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Current Pain and Headache Reports
Published in: Current Pain and Headache Reports 5/2012

01-10-2012 | Perimenstrual Headache (S Evers, Section Editor)

Transdermal Hormonal Therapy in Perimenstrual Migraine: Why, When and How?

Authors: Cristina Tassorelli, Rosaria Greco, Marta Allena, Erica Terreno, Rossella E. Nappi

Published in: Current Pain and Headache Reports | Issue 5/2012

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Abstract

Experimental and clinical evidence is strongly in favor of a role for estrogens in migraine. It is clear that estrogen fluctuations represent trigger factors for the attacks, while the resolution of these fluctuations (menopause) may be associated to the remission or, conversely, to the worsening of the disease. However, the exact mechanisms and mediators underlying the effects of estrogens in migraine are largely unknown. The exact mechanisms and mediators underlying the effects of estrogens in migraine are largely unknown. In this review, we summarize clinical and preclinical data that are relevant for the role of estrogens in migraine and we discuss how estrogen modulation can be exploited positively to improve hormonal-related migraine.
Literature
1.
•• Nappi RE, Nappi G. Neuroendocrine aspects of migraine in women. Gynecol Endocrinol. 2012;28 Suppl 1:37–41. Concise review on the role of endogenous estrogen at the level of brain circuitries which are involved in multiple cellular, neurochemical and neurophysiological processes associated with migraine and reproductive milestones, with a focus on the management.PubMedCrossRef
2.
3.
Johannes CB, Linet MS, Stewart WF, et al. Relationship of headache to phase of the menstrual cycle among young women: a daily diary study. Neurology. 1995;45:1076–82.PubMedCrossRef
4.
Stewart WF, Lipton RB, Chee E, et al. Menstrual cycle and headache in a population sample of migraineurs. Neurology. 2000;55:1517–23.PubMedCrossRef
5.
MacGregor EA, Hackshaw A. Prevalence of migraine on each day of the natural menstrual cycle. Neurology. 2004;63:351–3.PubMedCrossRef
6.
Stewart WF, Linet MS, Celentano DD, et al. Age- and sex-specific incidence rates of migraine with and without visual aura. Am J Epidemiol. 1991;134:1111–20.PubMed
7.
MacGregor EA. Oestrogen and attacks of migraine with and without aura. Lancet Neurol. 2004;3:354–61.PubMedCrossRef
8.
The International Classification of Headache Disorders. 8th ed. Cephalalgia. 2004(Suppl. 1);24:9–160.
9.
MacGregor EA, Chia H, Vohrah RC, Wilkinson M. Migraine and menstruation: a pilot study. Cephalalgia. 1990;10:305–10.PubMedCrossRef
10.
Couturier EG, Bomhof MA, Neven AK, van Duijn NP. Menstrual migraine in a representative Dutch population sample: prevalence, disability and treatment. Cephalalgia. 2003;23:302–8.PubMedCrossRef
11.
Granella F, Sances G, Allais G, et al. Characteristics of menstrual and non-menstrual attacks in women with menstrually-related migraine. Cephalalgia. 2004;24:707–16.PubMedCrossRef
12.
Mogil JS, Sternberg WF, Kest B, et al. Sex differences in the antagonism of swim stress-induced analgesia: effects of gonadectomy and estrogen replacement. Pain. 1993;53:17–25.PubMedCrossRef
13.
Kuba T, Wu HB, Nazarian A, et al. Estradiol and progesterone differentially regulate formalin-induced nociception in ovariectomized female rats. Horm Behav. 2006;49:441–9.PubMedCrossRef
14.
Fillingim RB, King CD, Ribeiro-Dasilva MC, et al. Sex, gender, and pain: a review of recent clinical and experimental findings. J Pain. 2009;10:447–85.PubMed
15.
Nappi G, Jensen R, Nappi RE, Sances G, Torelli P, Olesen J. Diaries and calendars for migraine. A review. Cephalalgia 2006;26:905–916.
16.
Wise EA, Price DD, Myers CD, et al. Gender role expectations of pain: Relationship to experimental pain perception. Pain. 2002;96:335–42.PubMedCrossRef
17.
18.
Mattsson P. Hormonal factors in migraine: A population-based study of women aged 40 to 74 years. Headache. 2003;43:27–35.PubMedCrossRef
19.
Granella F, Sances G, Pucci E, et al. Migraine with aura and reproductive life events: a case control study. Cephalalgia. 2000;20:701–7.PubMed
20.
Fillingim RB, Edwards RR. The association of hormone replacement therapy with experimental pain responses in postmenopausal women. Pain. 2001;92:229–34.PubMedCrossRef
21.
Flake NM, Bonebreak DB, Gold MS. Estrogen and inflammation increase the excitability of rat temporomandibular joint afferent neurons. J Neurophysiol. 2005;93:1585–97.PubMedCrossRef
22.
Ji Y, Tang B, Traub RJ. Spinal estrogen receptor alpha mediates estradiol-induced pronociception in a visceral pain model in the rat. Pain. 2011;152:1182–91.PubMedCrossRef
23.
• Rowan MP, Berg KA, Milam SB, et al. 17beta-estradiol rapidly enhances bradykinin signaling in primary sensory neurons in vitro and in vivo. J Pharmacol Exp Ther. 2010;335:190–6. Original paper on culture of rat sensory neurons and on an animal model of pain which shows that estradiol enhances inflammatory mediator responses.PubMedCrossRef
24.
Cairns BE, Hu JW, Arendt-Nielsen L, et al. Sex-related differences in human pain and rat afferent discharge evoked by injection of glutamate into the masseter muscle. J Neurophysiol. 2001;86:782–91.PubMed
25.
Gazerani P, Kaeseler Andersen O, Arendt-Nielsen L. A human experimental capsaicin model for trigeminal sensitization. Gender-specific differences. Pain. 2005;118:155–63.PubMedCrossRef
26.
Tsao CM, Ho CM, Tsai SK, et al. Effects of estrogen on autotomy in normal and ovariectomized rats. Pharmacology. 1999;59:142–8.PubMedCrossRef
27.
Giamberardino MA, Affaitati G, Valente R, et al. Changes in visceral pain reactivity as a function of estrous cycle in female rats with artificial ureteral calculosis. Brain Res. 1997;774:234–8.PubMedCrossRef
28.
Sarajari S, Oblinger MM. Estrogen effects on pain sensitivity and neuropeptide expression in rat sensory neurons. Exp Neurol. 2010;224:163–9.PubMedCrossRef
29.
Smith YR, Stohler CS, Nichols TE, et al. Pronociceptive and antinociceptive effects of estradiol through endogenous opioid neurotransmission in women. J Neurosci. 2006;26:5777–85.PubMedCrossRef
30.
Dondi D, Limonta P, Maggi R, Piva F. Effects of ovarian hormones on brain opioid binding sites in castrated female rats. Am J Physiol. 1992;S263:E507–11.
31.
Eckersell CB, Popper P, Micevych PE. Estrogen-induced alteration of mu-opioid receptor immunoreactivity in the medial preoptic nucleus and medial amygdala. J Neurosci. 1998;18:3967–76.PubMed
32.
Sinchak K, Eckersell C, Quezada V, et al. Preproenkephalin mRNA levels are regulated by acute stress and estrogen stimulation. Physiol Behav. 2000;69:425–32.PubMedCrossRef
33.
Ansonoff MA, Etgen AM. Estrogen increases G protein coupled receptor kinase 2 in the cortex of female rats. Brain Res. 2001;898:186–9.PubMedCrossRef
34.
Mogil JS, Chesler EJ, Wilson SG, et al. Sex differences in thermal nociception and morphine antinociception in rodents depend on genotype. Neurosci Biobehav Rev. 2000;24:375–89.PubMedCrossRef
35.
Stening KD, Berg G, Hammar M, Voster H, et al. Influence of estrogen levels on thermal perception, pain thresholds, and pain tolerance: Studies on women undergoing in vitro fertilization. J Pain. 2012;13:459–66.PubMed
36.
Tassorelli C, Sandrini G, Cecchini AP, et al. Changes in nociceptive flexion reflex threshold across the menstrual cycle in healthy women. Psychosom Med. 2002;64:621–6.PubMedCrossRef
37.
Bolay H, Berman NE, Akcali D. Sex-related differences in animal models of migraine headache. Headache. 2011;51:891–904.PubMedCrossRef
38.
39.
40.
Muneyvirci-Delale O, Nacharaju VL, Altura BM, et al. Sex steroid hormones modulate serum ionized magnesium and calcium levels throughout the menstrual cycle in women. Fertil Steril. 1998;69:958–62.
41.
Pitkin RM, Reynolds WA, Williams GA, et al. Calcium-regulating hormones during the menstrual cycle. J Clin Endocrinol Metab. 1978;47:626–32.PubMedCrossRef
42.
Zhao X, MacBride MM, Peterson BR, et al. Calcium flux in neuroblastoma cells is a coupling mechanism between non-genomic and genomic modes of estrogens. Neuroendocrinology. 2005;81:174–82.PubMedCrossRef
43.
Arulmani U, MaassenVanDenBrink A, Villalón CM, et al. Calcitonin gene-related peptide and its role in migraine pathophysiology. Eur J Pharmacol. 2004;500:315–30.PubMedCrossRef
44.
Gupta S, Mehrotra S, Villalón CM, et al. 17β-Estradiol potentiates CGRP-mediated relaxations in caudal mesenteric arteries in ovariectomized rats. J Headache Pain. 2006;7:S54.
45.
Dong YL, Vegiraju S, Gangula PR. Expression and regulation of calcitonin generelated Peptide receptor in rat placentas. Biol Reprod. 2002;67:1321–6.PubMedCrossRef
46.
Yallampalli C, Kondapaka SB, Lanlua P, et al. Female sex steroid hormones and pregnancy regulate receptors for calcitonin gene-related peptide in rat mesenteric arteries, but not in aorta. Biol Reprod. 2004;70:1055–62.PubMedCrossRef
47.
Moncada S. Nitric oxide: Physiology, pathophysiology and pharmacology. Pharmacol Rev. 1991;43:109–42.PubMed
48.
Pardutz A, Multon S, Malgrange B, et al. Effect of systemic nitroglycerin on CGRP and 5-HT afferents to rat caudal spinal trigeminal nucleus and its modulation by estrogen. Eur J Neurosci. 2002;15:1803–9.PubMedCrossRef
49.
Sarchielli P, Tognoloni M, Russo S, et al. Variations in the platelet arginine/nitric oxide pathway during the ovarian cycle in females affected by menstrual migraine. Cephalalgia. 1996;16:468–75.PubMedCrossRef
50.
Martin V, Behbehani M. Fos expression of trigeminal nucleus caudalis neurons after dural activation during different states of the rat estrous cycle [abstract]. Headache. 2005;45:788.
51.
Bereiter DA, Stanford LR, Barker DJ. Hormone-induced enlargement of receptive fields in trigeminal mechanoreceptive neurons. II. Possible mechanisms. Brain Res. 1980;184:411–23.PubMedCrossRef
52.
Gupta S, Mehrotra S, Villalón CM, et al. Potential role of female sex hormones in the pathophysiology of migraine. Pharmacol Ther. 2007;113:321–40.PubMedCrossRef
53.
Berman NE, Puri V, Chandrala S, et al. Serotonin in trigeminal ganglia of female rodents: relevance to menstrual migraine. Headache. 2006;46:1230–45.PubMedCrossRef
54.
Puri V, Puri S, Svojanovsky SR, et al. Effects of oestrogen on trigeminal ganglia in culture: Implications for hormonal effects on migraine. Cephalalgia. 2006;26:33–42.PubMedCrossRef
55.
Ji RR, Baba H, Brenner GJ, Woolf CJ. Nociceptive-specific activation of ERK in spinal neurons contributes to pain hypersensitivity. Nat Neurosci. 1999;2:1114–9.PubMedCrossRef
56.
Hershey AD, Tang Y, Powers SW, et al. Genomic abnormalities in patients with migraine and chronic migraine: Preliminary blood gene expression suggests platelet abnormalities. Headache. 2004;44:994–1004.PubMedCrossRef
57.
Tassorelli C, Joseph SA. Systemic nitroglycerin induces Fos immunoreactivity in brainstem and forebrain structures of the rat. Brain Res. 1995;682:167–78.PubMedCrossRef
58.
Tassorelli C, Joseph SA, Buzzi G, Nappi G. The effect on the central nervous system of nitroglycerin - Putative mechanisms and mediators. Prog Neurobiol. 1999;57:606–24.CrossRef
59.
Tassorelli C, Greco R, Wang D, Morelli G, Nappi G. Nitroglycerin induces hyperalgesia in rats: A time-course study. Eur J Pharm. 2003;464:159–62.CrossRef
60.
Ueyama T, Tanioku T, Nuta J, et al. Estrogen alters c-Fos response to immobilization stress in the brain of ovariectomized rats. Brain Res. 2006;1084:67–79.PubMedCrossRef
61.
Granella F, Sances G, Zanferrari C, et al. Migraine without aura and reproductive life events: a clinical epidemiological study in 1300 women. Headache. 1993;33:385–9.PubMedCrossRef
62.
63.
Martin V, Wernke S, Mandell K, Grumbach MM. Defining the relationship between ovarian hormones and migraine headache. Headache. 2005;45:1190–201.PubMedCrossRef
64.
Facchinetti F, Neri I, Martignoni E, Fioroni L, Nappi G, Genazzani AR. The association of menstrual migraine with the premenstrual syndrome. Cephalalgia. 1993;13:422–5.PubMedCrossRef
65.
• Hershey A, Horn P, Kabbouche M, O'Brien H, Powers S. Genomic expression patterns in menstrual-related migraine in adolescents. Headache. 2012;52:68–79. Original paper which suggests that menstrual-related migraine can be identified by specific biomarkers and that the disorder is associated to genes that regulate immunomodulation/inflammation, mitochondrial function, and DNA homeostasis.PubMedCrossRef
66.
Nappi RE, Sances G, Brundu B, et al. Neuroendocrine response to the serotonin agonist M-chlorophenylpiperazine in women with menstrual status migrainosus. Neuroendocrinology. 2003;78:52–60.PubMedCrossRef
67.
Nappi RE, Sances G, Brundu B, et al. Estradiol supplementation modulates neuroendocrine response to M-chlorophenylpiperazine in menstrual status migrainosus triggered by oral contraception-free interval. Hum Reprod. 2005;20:3423–8.PubMedCrossRef
68.
69.
Shuster LT, Faubion SS, Sood R, Casey PM. Hormonal manipulation strategies in the management of menstrual migraine and other hormonally related headaches. Curr Neurol Neurosci Rep. 2011;11:131–8.PubMedCrossRef
70.
Martin V, Wernke S, Mandell K, et al. Medical oophorectomy with and without estrogen add-back therapy in the prevention of migraine headache. Headache. 2003;43:309–21.PubMedCrossRef
71.
de Lignieres B, Vincens M, Mauvais-Jarvis P, et al. Prevention of menstrual migraine by percutaneous oestradiol. Br Med J. 1986;293:1540.CrossRef
72.
Dennerstein L, Morse C, Burrows G, et al. Menstrual migraine: a double-blind trial of percutaneous estradiol. Gynecol Endocrinol. 1988;2:113–20.PubMedCrossRef
73.
Pradalier A, Vincent D, Beaulieu P, et al. Correlation between oestradiol plasma level and therapeutic effect on menstrual migraine. In: Rose C, editor. New advances in headache research: 4. London: Smith-Gordon; 1994. p. 129–32.
74.
Smits MG, van der Meer YG, Pfeil JP, et al. Perimenstrual migraine: effect of Estraderm TTS and the value of contingent negative variation and exteroceptive temporalis muscle suppression test. Headache. 1994;34:103–6.PubMedCrossRef
75.
MacGregor EA, Frith A, Ellis J, et al. Prevention of menstrual attacks of migraine: a double-blind placebo-controlled crossover study. Neurology. 2006;67:2159–63.PubMedCrossRef
76.
Almén-Christensson A, Hammar M, Lindh-Åstrand L, et al. Prevention of menstrual migraine with perimenstrual transdermal 17-β-estradiol: a randomized, placebo-controlled, double-blind crossover study. Fertil Steril. 2011;96:498–500.PubMedCrossRef
77.
Nappi RE, Sances G, Detaddei S, et al. Hormonal management of migraine at menopause. Menopause Int. 2009;15:82–6.PubMedCrossRef
78.
•• MacGregor EA. Perimenopausal migraine in women with vasomotor symptoms. Maturitas. 2012;71:79–82. Another short, but exhaustive, review analyzing perimenopause as a condition associated with a peak rate of change of migraine prevalence in women. The usefulness of maintaining a stable estrogen environment, using the lowest possible doses, is discussed for both vasomotor symptoms and estrogen-withdrawal migraine.PubMedCrossRef
79.
MacGregor EA. Effect of oral and transdermal estrogen replacement on migraine. Cephalalgia. 1999;19:124–5.PubMedCrossRef
80.
Nappi RE, Cagnacci A, Granella F, et al. Course of primary headaches during hormone replacement therapy. Maturitas. 2001;38:157–63.PubMedCrossRef
Metadata
Title
Transdermal Hormonal Therapy in Perimenstrual Migraine: Why, When and How?
Authors
Cristina Tassorelli
Rosaria Greco
Marta Allena
Erica Terreno
Rossella E. Nappi
Publication date
01-10-2012
Publisher
Current Science Inc.
Published in
Current Pain and Headache Reports / Issue 5/2012
Print ISSN: 1531-3433
Electronic ISSN: 1534-3081
DOI
https://doi.org/10.1007/s11916-012-0293-8

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