Skip to main content
Top
Published in: Current Pain and Headache Reports 5/2010

01-10-2010

Genetics of Menstrual Migraine: The Molecular Evidence

Authors: Natalie Colson, Francesca Fernandez, Lyn Griffiths

Published in: Current Pain and Headache Reports | Issue 5/2010

Login to get access

Abstract

Migraine is considered to be a multifactorial disorder in which genetic, environmental, and, in the case of menstrual and menstrually related migraine, hormonal events influence the phenotype. Certainly, the role of female sex hormones in migraine has been well established, yet the mechanism behind this well-known relationship remains unclear. This review focuses on the potential role of hormonally related genes in migraine, summarizes results of candidate gene studies to date, and discusses challenges and issues involved in interpreting hormone-related gene results. In light of the molecular evidence presented, we discuss future approaches for analysis with the view to elucidate the complex genetic architecture that underlies the disorder.
Literature
1.
go back to reference Couturier EG, Bomhof MA, Neven AK, van Duijn NP: Menstrual migraine in a representative Dutch population sample: prevalence, disability and treatment. Cephalalgia 2003, 23:302–308.CrossRefPubMed Couturier EG, Bomhof MA, Neven AK, van Duijn NP: Menstrual migraine in a representative Dutch population sample: prevalence, disability and treatment. Cephalalgia 2003, 23:302–308.CrossRefPubMed
4.
go back to reference •• Gupta S, Mehrotra S, Villalón CM, et al.: Potential role of female sex hormones in the pathophysiology of migraine. Pharmacol Ther 2007, 113:321–340. This review details the changes in migraine throughout the female reproductive cycle and discusses the vascular and neuronal effects of sex hormones and how they may play a role in migraine.CrossRefPubMed •• Gupta S, Mehrotra S, Villalón CM, et al.: Potential role of female sex hormones in the pathophysiology of migraine. Pharmacol Ther 2007, 113:321–340. This review details the changes in migraine throughout the female reproductive cycle and discusses the vascular and neuronal effects of sex hormones and how they may play a role in migraine.CrossRefPubMed
5.
go back to reference MacGregor EA, Chia H, Vohrah RC, Wilkinson M: Migraine and menstruation: a pilot study. Cephalalgia 1990, 10:305–310.CrossRefPubMed MacGregor EA, Chia H, Vohrah RC, Wilkinson M: Migraine and menstruation: a pilot study. Cephalalgia 1990, 10:305–310.CrossRefPubMed
6.
go back to reference MacGregor EA: Oestrogen and attacks of migraine with and without aura. Lancet Neurol 2004, 3: 354–361.CrossRefPubMed MacGregor EA: Oestrogen and attacks of migraine with and without aura. Lancet Neurol 2004, 3: 354–361.CrossRefPubMed
7.
go back to reference Headache Classification Subcommittee of the International Headache Society: The International Classification of Headache Disorders: 2nd edition. Cephalalgia 2004, 24(Suppl 1):1–60. Headache Classification Subcommittee of the International Headache Society: The International Classification of Headache Disorders: 2nd edition. Cephalalgia 2004, 24(Suppl 1):1–60.
8.
go back to reference Dennerstein L, Morse C, Burrows G, et al.: Menstrual migraine: a double-blind trial of percutaneous estradiol. Gynecol Endocrinol 1988, 2:113–120.CrossRefPubMed Dennerstein L, Morse C, Burrows G, et al.: Menstrual migraine: a double-blind trial of percutaneous estradiol. Gynecol Endocrinol 1988, 2:113–120.CrossRefPubMed
9.
go back to reference Smitherman TA, Kolivas ED: Resolution of menstrually related migraine following aggressive treatment for breast cancer. Headache 2010, 50:485–488.CrossRefPubMed Smitherman TA, Kolivas ED: Resolution of menstrually related migraine following aggressive treatment for breast cancer. Headache 2010, 50:485–488.CrossRefPubMed
10.
go back to reference Somerville BW: The role of estradiol withdrawal in the etiology of menstrual migraine. Neurology 1972, 22:355–365.PubMed Somerville BW: The role of estradiol withdrawal in the etiology of menstrual migraine. Neurology 1972, 22:355–365.PubMed
11.
go back to reference Epstein MT, Hockaday JM, Hockaday TD: Migraine and reporoductive hormones throughout the menstrual cycle. Lancet 1975, 1:543–548.CrossRefPubMed Epstein MT, Hockaday JM, Hockaday TD: Migraine and reporoductive hormones throughout the menstrual cycle. Lancet 1975, 1:543–548.CrossRefPubMed
12.
go back to reference Ulrich V, Gervil M, Kyvik KO, et al.: Evidence of a genetic factor in migraine with aura: a population-based Danish twin study. Ann Neurol 1999, 45:242–246.CrossRefPubMed Ulrich V, Gervil M, Kyvik KO, et al.: Evidence of a genetic factor in migraine with aura: a population-based Danish twin study. Ann Neurol 1999, 45:242–246.CrossRefPubMed
13.
go back to reference Gervil M, Ulrich V, Kyvik KO, et al.: Migraine without aura: a population-based twin study. Ann Neurol 1999, 46:606–611.CrossRefPubMed Gervil M, Ulrich V, Kyvik KO, et al.: Migraine without aura: a population-based twin study. Ann Neurol 1999, 46:606–611.CrossRefPubMed
14.
go back to reference Gervil M, Ulrich V, Kaprio J, et al.: The relative role of genetic and environmental factors in migraine without aura. Neurology 1999, 53:995–999.PubMed Gervil M, Ulrich V, Kaprio J, et al.: The relative role of genetic and environmental factors in migraine without aura. Neurology 1999, 53:995–999.PubMed
15.
go back to reference Mulder EJ, Van Baal C, Gaist D, et al.: Genetic and environmental influences on migraine: a twin study across six countries. Twin Res 2003, 6:422–431.CrossRefPubMed Mulder EJ, Van Baal C, Gaist D, et al.: Genetic and environmental influences on migraine: a twin study across six countries. Twin Res 2003, 6:422–431.CrossRefPubMed
16.
go back to reference •• Martin VT, Behbehani M: Ovarian hormones and migraine headache: understanding mechanisms and pathogenesis: part I. Headache 2006, 46:3–23. This comprehensive review details the effects of steroid hormones in brain pathways believed to be involved in migraine.CrossRefPubMed •• Martin VT, Behbehani M: Ovarian hormones and migraine headache: understanding mechanisms and pathogenesis: part I. Headache 2006, 46:3–23. This comprehensive review details the effects of steroid hormones in brain pathways believed to be involved in migraine.CrossRefPubMed
17.
go back to reference Stoffel-Wagner B: Neurosteroid biosynthesis in the human brain and its clinical implications. Ann N Y Acad Sci 2003, 1007:64–78.CrossRefPubMed Stoffel-Wagner B: Neurosteroid biosynthesis in the human brain and its clinical implications. Ann N Y Acad Sci 2003, 1007:64–78.CrossRefPubMed
18.
go back to reference Compagnone NA, Mellon SH: Neurosteroids: biosynthesis and function of these novel neuromodulators. Front Neuroendocrinol 2000, 21:1–56.CrossRefPubMed Compagnone NA, Mellon SH: Neurosteroids: biosynthesis and function of these novel neuromodulators. Front Neuroendocrinol 2000, 21:1–56.CrossRefPubMed
19.
go back to reference • Martin VT, Behbehani M: Ovarian hormones and migraine headache: understanding mechanisms and pathogenesis: part 2. Headache 2006, 46:365–386. This review discusses the influence of reproductive events on migraine.CrossRefPubMed • Martin VT, Behbehani M: Ovarian hormones and migraine headache: understanding mechanisms and pathogenesis: part 2. Headache 2006, 46:365–386. This review discusses the influence of reproductive events on migraine.CrossRefPubMed
20.
go back to reference • Varlibas A, Erdemoglu AK: Altered trigeminal system excitability in menstrual migraine patients. J Headache Pain 2009, 10:277–282. This study implicates trigeminal excitability in patients with menstrual migraine.CrossRefPubMed • Varlibas A, Erdemoglu AK: Altered trigeminal system excitability in menstrual migraine patients. J Headache Pain 2009, 10:277–282. This study implicates trigeminal excitability in patients with menstrual migraine.CrossRefPubMed
21.
go back to reference Martin VT, Lee J, Behbehani MM: Sensitization of the trigeminal sensory system during different stages of the rat estrous cycle: implications for menstrual migraine. Headache 2007, 47:552–563.CrossRefPubMed Martin VT, Lee J, Behbehani MM: Sensitization of the trigeminal sensory system during different stages of the rat estrous cycle: implications for menstrual migraine. Headache 2007, 47:552–563.CrossRefPubMed
22.
go back to reference Lambert GA, Donaldson C, Hoskin KL, et al.: Dilatation induced by 5-HT in the middle meningeal artery of the anaesthetised cat. Naunyn Schmiedebergs Arch Pharmacol 2004, 369:591–601.CrossRefPubMed Lambert GA, Donaldson C, Hoskin KL, et al.: Dilatation induced by 5-HT in the middle meningeal artery of the anaesthetised cat. Naunyn Schmiedebergs Arch Pharmacol 2004, 369:591–601.CrossRefPubMed
23.
24.
go back to reference Pecins-Thompson M, Brown NA, Kohama SG, Bethea CL: Ovarian steroid regulation of tryptophan hydroxylase mRNA expression in rhesus macaques. J Neurosci 1996, 16:7021–7029.PubMed Pecins-Thompson M, Brown NA, Kohama SG, Bethea CL: Ovarian steroid regulation of tryptophan hydroxylase mRNA expression in rhesus macaques. J Neurosci 1996, 16:7021–7029.PubMed
25.
go back to reference Pecins-Thompson M, Brown NA, Bethea CL: Regulation of serotonin re-uptake transporter mRNA expression by ovarian steroids in rhesus macaques. Brain Res Mol Brain Res 1998, 53:120–129.CrossRefPubMed Pecins-Thompson M, Brown NA, Bethea CL: Regulation of serotonin re-uptake transporter mRNA expression by ovarian steroids in rhesus macaques. Brain Res Mol Brain Res 1998, 53:120–129.CrossRefPubMed
26.
go back to reference Smith LJ, Henderson JA, Abell CW, Bethea CL: Effects of ovarian steroids and raloxifene on proteins that synthesize, transport, and degrade serotonin in the raphe region of macaques. Neuropsychopharmacology 2004, 29:2035–2045.CrossRefPubMed Smith LJ, Henderson JA, Abell CW, Bethea CL: Effects of ovarian steroids and raloxifene on proteins that synthesize, transport, and degrade serotonin in the raphe region of macaques. Neuropsychopharmacology 2004, 29:2035–2045.CrossRefPubMed
27.
go back to reference Sabban EL, Maharjan S, Nostramo R, et al.: Divergent effects of estradiol on gene expression of catecholamine biosynthetic enzymes. Physiol Behav 2010, 99:163–168.CrossRefPubMed Sabban EL, Maharjan S, Nostramo R, et al.: Divergent effects of estradiol on gene expression of catecholamine biosynthetic enzymes. Physiol Behav 2010, 99:163–168.CrossRefPubMed
28.
go back to reference Pau KY, Hess DL, Kohama S, et al.: Oestrogen upregulates noradrenaline release in the mediobasal hypothalamus and tyrosine hydroxylase gene expression in the brainstem of ovariectomized rhesus macaques. J Neuroendocrinol 2000, 12:899–909.CrossRefPubMed Pau KY, Hess DL, Kohama S, et al.: Oestrogen upregulates noradrenaline release in the mediobasal hypothalamus and tyrosine hydroxylase gene expression in the brainstem of ovariectomized rhesus macaques. J Neuroendocrinol 2000, 12:899–909.CrossRefPubMed
29.
go back to reference Karkanias GB, Ansonoff MA, Etgen AM: Estradiol regulation of alpha 1b-adrenoceptor mRNA in female rat hypothalamus-preoptic area. J Neuroendocrinol 1996, 8:449–455.CrossRefPubMed Karkanias GB, Ansonoff MA, Etgen AM: Estradiol regulation of alpha 1b-adrenoceptor mRNA in female rat hypothalamus-preoptic area. J Neuroendocrinol 1996, 8:449–455.CrossRefPubMed
30.
go back to reference Karkanias GB, Petitti N, Etgen AM: Progesterone attenuation of alpha 1-adrenergic receptor stimulation of phosphoinositol hydrolysis in hypothalamus of estrogen-primed female rats. Endocrinology 1995, 136:1993–1999.CrossRefPubMed Karkanias GB, Petitti N, Etgen AM: Progesterone attenuation of alpha 1-adrenergic receptor stimulation of phosphoinositol hydrolysis in hypothalamus of estrogen-primed female rats. Endocrinology 1995, 136:1993–1999.CrossRefPubMed
31.
go back to reference Shughrue PJ, Merchenthaler I: Estrogen is more than just a "sex hormone": novel sites for estrogen action in the hippocampus and cerebral cortex. Front Neuroendocrinol 2000, 21:95–101.CrossRefPubMed Shughrue PJ, Merchenthaler I: Estrogen is more than just a "sex hormone": novel sites for estrogen action in the hippocampus and cerebral cortex. Front Neuroendocrinol 2000, 21:95–101.CrossRefPubMed
32.
go back to reference Epperson CN, Haga K, Mason GF, et al.: Cortical gamma-aminobutyric acid levels across the menstrual cycle in healthy women and those with premenstrual dysphoric disorder: a proton magnetic resonance spectroscopy study. Arch Gen Psychiatry 2002, 59:851–858.CrossRefPubMed Epperson CN, Haga K, Mason GF, et al.: Cortical gamma-aminobutyric acid levels across the menstrual cycle in healthy women and those with premenstrual dysphoric disorder: a proton magnetic resonance spectroscopy study. Arch Gen Psychiatry 2002, 59:851–858.CrossRefPubMed
33.
go back to reference • Eikermann-Haerter K, Dileköz E, Kudo C, et al.: Genetic and hormonal factors modulate spreading depression and transient hemiparesis in mouse models of familial hemiplegic migraine type 1. J Clin Invest 2009, 119:99–109. This animal study provides evidence for an additive effect of gene mutations and steroid hormones in migraine.PubMed • Eikermann-Haerter K, Dileköz E, Kudo C, et al.: Genetic and hormonal factors modulate spreading depression and transient hemiparesis in mouse models of familial hemiplegic migraine type 1. J Clin Invest 2009, 119:99–109. This animal study provides evidence for an additive effect of gene mutations and steroid hormones in migraine.PubMed
34.
go back to reference Eikermann-Haerter K, Baum MJ, Ferrari MD, et al.: Androgenic suppression of spreading depression in familial hemiplegic migraine type 1 mutant mice. Ann Neurol 2009, 66:564–568.CrossRefPubMed Eikermann-Haerter K, Baum MJ, Ferrari MD, et al.: Androgenic suppression of spreading depression in familial hemiplegic migraine type 1 mutant mice. Ann Neurol 2009, 66:564–568.CrossRefPubMed
35.
36.
go back to reference Agoulnik IU, Tong XW, Fischer DC, et al.: A germline variation in the progesterone receptor gene increases transcriptional activity and may modify ovarian cancer risk. J Clin Endocrinol Metab 2004, 89:6340–6347.CrossRefPubMed Agoulnik IU, Tong XW, Fischer DC, et al.: A germline variation in the progesterone receptor gene increases transcriptional activity and may modify ovarian cancer risk. J Clin Endocrinol Metab 2004, 89:6340–6347.CrossRefPubMed
37.
go back to reference Cenni B, Picard D: Ligand-independent activation of steroid receptors: new roles for old players. Trends Endocrinol Metab 1999, 10:41–46.CrossRefPubMed Cenni B, Picard D: Ligand-independent activation of steroid receptors: new roles for old players. Trends Endocrinol Metab 1999, 10:41–46.CrossRefPubMed
38.
go back to reference Curran JE, Lea RA, Rutherford S, et al.: Association of estrogen receptor and glucocorticoid receptor gene polymorphisms with sporadic breast cancer. Int J Cancer 2001, 95:271–275.CrossRefPubMed Curran JE, Lea RA, Rutherford S, et al.: Association of estrogen receptor and glucocorticoid receptor gene polymorphisms with sporadic breast cancer. Int J Cancer 2001, 95:271–275.CrossRefPubMed
39.
go back to reference Colson NJ, Lea RA, Quinlan S, et al.: The estrogen receptor 1 G594A polymorphism is associated with migraine susceptibility in two independent case/control groups. Neurogenetics 2004, 5:129–133.CrossRefPubMed Colson NJ, Lea RA, Quinlan S, et al.: The estrogen receptor 1 G594A polymorphism is associated with migraine susceptibility in two independent case/control groups. Neurogenetics 2004, 5:129–133.CrossRefPubMed
40.
go back to reference Colson NJ, Lea RA, Quinlan S, et al.: Investigation of hormone receptor genes in migraine. Neurogenetics 2005, 6:17–23.CrossRefPubMed Colson NJ, Lea RA, Quinlan S, et al.: Investigation of hormone receptor genes in migraine. Neurogenetics 2005, 6:17–23.CrossRefPubMed
41.
go back to reference Krithivas K, Yurgalevitch SM, Mohr BA, et al.: Evidence that the CAG repeat in the androgen receptor gene is associated with the age-related decline in serum androgen levels in men. J Endocrinol 1999, 162:137–142.CrossRefPubMed Krithivas K, Yurgalevitch SM, Mohr BA, et al.: Evidence that the CAG repeat in the androgen receptor gene is associated with the age-related decline in serum androgen levels in men. J Endocrinol 1999, 162:137–142.CrossRefPubMed
42.
go back to reference Donaldson CJ, Crapanzano JP, Watson JC, et al.: PROGINS Alu insertion and human genomic diversity. Mutat Res 2002, 501:137–141.PubMed Donaldson CJ, Crapanzano JP, Watson JC, et al.: PROGINS Alu insertion and human genomic diversity. Mutat Res 2002, 501:137–141.PubMed
43.
go back to reference Schuit SC, de Jong FH, Stolk L, et al.: Estrogen receptor alpha gene polymorphisms are associated with estradiol levels in postmenopausal women. Eur J Endocrinol 2005, 153:327–334.CrossRefPubMed Schuit SC, de Jong FH, Stolk L, et al.: Estrogen receptor alpha gene polymorphisms are associated with estradiol levels in postmenopausal women. Eur J Endocrinol 2005, 153:327–334.CrossRefPubMed
44.
go back to reference Shearman AM, Cooper JA, Kotwinski PJ, et al.: Estrogen receptor alpha gene variation and the risk of stroke. Stroke 2005, 36:2281–2282.CrossRefPubMed Shearman AM, Cooper JA, Kotwinski PJ, et al.: Estrogen receptor alpha gene variation and the risk of stroke. Stroke 2005, 36:2281–2282.CrossRefPubMed
45.
go back to reference Colson NJ, Lea RA, Quinlan S, Griffiths LR: No role for estrogen receptor 1 gene intron 1 Pvu II and exon 4 C325G polymorphisms in migraine susceptibility. BMC Med Genet 2006, 7:12.CrossRefPubMed Colson NJ, Lea RA, Quinlan S, Griffiths LR: No role for estrogen receptor 1 gene intron 1 Pvu II and exon 4 C325G polymorphisms in migraine susceptibility. BMC Med Genet 2006, 7:12.CrossRefPubMed
46.
go back to reference Oterino A, Pascual J, Ruiz de Alegría C, et al.: Association of migraine and ESR1 G325C polymorphism. Neuroreport 2006, 17:61–64.CrossRefPubMed Oterino A, Pascual J, Ruiz de Alegría C, et al.: Association of migraine and ESR1 G325C polymorphism. Neuroreport 2006, 17:61–64.CrossRefPubMed
47.
go back to reference Kaunisto MA, Kallela M, Hämäläinen E, et al.: Testing of variants of the MTHFR and ESR1 genes in 1798 Finnish individuals fails to confirm the association with migraine with aura. Cephalalgia 2006, 26:1462–1472.CrossRefPubMed Kaunisto MA, Kallela M, Hämäläinen E, et al.: Testing of variants of the MTHFR and ESR1 genes in 1798 Finnish individuals fails to confirm the association with migraine with aura. Cephalalgia 2006, 26:1462–1472.CrossRefPubMed
48.
go back to reference Lee H, Sininger L, Jen JC, et al.: Association of progesterone receptor with migraine-associated vertigo. Neurogenetics 2007, 8:195–200.CrossRefPubMed Lee H, Sininger L, Jen JC, et al.: Association of progesterone receptor with migraine-associated vertigo. Neurogenetics 2007, 8:195–200.CrossRefPubMed
49.
go back to reference • Oterino A, Toriello M, Cayón A, et al.: Multilocus analyses reveal involvement of the ESR1, ESR2, and FSHR genes in migraine. Headache 2008, 48:1438–1450. This study provides evidence for genetic interaction between three hormonally related genes. • Oterino A, Toriello M, Cayón A, et al.: Multilocus analyses reveal involvement of the ESR1, ESR2, and FSHR genes in migraine. Headache 2008, 48:1438–1450. This study provides evidence for genetic interaction between three hormonally related genes.
50.
go back to reference Corominas R, Ribasés M, Cuenca-León E, et al.: Lack of association of hormone receptor polymorphisms with migraine. Eur J Neurol 2009, 16:413–415.CrossRefPubMed Corominas R, Ribasés M, Cuenca-León E, et al.: Lack of association of hormone receptor polymorphisms with migraine. Eur J Neurol 2009, 16:413–415.CrossRefPubMed
51.
go back to reference Joshi G, Pradhan S, Mittal B: Role of the oestrogen receptor (ESR1 PvuII and ESR1 325 C-- > G) and progesterone receptor (PROGINS) polymorphisms in genetic susceptibility to migraine in a North Indian population. Cephalalgia 2010, 30:311–320.PubMed Joshi G, Pradhan S, Mittal B: Role of the oestrogen receptor (ESR1 PvuII and ESR1 325 C-- > G) and progesterone receptor (PROGINS) polymorphisms in genetic susceptibility to migraine in a North Indian population. Cephalalgia 2010, 30:311–320.PubMed
52.
go back to reference Yang Q, Khoury MJ, Friedman J, et al.: How many genes underlie the occurrence of common complex diseases in the population? Int J Epidemiol 2005, 34:1129–1137.CrossRefPubMed Yang Q, Khoury MJ, Friedman J, et al.: How many genes underlie the occurrence of common complex diseases in the population? Int J Epidemiol 2005, 34:1129–1137.CrossRefPubMed
53.
go back to reference Gorroochurn P, Hodge SE, Heiman GA, et al.: Non-replication of association studies: "pseudo-failures" to replicate? Genet Med 2007, 9:325–331.CrossRefPubMed Gorroochurn P, Hodge SE, Heiman GA, et al.: Non-replication of association studies: "pseudo-failures" to replicate? Genet Med 2007, 9:325–331.CrossRefPubMed
54.
go back to reference Welch KM, Brandes JL, Berman NE: Mismatch in how oestrogen modulates molecular and neuronal function may explain menstrual migraine. Neurol Sci 2006, 27(Suppl 2):S190–S192.CrossRefPubMed Welch KM, Brandes JL, Berman NE: Mismatch in how oestrogen modulates molecular and neuronal function may explain menstrual migraine. Neurol Sci 2006, 27(Suppl 2):S190–S192.CrossRefPubMed
55.
go back to reference Puri V, Cui L, Liverman CS, et al.: Ovarian steroids regulate neuropeptides in the trigeminal ganglion. Neuropeptides 2005, 39:409–417.CrossRefPubMed Puri V, Cui L, Liverman CS, et al.: Ovarian steroids regulate neuropeptides in the trigeminal ganglion. Neuropeptides 2005, 39:409–417.CrossRefPubMed
Metadata
Title
Genetics of Menstrual Migraine: The Molecular Evidence
Authors
Natalie Colson
Francesca Fernandez
Lyn Griffiths
Publication date
01-10-2010
Publisher
Current Science Inc.
Published in
Current Pain and Headache Reports / Issue 5/2010
Print ISSN: 1531-3433
Electronic ISSN: 1534-3081
DOI
https://doi.org/10.1007/s11916-010-0129-3

Other articles of this Issue 5/2010

Current Pain and Headache Reports 5/2010 Go to the issue