Abstract
Migraine is a prevalent headache disorder affecting three times more women than men during the reproductive years. Menstruation is a significant risk factor for migraine, with attacks most likely to occur on or between 2 days before the onset of menstruation and the first 3 days of bleeding. Although menstrual migraine has been recognized for many years, diagnostic criteria have only recently been published. These have enabled better comparison of the efficacy of drugs for this condition. Acute treatment, if effective, may be all that is necessary for control. Evidence of efficacy, with acceptable safety and tolerability, exists for sumatriptan 50 and 100 mg, mefenamic acid 500 mg, rizatriptan 10 mg and combination sumatriptan/naproxen 85 mg/500 mg. However, there is evidence that menstrual attacks are more severe, longer, less responsive to treatment, more likely to relapse and associated with greater disability than attacks at other times of the cycle. Prophylactic strategies can reduce the frequency and severity of attacks and acute treatment is more effective. Predictable menstrual attacks offer the opportunity for perimenstrual prophylaxis taken only during the time of increased migraine incidence. There is grade B evidence of efficacy for short-term prophylaxis with transcutaneous estradiol 1.5 mg, frovatriptan 2.5 mg twice daily and naratriptan 1 mg twice daily. Contraceptive strategies offer the opportunity for treating menstrual migraine in women who also require effective contraception.
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References
Victor TW, Hu X, Campbell JC, et al. Migraine prevalence by age and sex in the United States: a life span study. Cephalalgia 2010; 30(9): 1065–72
Steiner TJ, Scher AI, Stewart WF, et al. The prevalence and disability burden of adult migraine in England and their relationships to age, gender and ethnicity. Cephalalgia 2003 Sep; 23(7): 519–27
Stovner L, Hagen K, Jensen R, et al. The global burden of headache: a documentation of headache prevalence and disability worldwide. Cephalalgia 2007 Mar; 27(3): 193–210
Headache Classification Subcommittee of the International Headache Society (IHS). The International Classification of Headache Disorders 2nd edition. Cephalalgia 2004; 24 Suppl. 1: 1–160
Lipton RB, Dodick D, Sadovsky R, et al. A self-administered screener for migraine in primary care: the ID Migraine validation study. Neurology 2003 Aug 12; 61(3): 375–82
Stewart WF, Wood C, Reed ML, et al. Cumulative lifetime migraine incidence in women and men. Cephalalgia 2008; 28(11): 1170–8
Wober C, Brannath W, Schmidt K, et al. Prospective analysis of factors related to migraine attacks: the PAMINA study. Cephalalgia 2007 Apr; 27(4): 304–14
Vetvik KG, Macgregor EA, Lundqvist C, et al. Selfreported menstrual migraine in the general population. J Headache Pain 2010 Apr; 11(2): 87–92
MacGregor EA, Igarashi H, Wilkinson M. Headaches and hormones: subjective versus objective assessment. Headache Q 1997; 8: 126–36
Couturier EG, Bomhof MA, Neven AK, et al. Menstrual migraine in a representative Dutch population sample: prevalence, disability and treatment. Cephalalgia 2003 May; 23(4): 302–8
Dzoljic E, Sipetic S, Vlajinac H, et al. Prevalence of menstrually related migraine and nonmigraine primary headache in female students of Belgrade University. Headache 2002 Mar; 42(3): 185–93
Granella F, Sances G, Zanferrari C, et al. Migraine without aura and reproductive life events: a clinical epidemiological study in 1300 women. Headache 1993 Jul–Aug; 33(7): 385–9
MacGregor EA, Chia H, Vohrah RC, et al. Migraine and menstruation: a pilot study. Cephalalgia 1990 Dec; 10(6): 305–10
MacGregor EA, Brandes J, Eikermann A, et al. Impact of migraine on patients and their families: the Migraine And Zolmitriptan Evaluation (MAZE) survey — phase III. Curr Med Res Opin 2004 Jul; 20(7): 1143–50
Waters W, O’Connor P. Epidemiology of headache and migraine in women. J Neurol Neurosurg Psychiat 1971; 34: 148–53
Dalton K. Progesterone suppositories and pessaries in the treatment of menstrual migraine. Headache 1973; 13: 151–9
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 Jun; 45(6): 1076–82
Stewart WF, Lipton RB, Chee E, et al. Menstrual cycle and headache in a population sample of migraineurs. Neurology 2000 Nov 28; 55(10): 1517–23
MacGregor EA, Hackshaw A. Prevalence of migraine on each day of the natural menstrual cycle. Neurology 2004 Jul 27; 63(2): 351–3
MacGregor EA, Frith A, Ellis J, et al. Incidence of migraine relative to menstrual cycle phases of rising and falling estrogen. Neurology 2006 Sep 13; 67: 2154–8
Cupini LM, Matteis M, Troisi E, et al. Sex-hormone-related events in migrainous females: a clinical comparative study between migraine with aura and migraine without aura. Cephalalgia 1995 Apr; 15(2): 140–4
Rasmussen BK, Olesen J. Migraine with aura and migraine without aura: an epidemiological study. Cephalalgia 1992 Aug; 12(4): 221–8; discussion 186
Granella F, Sances G, Pucci E, et al. Migraine with aura and reproductive life events: a case control study. Cephalalgia 2000 Oct; 20(8): 701–7
Beckham JC, Krug LM, Penzien DB, et al. The relationship of ovarian steroids, headache activity and menstrual distress: a pilot study with female migraineurs. Headache 1992 Jun; 32(6): 292–7
Kibler JL, Rhudy JL, Penzien DB, et al. Hormones, menstrual distress, and migraine across the phases of the menstrual cycle. Headache 2005 Oct; 45(9): 1181–9
MacGregor EA, Victor TW, Hu X, et al. Characteristics of menstrual vs nonmenstrual migraine: a post hoc, within-woman analysis of the usual-care phase of a non-randomized menstrual migraine clinical trial. Headache 2010 Apr; 50(4): 528–38
Gross M, Barrie M, Bates D, et al. The efficacy of sumatriptan in menstrual migraine. Eur J Neurol 1995; 2: 144–5
Visser WH, Jaspers NMW, de Vriend RHM, et al. Risk factors for headache recurrence after sumatriptan: a study in 366 migraine patients. Cephalalgia 1996; 16: 264–9
Dowson AJ, Massiou H, Aurora SK. Managing migraine headaches experienced by patients who self-report with menstrually related migraine: a prospective, placebo-controlled study with oral sumatriptan. J Headache Pain 2005 Apr; 6(2): 81–7
Martin VT, Wernke S, Mandell K, et al. Defining the relationship between ovarian hormones and migraine headache. Headache 2005 Oct; 45(9): 1190–201
MacGregor EA. “Menstrual” migraine: towards a definition. Cephalalgia 1996 Feb; 16(1): 11–21
Silberstein SD, Armellino JJ, Hoffman HD, et al. Treatment of menstruation-associated migraine with the non-prescription combination of acetaminophen, aspirin, and caffeine: results from three randomized, placebo-controlled studies. Clin Ther 1999 Mar; 21(3): 475–91
Al-Waili NS. Treatment of menstrual migraine with prostaglandin synthesis inhibitor mefenamic acid: double-blind study with placebo. Eur J Med Res 2000 Apr 19; 5(4): 176–82
Diamond ML, Cady RK, Mao L, et al. Characteristics of migraine attacks and responses to almotriptan treatment: a comparison of menstrually related and nonmenstrually related migraines. Headache 2008 Feb; 48(2): 248–58
Allais G, Acuto G, Cabarrocas X, et al. Efficacy and tolerability of almotriptan versus zolmitriptan for the acute treatment of menstrual migraine. Neurol Sci 2006 May; 27 Suppl. 2: S193–7
Allais G, Bussone G, Airola G, et al. Oral contraceptive-induced menstrual migraine: clinical aspects and response to frovatriptan. Neurol Sci 2008 May; 29 Suppl. 1: S186–90
Massiou H, Jamin C, Hinzelin G, et al. Efficacy of oral naratriptan in the treatment of menstrually related migraine. Eur J Neurol 2005; 12(10): 774–81
Martin V, Cady R, Mauskop A, et al. Efficacy of rizatriptan for menstrual migraine in an early intervention model: a prospective subgroup analysis of the rizatriptan TAME (Treat A Migraine Early) studies. Headache 2008 Feb; 48(2): 226–35
Nett R, Mannix LK, Mueller L, et al. Rizatriptan efficacy in ICHD-II pure menstrual migraine and menstrually related migraine. Headache 2008; 48(8): 1194–201
Mannix LK, Loder E, Nett R, et al. Rizatriptan for the acute treatment of ICHD-II proposed menstrual migraine: two prospective, randomized, placebo-controlled, double-blind studies. Cephalalgia 2007 May; 27(5): 414–21
Silberstein SD, Massiou H, McCarroll KA, et al. Further evaluation of rizatriptan in menstrual migraine: retrospective analysis of long-term data. Headache 2002; 42: 917–23
Silberstein SD, Massiou H, Le Jeunne C, et al. Rizatriptan in the treatment of menstrual migraine. Obstet Gynecol 2000 Aug; 96(2): 237–42
Schreiber CP, Cady RK. Diagnosis of menstrual headache and an open-label study among those with previously undiagnosed menstrually related migraine to evaluate the efficacy of sumatriptan 100mg. Clin Ther 2007; 29 Suppl.: 2511–9
Landy S, Savani N, Shackelford S, et al. Efficacy and tolerability of sumatriptan tablets administered during the mild-pain phase of menstrually associated migraine. Int J Clin Pract 2004 Oct; 58(10): 913–9
Nett R, Landy S, Shackelford S, et al. Pain-free efficacy after treatment with sumatriptan in the mild pain phase of menstrually associated migraine. Obstet Gynecol 2003 Oct; 102(4): 835–42
Facchinetti F, Bonellie G, Kangasniemi P, et al. The efficacy and safety of subcutaneous sumatriptan in the acute treatment of menstrual migraine: the Sumatriptan Menstrual Migraine Study Group. Obstet Gynecol 1995 Dec; 86(6): 911–6
Solbach MP, Waymer RS. Treatment of menstruation-associated migraine headache with subcutaneous sumatriptan. Obstet Gynecol 1993 Nov; 82(5): 769–72
Mannix LK, Martin VT, Cady RK, et al. Combination treatment for menstrual migraine and dysmenorrhea using sumatriptan-naproxen: two randomized controlled trials. Obstet Gynecol 2009 Jul; 114(1): 106–13
Tuchman M, Hee A, Emeribe U, et al. Efficacy and tolerability of zolmitriptan oral tablet in the acute treatment of menstrual migraine. CNS Drugs 2006; 20(12): 1019–26
Loder E, Silberstein SD, Abu-Shakra S, et al. Efficacy and tolerability of oral zolmitriptan in menstrually associated migraine: a randomized, prospective, parallel-group, double-blind, placebo-controlled study. Headache 2004 Feb; 44(2): 120–30
Pringsheim T, Davenport WJ, Dodick D. Acute treatment and prevention of menstrually related migraine headache: evidence-based review. Neurology 2008 April 22; 70(17): 1555–63
Massiou H, Pitei D, Poole P, et al. Efficacy of eletriptan for the treatment of migraine in women with menstrually associated migraine, and in women on contraceptives or hormone replacement therapy: meta-analyses of randomized clinical trials [abstract]. Cephalalgia 2000; 20: 435
MacGregor EA, Keywood C. Frovatriptan is effective in menstrually associated migraine [abstract]. Cephalalgia 2000; 20: 345
Newman LC, Harper S, Jones BA, et al. Frovatriptan for acute treatment of migraine associated with menstruation: results from an open-label postmarketing surveillance study. J Womens Health (Larchmt) 2009 Aug; 18(8): 1265–73
MacGregor E, Victor T, Hu X, et al. Characteristics of menstrual vs nonmenstrual migraine: a post hoc, within-woman analysis of the usual-care phase of a non-randomized menstrual migraine clinical trial. Headache 2010 Apr; 50(4): 528–38
US Headache Consortium. Evidence-based guidelines for migraine headache in the primary care setting: pharmacological management for prevention of migraine. 2000 [online]. Available from URL: http://www.americanheadachesociety.org/professionalresources/USHeadacheConsortiumGuidelines.asp [Accessed 2006 Sep 10]
Guidotti M, Mauri M, Barrila C, et al. Frovatriptan vs. transdermal oestrogens or naproxen sodium for the prophylaxis of menstrual migraine. J Headache Pain 2007 Oct; 8(5): 283–8
North American Menopause Society. Estrogen and progestogen use in postmenopausal women: 2010 position statement of The North American Menopause Society. Menopause 2010 Mar; 17(2): 242–55
Allais G, Bussone G, De Lorenzo C, et al. Naproxen sodium in short-term prophylaxis of pure menstrual migraine: pathophysiological and clinical considerations. Neurol Sci 2007 May; 28 Suppl. 2: S225–8
Sances G, Martignoni E, Fioroni L, et al. Naproxen sodium in menstrual migraine prophylaxis: a double-blind placebo controlled study. Headache 1990 Nov; 30(11): 705–9
Szekely B, Meeryman S, Post G. Prophylactic effects of naproxen sodium on perimenstrual headache: a double-blind, placebo-controlled study. Cephalalgia 1989; 9: 452–3
Giacovazzo M, Gallo MF, Guidi V, et al. Nimesulide in the treatment of menstrual migraine. Drugs 1993; 46 Suppl. 1: 140–1
Von Seggern RL, Mannix LK, Adelman JU. Rofecoxib in the prevention of perimenstrual migraine: an open-label pilot trial. Headache 2004 Feb; 44(2): 160–5
Silberstein SD, Berner T, Tobin J, et al. Scheduled short-term prevention with frovatriptan for migraine occurring exclusively in association with menstruation. Headache 2009 Oct; 49(9): 1283–97
Silberstein SD, Elkind AH, Schreiber C, et al. A randomized trial of frovatriptan for the intermittent prevention of menstrual migraine. Neurology 2004; 63: 261–9
Brandes JL, Poole A, Kallela M, et al. Short-term frovatriptan for the prevention of difficult-to-treat menstrual migraine attacks. Cephalalgia 2009 Nov; 29(11): 1133–48
Mannix LK, Savani N, Landy S, et al. Efficacy and tolerability of naratriptan for short-term prevention of menstrually related migraine: data from two randomized, double-blind, placebo-controlled studies. Headache 2007 Jul–Aug; 47(7): 1037–49
Moschiano F, Allais G, Grazzi L, et al. Naratriptan in the short-term prophylaxis of pure menstrual migraine. Neurol Sci 2005 May; 26 Suppl. 2: s162–6
Newman L, Mannix LK, Landy S, et al. Naratriptan as short-term prophylaxis of menstrually associated migraine: a randomized, double-blind, placebo-controlled study. Headache 2001 Mar; 41(3): 248–56
Newman LC, Lipton RB, Lay CL, et al. A pilot study of oral sumatriptan as intermittent prophylaxis of menstruation-related migraine. Neurology 1998 Jul; 51(1): 307–9
Tuchman MM, Hee A, Emeribe U, et al. Oral zolmitriptan in the short-term prevention of menstrual migraine: a randomized, placebo-controlled study. CNS Drugs 2008; 22(10): 877–86
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
Pradalier A, Vincent D, Beaulieu P, et al. Correlation between estradiol plasma level and therapeutic effect on menstrual migraine. In: Rose F, editor. New advances in headache research. London: Smith-Gordon, 1994: 129–32
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 Feb; 34(2): 103–6
Pfaffenrath V. Efficacy and safety of percutaneous estradiol vs. placebo in menstrual migraine [abstract]. Cephalalgia 1993; 13 Suppl. 13: 244
Dennerstein L, Morse C, Burrows G, et al. Menstrual migraine: a double-blind trial of percutaneous estradiol. Gynecol Endocrinol 1988; 2: 113–20
de Lignières B, Vincens M, Mauvais-Jarvis P, et al. Prevention of menstrual migraine by percutaneous oestradiol. Br Med J (Clin Res Ed) 1986 Dec 13; 293(6561): 1540
Facchinetti F, Sances G, Borella P, et al. Magnesium prophylaxis of menstrual migraine: effects on intracellular magnesium. Headache 1991 May; 31(5): 298–301
Ziaei S, Kazemnejad A, Sedighi A. The effect of vitamin E on the treatment of menstrual migraine. Med Sci Monit 2009 Jan; 15(1): CR16–9
MacGregor EA, Frith A, Ellis J, et al. Predicting menstrual migraine with a home-use fertility monitor. Neurology 2005 Feb 8; 64(3): 561–3
Brandes JL. The influence of estrogen on migraine: a systematic review. JAMA 2006 Apr 19; 295(15): 1824–30
Mannix LK. Menstrual-related pain conditions: dysmenorrhea and migraine. J Womens Health (Larchmt) 2008 Jun; 17(5): 879–91
MacGregor EA, Brandes JL, Silberstein S, et al. Safety and tolerability of short-term preventive frovatriptan: a combined analysis. Headache 2009 Oct; 49(9): 1298–314
MacGregor E, Pawsey S, Campbell J, et al. Safety and tolerability of frovatriptan in the acute treatment of migraine and prevention of menstrual migraine: results of a new analysis of data from five previously published studies. Gend Med 2010 Apr; 7(2): 88–108
Brandes JL, Smith T, Diamond M, et al. Open-label, long-term tolerability of naratriptan for short-term prevention of menstrually related migraine. Headache 2007 Jun; 47(6): 886–94
MacGregor EA. Oestrogen and attacks of migraine with and without aura. Lancet Neurol 2004 Jun; 3(6): 354–61
Somerville BW. The role of estradiol withdrawal in the etiology of menstrual migraine. Neurology 1972; 22(4): 355–65
Somerville BW. Estrogen-withdrawal migraine: II. Attempted prophylaxis by continuous estradiol administration. Neurology 1975; 25(3): 245–50
Watson NR, Studd JW, Savvas M, et al. The long-term effects of estradiol implant therapy for the treatment of premenstrual syndrome. Gynecol Endocrinol 1990 Jun; 4(2): 99–107
Machado R, Pereira A, Coelho G, et al. Epidemiological and clinical aspects of migraine in users of combined oral contraceptives. Contraception 2010 Mar 1; 81(3): 202–8
MacGregor EA, Hackshaw A. Prevention of migraine in the pill-free interval of combined oral contraceptives: a double-blind, placebo-controlled pilot study using natural oestrogen supplements. J Fam Plann Reprod Health Care 2002 Jan; 28(1): 27–31
Facchinetti F, Montorsi S, Borella P, et al. Magnesium prevention of premenstrual migraine: a placebo controlled study. In: Rose FC, editor. New advances in headache research. London: Smith-Gordon, 1991: 329–32
Calhoun AH. A novel specific prophylaxis for menstrual-associated migraine. Southern Med J 2004; 97(9): 819–22
Magos AL, Zilkha KJ, Studd JW. Treatment of menstrual migraine by oestradiol implants. J Neurol Neurosurg Psychiat 1983; 46(11): 1044–6
Ferrante F, Fusco E, Calabresi P, et al. Phyto-oestrogens in the prophylaxis of menstrual migraine. Clin Neuropharmacol 2004; 27(3): 137–40
Burke BE, Olson RD, Cusack BJ. Randomized, controlled trial of phytoestrogen in the prophylactic treatment of menstrual migraine. Biomed Pharmacother 2002 Aug; 56(6): 283–8
Murray SC, Muse KN. Effective treatment of severe menstrual migraine headaches with gonadotropin-releasing hormone agonist and ‘add-back’ therapy. Fertil Steril 1997 Feb; 67(2): 390–3
Herzog AG. Continuous bromocriptine therapy in menstrual migraine. Neurology 1997 Jan; 48(1): 101–2
Hockaday JM, Peet KM, Hockaday TD. Bromocriptine in migraine. Headache 1976 Jul; 16(3): 109–14
World Health Organization. Medical eligibility criteria for contraceptive use. 4th ed. Geneva: WHO, 2009
Archer DF. Menstrual-cycle-related symptoms: a review of the rationale for continuous use of oral contraceptives. Contraception 2006 Nov; 74(5): 359–66
Sulak PJ, Cressman BE, Waldrop E, et al. Extending the duration of active oral contraceptive pills to manage hormone withdrawal symptoms. Obstet Gynecol 1997 Feb; 89(2): 179–83
Sulak P, Willis S, Kuehl T, et al. Headaches and oral contraceptives: impact of eliminating the standard 7-day placebo interval. Headache 2007 Jan; 47(1): 27–37
LaGuardia KD, Fisher AC, Bainbridge JD, et al. Suppression of estrogen-withdrawal headache with extended transdermal contraception. Fertil Steril 2005 Jun; 83(6): 1875–7
Holdaway IM, Parr CE, France J. Treatment of a patient with severe menstrual migraine using the depot LHRH analogue Zoladex. Aust N Z J Obstet Gynaecol 1991; 31(2): 164–5
Calton G, Burnett J. Danazol and migraine. N Engl J Med 1984; 310: 721–2
Lichten EM, Bennett RS, Whitty AJ, et al. Efficacy of danazol in the control of hormonal migraine. J Reprod Med 1991 Jun; 36(6): 419–24
Powles T. Prevention of migrainous headaches by tamoxifen [letter]. Lancet 1986; 2: 1344
O’Dea JP, Davis EH. Tamoxifen in the treatment of menstrual migraine. Neurology 1990; 40: 1470–1
Mathew P, Fung F. Recapitulation of menstrual migraine with tamoxifen. Lancet 1999; 353(9151): 467–8
Acknowledgements
Anne MacGregor has acted as a paid consultant to and/or her department has received research funding from Addex, Allergan, AstraZeneca, BTG, Endo Pharmaceuticals, GlaxoSmithKline, Menarini, Merck, Pozen and Unipath. She received no financial support for the preparation of this review.
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MacGregor, E.A. Prevention and Treatment of Menstrual Migraine. Drugs 70, 1799–1818 (2010). https://doi.org/10.2165/11538090-000000000-00000
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DOI: https://doi.org/10.2165/11538090-000000000-00000