ring, the dose of estrogen pills is best limited to the 10-μg EE pill pack, with careful assurance that it is inhibiting ovulation.
      In younger adolescent girls, CHC should be used judiciously for preventing MRM because linear growth usually stops about 2 years after menarche, an event thought to be related to the hormones of puberty. When feasible, CHC should not be used until the patient has reached full height; however, this approach increases the risk of undertreatment, which may lead to school absences and chronic migraine.
      • Drop S.L.
      • De Waal W.J.
      • De Muinck Keizer-Schrama S.M.
      Sex steroid treatment of constitutionally tall stature.
      Gonadotropin-releasing hormone antagonists can eliminate pure MRM, but they may also cause adverse effects of estrogen deficiency, limiting the duration of their use. These adverse effects include sleep disruption, a marked reduction in bone density, and severe vasomotor symptoms. They should not be used for more than 6 months without appropriate follow-up.
      • Weiss J.M.
      • Diedrich K.
      • Ludwig M.
      Gonadotropin-releasing hormone antagonists: pharmacology and clinical use in women.
      Progestin-only contraceptive pills and intrauterine devices are unlikely to help with MRM because they do not reliably control ovulation.
      • Curtis K.M.
      • Tepper N.K.
      • Jatlaoui T.C.
      • et al.
      U.S. medical eligibility criteria for contraceptive use, 2016.
      Use of standard-cycle (21 days of hormone and 7 days of placebo) oral CHC is also ineffective, with 2 exceptions: (1) ultralow-dose 10-μg EE CHC (24 days of 10 μg EE with 1 mg norethindrone followed by 2 days of 10 μg EE alone and 2 days of placebo) and (2) quadriphasic estradiol valerate CHC. All other regimens provide at least a 20-μg EE decrease (equivalent to the cyclic decline in natural estrogen) and can therefore trigger MRM in susceptible individuals.
      • Calhoun A.H.
      • Hutchinson S.
      Hormonal therapies for menstrual migraine.

      Migraine in Pregnancy

      During pregnancy, migraine often improves as estradiol levels steadily increase from the first trimester to the third, particularly in women with a history of MRM and migraine without aura.
      • Kvisvik E.V.
      • Stovner L.J.
      • Helde G.
      • Bovim G.
      • Linde M.
      Headache and migraine during pregnancy and puerperium: the MIGRA-study.
      After pregnancy, women who experienced improvement with pregnancy often have a particularly intense migraine shortly after delivery because of the precipitous decrease in estradiol levels.
      • Sacco S.
      • Ripa P.
      Migraine in pregnancy.
      However, some women do not report improvement in migraine with pregnancy, and those in whom migraine continues in the first trimester are likely to continue to have migraine throughout pregnancy and the postpartum period.
      • Sacco S.
      • Ripa P.
      Migraine in pregnancy.
      A minority of women report worsening of migraine in pregnancy, and some experience de novo migraine during pregnancy, most commonly in the first trimester and associated with aura, most likely related to the much higher (and increasing) estrogen levels in pregnancy.
      • Kvisvik E.V.
      • Stovner L.J.
      • Helde G.
      • Bovim G.
      • Linde M.
      Headache and migraine during pregnancy and puerperium: the MIGRA-study.
      Health care professionals may, therefore, find themselves caring for pregnant women with migraine. Preventive regimens during pregnancy are best managed in collaboration with a gynecologist and headache specialist.
      Before the recent US Food and Drug Administration changes in pregnancy and lactation labeling, which went into effect in June 2015, sumatriptan was classified as a category C medication in pregnancy (ie, medications for which risk cannot be ruled out given a lack of adequate, well-controlled human studies; a chance of causing fetal harm exists, although the potential benefits may outweigh the risks) because offspring were harmed when extreme doses were given to pregnant rats. But researchers also calculated the highest no-effect (ie, safe) dose, which was 60 mg/kg daily, or the equivalent of 4200 mg/daily for a 70-kg person (the highest available dose is 100 mg).
      IMITREX nasal spray (sumatriptan)
      GlaxoSmithKline website.
      An opinion stated in a 1998 literature review
      • Pfaffenrath V.
      • Rehm M.
      Migraine in pregnancy: what are the safest treatment options?.
      opposed the use of triptans during pregnancy; however, a more recent review
      • Cunnington M.
      • Ephross S.
      • Churchill P.
      The safety of sumatriptan and naratriptan in pregnancy: what have we learned?.
      did not find evidence of sumatriptan teratogenicity. These data included a prospective pregnancy registry from the United States and Canada.
      • Cunnington M.
      • Ephross S.
      • Churchill P.
      The safety of sumatriptan and naratriptan in pregnancy: what have we learned?.
      In the large Norwegian Mother and Child Cohort Study,
      • Nezvalová-Henriksen K.
      • Spigset O.
      • Nordeng H.
      Triptan exposure during pregnancy and the risk of major congenital malformations and adverse pregnancy outcomes: results from the Norwegian Mother and Child Cohort Study.
      2.2% of the 69,929 pregnant women in the study used a triptan during pregnancy (mostly sumatriptan). Triptan use during pregnancy was not associated with congenital malformations compared with controls. Adjusted odds ratios were 0.9 (95% CI, 0.7-1.2) for any malformation and 1.0 (95% CI, 0.7-1.3) for major congenital malformation. Similarly in Sweden, where more than 95% of all first-trimester drug exposures are identified through interviews with a midwife, the risk of birth defects (major or minor) was 3.6% in the general population.
      • Källén B.
      • Nilsson E.
      • Otterblad Olausson P.
      Delivery outcome after maternal use of drugs for migraine: a register study in Sweden.
      With sumatriptan exposure in the first trimester (n=2229), the risk was identical (3.6%).
      Not all triptans should be considered safe during pregnancy. The relative hydrophilicity of sumatriptan makes it less likely to traverse the placental membrane (only about 15% of a sumatriptan dose crosses into the fetal compartment over 4 hours), whereas the other triptans are lipophilic.
      The ideal choice for a triptan during pregnancy is sumatriptan administered either by the nasal delivery system or by nasal spray for 2 reasons: (1) they deliver maternal serum concentrations that are equivalent to or less than the 25-mg sumatriptan tablet
      IMITREX nasal spray (sumatriptan)
      GlaxoSmithKline website.
      and (2) parenteral administration maintains efficacy in the presence of gastric stasis or nausea, which are conditions commonly present when migraines tend to peak at the end of the first trimester. To prevent medication overuse headache, triptans are usually limited to 9 days per month.

      Migraine Treatment During Lactation

      Nearly all maternal drugs that are compatible with breastfeeding will appear in the breast milk. Drugs that are relatively toxic are contraindicated during breastfeeding, but if the relative infant dose is no more than 10% of the mother’s (an arbitrary cutoff), the drug is considered safe during lactation.
      • Hale T.W.
      • Rowe H.E.
      Medications and Mother’s Milk.
      Both sumatriptan and eletriptan have low relative infant doses (0.2%-3.5%), suggesting that their use during lactation should not pose substantial risk to the infant.
      • David P.S.
      • Kling J.M.
      • Starling A.J.
      Migraine in pregnancy and lactation.
      The Canadian Headache Society
      • Worthington I.
      • Pringsheim T.
      • Gawel M.J.
      • et al.
      Canadian Headache Society Acute Migraine Treatment Guideline Development Group
      Canadian Headache Society Guideline: acute drug therapy for migraine headache.
      and the American Academy of Pediatrics
      American Academy of Pediatrics Committee on Drugs
      Transfer of drugs and other chemicals into human milk.
      suggest that sumatriptan is compatible with lactation. In contrast, rizatriptan is concentrated in rat breast milk, with a relative infant dose at least 5 times greater than maternal plasma concentrations per product labeling. Current information on the excretion of drugs in breast milk and possible adverse effects in a nursing infant can be obtained on the new LactMed website.
      National Institutes of Health, National Library of Medicine
      LactMed. TOXNET Toxicology Data Network website.
      Migraine prevention in lactation should center around good, restorative sleep—which can be difficult with a new baby. A good review of medication options for treatment during lactation can be found in an article commissioned by the American Headache Society.
      • Hutchinson S.
      • Marmura M.J.
      • Calhoun A.
      • Lucas S.
      • Silberstein S.
      • Peterlin B.L.
      Use of common migraine treatments in breast-feeding women: a summary of recommendations.
      As during pregnancy, sumatriptan at the lowest effective dose is the triptan of choice for lactating women.

      Migraine in Menopause

      Data are fairly consistent in showing a perimenopausal increase in migraine prevalence and a postmenopausal decrease. Additionally, the prevalence of high-frequency headache (ie, occurring ≥10 d/mo) is higher during perimenopause than during premenopausal years.
      • Martin V.T.
      • Pavlovic J.
      • Fanning K.M.
      • Buse D.C.
      • Reed M.L.
      • Lipton R.B.
      Perimenopause and menopause are associated with high frequency headache in women with migraine: results of the American Migraine Prevalence and Prevention Study.
      Sleep disturbances are common in women around the menopausal transition and likely contribute to this increased frequency.
      Treatment strategies for perimenopausal migraineurs include minimizing decreases in estrogen levels, which may benefit not only migraine but also vasomotor symptoms.
      • MacGregor E.A.
      Perimenopausal migraine in women with vasomotor symptoms.
      Continuous or extended-cycle CHC can be used in perimenopause with consideration of estrogen add-back during the hormone-free interval to prevent estradiol levels from decreasing and triggering migraine (Table 2). Most women will see improvement in their migraines once in menopause. Menopausal hormone therapy can be used with certain caveats and is not contraindicated in postmenopausal women with migraine (with or without aura).
      • MacGregor E.A.
      Perimenopausal migraine in women with vasomotor symptoms.
      Fortunately, there is now clarity regarding the favorable risk-to-benefit balance for the use of menopausal hormone therapy in symptomatic women without contraindication who are in their 50s and within 10 years of the menopause transition.
      The 2017 hormone therapy position statement of the North American Menopause Society.
      For women with a history of MRM, administration should be transdermal in the lowest dose sufficient to meet treatment goals.
      • MacGregor E.A.
      Perimenopausal migraine in women with vasomotor symptoms.
      Oral estrogens with short half-lives and hormonal therapy injections should be avoided because both can produce problematic decreases in estrogen concentration between doses.
      Triptans are commonly used as abortive therapy for migraine, and age alone is not a contraindication for their use. Women at low risk for cardiovascular disease can use triptans without additional cardiac assessment, but the use of triptans should be avoided in women (or men) with known coronary heart disease, uncontrolled hypertension, cerebrovascular syndromes (stroke or transient ischemic attack), or peripheral vascular disease (including ischemic bowel disease).
      • Jamieson D.G.
      The safety of triptans in the treatment of patients with migraine.

      Conclusion

      Migraine is more prevalent in women than in men, and hormonal influences during the reproductive life cycle (including menarche, the use of CHC, pregnancy and lactation, and the menopause transition) affect not only the frequency and severity of migraine but also its treatment. Hormonal manipulation strategies aimed at eliminating or minimizing decreases in estrogen levels may prevent migraine attacks. The use of triptans may need to be modified in pregnant or lactating women and avoided in women with coronary heart disease or an equivalent disease. Health care professionals caring for women throughout their life should be familiar with these sex-based differences in women with migraine and with targeted strategies for management.

      Acknowledgments

      Mayo Clinic does not endorse specific products or services discussed in this article.

      Supplemental Online Material

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