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Drugs 2010; 70 (14): 1799-1818 0012-6667/10/0014-1799/$55.55/0
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Prevention and Treatment of Menstrual Migraine
E. Anne MacGregor1,2
1 The City of London Migraine Clinic, London, England 2 Centre for Neuroscience and Trauma, Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, London, England
Abstract. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. Literature Search Strategy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2. Acute Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Efficacy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Safety and Tolerability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3. Prophylaxis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Perimenstrual (Short-Term/Intermittent Prevention) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1.1 NSAIDs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1.2 Triptans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1.3 Estrogen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1.4 Magnesium. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1.5 Vitamin E . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Continuous Hormonal Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2.1 Combined Hormonal Contraceptives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2.2 Estradiol Implants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2.3 Phytoestrogens. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2.4 Gonadotrophin-Releasing Hormone Analogues. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3 Continuous Nonhormonal Methods. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3.1 Bromocriptine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3.2 Anti-Estrogens. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4 Practical Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1799 1800 1800 1801 1806 1806 1806 1806 1810 1812 1812 1812 1813 1813 1813 1813 1813 1813 1813 1815 1815 1815
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 shortterm 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.
Migraine is a prevalent disorder, affecting at least 11–14% of the population.[1-3] Diagnostic features accompanying headache include photophobia, nausea and limitation of usual daily activities (table I). Four of every ten women and two of every ten men will experience migraine in their lifetime, most before the age of 35 years. For both sexes, migraine prevalence is highest in the peak reproductive years, although the prevalence is greater in women. By age 30 years, migraine is 3-fold higher in women than in men, the peak periods for migraine risk in women being at age 25 – 8.6 years and 50 – 15.8 years. Menstruation is a significant risk factor for migraine. In population- and clinic-based studies, between 20% and 60% of women with migraine report an association between migraine and menstruation.[8-14] Attacks are most likely to occur on or between 2 days before menstruation and the first 3 days of bleeding.[13,15-22] Menstrual attacks are almost invariably without aura, even in women who have attacks with aura at other times of the cycle.[13,17,22,23] Based on these findings, the International Headache Society (IHS) Classification of Headache Disorders includes specific definitions for pure menstrual migraine and menstrually related migraine (table II). For most women with menstrual attacks, migraine also occurs at other times of the month (‘menstrually related’ migraine).[4,13] Fewer than 10% of women report migraine exclusively with menstruation and at no other time of the month (‘pure’ menstrual migraine).[4,8,11-14] Menstrual migraine is also associated with increased menstrual distress and disability.[24,25] Attacks are more severe and disabling, last longer
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and are less responsive to symptomatic medication than attacks at other times of the cycle.[10,14,19,26-30] Disability does not only affect the individual but extends to affect family members, friends and work colleagues. The recognition of menstrual migraine as a clinical entity has resulted in specific clinical trials assessing the efficacy, safety and tolerability of acute and prophylactic treatments for this condition, which are discussed in this review. Proposed research criteria for menstrual migraine were only issued in 2004. The considerable variability in definitions used for earlier studies limits direct comparison of the results. 1. Literature Search Strategy Data for this review were identified by a MEDLINE search last conducted in July 2010 using the search terms ‘estrogen’, ‘estradiol’, ‘menstruation’, ‘menstrual cycle’, ‘menstrual migraine’, ‘menstrually related migraine’, ‘menstrually associated migraine’, ‘migraine’, ‘prevention’, ‘treatment’. No inclusion/exclusion criteria were specified. Publications were scrutinized for relevancy to this review. In addition, references from the author’s own files, a hand-search of the journals Cephalalgia and Headache, and peer-reviewed presentations at international congresses were considered. 2. Acute Treatment No drugs are approved specifically for the acute treatment of menstrual migraine; however, since menstrual attacks, by definition, fulfil the IHS criteria for migraine, treatments licensed for
Drugs 2010; 70 (14)
C. B.g. there is no day 0. the NSAID mefenamic acid. not within-woman analyses of trials undertaken specifically on menstrual migraine. Diagnostic criteria for migraine without aura (adapted from the Headache Classification Subcommittee of the International Headache Society) A. aspirin and caffeine (AAC. mefenamic acid 500 mg and rizatriptan 10 mg for acute treatment of menstrual migraine. Unilateral location 2. respectively. An evidence-based systematic review and metaanalysis concluded that. days -2 to +3)a of menstruationb in at least two out of three menstrual cycles and at no other times of the cycle Attacks.e. Trial quality also supports grade B recommendations (good evidence of efficacy. benefits outweigh harms. It is important to note that post hoc analyses of efficacy comparing menstrual and nonmenstrual attacks are based on pooled data from migraine trials. based on trial quality. Aggravation by or causing avoidance of routine physical activity (e. improves important health outcomes) for the combination of sumatriptan/naproxen 85 mg/500 mg. as in the case of combined oral contraceptives and cyclical hormone replacement therapy. During headache at least one of the following: 1. a b Drugs 2010. menstruation is considered to be endometrial bleeding resulting from either the normal menstrual cycle or from the withdrawal of exogenous progestogens. NY. Abstract reports of efficacy are available for eletriptan and frovatriptan. 70 (14) . All rights reserved. zolmitriptan). sumatriptan. Not attributed to another disorder migraine are also indicated for the treatment of menstrual migraine. Moderate or severe pain intensity 4. With respect to eletriptan.001 for both comparisons). 68% of the 80 mg group and 26% of the placebo group (p < 0. five of the seven available triptans (almotriptan. days -2 to +3)a of menstruationb in at least two out of three menstrual cycles and additionally at other times of the cycle The first day of menstruation is day 1 and the preceding day is day -1. cycle. Headache response at 2 hours after treatment was achieved in 64% of the eletriptan 40 mg group. in a menstruating woman. Pulsating quality 3. fulfilling IHS criteria for migraine without aura Attacks occur exclusively on day 1 – 2 (i.5 vs 3. postmarketing surveillance study of acute treatment with frovatriptan rated prestudy medications as good or very good for effectiveness by 20. respectively.Prevention and Treatment of Menstrual Migraine 1801 Table I.3% and 19. At least five attacks fulfilling criteria B–D Headache attacks lasting 4–72 hours (untreated or unsuccessfully treated) Headache has at least two of the following characteristics: 1. The time to overall relief was a little longer in menstrual attacks (5. USA).e. For the purposes of this classification.6 hours). ExcedrinÒ Migraine. walking or climbing stairs) D.7% and 90. Photophobia and phonophobia E. B. New York.9% of women in the menstrual migraine and nonmenstrual migraine groups.2% of the menstrual migraine and nonmenstrual migraine groups. An abstract of a post hoc analysis of frovatriptan for acute treatment reported overall migraine relief within 24 hours in 82% of menstrual attacks and 87% of nonmenstrual attacks. In contrast. Nausea and/or vomiting 2. the effectiveness of frovatriptan was rated as very good or good by 92. rizatriptan. A post hoc subanalysis of an open-label. B. evidence supported grade B recommendations for use of sumatriptan 50 and 100 mg. and a sumatriptan/naproxen combination (table III). fulfilling IHS criteria for migraine without aura Attacks occur on day 1 – 2 (i. Attacks. Bristol-Myers Squibb Company. Results from pooled data suggest no difference in efficacy of acute treatments for menstrual versus nonTable II. in a menstruating woman. Diagnostic criteria for pure menstrual migraine and menstrually related migraine (adapted from the Headache Classification Subcommittee of the International Headache Society [IHS]) Pure menstrual migraine without aura A. 2.1 Efficacy Data from randomized placebo-controlled trials for the acute treatment of menstrual attacks of migraine are available for the nonprescription combination of acetaminophen (paracetamol). naratriptan. Menstrually related migraine without aura A. an abstract report of a post hoc analysis of six randomized controlled trials evaluated efficacy in the acute treatment of migraine occurring between day -1 and day +4 of the menstrual ª 2010 Adis Data Information BV.
moderate or severe pain within 1 h of onset (placebo data not reported) Menstrual attacks: 2-h response: almotriptan 77.2% (p = 0. aspirin 500 mg.9) 2-h pain free: almotriptan 12.4% (p < 0.3% vs zolmitriptan 2.001) Trial design No. 2006 Parallel RCT 255 Almotriptan 12. 393 nonmenstrual attacks Acetaminophen (paracetamol) 500 mg..1% vs placebo 16.5 mg 58% vs placebo 30% (p < 0.5 mg 41. year AAC Silberstein et al.9% vs zolmitriptan 2.a Treatment Resultsb Mefenamic acid Al-Waili..4% Sustained pain free: almotriptan 22.1% (p = 0.5 mg 67.5 mg 10% Naratriptan Massiou et al.5 mg for migraine in the pill-free wk of combined oral contraceptives 2-h relief: frovatriptan 2. 1999 Post hoc analysis of pooled data from three single-attack RCTs 185 menstrual attacks. caffeine 130 mg vs placebo during moderate or severe pain Menstrual attacks: 2-h response: AAC 61% vs placebo 29% (p < 0.5 mg 29.5 mg 43% vs placebo 25% (p = 0.001) Continued next page MacGregor .6% (p = 0.5 mg 55% 2-h pain free: frovatriptan 2.001) 2-h pain free: AAC 25% vs placebo 6% (p < 0. 2000 Crossover 24 Mefenamic acid 500 mg vs placebo tid from onset of menstrual migraine until end of bleeding 2-h pain response: mefenamic acid 79.554) Sustained pain free: almotriptan 12.9% Sustained pain free: almotriptan 23. 70 (14) 1802 Table III.5 mg during moderate or severe pain Frovatriptan Allais et al.9% vs zolmitriptan 2.8% 2-h response: almotriptan 12. 2008 Open-label 20 Frovatriptan 2..5 mg 68.001) 2-h pain free: AAC 21% vs placebo 7% (p < 0.5 mg vs placebo during mild.05) Triptans Almotriptan Diamond et al. 2005 Single-attack RCT 229 Naratriptan 2.ª 2010 Adis Data Information BV.001) Nonmenstrual attacks: 2-h response: AAC 58% vs placebo 33% (p < 0.9% Nonmenstrual attacks: 2-h response: almotriptan 68.004) 4-h pain free: naratriptan 2. Acute treatment of menstrual attacks of migraine Trial..5 mg vs zolmitriptan 2.4% 2-h pain free: almotriptan 35.698) Allais et al.. moderate or severe pain 2-h pain free: naratriptan 2.5 mg vs placebo during mild. 2008 Post hoc analysis of parallel RCT 190 Almotriptan 12. Drugs 2010. All rights reserved.5 mg 44.3% 2-h pain free: almotriptan 35.5 mg 27.
 2008. 1418 nonmenstrual attacks Rizatriptan 10 mg during moderate or severe pain Silberstein et al. 70 (14) Prevention and Treatment of Menstrual Migraine Table III. 2002 Post hoc analysis of openlabel extension study 95 421 menstrual attacks. 2000 Post hoc analysis of pooled data from two crossover RCTs 335 menstrual attacks.001) 2-h pain free: rizatriptan 10 mg 36% vs placebo 19% (p-value not assessed) Sustained pain free: rizatriptan 10 mg 24% vs placebo 14% (p-value not assessed) Menstrual attacks (ICHD timing): 2-h response: rizatriptan 10 mg 78% 2-h pain free: rizatriptan 10 mg 48% Sustained pain free: rizatriptan 10 mg 32% Nonmenstrual attacks: 2-h response: rizatriptan 10 mg 78% 2-h pain free: rizatriptan 10 mg 52% Sustained pain free: rizatriptan 10 mg 37% Menstrual attacks: 2-h response: rizatriptan 10 mg 68% vs rizatriptan 5 mg 70% vs placebo 44% (p < 0.. 2008 Post hoc analysis of pooled data from two single-attack RCTs 94 Rizatriptan 10 mg vs placebo during mild pain Menstrual attacks: 2-h pain free: rizatriptan 10 mg 63.05) 2-h pain free: rizatriptan 10 mg 42% vs rizatriptan Continued next page Trial design No.9% (p > 0. Contd Trial.006) 2-h pain free: rizatriptan 10 mg 42% vs placebo 12% (p-value not assessed) Sustained pain free: rizatriptan 10 mg 23% vs placebo 10% (p-value not assessed) Pooled data – ICHD menstrually related migraine: 2-h response: rizatriptan 10 mg 71% vs placebo 52% (p < 0.002) Nonmenstrual attacks: 2-h pain free: rizatriptan 10 mg 57. year Rizatriptan Martin et al. 393 nonmenstrual attacks Rizatriptan 5 mg vs rizatriptan 10 mg vs placebo during moderate or severe pain 1803 .5% vs placebo 29% (p = 0.5% vs rizatriptan 5 mg 32.. 2007 Two single-attack RCTs of ICHD menstrual migraine 707 Rizatriptan 10 mg vs placebo during moderate or severe pain Silberstein et al. Mannix et al.. All rights reserved.ª 2010 Adis Data Information BV.05) Study 1: 2-h response: rizatriptan 10 mg 70% vs placebo 53% (p = 0. Drugs 2010...a Treatment Resultsb Nett et al.001) Pooled data – ICHD pure menstrual migraine: 2-h response: rizatriptan 10 mg 73% vs placebo 50% (p = 0.001) Study 2: 2-h response: rizatriptan 10 mg 73% vs placebo 50% (p = 0.
. 2003 Two single-attack RCTs 752 Sumatriptan 50 mg vs sumatriptan 100 mg vs placebo during mild. 1995 Parallel RCT 179 Subcutaneous sumatriptan 6 mg vs placebo during moderate or severe pain MacGregor . moderate and severe pain Facchinetti et al. 2007 Dowson et al. All rights reserved.05) Nonmenstrual attacks: 2-h response: rizatriptan 10 mg 69% vs rizatriptan 5 mg 66% (p > 0.a Treatment Resultsb 5 mg 33% vs placebo 12% (p < 0.0072) 4-h pain free: sumatriptan 100 mg 49% vs placebo 10% (p = 0. Contd Trial.001) 2-h response: sumatriptan 73% vs placebo 31% (p < 0. 2005 Open-label 31 Sumatriptan 100 mg during moderate or severe pain Sumatriptan 100 mg vs placebo during moderate or severe pain 2-h response: sumatriptan 70% 2-h pain free: sumatriptan 41% Menstrual attacks: 4-h response: sumatriptan 100 mg 67% vs placebo 33% (p = 0.001) Study 2: 2-h pain free: sumatriptan 50 mg 51% vs sumatriptan 100 mg 61% vs placebo 29% (p < 0. 70 (14) 1804 Table III..0001) Nonmenstrual attacks: 4-h response: sumatriptan 100 mg 79% vs placebo 31% (p < 0. Drugs 2010.. Nett et al.0001) 4-h pain free: sumatriptan 100 mg 60% vs placebo 9% (p < 0.ª 2010 Adis Data Information BV.001) Sustained pain free: sumatriptan 50 mg 30% vs sumatriptan 100 mg 31% vs placebo 14% (p < 0.0001) Study 1: 2-h pain free: sumatriptan 50 mg 51% vs sumatriptan 100 mg 58% vs placebo 22% (p < 0.001) 2-h pain free: sumatriptan 55% vs placebo 14% Continued next page Crossover RCT 93 Landy et al.001) Sustained pain free: sumatriptan 50 mg 30% vs sumatriptan 100 mg 35% vs placebo 8% (p < 0.001) Attack 1: 1-h response: sumatriptan 71% vs placebo 22% (p < 0. 2004. year Trial design No.05) Sumatriptan Schreiber and Cady.05) 2-h pain free: rizatriptan 10 mg 37% vs rizatriptan 5 mg 31% (p > 0..
554) Sustained pain free: zolmitriptan 2.001) 2-h response: sumatriptan 81% vs placebo 29% (p < 0.5 mg 27. tid = three times daily.5 mg vs almotriptan 12..5 mg (for moderate pain) or 5 mg (for severe pain) vs placebo No. naproxen 500 mg vs placebo during mild pain Study 1: 2-h pain free: sumatriptan/naproxen 42% vs placebo 23% (p < 0. 1993 Post hoc analysis of pooled data from two single-attack RCTs 157 menstrual.5 mg during moderate or severe pain 2-h response: zolmitriptan 2. aspirin plus caffeine.001) Sumatriptan/naproxen Mannix et al. 2006 Allais et al.5 mg 65.0001) Post hoc analysis of parallel RCT 255 Loder et al.8% (p < 0. 1805 .5 mg 68. All rights reserved. Percentage of patients unless specified.5 mg 44.001) Nonmenstrual attacks: 1-h response: sumatriptan 70% vs placebo 20% (p < 0. 512 nonmenstrual attacks Subcutaneous sumatriptan 6 mg vs placebo during moderate or severe pain Menstrual attacks: 1-h response: sumatriptan 80% vs placebo 19% (p < 0. Contd Trial.5 mg 41.0001) 2-h response: zolmitriptan 2.5 mg 29.7% vs placebo 32.6% vs almotriptan 12..9% (p = 0. Drugs 2010. RCTs = randomized controlled trials.9% (p = 0.2% vs almotriptan 12. year Trial design No.. 2004 a b Parallel RCT 597 Zolmitriptan 1.5 mg 48% vs placebo 27% (p < 0.698) 2-h response: zolmitriptan 2.5 mg vs placebo during moderate or severe pain Zolmitriptan 2.001) Pain free through 48 h: sumatriptan/naproxen 26% vs placebo 17% (p = 0.9) 2-h pain free: zolmitriptan 2.a Treatment Resultsb Attack 2: 1-h response: sumatriptan 70% vs placebo 24% (p < 0.001) 2-h pain free: sumatriptan 55% vs placebo 14% Solbach and Waymer.001) Zolmitriptan Tuchman et al. 2009 Two single-attack RCTs 621 Sumatriptan 85 mg.. of patients unless specified. 2006 Single-attack RCT 334 Zolmitriptan 2.5 mg 67.001) Pain free through 48 h: sumatriptan/naproxen 28% vs placebo 8% (p < 0. 2. AAC = acetaminophen (paracetamol).25 mg (for mild pain).04) Study 2: 2-h pain free: sumatriptan/naproxen 52% vs placebo 22% (p < 0.1% vs almotriptan 12.3% (p = 0.ª 2010 Adis Data Information BV. ICHD = International Headache Society Classification of Headache Disorders. 70 (14) Prevention and Treatment of Menstrual Migraine Table III.
70 (14) . Prophylaxis The goals of prophylactic strategies are to reduce attack frequency.[29.7%.[29.34-43. Short-term prevention strategies have the advantage that treatment is only used at the time of need. frovatriptan 2. It must be noted that none of the perimenstrual or continuous strategies reviewed is licensed for prevention of menstrual migraine. dizziness (menstrual attacks: AAC 1.1. Triptans are also well tolerated for the acute treatment of menstrual migraine. placebo 1.1 Perimenstrual (Short-Term/Intermittent Prevention) Women who have regular periods and a predictable relationship between migraine and menstruation can be treated with short-term preventive therapy during the perimenstrual period. nonsignificant.34.35. noted that 25% of women taking naproxen reported mild or moderate nausea and epigastric distress but all continued treatment. Nausea (menstrual attacks: AAC 10.0%. An evidence-based systematic review and meta-analysis concluded that. thus avoiding continuous exposure to active drug and the potential for adverse events associated with daily prophylaxis.8%.5%.001) were the most common adverse events. p = 0. p = 0.004. based on trial quality.[32. Prescribers should ensure that they follow their organization’s policy on the use of medicines outside of the terms of the product licence. Rofecoxib was not associated with gastrointestinal symptoms in an open-label study. Treatment with the NSAID mefenamic acid 500 mg initiated at the onset of a menstrual attack and continued 8-hourly for the duration of menstruation resulted in no adverse effects reported except for two patients who experienced mild epigastric pain with mefenamic acid but who continued the study. and improve function and reduce disability. placebo 0%.030) and nervousness (menstrual attacks: AAC 8. Prophylaxis is particularly suited to those women who have inadequate relief from the usual forms of acute therapy or who are troubled by headache recurrence and require multiple doses of acute migraine medications. considering also the need for contraception and co-morbid menstrual problems. nonmenstrual: AAC 3.1%. nonmenstrual: AAC 4. p = 0.55] This difference may be because pooled data will include menstrual attacks occurring by chance rather than by a confirmed association between migraine and menstruation.5 mg. p = 0. severity and duration.5%. results from prospective clinical trials in women diagnosed with menstrual migraine confirm the clinical impression that menstrual attacks do not respond as well to acute treatment as nonmenstrual attacks. improve responsiveness to treatment of acute attacks. estradiol 1.[60.0%. Since no investigations can identify the most effective prophylactic for each individual.59] Randomized studies using naproxen 550 mg twice daily perimenstrually have confirmed efficacy with good tolerability.1%. nonsignificant).42. 2.3%.45-50. nonmenstrual: AAC 4.38.[57. placebo 0.1 NSAIDs Open-label studies using perimenstrual naproxen 500–550 mg once daily suggest efficacy of this approach for menstrual migraine. placebo 1.006.5 mg twice daily and naratriptan 1 mg twice daily for prophylactic treatment of menstrual migraine. with adverse events similar to those reported in other triptan clinical trials. typically starting treatment a few days before expected onset of menstruation or the anticipated menstrual attack (table IV). placebo 2. placebo 1. evidence supported grade B recommendations for use of transcutaneous ª 2010 Adis Data Information BV.54] 3. 3. Women with menstrual irregularity can use a home-use fertility monitor to predict menstruation. Drugs 2010. All rights reserved.3%.2 Safety and Tolerability The single-dose combination of AAC was well tolerated for both menstrual and nonmenstrual attacks.61] Sances et al. A number of different treatment strategies have been studied for the prevention of menstrual migraine in randomized placebo-controlled trials and open-label studies.1806 MacGregor menstrual attacks. 3. an empirical approach is necessary.0%.47] In contrast.
then three treated cycles on days -5 to +5 Open-label Baseline untreated two cycles followed by three treated cycles Days -7 days to +6 RCT Baseline untreated two cycles followed by four treated cycles Treatment started 8 days after ovulatory temperature rise (day -2/-3) to day +8 RCT Baseline no.7 – 0..03) Szekely et al. timing and trial design Results ª 2010 Adis Data Information BV.07 (p < 0. Reduction in frequency by naproxen greater than placebo (p = 0. of attacks: 1. North American Menopause Society. 2007 14 500 mg PO od Baseline untreated cycle followed by one treated cycle 2 days before anticipated menstrual migraine Duration 6 days Open-label Median score of headache severity: baseline 4.Table IV. during treatment 3. of pts Dose Treatment cycles..1% with placebo Continued next page 1807 .0001) Rofecoxib Von Seggern et al. 67.3% during od treatment (p = 0.0001) Sances et al.1 – 0. Perimenstrual prophylaxis Trial. 51.11 End of month 3: 1.005) 57% reported ‡50% reduction in headache frequency Triptans Frovatriptan Silberstein et al. of attacks + (duration · severity)] 16. 2004 14 25 mg or 50 mg PO od Baseline untreated cycle followed by two treated cycles Days -5 to +5 Mean migraine frequency decreased from 5.10 (p < 0. 2009 179 2.7% during bid treatment. year NSAIDs Naproxen Guidotti et al.02) Reduction in HI >44%: naproxen 68% vs placebo 36% (p = 0. 70 (14) Prevention and Treatment of Menstrual Migraine 20 550 mg PO od Baseline untreated cycle followed by three treated cycles on days -7 to +7..6 migraines per menstrual cycle (p = 0. 1993 30 100 mg PO tid Two cycles First day of menstrual migraine Duration 10 days Parallel RCT Pain intensity and duration reduced during treatment with nimesulide vs placebo (p = 0.002). Drugs 2010.7% patients in first treatment month with naproxen and 33% in second and third month reported absence of migraine vs 0% placebo Frequency reduced with both naproxen and placebo.3. 2010 Allais et al.. 2007.2 – 0..5 mg PO od Three cycles 2 days before anticipated menstrual migraine Duration 6 days Post hoc subgroup analysis of Silberstein et al.9 No.001) End of month 6: 1. Migraine incidence 37. 1990 35 550 mg PO bid No significant difference in Pain Total Index [no.5 mg PO bid 2. All rights reserved.6 to 2.. 1989 22 550 mg PO bid Nimesulide Giacovazzo et al..
003) Mean no.42 with placebo (p < 0.6% reported ‡50% reduction in migraine with 2.5 mg PO bid 2.3 per 3 months 61..5 mg PO od Median score of headache severity: baseline 4. 67% with placebo (p < 0. 0. Contd Trial.6. 2004 546 2.5 – 1....5 mg tid vs 54.5 mg PO od Migraine incidence 41% during bid treatment. year Brandes et al.0 with 1 mg bid vs 4..002) vs placebo Continued next page MacGregor . 2007 Study 1: 287 Study 2: 346 59 1 mg PO bid Four cycles 3 days before anticipated menstrual migraine Duration 6 days Parallel RCT Baseline untreated three cycles followed by three treated cycles Days -2 to +4 Open-label Four cycles Days -2 to +3 Parallel RCT Study 1: mean 40% of treatment periods without migraine per patient with naratriptan vs 27% with placebo (p < 0.5 mg PO tid Three cycles Days -2 to +5 Parallel RCT 58.05) No significant difference with 2.05) Study 2: mean 37% of treatment periods without migraine per patient with naratriptan vs 24% with placebo (p < 0.5 mg PO bid 50% headache-free treatment periods per patient with 1 mg bid vs 25% with placebo (p = 0. 2008 244 2..0001 vs placebo) Naratriptan Mannix et al. 1998 20 25 mg PO tid Baseline untreated two cycles followed by up to 14 treated cycles 2–3 days before anticipated menstrual migraine Duration 5 days Open-label 52.4% reported ‡50% reduction in mean no. 2007 14 2.92 headache-free treatment periods during bid treatment.05) Baseline no.4% treated cycles with no headache 42% treated cycles with ‡50% reduction in severity of pain Zolmitriptan Tuchman et al. All rights reserved. 52% during od treatment.049 vs estradiol or naproxen) Silberstein et al.6 – 1.001 and p < 0. 70 (14) 1808 Guidotti et al. Drugs 2010.Table IV.02 vs placebo) ª 2010 Adis Data Information BV. 2009 No. of pts 410 Dose 2. 2001 206 1 mg PO bid 2.5 mg bid Sumatriptan Newman et al. 2005 1 mg PO bid Newman et al. timing and trial design Three cycles 2 days before anticipated menstrual migraine Duration 6 days Parallel RCT Baseline untreated cycle followed by one treated cycle 2 days before anticipated menstrual migraine Duration 6 days Open-label Three cycles 2 days before anticipated menstrual migraine Duration 6 days Crossover RCT Results 0.8% with placebo (p = 0..69 during od treatment.0 with placebo (p < 0. 0. of migraines 2. of attacks: 3. of attacks Moschiano et al. during treatment 2.5 mg PO bid 2.5 mg PO od Treatment cycles.7% with 2..5 mg PO bid 2.0007 and p = 0.5 mg tid and 37.4 per 3 months End of month 3: 1.5 (p = 0.
timing and trial design Results ª 2010 Adis Data Information BV.5 mg patch Baseline of two untreated cycles followed by four treated cycles 2 days before anticipated menstrual migraine Duration not stated Crossover RCT No significant difference in reduction in headache duration. 2007 10 0. intensity and impairment Dennerstein et al. during treatment 3. of pts Dose Treatment cycles. 70 (14) Prevention and Treatment of Menstrual Migraine MacGregor et al.3% with placebo (p < 0. 1994 20 0. 1988 18 1.99 (p = 0..1 mg transdermal patch Baseline untreated cycle followed by two treated cycles Days -4 to +4 Open-label Presence of menstrual migraine in baseline cycle 22/24.62.01) Continued next page 1809 .. estradiol 0.04) Pradalier et al. 2006 35 1. All rights reserved.025 mg transdermal patch Baseline untreated cycle followed by one treated cycle 2 days before anticipated menstrual migraine Duration 6 days Open-label Median score of headache severity: baseline 4. 0.5 mg patch Three cycles Days -2 to +6 Crossover RCT No significant difference in percentage of treatment periods with migraine Pfaffenrath.1 mg 6/12 Smits et al.025 mg 11/12.78.. 95% CI 0.5 mg gel Baseline untreated three cycles followed by six treated cycles Treatment started 9 days after luteinizing hormone surge (day -5/-6) to day +2 Crossover RCT 22% reduction in migraine days during estradiol treated cycles vs placebo RR 0.5 mg gel Three cycles 2 days before anticipated menstrual migraine Duration 7 days Crossover RCT Migraine in 30.8% estradiol treated cycles vs 96.2.Table IV. In second treated cycle: estradiol 0. de Lignie 1986 18 1. 1993 41 0. 1994 24 0.. Contd Trial. year Estrogens (estradiol) Guidotti et al.. Drugs 2010.001) `res et al.0 No.025 mg or 0..5 mg gel Baseline of two untreated cycles followed by four treated cycles 2 days before anticipated menstrual migraine Duration 7 days Crossover RCT Days of moderate to severe migraine during treatment: estradiol 47 vs placebo 86 (p < 0.
68] Perimenstrual triptan prophylaxis is well tolerated and the incidence and type of adverse events reported is consistent with those reported in trials of acute treatment. PO = oral.001] Mean – SD ibuprofen consumption dose (mg): vitamin E 219 – 195 vs placebo 388 – 220 (p < 0.64-71] Although the definitions of menstrual migraine appear to be similar. with the percentage of patients reporting migraine during the immediate post-treatment period being higher in those treated with naratriptan than in patients receiving placebo. year Ziaei et al. although direct comparison of the results is limited by the different endpoints used (table V). Pain Total Index decreased in both treated and placebo groups (NS) Menstrual Distress Questionnaire decreased in treated group vs placebo (p < 0. During treatment of up to 12 perimenstrual periods over a 12.[57.01) Median Pain Severity (IQR)/day: vitamin E 1 (1-2) vs placebo 2 (2-3) [p < 0. the drug has since been withdrawn because of cardiovascular safety concerns with long-term use of high dosages. NSAIDs have the additional benefit of treating associated dysmenorrhoea. 3.1810 MacGregor bid = twice daily.[66. SD = standard deviation. sumatriptan and zolmitriptan for perimenstrual prophylaxis have suggested efficacy. 70 (14) Results Baseline of two untreated cycles followed by two treated cycles (then two open-label cycles) Day +15 to day +1a of next cycle Parallel RCT 360 mg PO od Dose 400 IU Two placebo cycles followed one untreated then two treated cycles Days -2 to +3 Crossover RCT Treatment cycles.2 Triptans Trials of frovatriptan. as the latter group may be more responsive to perimenstrual prophylaxis. This difference is clinically relevant. only one trial required review of documented diary data as confirmation for inclusion.8 vs placebo 8. od = once daily. The high completion rates in the clinical trials are notable. Increased migraine post-treatment has been reported not to occur following perimenstrual frovatriptan..001) Mean – SD duration of pain (hours): vitamin E 6. RCT = randomized controlled trial. Limited data from a single randomized placebo-controlled trial suggest nimesulide may be an effective alternative. timing and trial design Facchinetti et al. Only two studies required confirmation of menstrual migraine as a specific diagnosis. 2009 Vitamin E ª 2010 Adis Data Information BV. IQR = interquartile range. tid = three times daily. there is potential concern that treatment may defer attacks or result in ‘rebound’ migraine following treatment. SEM = standard error of the mean. This has been noted with naratriptan. naratriptan.001) However. All rights reserved.29] Women who have migraine attacks occurring at the time of menstruation may not have menstrual migraine (the latter definition reserved for women who experience regular and predictable menstrual attacks rather than a chance association). a Day +1 = first day of bleeding.001] Median Functional Disability (IQR)/day: vitamin E 1 (1-2) vs placebo 2 (2-3) [p < 0. RR = relative risk.9 – 6. 1991 Table IV. No. Diary evidence should be a prerequisite given that a patient-reported history of a menstrual association can be unreliable.to 15-month period. IU = international units. However.. of pts 20 67 .1. Specific analyses of safety and tolerability have been undertaken on long-term trials of frovatriptan and naratriptan. Contd Magnesium Trial. NS = not significant.[9. pts = patients.4 – 4.1 (p < 0. HI = Headache Index. Drugs 2010.
. Differences between triptan trials for perimenstrual migraine prophylaxis (PMP) Trial. od = once daily.5 mg PO bid 2. label 1998 25 mg PO tid 2 baseline £14 treated 5 Association of migraine headache with each menstrual cycle at a predictable time relative to the onset of flow Proportion of treated cycles with no headache Proportion of treated cycles with ‡50% reduction in the severity of MM vs baseline Proportion of patients with ‡50% reduction in frequency of MM (per menstrual period) vs baseline Zolmitriptan Tuchman et al.5 mg PO tid 3 2 days before anticipated menstruation 7 Migraine starting between day -2 through to the end of menses.5 mg PO od (double dose on day 1) 1 mg PO bid 3 2 days before anticipated MM 2 days before anticipated MM 2 days before anticipated MM 2 days before anticipated MM Migraine starting between day -2 to day +3 (inclusive)a and at no other time Percentage of patients who experienced MM attacks during each of the three different treatment periods No.5 mg PO bid 2.5 mg PO od (double dose on day 1) 2.. 2004 Naratriptan Mannix et al. All rights reserved. year Design Dose No.5 mg PO bid 5 Sumatriptan Newman Openet al. PO = orally.. 2009 Brandes et al... 2009 Guidotti et al.. of headache-free PMPs out of three treated PMPs 3 6 Migraine starting between day -2 to day +3 (inclusive)a in at least two out of three menstrual cycles Migraine starting between day -2 to day +3 (inclusive)a in at least two out of three menstrual cycles Migraine starting between day -2 to day +4 (inclusive)a Openlabel Crossover 1 baseline 1 treated 3 6 Percentage of patients with MM Score of headache intensity or severity from day -2 to day +3* Incidence of MM during the treated PMP 6 Parallel 4 3 days before anticipated MM 2 days before anticipated menstruation 2 days before anticipated menstruation 2–3 days before anticipated MM 6 Migraine starting between day -2 to day +4 (inclusive)a Migraine starting between day -2 to day +3 (inclusive)a and at no other time Migraine starting between day -2 to day +4 (inclusive)a Mean percentage of treated PMPs without migraine per patient.5 mg PO od (double dose on day 1) 2. 2007 Moschiano et al.. Drugs 2010.5 mg PO od (double dose on day 1) 2.ª 2010 Adis Data Information BV. of cycles Timing of treatment Duration of PMP treatment (days) 6 Definition of MM Primary outcome measure Frovatriptan Silberstein et al. Mean no. and at no other time Day +1 = first day of bleeding. 70 (14) Prevention and Treatment of Menstrual Migraine Table V. 1811 bid = twice daily. 2007 Silberstein et al. of MMs that occurred over four PMPs Openlabel Parallel 1 mg PO bid 3 baseline 3 treated 4 6 1 mg PO bid 2. of MM over three treated cycles vs three baseline cycles No. 2008 a Parallel 2. MM = menstrual migraine.5 mg PO bid 2. tid = three times daily. 2001 Post hoc subgroup analysis Parallel 2. . 2005 Newman et al..5 mg PO bid 2..
The generalizability of the results to women whose menstrual headaches do not occur in association with other premenstrual symptoms is unclear. Results of subgroup analyses of women whose medical histories included co-morbidities that might suggest increased cardiovascular risk.4 Magnesium Magnesium prolidone carboxylic acid 360 mg decreased the duration and intensity of premenstrually occurring migraine in a placebocontrolled. is associated with an increased risk of migraine.05 mg patches during this time suggested that this dose is suboptimal for prophylaxis. A trial of vitamin E 400 IU given perimenstrually in a crossover study of two menstrual cycles showed limited effect as a prophylactic. Menstrual migraine also occurs in relation to the hormone-free interval of combined hormonal contraceptives. Several trials have confirmed the efficacy of transcutaneous estradiol for menstrual migraine prophylaxis. not surprisingly.92. All rights reserved. although headache pain and associated symptoms were reduced Drugs 2010. Diarrhoea was reported by one woman during treatment with magnesium.1. Somerville showed that migraine could be postponed by maintaining high plasma estradiol levels with an intramuscular injection of longacting estradiol valerate in oil. This study was principally aimed at identifying the effect of magnesium on a number of premenstrual problems. p = 0. Since estrogen withdrawal is also the most likely mechanism of attacks. Possible reasons for this post-treatment migraine may be that the dose of estradiol was inadequate.1812 MacGregor adverse events with frovatriptan were generally mild or moderate in severity and were similar to those observed with acute use of triptans.40. MacGregor et al. Somerville noted that estradiol treatment delayed migraine by between 3 ` res and 9 days in all six women studied. vital signs or clinical laboratory tests. Lower doses of 25 and 50 mg estradiol are not effective.03).[72-77] The effective dose is a 100 mg patch or estradiol gel 1. Menstrual irregularity can occur. et al. reported that 1 of 20 women had migraine 3 days after stopping estradiol treatment. 95% CI 1. although post-trial treatment with 0. Somerville further attempted to control estrogen fluctuations with oral estrogens and estrogen implants. No serious drugrelated adverse events were reported and no patient experienced clinically relevant drug-related changes in 12-lead ECGs. 3. probably due to suppression of endogenous estrogen during treatment.5 Vitamin E Vitamin E is an antiprostaglandin agent. the duration of treatment was too short or perhaps that exogenous estrogen prevents the normal secretion of endogenous estrogen. Both of these routes of delivery failed to provide stable plasma estradiol levels and so. A study using estradiol 0. There is no evidence that estradiol supplements increase the risks of cancer or thrombosis in premenopausal women.1 mg doses was effective. 3.73-75] Estradiol is well tolerated but post-treatment migraine can occur. supplementing estrogen during this time should be effective. provide preliminary evidence of the safety of frovatriptan in this population.3 Estrogen The rationale for perimenstrual estrogen supplementation is based on evidence that the natural decline in estrogen in the late luteal phase of the menstrual cycle. migraine subsequently occurred when the plasma estradiol fell.1. which produce serum estradiol levels of 75 pg/mL. 70 (14) . Patients completing 6–12 months of perimenstrual prophylaxis with naratriptan noted that no specific adverse event considered to be at least possibly related to study medication occurred in more than 2% of patients. but were not themselves contraindications to frovatriptan. This supports the hypothesis that prolonged estrogen exposure is necessary for ‘withdrawal’ to trigger migraine.5 mg. de Lignie ª 2010 Adis Data Information BV. double-blind study of 24 women with premenstrual syndrome and migraine. just prior to menstruation. not just headache. were of no benefit to migraine. 1. found an increase in migraine occurrence in the 5 days immediately following estradiol use compared with placebo (relative risk 1. 3.1.[57.03.
although this has yet to be established.02 mg oral contraceptive for 21 days followed by conjugated equine estrogen 0. this confers greater long-term safety than with estradiol treatment. Continued use induces amenorrhoea in 80–100% of women by 10–12 months of treatment.3. An open-label and a randomized placebocontrolled trial suggest efficacy and tolerability of daily phytoestrogens. data from an open-label study suggest that continuous use of combined hormonal contraceptives is effective.2. Tolerability was not reported. 70 (14) .9 mg daily for 7 days.g. an 168-day extended placebo-free regimen led to a decrease in headache severity along with improvement in work productivity ª 2010 Adis Data Information BV. Similarly. Treatment was well tolerated. although unscheduled bleeding is a common reason for withdrawal from clinical trials in the first 6 months of treatment. no clinical trial data are available for women with menstrual migraine during ovulatory cycles. e.2. compared with the usual 21/7-day regimen of combined hormonal contraceptives. Its use can result in reduced peak luteal estradiol levels and consequent reduced premenstrual estrogen withdrawal. 3. 3. estradiol implants given in doses large enough to suppress ovulation and produce constant plasma estrogen levels achieved a 96% response rate in 24 women with menstrual migraine treated for up to 5 years.2 Continuous Hormonal Methods and involvement in activities. adverse effects of estrogen deficiency. Two studies have suggested efficacy of bromocriptine in migraine.1 Combined Hormonal Contraceptives In an open-label study. Despite its potential benefit for management of menstrual migraine. 11 women with menstrual migraine were treated with a 28-day cycle of an ethinylestradiol 0. without stimulation of the endometrium.2 Estradiol Implants Continuous hormonal methods are particularly useful if cycles are irregular or when a woman also requires contraception (table VI).2. Theoretically.[95.96] Phytoestrogens have estrogenic effects in some tissues.3 Phytoestrogens In a small open-label study. 3.9% reduction). A trial of 102 women taking drospirenone 3 mg and ethinylestradiol 0. with 46% of women becoming completely headache free. restrict the use of gonadotrophin-releasing hormone analogues. an extended 84-day regimen of a transdermal contraceptive reduced the total incidence of mean headache days compared with a 21/7-day regimen. All women achieved at least a 50% reduction in number of headache days per cycle (mean 77. This regimen is well tolerated. although larger double-blind placebo-controlled Drugs 2010. inhibits gonadotrophin-releasing hormone and luteinizing hormone. All rights reserved. hot flushes. contraceptive doses of synthetic estrogens should not be used by women who also have migraine with aura because of the synergistic increased risk of ischaemic stroke.1 Bromocriptine Bromocriptine. Continuous use of combined hormonal contraceptives is an alternative safe and effective method of eliminating menstrual symptoms. 3.3 Continuous Nonhormonal Methods There is limited evidence of efficacy of nonhormonal drugs used for menstrual migraine prevention (table VI).4 Gonadotrophin-Releasing Hormone Analogues Although effective. For women who experience migraine during the 7-day hormonefree interval of standard regimens. larger trials have only assessed headaches in the hormone-free interval and not specifically migraine. ‘Add-back’ continuous combined estrogen and progestogen treatment can be given to counter these difficulties. 3.2.Prevention and Treatment of Menstrual Migraine 1813 compared with placebo. International guidelines for safe prescribing are available.03 mg continuously showed that. a dopamine agonist. The hormones are also associated with a marked reduction in bone density and should not usually be used for longer than 6 months without regular monitoring and bone densitometry. 3. In particular. 3. To date.
 2004 11 Ethinylestradiol 0.3 – 2. All rights reserved. pts = patients.9% reduction in number of headache days per cycle No..3 – 2. 70 (14) 1814 Estradiol Magos et al.2 days per month (p < 0.4 (p < 0.7 Bromocriptine Herzog. SC = subcutaneous..8 vs placebo 10. of pts Dose Treatment cycles. Drugs 2010. IM = intramuscular. Additional estradiol 0. conjugated equine estrogen Calhoun.Table VI. 1983 24 Estradiol 50–100 mg SC Mean 2.005) Burke et al.5–5) Open-label 83% patients became completely or almost completely headache free Phytoestrogens Ferrante et al..5 years (range 0. 2002 49 Soy isoflavones 60 mg.1 – 0. timing and trial design Results ª 2010 Adis Data Information BV. ..4 GnRH analogue treatment months 4.5 mg PO daily from treatment month 5 Baseline of 2 untreated months followed by 10 treated months Open-label Headache scores per month mean – SEM: Control months 15.02 mg for 21 days Conjugated equine estrogen 0. SEM = standard error of the mean.01) Hockaday et al. 2004 11 Genisteine 56 mg and diadzeine 20 mg PO od Baseline of three untreated cycles followed by three treated cycles Open-label Reduction in number of days of headache Baseline: 5. od = once daily.01) GnRH analogue Murray and Muse. dong quai 100 mg and black cohosh 50 mg PO od 24 weeks Daily Parallel RCT Average frequency of menstrual attacks during weeks 9–24 (mean – SEM) Phytoestrogen 4.7 days per month End of month 3: 2.1 mg transdermal patch and medroxyprogesterone acetate 2.5 GnRH analogue and ‘add-back’ treatment months 3. tid = three times daily.5 mg tid One treated year compared with prior untreated year Open-label 72% overall reduction in migraine frequency (p < 0. 1997 21 2. 1997 5 Leuprolide acetate (leuprorelin) 3. year Estrogens Ethinylestradiol. PO = oral.9 mg for 7 days PO Two consecutive 28-day cycles Open-label 77. 1976 7 1 mg tid at 4-day intervals 15 menstrual cycles Open-label One migraine attack occurred in 12 treated cycles MacGregor GnRH = gonadotrophin-releasing hormone.0 – 1. RCT = randomized controlled trial.7 – 1.75 mg IM monthly. Continuous menstrual migraine prophylaxis Trial.
If migraine remains refractory despite trials of several different strategies given in an adequate dose for an adequate duration. The prevalence and disability burden of adult migraine in England and their relationships to age. Cephalalgia 2008. In particular. rizatriptan 10 mg and combination sumatriptan/naproxen 85 mg/500 mg. 27 (4): 304-14 8. Acknowledgements Anne MacGregor has acted as a paid consultant to and/or her department has received research funding from Addex. Vetvik KG. et al. restrict their use. fatigue and joint pains. 30 (9): 1065-72 2. Reed ML. Sadovsky R. et al. Cephalalgia 2007 Mar. Pozen and Unipath. use of an adequate dose of the medication. Dodick D. there is no clinical trial evidence to confirm or refute their efficacy. et al. and use of the medication at a mild stage of the attack.5 mg. A self-administered screener for migraine in primary care: the ID Migraine validation study. et al. but symptoms of estrogen deficiency such as hot flushes. Scher AI. 70 (14) .2 Anti-Estrogens There is some limited evidence of efficacy for danazol and tamoxifen. gender and ethnicity. Schmidt K. Victor TW. All rights reserved.[98. Cephalalgia 2004. Wood C.Prevention and Treatment of Menstrual Migraine 1815 studies are necessary before it can be recommended. The International Classification of Headache Disorders (2nd edition).[106-110] 3. Migraine prevalence by age and sex in the United States: a life span study. Conclusions Women experiencing pure menstrual or menstrually related migraine can be informed that there is evidence of efficacy for a number of acute medications to control the symptoms of menª 2010 Adis Data Information BV. She received no financial support for the preparation of this review. Stovner L. The global burden of headache: a documentation of headache prevalence and disability worldwide. timing of the attack in relation to bleeding. J Headache Pain 2010 Apr. Menarini. there is grade B evidence of efficacy for short-term prophylaxis with transcutaneous estradiol 1. 23 (7): 519-27 3. perimenstrual prophylaxis is usually considered in addition to symptomatic medication. 24 Suppl. 28 (11): 1170-8 7. In particular.5 mg twice daily and naratriptan 1 mg twice daily. Headache Classification Subcommittee of the International Headache Society (IHS). reconsider the diagnosis. Steiner TJ. Although other acute treatments may be as effective. Endo Pharmaceuticals. GlaxoSmithKline. Of the noncontraceptive option available. These include use of an appropriate medication. Hagen K. when triptans are used more often than 10 days a month. Jensen R. is an often overlooked cause of refractory headache. Lipton RB. rather than waiting until the attack is moderate to severe. presence of dysmenorrhoea and/or menorrhagia. frovatriptan 2. Lundqvist C.g. Stewart WF. Any prophylactic strategy should be tried for 3 months before considering an alternative option. With respect to prophylaxis. Wober C. 1: 1-160 5. menstrual irregularity. Factors that enhance the likelihood of successful treatment for other nonmenstrual attacks apply equally to menstrual attacks. et al. adverse events related to treatment included light-headedness or nausea. grade B evidence exists for sumatriptan 50 and 100 mg. Merck. the choice of which will depend on individual patient need and preference. Selfreported menstrual migraine in the general population. Prospective analysis of factors related to migraine attacks: the PAMINA study. Hu X. nausea or vomiting). 11 (2): 87-92 Drugs 2010. mefenamic acid 500 mg.3. If this is insufficient for effective control. 3. Cephalalgia 2010. strual attacks. Brannath W. AstraZeneca. use of appropriate treatment of associated symptoms (e. BTG. Cephalalgia 2003 Sep. Diary cards should be used to keep contemporaneous records of the outcomes. Stewart WF. 27 (3): 193-210 4. Macgregor EA. Allergan. medication overuse. there are a number of contraceptive and noncontraceptive options available. Cephalalgia 2007 Apr. 61 (3): 375-82 6.99] Although generally well tolerated. et al. Choice of prophylaxis depends on the regularity of the menstrual cycle. Cumulative lifetime migraine incidence in women and men. The choice of acute treatment should be based on clinical indication and patient preference. et al.4 Practical Recommendations The majority of women with menstrual migraine only need to optimize symptomatic treatment. and the need for contraception. Campbell JC. References 1. 4. Neurology 2003 Aug 12.
Headaches and hormones: subjective versus objective assessment. Headache 2002 Mar. Granella F. et al. J Neurol Neurosurg Psychiat 1971. Victor TW. 2: S193-7 Allais G. Further evaluation of rizatriptan in menstrual migraine: retrospective analysis of long-term data. Cephalalgia 1996. Headache 2005 Oct. Nett R. Migraine with aura and migraine without aura: an epidemiological study. et al. 96 (2): 237-42 ª 2010 Adis Data Information BV. Rasmussen BK. ‘‘Menstrual’’ migraine: towards a definition. Wernke S. McCarroll KA. menstrual distress. Stewart WF. Headache 2005 Oct. Ellis J. 32 (6): 292-7 25. Cephalalgia 1995 Apr. et al. and caffeine: results from three randomized. 30. Krug LM. Efficacy of rizatriptan for menstrual migraine in an early intervention model: a prospective subgroup analysis of the rizatriptan TAME (Treat A Migraine Early) studies. et al. Cephalalgia 1990 Dec. Neven AK. Stewart WF. et al. Barrie M. Eikermann A. MacGregor EA. 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