Gender Differences in Imaging Studies in Migraine

  • Nasim MalekiEmail author
Part of the Headache book series (HEAD)


Migraine is a common neurological disorder that is characterized by recurrent intermittent headaches (1–14 headache days per month in episodic migraine and >14 headache days in chronic migraine) that last 4–72 h. Migraine is considered by the World Health Organization (WHO) to be in the top 20 causes of disability worldwide [1] and affects patients during their formative and most productive periods of their lives. In the United States, migraine affects 30 million adults, and some 17% of American children have headaches including migraine [2] (Fig. 8.1).


  1. 1.
    Buse DC, Rupnow MF, Lipton RB. Assessing and managing all aspects of migraine: migraine attacks, migraine-related functional impairment, common comorbidities, and quality of life. Mayo Clin Proc. 2009;84(5):422–35. 84/5/422 [pii].CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Lateef TM, Merikangas KR, He J, Kalaydjian A, Khoromi S, Knight E, Nelson KB. Headache in a national sample of American children: prevalence and comorbidity. J Child Neurol. 2009;24(5):536–43. 24/5/536 [pii].CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Lipton RB, Stewart WF, Diamond S, Diamond ML, Reed M. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache 2001;41(7):646–57. PMID: 11554952.Google Scholar
  4. 4.
    Stewart WF, Linet MS, Celentano DD, Van Natta M, Ziegler D. Age- and sex-specific incidence rates of migraine with and without visual aura. Am J Epidemiol 1991;134(10):1111–20. PMID: 1746521.CrossRefGoogle Scholar
  5. 5.
    Stewart WF, Lipton RB, Celentano DD, Reed ML. Prevalence of migraine headache in the United States. Relation to age, income, race, and other sociodemographic factors. JAMA. 1992;267(1):64–9.CrossRefGoogle Scholar
  6. 6.
    Brandes JL. The influence of estrogen on migraine: a systematic review. JAMA. 2006;295(15):1824–30.CrossRefGoogle Scholar
  7. 7.
    Le H, Tfelt-Hansen P, Russell MB, Skytthe A, Kyvik KO, Olesen J. Co-morbidity of migraine with somatic disease in a large population-based study. Cephalalgia. 2011;31(1):43–64. Scholar
  8. 8.
    Russell MB, Rasmussen BK, Thorvaldsen P, Olesen J. Prevalence and sex-ratio of the subtypes of migraine. Int J Epidemiol. 1995;24(3):612–8.CrossRefGoogle Scholar
  9. 9.
    Pakalnis A, Gladstein J. Headaches and hormones. Semin Pediatr Neurol. 2010;17(2):100–4. S1071-9091(10)00036-7 [pii].CrossRefPubMedGoogle Scholar
  10. 10.
    Russell MB, Rasmussen BK, Fenger K, Olesen J. Migraine without aura and migraine with aura are distinct clinical entities: a study of four hundred and eighty-four male and female migraineurs from the general population. Cephalalgia. 1996;16(4):239–45.CrossRefGoogle Scholar
  11. 11.
    Silberstein SD, Lipton RB, Dodick D, Wolff HG. Wolff’s headache and other head pain. 8th ed. Oxford; New York, NY: Oxford University Press; 2008.Google Scholar
  12. 12.
    Greenspan JD, Craft RM, LeResche L, Arendt-Nielsen L, Berkley KJ, Fillingim RB, et al. Studying sex and gender differences in pain and analgesia: a consensus report. Pain. 2007;132(Suppl 1):S26–45.CrossRefGoogle Scholar
  13. 13.
    Epstein MT, Hockaday JM, Hockaday TD. Migraine and reproductive hormones throughout the menstrual cycle. Lancet. 1975;1(7906):543–8.CrossRefGoogle Scholar
  14. 14.
    Goldstein M, Chen TC. The epidemiology of disabling headache. Adv Neurol. 1982;33:377–90.PubMedGoogle Scholar
  15. 15.
    Lipton RB, Stewart WF. Migraine in the United States: a review of epidemiology and health care use. Neurology. 1993;43(6 Suppl 3):S6–10.PubMedGoogle Scholar
  16. 16.
    Silberstein SD. Sex hormones and headache. Rev Neurol. 2000;156(Suppl 4):4S30–41.PubMedGoogle Scholar
  17. 17.
    Silberstein SD, Merriam GR. Estrogens, progestins, and headache. Neurology. 1991;41(6):786–93.CrossRefGoogle Scholar
  18. 18.
    Silberstein SD, Merriam GR. Physiology of the menstrual cycle. Cephalalgia. 2000;20(3):148–54.CrossRefGoogle Scholar
  19. 19.
    Silberstein S, Merriam G. Sex hormones and headache 1999 (menstrual migraine). Neurology. 1999;53(4 Suppl 1):S3–13.PubMedGoogle Scholar
  20. 20.
    Martin VT. New theories in the pathogenesis of menstrual migraine. Curr Pain Headache Rep. 2008;12(6):453–62.CrossRefGoogle Scholar
  21. 21.
    Martin VT, Behbehani M. Ovarian hormones and migraine headache: understanding mechanisms and pathogenesis--part I. Headache. 2006;46(1):3–23. Scholar
  22. 22.
    Sacco S, Ricci S, Degan D, Carolei A. Migraine in women: the role of hormones and their impact on vascular diseases. J Headache Pain. 2012;13(3):177–89. Scholar
  23. 23.
    Sisk CL, Zehr JL. Pubertal hormones organize the adolescent brain and behavior. Front Neuroendocrinol. 2005;26(3-4):163–74. Scholar
  24. 24.
    Calhoun A, Ford S. Elimination of menstrual-related migraine beneficially impacts chronification and medication overuse. Headache. 2008;48(8):1186–93.CrossRefGoogle Scholar
  25. 25.
    Loder G, Silberstein S. Headaches in women. In: Wolff’s headache. 8th ed. New York, NY: Oxford University Press; 2008. p. 691–710.Google Scholar
  26. 26.
    Burstein R, Jakubowski M, Garcia-Nicas E, Kainz V, Bajwa Z, Hargreaves R, et al. Thalamic sensitization transforms localized pain into widespread allodynia. Ann Neurol. 2010;68(1):81–91. Scholar
  27. 27.
    Mailis-Gagnon A, Giannoylis I, Downar J, Kwan CL, Mikulis DJ, Crawley AP, et al. Altered central somatosensory processing in chronic pain patients with “hysterical” anesthesia. Neurology. 2003;60(9):1501–7.CrossRefGoogle Scholar
  28. 28.
    Maleki N, Becerra L, Brawn J, Bigal M, Burstein R, Borsook D. Concurrent functional and structural cortical alterations in migraine. Cephalalgia. 2012a;32(8):607–20. Scholar
  29. 29.
    Maleki N, Becerra L, Upadhyay J, Burstein R, Borsook D. Direct optic nerve pulvinar connections defined by diffusion MR tractography in humans: implications for photophobia. Hum Brain Mapp. 2012b;33(1):75–88. Scholar
  30. 30.
    Moulton EA, Burstein R, Tully S, Hargreaves R, Becerra L, Borsook D. Interictal dysfunction of a brainstem descending modulatory center in migraine patients. PLoS One. 2008;3(11):e3799. Scholar
  31. 31.
    Russo A, Tessitore A, Esposito F, Marcuccio L, Giordano A, Conforti R, et al. Pain processing in patients with migraine: an event-related fMRI study during trigeminal nociceptive stimulation. J Neurol. 2012;259:1903–12. Scholar
  32. 32.
    Schmidt-Wilcke T, Ganssbauer S, Neuner T, Bogdahn U, May A. Subtle grey matter changes between migraine patients and healthy controls. Cephalalgia. 2008;28(1):1–4. Scholar
  33. 33.
    Tessitore A, Russo A, Esposito F, Giordano A, Taglialatela G, De Micco R, et al. Interictal cortical reorganization in episodic migraine without aura: an event-related fMRI study during parametric trigeminal nociceptive stimulation. Neurol Sci. 2011;32(Suppl 1):S165–7. Scholar
  34. 34.
    Maleki N, Linnman C, Brawn J, Burstein R, Becerra L, Borsook D. Her versus his migraine: multiple sex differences in brain function and structure. Brain. 2012c;135(Pt 8):2546–59. Scholar
  35. 35.
    Craig AD. How do you feel--now? The anterior insula and human awareness. Nat Rev Neurosci. 2009;10(1):59–70. Scholar
  36. 36.
    Beissner F, Meissner K, Bar KJ, Napadow V. The autonomic brain: an activation likelihood estimation meta-analysis for central processing of autonomic function. J Neurosci. 2013;33(25):10503–11. Scholar
  37. 37.
    Critchley HD, Nagai Y, Gray MA, Mathias CJ. Dissecting axes of autonomic control in humans: insights from neuroimaging. Auton Neurosci. 2011;161(1-2):34–42. Scholar
  38. 38.
    Henderson LA, Gandevia SC, Macefield VG. Somatotopic organization of the processing of muscle and cutaneous pain in the left and right insula cortex: a single-trial fMRI study. Pain. 2007;128(1-2):20–30. Scholar
  39. 39.
    Nieuwenhuys R. The insular cortex: a review. Prog Brain Res. 2012;195:123–63. Scholar
  40. 40.
    Maleki N, Barmettler G, Moulton EA, Scrivani S, Veggeberg R, Spierings EL, et al. Female migraineurs show lack of insular thinning with age. Pain. 2015;156(7):1232–9. Scholar
  41. 41.
    Grieve SM, Clark CR, Williams LM, Peduto AJ, Gordon E. Preservation of limbic and paralimbic structures in aging. Hum Brain Mapp. 2005;25(4):391–401. Scholar
  42. 42.
    Bahra A, Matharu MS, Buchel C, Frackowiak RS, Goadsby PJ. Brainstem activation specific to migraine headache. Lancet. 2001;357(9261):1016–7.CrossRefGoogle Scholar
  43. 43.
    Kim JH, Kim S, Suh SI, Koh SB, Park KW, Oh K. Interictal metabolic changes in episodic migraine: a voxel-based FDG-PET study. Cephalalgia. 2010;30(1):53–61. Scholar
  44. 44.
    Xue T, Yuan K, Zhao L, Yu D, Zhao L, Dong T, et al. Intrinsic brain network abnormalities in migraines without aura revealed in resting-state fMRI. PLoS One. 2012;7(12):e52927. Scholar
  45. 45.
    Yang J, Zeng F, Feng Y, Fang L, Qin W, Liu X, et al. A PET-CT study on the specificity of acupoints through acupuncture treatment in migraine patients. BMC Complement Altern Med. 2012;12:123. Scholar
  46. 46.
    Raichle ME, Snyder AZ. A default mode of brain function: a brief history of an evolving idea. Neuroimage. 2007;37(4):1083–90. discussion 1097–1089.CrossRefPubMedGoogle Scholar
  47. 47.
    Buckner RL, Andrews-Hanna JR, Schacter DL. The brain’s default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci. 2008;1124:1–38. Scholar
  48. 48.
    Petersen N, Kilpatrick LA, Goharzad A, Cahill L. Oral contraceptive pill use and menstrual cycle phase are associated with altered resting state functional connectivity. Neuroimage. 2014;90:24–32. Scholar
  49. 49.
    Zhang J, Su J, Wang M, Zhao Y, Zhang QT, Yao Q, et al. The posterior insula shows disrupted brain functional connectivity in female migraineurs without aura based on brainnetome atlas. Sci Rep. 2017;7(1):16868. Scholar
  50. 50.
    Fan L, Li H, Zhuo J, Zhang Y, Wang J, Chen L, et al. The human Brainnetome Atlas: a new brain atlas based on connectional architecture. Cereb Cortex. 2016;26(8):3508–26. Scholar
  51. 51.
    Liu J, Qin W, Nan J, Li J, Yuan K, Zhao L, et al. Gender-related differences in the dysfunctional resting networks of migraine suffers. PLoS One. 2011;6(11):e27049. Scholar
  52. 52.
    Androulakis XM, Krebs K, Peterlin BL, Zhang T, Maleki N, Sen S, et al. Modulation of intrinsic resting-state fMRI networks in women with chronic migraine. Neurology. 2017;89(2):163–9. Scholar
  53. 53.
    Kruit MC, van Buchem MA, Launer LJ, Terwindt GM, Ferrari MD. Migraine is associated with an increased risk of deep white matter lesions, subclinical posterior circulation infarcts and brain iron accumulation: the population-based MRI CAMERA study. Cephalalgia. 2010;30(2):129–36. CHA1904 [pii].CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Maniyar FH, Sprenger T, Monteith T, Schankin C, Goadsby PJ. Brain activations in the premonitory phase of nitroglycerin-triggered migraine attacks. Brain. 2013; Scholar
  55. 55.
    Afridi SK, Matharu MS, Lee L, Kaube H, Friston KJ, Frackowiak RS, Goadsby PJ. A PET study exploring the laterality of brainstem activation in migraine using glyceryl trinitrate. Brain. 2005;128(Pt 4):932–9. Scholar
  56. 56.
    Li W, Diao X, Chen C, Li C, Zhang Y, Li Y. Changes in hormones of the hypothalamic-pituitary-gonadal axis in migraine patients. J Clin Neurosci. 2018; Scholar
  57. 57.
    Guidetti V, Alberton S, Galli F, Salvi E. Gender, migraine and affective disorders in the course of the life cycle. Funct Neurol. 2009;24(1):29–40. 3374 [pii].PubMedGoogle Scholar
  58. 58.
    Hedborg K, Anderberg UM, Muhr C. Stress in migraine: personality-dependent vulnerability, life events, and gender are of significance. Ups J Med Sci. 2011;116(3):187–99. Scholar
  59. 59.
    Zielman R, Wijnen JP, Webb A, Onderwater GLJ, Ronen I, Ferrari MD, et al. Cortical glutamate in migraine. Brain. 2017;140(7):1859–71. Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Psychiatric Neuroimaging Division, Department of Psychiatry, Massachusetts General HospitalHarvard Medical SchoolBostonUSA

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