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Epidemiological data suggest a link between migraine and the female sex hormones. Indeed, it is known that estrogen affects various brain functions, including pain perception. The prevalence of migraine is similar in boys and girls before puberty, but is 3-fold higher in postpubertal females compared with males. Migraine attacks in women are more likely to occur in the perimenstrual period and occur exclusively so in some women. The acute treatment of menstrual migraine is similar to that of non-menstrually related attacks, but the response to treatment may be less favourable. Perimenstrual prophylaxis, with NSAIDs, triptans or estradiol, is effective in decreasing attack frequency and severity. The use of oral contraceptives (OCs) may change migraine frequency and severity. Since both migraine and hormonal contraceptive use are risk factors for ischaemic stroke, the use of OCs in women who experience migraine should be made only after consideration of the benefit-risk ratio. Migraine typically, but not invariably, improves during the last two trimesters of pregnancy, and may worsen in the postpartum period. When using drugs to treat migraine during pregnancy, potential risks to the mother and fetus should be considered. The prevalence of migraine decreases with advancing age and it improves in many, but not all, women after the menopause. However, in the perimenopausal period, migraine may worsen as a result of fluctuations in estrogen levels. Reducing the estrogen dose and changing the estrogen type or the route of administration of hormone replacement therapy (HRT) from oral to transdermal may reduce headache. Migraine is not a risk factor for stroke in postmenopausal women. When considering symptomatic HRT for postmenopausal migraneurs, the usual indications and contraindications should be applied. HRT may also exacerbate migraine.
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PMID:Hormone-related headache: pathophysiology and treatment. 1647 88

This paper is designed to provide concepts and stimulate directions for further investigation of menstrual migraine. On the basis of experimental studies and literature review, we propose that abnormalities in how estrogen modulates neuronal function in migraine are due to a mismatch between its gene-regulation and membrane effects. In the interictal phase when estrogen levels peak, increased neuronal excitability is balanced by homeostatic gene regulation in brain cortex, and nociceptive systems. When levels fall at menses, mismatch in homeostatic gene regulation by estrogen unmasks non-nuclear mitogen-activated hyperexcitability of cell membranes, sensitizing neurons to triggers that activate migraine attacks. At the trough of estrogen levels, the down-regulating effect on inflammatory genes is lost and peptide modulated central sensitization is increased as is pain and disability of the migraine attack.
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PMID:Mismatch in how oestrogen modulates molecular and neuronal function may explain menstrual migraine. 1668 28

Menstrual migraine (MM) attacks are a challenge for the headache specialist, because they are particularly difficult to treat. Almotriptan is a second-generation triptan successfully used for the acute treatment of migraine. No data on the efficacy and safety of almotriptan in MM treatment have been published previously. The objective was to evaluate the efficacy and tolerability of almotriptan in the symptomatic treatment of MM attacks and to compare these parameters to those obtained with zolmitriptan, another second-generation triptan. Data from a multicentre, multinational, randomised, double-blind, parallel clinical trial, conducted at 118 centres in 9 European countries, to evaluate the efficacy and tolerability of almotriptan 12.5 mg vs. zolmitriptan 2.5 mg in the acute treatment of migraine were analysed retrospectively. Of the 1061 patients included, 902 were women and 255 of these treated a MM attack: 136 with almotriptan and 119 with zolmitriptan. No significant difference between the two treatments was found. Two hours after dosing, 67.9% of almotriptan-treated and 68.6% of zolmitriptan-treated patients had obtained pain relief; while 44.9% and 41.2%, respectively, were pain free. Recurrence rates 2-24 h after dosing were 32.8% for almotriptan and 34.7% for zolmitriptan. Adverse events in the 24 h after dosing were reported by 19.8% of those taking almotriptan and 23.1% of those taking zolmitriptan. In conclusion, almotriptan is effective and safe in the treatment of MM attacks.
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PMID:Efficacy and tolerability of almotriptan versus zolmitriptan for the acute treatment of menstrual migraine. 1668 29

These are the first prospective studies to use criteria for menstrual migraine proposed in the 2004 revision of the International Classification of Headache Disorders (ICHD-II) to examine the efficacy of rizatriptan for treatment of a menstrual attack. Two identical protocols (MM1 and MM2) were randomized, parallel, placebo-controlled, double-blind studies. Adult women with ICHD-II menstrual migraine were assigned to either rizatriptan 10-mg tablet or placebo in a 2 : 1 ratio. Patients treated a single menstrual migraine attack of moderate or severe pain intensity. The primary end-point was 2-h pain relief and the secondary end-point was 24-h sustained pain relief. A total of 707 patients (MM1 357, MM2 350) treated a menstrual migraine attack. The percentage of patients reporting 2-h pain relief was significantly greater for rizatriptan than for placebo (MM1 70% vs. 53%, MM2 73% vs. 50%), as was the percentage of patients reporting 24-h sustained pain relief (MM1 46% vs. 33%; MM2 46% vs. 33%). Rizatriptan 10 mg was effective for the treatment of ICHD-II menstrual migraine, as measured by 2-h pain relief and 24-h sustained pain relief.
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PMID:Rizatriptan for the acute treatment of ICHD-II proposed menstrual migraine: two prospective, randomized, placebo-controlled, double-blind studies. 1744 79

More than 20 million US women suffer with migraine, two thirds of whom experience menstrually related migraine. Estrogen plays an important role in triggering migraine, and given the numerous hormonal fluctuations throughout a woman's lifetime, there are many opportunities for a hormonal impact. Accurate diagnosis is key to initiating effective treatment, and when acute therapy fails, the unique predictability of menstrual migraine lends itself to preventative treatment.
Curr Pain Headache Rep 2007 Jun
PMID:Preventative treatment of menstrual migraine. 1750 50

Acute treatment of menstrual migraine (MM) attacks is often incomplete and unsatisfactory, and perimenstrual prophylaxis with triptans, oestrogen supplementation or naproxen sodium may be needed for decreasing frequency and severity of the attack. In this pilot, open-label, non-randomised, parallel group study we evaluated, in 38 women with a history of MM, the efficacy of frovatriptan (n=14) 2.5 mg per os or transdermal oestrogens (n=10) 25 microg or naproxen sodium (n=14) 500 mg per os once-daily for the short-term prevention of MM. All treatments were administered in the morning for 6 days, beginning 2 days before the expected onset of menstrual headache. All women were asked to fill in a diary card, in the absence of (baseline) and under treatment, in order to score headache severity. All women reported at least one episode of MM at baseline. During treatment all patients taking transdermal oestrogens or naproxen sodium and 13 out of the 14 patients (93%) taking frovatriptan had at least one migraine attack (p=0.424). Daily incidence of migraine was significantly (p=0.045) lower under frovatriptan than under transdermal oestrogens or NS. At baseline, the overall median score of headache severity was 4.6, 4.2 and 4.3 in the group subsequently treated with frovatriptan, transdermal oestrogens and naproxen sodium, respectively (p=0.819). During treatment the median score was significantly lower under frovatriptan (2.5) than under transdermal oestrogens (3.0) and naproxen sodium (3.9, p=0.049). This was evident also for each single day of observation (p=0.016). Among treatments differences were particularly evident for the subgroup of patients with true MM (n=22) and for frovatriptan vs. naproxen sodium. This study suggests that short-term prophylaxis of MM with frovatriptan may be more effective than that based on transdermal oestrogens or naproxen sodium.
J Headache Pain 2007 Oct
PMID:Frovatriptan vs. transdermal oestrogens or naproxen sodium for the prophylaxis of menstrual migraine. 1795 67

Migraine is a common disorder associated with considerable individual and economic burden. Triptans are recommended for the treatment of migraine of any severity in patients who have failed to gain adequate relief with nonspecific medication; early transition to triptans avoids prolonged morbidity in patients failing to respond to nonspecific medications. There is evidence that early intervention therapy with oral formulations in migraine, soon after the onset of an attack and when pain is still mild, improves efficacy. Seven different triptans are currently marketed, with differing pharmacologic, efficacy and tolerability profiles. Almotriptan has many positive features, which include rigorously demonstrated efficacy in sumatriptan nonresponders, as early therapy and in menstrual migraine. In addition, almotriptan has a favorable pharmacologic profile with a lack of clinically relevant pharmacokinetic interventions with other drugs, adverse reactions rate similar to placebo, superior cost-effectiveness and excellent performance on composite clinical outcome measures that incorporate features of greatest importance to patients. Although effective in both triptan-naive and -experienced patients, and as both early and standard therapy, almotriptan shows greater efficacy in triptan-naive patients and as early treatment, and is consistently one of the preferred triptans in multiattribute decision-making analyses incorporating attributes of significance for patients and physicians. Therefore, almotriptan has many features that make it an ideal choice for a triptan-naive patient moving from nonspecific medication, a patient switching from another triptan owing to inefficacy or tolerability issues and patients being advised to take a triptan early in the course of a migraine attack.
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PMID:Almotriptan: meeting today's needs in acute migraine treatment. 1805 62

Menstrual disorders affect millions of women in the United States and represent an important health burden. The most common menstrual disorders are dysmenorrhea and headache; these conditions are leading causes of work or school absenteeism and substantially impact quality of life. Headache associated with menses is often migraine and referred to as menstrual migraine. Although the pathogenesis of menstrual-related pain conditions is not fully understood, menstrual-related overproduction of prostaglandins is implicated in the pathophysiology of both menstrual migraine and dysmenorrhea. In clinical practice, nonsteroidal anti-inflammatory drugs (NSAIDs) are considered the first-line therapeutic option for managing pain associated with dysmenorrhea. NSAIDs also play a role in the acute treatment and intermittent prophylaxis of migraine. Triptans, a class of highly selective serotonin receptor agonists, represent the gold standard for acute treatment of migraine. In addition, hormone therapy is effective in many cases for treating dysmenorrhea and may be beneficial in the management of menstrual migraine. Thus, overlapping treatment regimens may be advantageous in treating the coexisting menstrual-related pain conditions of dysmenorrhea and migraine.
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PMID:Menstrual-related pain conditions: dysmenorrhea and migraine. 1853 89

Oral contraceptive-induced menstrual migraine (OCMM) is a poorly defined migraine subtype mainly triggered by the cyclic pill suspension. In this pilot, open-label trial we describe its clinical features and evaluate the efficacy of frovatriptan in the treatment of its acute attack. During the first 3 months of the study 20 women (mean age 32.2+/-7.0, range 22-46) with a 6-month history of pure OCMM recorded, in monthly diary cards, clinical information about their migraine. During the 4th menstrual cycle they treated an OCMM attack with frovatriptan 2.5 mg. The majority of attacks were moderate/severe and lasted 25-72 h or more, in the presence of usual treatment. Generally an OCMM attack appeared within the first 5 days after the pill suspension, but in 15% of cases it started later. After frovatriptan administration, headache intensity progressively decreased (2.4 at onset, 1.6 after 2 h, 1.1 after 4 h and 0.8 after 24 h; p=0.0001). In 55% of patients pain relief was reported after 2 h. Ten percent of subjects were pain-free subjects after 2 h, 35% after 4 h and 60% after 24 h (p=0.003 for trend); 36% relapsed within 24 h. Rescue medication was needed by 35% of patients; 50% of frovatriptan-treated required a second dose. Concomitant nausea and/or vomiting, photophobia and phonophobia decreased significantly after drug intake. OCMM is a severe form of migraine; actually its clinical features are not always exactly identified by the ICHD-II classification. However, treatment with frovatriptan 2.5 mg might be effective in its management.
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PMID:Oral contraceptive-induced menstrual migraine. Clinical aspects and response to frovatriptan. 1854 31

Migraine commonly affects adolescents, and menstrual migraine often begins in young girls. If undiagnosed or ineffectively treated, migraine can lead to disability, school absenteeism, emotional or social difficulties, and chronification of headache. Thus, recognizing and accurately diagnosing migraine and menstrual migraine, developing effective treatment strategies (both pharmacologic and nonpharmacologic), and educating both the adolescent and her parents are important in order to minimize the potential early disability of this disorder and limit the otherwise likely progression of migraine to a disabling disorder of adulthood.
Curr Pain Headache Rep 2008 Oct
PMID:Adolescent issues in migraine: a focus on menstrual migraine. 1876 46


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