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Neurological Sciences
Published in: Neurological Sciences 2/2020

Open Access 01-12-2020 | Migraine | KEY LECTURE

Gender-related differences in migraine

Authors: Gianni Allais, Giulia Chiarle, Silvia Sinigaglia, Gisella Airola, Paola Schiapparelli, Chiara Benedetto

Published in: Neurological Sciences | Special Issue 2/2020

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Abstract

Migraine is considered mostly a woman’s complaint, even if it affects also men. Epidemiological data show a higher incidence of the disease in women, starting from puberty throughout life. The sex-related differences of migraine hold clinical relevance too. The frequency, duration, and disability of attacks tend to be higher in women. Because of this, probably, they also consult specialists more frequently and take more prescription drugs than men. Different mechanisms have been evaluated to explain these differences. Hormonal milieu and its modulation of neuronal and vascular reactivity is probably one of the most important aspects. Estrogens and progesterone regulate a host of biological functions through two mechanisms: nongenomic and genomic. They influence several neuromediators and neurotransmitters, and they may cause functional and structural differences in several brain regions, involved in migraine pathogenesis. In addition to their central action, sex hormones exert rapid modulation of vascular tone. The resulting specific sex phenotype should be considered during clinical management and experimental studies.
Literature
1.
Victor TW, Hu X, Campbell JC et al (2010) Migraine prevalence by age and sex in the United States: a life-span study. Cephalalgia 30(9):1065–1072
2.
Macgregor EA, Rosenberg JD, Kurth T (2011) Sex-related differences in epidemiological and clinic-based headache studies. Headache 51(5):843–859PubMedCrossRef
3.
4.
5.
Stewart WF, Wood C, Reed ML et al (2008) Cumulative lifetime migraine incidence in women and men. Cephalalgia 28(11):1170–1178
6.
Allais G, Chiarle G, Sinigaglia S et al (2018) Menstrual migraine: a review of current and developing pharmacotherapies for women. Expert Opin Pharmacother 19(2):123–136
7.
8.
Brusa P, Allais G, Scarinzi C et al (2019) Self-medication for migraine: a nationwide cross-sectional study in Italy. PLoS One 14(1):e0211191
9.
Bolay H, Ozge A, Saginc P et al (2015) Gender influences headache characteristics with increasing age in migraine patients. Cephalalgia 35(9):792–800
10.
Buse DC, Loder EW, Gorman JA et al (2013) Sex differences in the prevalence, symptoms, and associated features of migraine, probable migraine and other severe headache: results of the American Migraine Prevalence and Prevention (AMPP) study. Headache 53(8):1278–1299
11.
Vetvik KG, MacGregor EA (2017) Sex differences in the epidemiology, clinical features, and pathophysiology of migraine. Lancet Neurol 16(1):76–87PubMedCrossRef
12.
Steiner TJ, Scher AI, Stewart WF et al (2003) The prevalence and disability burden of adult migraine in England and their relationships to age, gender and ethnicity. Cephalalgia 23(7):519–527
13.
Schroeder RA, Brandes J, Buse DC et al (2018) Sex and gender differences in migraine-evaluating knowledge gaps. J Women’s Health (Larchmt) 27(8):965–973
14.
Robinson ME, Riley JL 3rd, Myers CD et al (2001) Gender role expectations of pain: relationship to sex differences in pain. J Pain 2(5):251–257PubMedCrossRef
15.
Russell MB, Rasmussen BK, Thorvaldsen P et al (1995) Prevalence and sex-ratio of the subtypes of migraine. Int J Epidemiol 24(3):612–618PubMedCrossRef
16.
17.
Vos T, Allen C, Arora M et al (2016) Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the global burden of disease study 2015. Lancet 388:1545–1602
18.
Hu XH, Markson LE, Lipton RB et al (1999) Burden of migraine in the United States: disability and economic costs. Arch Intern Med 159(8):813–818
19.
Linde M, Gustavsson A, Stovner LJ et al (2012) The cost of headache disorders in Europe: the Eurolight project. Eur J Neurol 19(5):703–711
20.
Brusa P, Allais G, Rolando S, Baratta F, Giaccone M, Bussone G, Allais R, Benedetto C (2015) Migraine attacks in the pharmacy: a gender subanalysis on treatment preferences. Neurol Sci 36(1):93–95PubMedCrossRef
21.
Ferrari A, Tiraferri I, Neri L et al (2011) Why pharmacokinetic differences among oral triptans have little clinical importance: a comment. J Headache Pain 12(1):5–12
22.
Franconi F, Finocchi C, Allais G et al (2014) Gender and triptan efficacy: a pooled analysis of three double-blind, randomized, crossover, multicenter, Italian studies comparing frovatriptan vs other triptans. Neurol Sci 35(1):99–105PubMedPubMedCentralCrossRef
23.
Munakata J, Hazard E, Serrano D et al (2009) Economic burden of transformed migraine: results from the American Migraine Prevalence and Prevention (AMPP) study. Headache 49(4):498–508
24.
Yang FC, Lin TY, Chen HJ et al (2016) Increased risk of restless legs syndrome in patients with migraine: a nationwide population-based cohort study. Medicine (Baltimore) 95(5):e2646
25.
Spector JT, Kahn SR, Jones MR et al (2010) Migraine headache and ischemic stroke risk: an updated meta-analysis. Am J Med 123(7):612–624
26.
Kelly MJ, Levin ER (2001) Rapid actions of plasma membrane estrogen receptors. Trends Endocrinol Metab 12(4):152–156PubMedCrossRef
27.
Lau YT (2002) Receptor-dependent and genomic-independent actions of estrogen in vascular protection. Chang Gung Med J 25(10):636–644PubMed
28.
Aloisi AM (2003) Gonadal hormones and sex differences in pain reactivity. Clin J Pain 19(3):168–174PubMedCrossRef
29.
Stoffel-Wagner B (2003) Neurosteroid biosynthesis in the human brain and its clinical implications. Ann N Y Acad Sci 1007:64–78PubMedCrossRef
30.
Martin VT, Behbehani M (2006) Ovarian hormones and migraine headache: understanding mechanisms and pathogenesis-part I. Headache 46(1):3–23PubMedCrossRef
31.
Gupta S, Mehrotra S, Villalón CM et al (2007) Potential role of female sex hormones in the pathophysiology of migraine. Pharmacol Ther 113(2):321–340
32.
Teoh H, Quan A, Leung SW et al (2000) Differential effects of 17beta-estradiol and testosterone on the contractile responses of porcine coronary arteries. Br J Pharmacol 129(7):1301–1308PubMedPubMedCentralCrossRef
33.
Dubey RK, Jackson EK (2001) Estrogen-induced cardiorenal protection: potential cellular, biochemical, and molecular mechanisms. Am J Physiol Renal Physiol 280(3):F365–F388PubMedCrossRef
34.
White RE, Han G, Maunz M et al (2002) Endothelium-independent effect of estrogen on Ca(2+)- activated K(+) channels in human coronary artery smooth muscle cells. Cardiovasc Res 53(3):650–661
35.
Mügge A, Barton M, Fieguth HG et al (1997) Contractile responses to histamine, serotonin, and angiotensin II are impaired by 17 beta-estradiol in human internal mammary arteries in vitro. Pharmacology 54(3):162–168PubMedCrossRef
36.
Murphy JG, Kahlil RA (1999) Decreased [Ca(2+)](i) during inhibition of coronary smooth muscle contraction by 17beta-estradiol, progesterone, and testosterone. J Pharmacol Exp Ther 291(1):44–52PubMed
37.
Ding AQ, Stallone JN (2001) Testosterone-induced relaxation of rat aorta is androgen structure specific and involves K+ channel activation. J Appl Physiol 91(6):2742–2750PubMedCrossRef
38.
Mügge A, Riedel M, Barton M et al (1993) Endothelium independent relaxation of human coronary arteries by 17 beta-oestradiol in vitro. Cardiovasc Res 27(11):1939–1942PubMedCrossRef
39.
Shaw L, Taggart MJ, Austin C (2000) Mechanisms of 17 beta-oestradiol induced vasodilatation in isolated pressurized rat small arteries. Br J Pharmacol 129(3):555–565PubMedPubMedCentralCrossRef
40.
Okamoto K, Hirata H, Takeshita S et al (2003) Response properties of TMJ units in superficial laminae at the spinomedullary junction of female rats vary over the estrous cycle. J Neurophysiol 89(3):1467–1477
41.
Cutrer FM, Moskowitz MA (1996) The actions of valproate and neurosteroids in a model of trigeminal pain. Headache 36(10):579–585PubMedCrossRef
42.
Labastida-Ramírez A, Rubio-Beltrán E, Villalón CM et al (2019) Gender aspects of CGRP in migraine. Cephalalgia 39(3):435–444
43.
Gupta S, Villalón CM, Mehrotra S et al (2007) Female sex hormones and rat dural vasodilatation to CGRP, periarterial electrical stimulation and capsaicin. Headache 47(2):225–235
44.
Gangula PR, Lanlua P, Wimalawansa S et al (2000) Regulation of calcitonin gene-related peptide expression in dorsal root ganglia of rats by female sex steroid hormones. Biol Reprod 62(4):1033–1039PubMedCrossRef
45.
Wang D, Zhao J, Wang J et al (2014) Deficiency of female sex hormones augments PGE2 and CGRP levels within midbrain periaqueductal gray. J Neurol Sci 346(1–2):107–111
46.
Ma QL, Zhou HY, Sun M (2001) Relationship between sex hormone levels and blood calcitonin gene-related peptide/endothelin-1 in postmenopausal women with coronary heart disease. Hunan Yi Ke Da Xue Xue Bao 26(2):146–148PubMed
47.
Stevenson JC, Macdonald DW, Warren RC et al (1986) Increased concentration of circulating calcitonin gene related peptide during normal human pregnancy. Br Med J 293(6558):1329–1330
48.
Valdemarsson S, Edvinsson L, Hedner P et al (1990) Hormonal influence on calcitonin gene-related peptide in man: effects of sex difference and contraceptive pills. Scand J Clin Lab Invest 50(4):385–388
49.
Dong YL, Vegiraju S, Gangula PR et al (2002) Expression and regulation of calcitonin gene-related peptide receptor in rat placentas. Biol Reprod 67(4):1321–1326
50.
Ibrahimi K, Vermeersch S, Frederiks P et al (2017) The influence of migraine and female hormones on capsaicin-induced dermal blood flow. Cephalalgia 37(12):1164–1172
51.
Ibrahimi K, van Oosterhout WP, van Dorp W et al (2015) Reduced trigeminovascular cyclicity in patients with menstrually related migraine. Neurology 84(2):125–131PubMedCrossRef
52.
Karkhaneh A, Ansari M, Emamgholipour S et al (2015) The effect of 17 β-estradiol on gene expression of calcitonin gene-related peptide and some pro-inflammatory mediators in peripheral blood mononuclear cells from patients with pure menstrual migraine. Iran J Basic Med Sci 18(9):894–901PubMedPubMedCentral
53.
Etgen AM, Karkanias GB (1994) Estrogen regulation of noradrenergic signaling in the hypothalamus. Psychoneuroendocrinology 19(5–7):603–610PubMedCrossRef
54.
Mitrovic I, Margeta-Mitrovic M, Bader S et al (2003) Contribution of GIRK2-mediated postsynaptic signaling to opiate and α2-adrenergic analgesia and analgesic sex differences. Proc Natl Acad Sci U S A 100(1):271–276
55.
Ansonoff MA, Etgen AM (2001) Estrogen increases G protein coupled receptor kinase 2 in the cortex of female rats. Brain Res 898(1):186–189PubMedCrossRef
56.
Nag S, Mokha SS (2004) Estrogen attenuates antinociception produced by stimulation of Kölliker-fuse nucleus in the rat. Eur J Neurosci 20(11):3203–3207PubMedCrossRef
57.
Khasar SG, Dina OA, Green PG et al (2005) Estrogen regulates adrenal medullary function producing sexual dimorphism in nociceptive threshold and beta-adrenergic receptor-mediated hyperalgesia in the rat. Eur J Neurosci 21(12):3379–3386
58.
Nagel-Leiby S, Welch KM, Grunfeld S (1990) Ovarian steroid levels in migraine with and without aura. Cephalalgia 10(3):147–152PubMedCrossRef
59.
Mehrotra S, Gupta S, Villalón CM et al (2007) Rat carotid artery responses to alpha-adrenergic receptor agonists and 5-HT after ovariectomy and hormone replacement. Headache 47(2):236–246
60.
61.
Ferrer M, Osol G (1998) Estrogen replacement modulates resistance artery smooth muscle and endothelial alpha2-adrenoceptor reactivity. Endothelium 6(2):133–141PubMedCrossRef
62.
Nappi RE, Sances G, Brundu B et al (2005) Estradiol supplementation modulates neuroendocrine response to M-chlorophenylpiperazine in menstrual status migrainosus triggered by oral contraception-free interval. Hum Reprod 20(12):3423–3428
63.
Klink R, Robichaud M, Debonnel G (2002) Gender and gonadal status modulation of dorsal raphe nucleus serotonergic neurons. Part I: effects of gender and pregnancy. Neuropharmacology 43(7):1119–1128PubMedCrossRef
64.
Pecins-Thompson M, Brown NA, Kohama SG et al (1996) Ovarian steroid regulation of tryptophan hydroxylase mRNA expression in rhesus macaques. J Neurosci 16(21):7021–7029
65.
Chen Z, Yuhanna IS, Galcheva-Gargova Z et al (1999) Estrogen receptor alpha mediates the nongenomic activation of endothelial nitric oxide synthase by estrogen. J Clin Invest 103(3):401–406
66.
Sarchielli P, Tognoloni M, Russo S et al (1996) Variations in the platelet arginine/nitric oxide pathway during the ovarian cycle in females affected by menstrual migraine. Cephalalgia 16(7):468–475
67.
Zheng X, He FF, Nie M et al (2002) Effects of sex hormones on serum levels of nitric oxide and plasma angiotensin II in postmenopausal women. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 24(6):635–638
68.
Twyman RE, Macdonald RL (1992) Neurosteroid regulation of GABAA receptor single-channel kinetic properties of mouse spinal cord neurons in culture. J Physiol 456:215–245PubMedPubMedCentralCrossRef
69.
Kelly MJ, Loose MD, Ronnekleiv OK (1992) Estrogen suppresses mu-opioid- and GABAB –mediated hyperpolarization of hypothalamic arcuate neurons. J Neurosci 12(7):2745–2750PubMedPubMedCentralCrossRef
70.
Cyr M, Ghribi O, Thibault C et al (2001) Ovarian steroids and selective estrogen receptor modulators activity on rat brain NMDA e AMPA receptors. Brain Res Brain Res Rev 37(1–3):153–161
71.
Sarton E, Olofsen E, Romberg R et al (2000) Sex differences in morphine analgesia: an experimental study in healthy volunteers. Anesthesiology 93(5):1245–1254
72.
Medina VM, Dawson-Basoa ME, Gintzler AR (1993) 17 beta-estradiol and progesterone positively modulate spinal cord dynorphin: relevance to the analgesia of pregnancy. Neuroendocrinology 58(3):310–315PubMedCrossRef
73.
Liu J, Qin W, Nan J et al (2011) Gender-related differences in the dysfunctional resting networks of migraine suffers. PLoS One 6(11):e27049
74.
Borsook D, Erpelding N, Lebel A et al (2014) Sex and the migraine brain. Neurobiol Dis 68:200–214
75.
Metadata
Title
Gender-related differences in migraine
Authors
Gianni Allais
Giulia Chiarle
Silvia Sinigaglia
Gisella Airola
Paola Schiapparelli
Chiara Benedetto
Publication date
01-12-2020
Publisher
Springer International Publishing
Published in
Neurological Sciences / Issue Special Issue 2/2020
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI
https://doi.org/10.1007/s10072-020-04643-8

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