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Menstrual migraine is an important condition in which women experience regular migraine around the time of their period. This is defined as migraine attacks that occur within a 5-day window starting 2 days before the first day of menstruation through to the third day of bleeding.1 Recognizing menstrual migraine is important for management. Research has shown that migraine attacks that happen near the menstrual period are more severe, last longer, and are less responsive to treatment than attacks that happen at other times.2 Little is known about whether perimenstrual migraine attacks are more troublesome for women who have not received a specific diagnosis of menstrual migraine. The study by van Casteren et al.3 compared perimenstrual migraine attacks with migraine attacks occurring at other times of the cycle. This study examines whether differences between perimenstrual and nonperimenstrual attacks exist in women with and without a specific diagnosis of menstrual migraine.

Background Perimenstrual migraine attacks in women with menstrual migraine is difficult to treat. This post-hoc analysis evaluated the efficacy of lasmiditan, a high affinity and selective 5-HT1F receptor agonist, for perimenstrual attacks. Methods Patients from two randomized, double-blind, placebo-controlled clinical trials (MONONOFU and CENTURION) were instructed to treat an attack with a single dose of study medication within four hours of pain onset. After dosing, the proportion of patients who achieved freedom from migraine-related head pain, most bothersome symptom, and disability was reported at baseline up to 48 hours after dose and pooled data were evaluated. Results A total of 303 patients (MONONOFU N = 78; CENTURION N = 225) treated perimenstrual migraine attacks with lasmiditan 50 mg (N = 24), 100 mg (N = 90), 200 mg (N = 110), and placebo (N = 79). More patients achieved migraine-related head pain freedom with lasmiditan 200 mg versus placebo at all time points assessed. At 2 hours, 33.6% of patients in the 200-mg group (p Conclusions Lasmiditan treatment of perimenstrual migraine attacks was associated with freedom from migraine-related head pain at two hours, early onset of efficacy, and sustained efficacy. Clinical Trial registration: NCT03962738 and NCT03670810

Background Migraine is a prevalent and disabling headache disorder that affects more than 1.04 billion individuals world-wide. It can result in reduction in quality of life, increased disability, and high socio-economic burden. Nevertheless, and despite the availability of evidence-based national and international guidelines, the management of migraine patients often remains suboptimal, especially for chronic migraine (CM) patients. Methods My-LIFE anamnesis project surveyed 201 General practitioners (GPs) from 5 European countries (France, Germany, Italy, Spain, and the UK) with the aim of understanding chronic migraine (CM) patients’ management in the primary care setting. Results In our survey, GPs diagnosed episodic migraine (EM) more often than CM (87% vs 61%, p Conclusions There is a need of guidance in the primary care setting to both leverage the management of CM patients and earlier referral to specialists, when appropriate.

International audience; Introduction: Migraine and combined hormonal contraceptives (CHCs) increase the risk of ischemic stroke in young women; however, the contribution of low-dose (

BackgroundOver the last 20 years, new contraceptive methods became available and incentives to increase contraceptive uptake were introduced. We aimed to describe temporal trends in non-barrier contraceptive prescribing in UK primary care for the period 2000–2018.MethodsA repeated cross-sectional study using patient data from the IQVIA Medical Research Data (IMRD) database. The proportion (95% CI) of women prescribed non-barrier contraception per year was captured.ResultsA total of 2 705 638 women aged 15–49 years were included. Between 2000 and 2018, the proportion of women prescribed combined hormonal contraception (CHC) fell from 26.2% (26.0%–26.3%) to 14.3% (14.2%–14.3%). Prescriptions for progestogen-only pills (POPs) and long-acting reversible contraception (LARC) rose from 4.3% (4.3%–4.4%) to 10.8% (10.7%–10.9%) and 4.2% (4.1%–4.2%) to 6.5% (6.5%–6.6%), respectively. Comparing 2018 data for most deprived versus least deprived areas, women from the most deprived areas were more likely to be prescribed LARC (7.7% (7.5%–7.9%) vs 5.6% (5.4%–5.8%)) while women from the least deprived areas were more likely to be prescribed contraceptive pills (20.8% (21.1%–21.5%) vs 26.2% (26.5%–26.9%)). In 2009, LARC prescriptions increased irrespective of age and social deprivation in line with a pay-for-performance incentive. However, following the incentive's withdrawal in 2014, LARC prescriptions for adolescents aged 15–19 years fell from 6.8% (6.6%–7.0%) in 2013 to 5.6% (5.4%–5.8%) in 2018.ConclusionsCHC prescribing fell by 46% while POP prescribing more than doubled. The type of contraception prescribed was influenced by social deprivation. Withdrawal of a pay-for-performance incentive may have adversely affected adolescent LARC uptake, highlighting the need for further intervention to target this at-risk group.

Background Many studies have described the features of menstrually-related migraines (MRM) in the natural cycle and the efficacy of prevention. MRM in combined hormonal contraceptive (CHC) users has scarcely been researched. Estrogen and progestin withdrawal in CHC users are both more abrupt and from higher hormone levels compared with the natural cycle. An advantage for prevention of MRM in CHC users is that the hormone withdrawal is predictable. It is unknown, whether the attacks during the hormone-free interval are associated with the hormone withdrawal or onset of bleeding. Improved understanding of this relation might contribute to better define and shorten the time interval for prevention. Methods For this prospective diary-based trial we collected migraine and bleeding data from CHC users with MRM in at least two of three cycles. We analyzed frequency of migraines over the whole CHC cycle. During the hormone-free phase the relation between onset of migraine and onset of bleeding was studied. We compared pain intensity and identified prolonged-migraine attacks during hormone use and the hormone-free phase. Results During the hormone-free interval the number of migraine days and the pain score/migraine day were significantly higher in comparison with the mean during hormone use. The prevalence of migraine attacks was fourfold on hormone-free days 3–6. Migraine typically started on days 1–4. Migraine in relation to bleeding mostly occurred on days − 1 to + 4. In 78% of the cycles the first migraine day occurred during bleeding days 1 ± 2 and 48% started on days − 1 and day 1. The predictability of the first bleeding day was very high. Conclusion The day of hormone-withdrawal migraine and the first bleeding day are highly predictable in CHC users. Migraine onset is mostly day − 1 and 1 of the bleeding and on days 1–4 of the hormone-free interval. Migraine attacks of CHC users in the hormone-free interval are severe and long lasting. Further trials are necessary to investigate if this knowledge can be used to optimise prevention.

Migraine is affected by the changing hormone environment, with perimenopause associated with increased migraine, particularly menstrual migraine. Menstrual attacks are recognised to be more disabling and less responsive to treatment compared with non-menstrual attacks. Perimenstrual estrogen 'withdrawal' is implicated in the pathophysiology of menstrual migraine, with increased prevalence of migraine in perimenopause associated with unpredictable estrogen fluctuations. Perimenopausal women often have contraceptive needs as well as menopause symptoms and it is important to understand the potential effects of exogenous hormones on migraine. Maintaining stable estrogen levels with exogenous hormones can benefit migraine but clinical trial data are limited. This short narrative review addresses the diagnosis and management of menstrual migraine in perimenopausal women, and discusses the management of menopause symptoms in peri- and postmenopausal women with migraine.

The term menstrual migraine refers to migraine that is associated with menstruation by more than chance, but it does not define pathophysiology. Menstrual migraine affects about 20-25% of female migraineurs in the general population, and 22-70% of patients presenting to headache clinics. In women diagnosed with menstrual migraine, perimenstrual migraine attacks are associated with substantially greater disability than their non-menstrual attacks. Loose interpretation of diagnostic criteria has led to conflicting results in studies on prevalence figures, clinical characteristics, and response to treatment. Importantly, clinical trials often do not distinguish between perimenstrual attacks in women diagnosed with menstrual migraine and attacks associated with menstruation by chance. Two pathophysiological mechanisms have been identified: oestrogen withdrawal and prostaglandin release. Although management strategies targeting these mechanisms might be effective, the evidence is not robust. Given how common and debilitating this distinct condition is, more research investment is needed to expand understanding of its pathophysiology and to develop more effective treatment strategies.

Objective To develop a robust statistical tool for the diagnosis of menstrually related migraine. Background The International Classification of Headache Disorders (ICHD) has diagnostic criteria for menstrual migraine within the appendix. These include the requirement for menstrual attacks to occur within a 5-day window in at least \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\frac {2}{3}$\end{document}23 menstrual cycles (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\frac {2}{3}$\end{document}23-criterion). While this criterion has been shown to be sensitive, it is not specific. Yet in some circumstances, for example to establish the underlying pathophysiology of menstrual attacks, specificity is also important, to ensure that only women in whom the relationship between migraine and menstruation is more than a chance occurrence are recruited. Methods Using a simple mathematical model, a Markov chain, to model migraine attacks we developed a statistical criterion to diagnose menstrual migraine (sMM). We then analysed a data set of migraine diaries using both the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\frac {2}{3}$\end{document}23-criterion and the sMM. Results sMM was superior to the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\frac {2}{3}$\end{document}23-criterion for varying numbers of menstrual cycles and increased in accuracy with more cycle data. In contrast, the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\frac {2}{3}$\end{document}23-criterion showed maximum sensitivity only for three cycles, although specificity increased with more cycle data. Conclusions While the ICHD \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\frac {2}{3}$\end{document}23-criterion is a simple screening tool for menstrual migraine, the sMM provides a more specific diagnosis and can be applied irrespective of the number of menstrual cycles recorded. It is particularly useful for clinical trials of menstrual migraine where a chance association between migraine and menstruation must be excluded.

Background Menstrual migraine (MM) and premenstrual syndrome (PMS) are two conditions linked to specific phases of the menstrual cycle. The exact pathophysiological mechanisms are not fully understood, but both conditions are hypothesized to be triggered by female sex hormones. Co-occurrence of MM and PMS is controversial. The objective of this population-based study was to compare self-assessed symptoms of PMS in female migraineurs with and without MM. A total of 237 women from the general population who self-reported migraine in at least50% of their menstruations in a screening questionnaire were invited to a clinical interview and diagnosed by a neurologist according to the International Classification of Headache Disorders II (ICHD II), including the appendix criteria for MM. All women were asked to complete a self-administered form containing 11 questions about PMS-symptoms adapted from the Diagnostic and Statistical Manual of Mental Disorders. The number of PMS symptoms was compared among migraineurs with and without MM. In addition, each participant completed the Headache Impact test (HIT-6) and Migraine Disability Assessment Score (MIDAS). Findings A total of 193 women returned a complete PMS questionnaire, of which 67 women were excluded from the analyses due to current use of hormonal contraception (n = 61) or because they did not fulfil the ICHD-criteria for migraine (n = 6). Among the remaining 126 migraineurs, 78 had MM and 48 non-menstrually related migraine. PMS symptoms were equally frequent in migraineurs with and without MM (5.4 vs. 5.9, p = 0.84). Women with MM reported more migraine days/month, longer lasting migraine attacks and higher HIT-6 scores than those without MM, but MIDAS scores were similar. Conclusion We did not find any difference in number of self-reported PMS-symptoms between migraineurs with and without MM.

Background In 2016, a large meta-analysis brought the number of susceptibility loci for migraine to 38. While sub-type analysis for migraine without aura (MO) and migraine with aura (MA) found some loci showed specificity to MO, the study did not test the loci with respect to other subtypes of migraine. This study aimed to test the hypothesis that single nucleotide polymorphisms (SNPs) robustly associated with migraine are individually or collectively associated with menstrual migraine (MM). Methods Genotyping of migraine susceptibility SNPs was conducted using the Agena MassARRAY platform on DNA samples from 235 women diagnosed with menstrual migraine as per International Classification for Headache Disorders II (ICHD-II) criteria and 140 controls. Alternative genotyping methods including restriction fragment length polymorphism, pyrosequencing and Sanger sequencing were used for validation. Statistical analysis was performed using PLINK and SPSS. Results Genotypes of 34 SNPs were obtained and investigated for their potential association with menstrual migraine. Of these SNPs, rs2506142 located near the neuropilin 1 gene (NRP1), was found to be significantly associated with menstrual migraine (p = 0.003). Genomic risk scores were calculated for all 34 SNPs as well as a subset of 7 SNPs that were nearing individual significance. Overall, this analysis suggested these SNPs to be weakly predictive of MM, but of no prognostic or diagnostic value. Conclusions Our results suggest that NRP1 may be important in the etiology of MM. It also suggests some genetic commonality between common migraine subtypes (MA and MO) and MM. The identification of associated SNPs may be the starting point to a better understanding of how genetic factors may contribute to the menstrual migraine sub-type.

Aim The aim of this article is to evaluate the safety and efficacy of perimenstrual telcagepant, a CGRP receptor antagonist, for headache prophylaxis. Methods We conducted a randomized, double-blind, placebo-controlled, six-month trial in women with migraine for ≥3 months who experienced perimenstrual headaches. Women were randomized to telcagepant 140 mg or placebo (2:1 ratio) for seven consecutive days perimenstrually. Safety was assessed by adverse events and laboratory tests. The primary efficacy endpoint was mean monthly headache days in the subset of women reporting perimenstrual migraine (−2 days to +3 days of menses onset) and ≥5 moderate or severe migraines per month prior to entering the trial. Results Telcagepant was generally well tolerated: 66/2660 (2.5%) on telcagepant and 36/1326 (2.7%) on placebo discontinued because of a clinical adverse event. The percentages of patients with clinical adverse events, laboratory adverse events, or discontinuation because of a laboratory adverse event were also similar between treatments. Alanine aminotransferase elevations ≥3× normal occurred in 0.6% of women on telcagepant and 0.4% on placebo. Three women on telcagepant vs none on placebo had alanine aminotransferase elevations ≥8× normal. In the efficacy subset there was no significant effect of telcagepant ( n = 887) vs placebo ( n = 447) in mean monthly headache days (treatment difference −0.5 day (95% CI: −1.1, 0.1)). However, telcagepant was associated with a reduction in on-drug headache days (treatment difference −0.4 day (95% CI: –0.5, –0.2), nominal p Conclusions Telcagepant 140 mg taken perimenstrually for seven days was generally well tolerated, but was associated with transaminase elevations . Telcagepant did not reduce monthly headache frequency, but did reduce perimenstrual headaches.

Perimenopause marks a period of increased migraine prevalence in women and many women also report troublesome vasomotor symptoms. Migraine is affected by fluctuating estrogen levels with evidence to support estrogen 'withdrawal' as a trigger of menstrual attacks of migraine without aura, while high estrogen levels can trigger migraine aura. Maintaining a stable estrogen environment with estrogen replacement can benefit estrogen-withdrawal migraine particularly in women who would also benefit from relief of vasomotor symptoms. In contrast to contraceptive doses of ethinylestradiol, migraine aura does not contraindicate use of physiological doses of natural estrogen. In women with migraine with or without aura, using only the lowest doses of transdermal estrogen necessary to control vasomotor symptoms minimizes the risk of unwanted side effects. Cyclical progestogens can have an adverse effect on migraine so continuous progestogens, as provided by the levonorgestrel intrauterine system or in continuous combined transdermal preparation, are preferred. There are no data on the effect of micronized progesterone on migraine, either cyclical or continuous. Non-hormonal options for both conditions are limited but there is evidence of efficacy for escitalopram and venflaxine.

Migraine in pregnancy can cause considerable concern to both patient and doctor, particularly if migraine starts for the first time during pregnancy or if the woman has her first attack with aura. There is often confusion regarding which medicines are safe to use during pregnancy and breastfeeding, leaving many women unable to control their attacks effectively. This paper reviews the diagnosis as well as the management of migraine, which is similar to the non-pregnant state, with a few exceptions.

This article provides an overview of the diagnosis and management of primary and secondary headaches that may occur during pregnancy and postpartum. Headache presenting in pregnancy is of significant concern to the affected woman. Quick and correct diagnosis leads to the optimal management, minimizing risks to the pregnancy.Several strategies have been developed to distinguish secondary headaches that need urgent assessment and management from benign primary and secondary headaches and to minimize the risk of misdiagnosis. Recent guidelines for the drug treatment of headaches are considered in the context of updated information on the safety of drugs in pregnancy and lactation.Primary headaches are common and typically improve during pregnancy. Management during pregnancy and lactation is similar to management in the nonpregnant state, with a few exceptions. Secondary causes of headache that are more likely to occur during pregnancy include cerebral venous thrombosis, posterior reversible encephalopathy syndrome resulting from eclampsia, post-dural puncture headache, stroke, and pituitary apoplexy.

Several data indicate that migraine, especially migraine with aura, is associated with an increased risk of ischemic stroke and other vascular events. Of concern is whether the risk of ischemic stroke in migraineurs is magnified by the use of hormonal contraceptives. As migraine prevalence is high in women of reproductive age, it is common to face the issue of migraine and hormonal contraceptive use in clinical practice. In this document, we systematically reviewed data about the association between migraine, ischemic stroke and hormonal contraceptive use. Thereafter a consensus procedure among international experts was done to develop statements to support clinical decision making, in terms of cardiovascular safety, for prescription of hormonal contraceptives to women with migraine. Overall, quality of current evidence regarding the risk of ischemic stroke in migraineurs associated with the use of hormonal contraceptives is low. Available data suggest that combined hormonal contraceptive may further increase the risk of ischemic stroke in those who have migraine, specifically migraine with aura. Thus, our current statements privilege safety and provide several suggestions to try to avoid possible risks. As the quality of available data is poor further research is needed on this topic to increase safe use of hormonal contraceptives in women with migraine.

Highlights • Polymorphisms in estrogen metabolism genes were investigated in menstrual migraine. • Polymorphisms were genotyped in a specific menstrual migraine case-control cohort. • COMT Val158Met, CYP1A1 Ile462Val and 3798T > C, and CYP19A1 Cys264Arg were studied. • None of the polymorphisms were significantly associated with menstrual migraine. Abstract Migraine is a common, disabling headache disorder, which is influenced by multiple genes and environmental triggers. After puberty, the prevalence of migraine in women is three times higher than in men and > 50% of females suffering from migraine report a menstrual association, suggesting hormonal fluctuations can influence the risk of migraine attacks. It has been hypothesized that the drop in estrogen during menses is an important trigger for menstrual migraine. Catechol-O-methyltransferase (COMT) and Cytochrome P450 (CYP) enzymes are involved in estrogen synthesis and metabolism. Functional polymorphisms in these genes can influence estrogen levels and therefore may be associated with risk of menstrual migraine. In this study we investigated four single nucleotide polymorphisms in three genes involved in estrogen metabolism that have been reported to impact enzyme levels or function, in a specific menstrual migraine cohort. 268 menstrual migraine cases and 142 controls were genotyped for rs4680 in COMT (Val158Met), rs4646903 and rs1048943 in CYP1A1 (T3801C and Ile462Val) and rs700519 in CYP19A1 (Cys264Arg). Neither genotype nor allele frequencies for the COMT and CYP SNPs genotyped were found to be significantly different between menstrual migraineurs and controls by chi-square analysis (P > 0.05). Therefore we did not find association of functional polymorphisms in the estrogen metabolism genes COMT, CYP1A1 or CYP19A1 with menstrual migraine. Further studies are required to assess whether menstrual migraine is genetically distinct from the common migraine subtypes and identify genes that influence risk.

Summary Migraine is two to three times more prevalent in women than men, and women report a longer attack duration, increased risk of headache recurrence, greater disability, and a longer period of time required to recover. Conditions recognised to be comorbid with migraine include asthma, anxiety, depression, and other chronic pain conditions, and these comorbidities add to the amount of disability in both sexes. Migraine—specifically migraine with aura—has been identified as a risk factor for vascular disorders, particularly in women, but because of the scarcity of data, the comparative risk in men has yet to be established. There is evidence implicating the role of female sex hormones as a major factor in determining migraine risk and characteristics, which accounts for sex differences, but there is also evidence to support underlying genetic variance. Although migraine is often recognised in women, it is underdiagnosed in men, resulting in suboptimal management and less participation of men in clinical trials.

The HURT Questionnaire consists of eight questions which the patient answers as a measure of effectiveness of intervention against headache. This first assessment of clinical utility was conducted in headache specialist centres in three countries in order to demonstrate that HURT was responsive to change induced by effective management. We administered HURT on three occasions to 159 consecutive patients seeking non-urgent care from centres in Denmark and the United Kingdom: the first before the initial visit to the centres; the second at the initial visit; and the third when the specialist judged that the best possible outcome had been achieved in each patient. Questionnaires were also answered by 42 patients at initial and final visits to a centre in Italy. Internal consistency reliability was very good ( α = 0.85) while test-retest reliability was fair to low ( κ = 0.38–0.62 and rs = 0.49–0.76), possibly because headache was unstable prior to start of management. There were significant changes in responses post-intervention compared with baseline ( p

Significant sex differences exist in migraine and other headache disorders. Several hypotheses have been proposed to explain these differences, including fluctuations in sex hormones and receptor binding, genetic factors, differences in exposure to environmental stressors, as well as differences in response to stress and pain perception; but how valid are some of these findings and can we improve the quality of research in this field? It is notable that the preponderance of animal pain studies use male subjects to study a predominantly female disorder. Furthermore, with respect to headache and migraine sex differences, limited data have been derived from animal models. Additionally, although sex differences (based on the categorization of male vs female) may be more routinely evaluated in clinical headache research than in the basic science research, greater attention to potential differences across the life cycle of women (ie, premenopausal vs postmenopausal differences) and menstrual cycle is warranted. In this manuscript we define the differences between “sex” and “gender” and highlight the importance of their application and use in headache research. The enhanced recognition and implementation of attention to sex differences throughout the hormonal and life-cycle phase in both human and animal research will only help to strengthen and further our understanding of migraine and may help guide the direction of future headache research.

Objective.— To compare, using a within-woman analysis, the severity, duration, and relapse of menstrual vs nonmenstrual episodes of migraine during treatment with usual migraine therapy. Background.— Studies comparing the clinical characteristics of menstrual and nonmenstrual migraine attacks have yielded conflicting results, contributing to disagreement regarding whether menstrual migraine attacks are clinically more problematic than nonmenstrual migraine attacks. Methods.— Post hoc within-woman analysis of the usual-care phase (month 1) of a 2-month, multicenter, prospective, open-label study at 21 US medical practices (predominantly primary care). Participants were women ≥18 years of age with regular predictable menstrual cycles (28 ± 4 days) who self-reported a ≥1-year history of migraine attacks occurring between days −2 and +3 (menses onset = day +1) and ≥8 such attacks within the previous 12 cycles. Migraine treatment episodes were categorized as menstrual (occurring on days −2 to +3 of menses) or nonmenstrual (occurring on days +4 to −3 of menses). Pain severity, functional impairment, duration, relapse in 24 hours, and use of rescue medication were compared. Sources of variability (within- or between-patient) were determined using mathematical modeling. The http://www.clinicaltrial.gov code for trial is NCT00904098. Results.— Women (n = 153; intent to treat) reported 212 menstrual (59.2%) and 146 nonmenstrual (40.8%) migraine treatment episodes. Compared with nonmenstrual treatment episodes, menstrual episodes were more likely to cause impairment (unadjusted odds ratio, 1.65, 95% CI, 1.05-2.60; P = .03), were longer (unadjusted hazard ratio 1.68; 95% CI, 1.31-2.16; P

A number of women with migraine experience increased incidence of attacks during the perimenstrual period. The Appendix of the International Classification of Headache Disorders (ICHD II) describes two types of migraine without aura related to menstruation: pure menstrual migraine (PMM) and menstrually related migraine (MRM). The phrase “menstrual migraine” is often used to cover both PMM and MRM. Although menstrual migraine is well recognized, further scientific evidence is needed before these definitions can be formally included in the ICHD III. The aim of the present study was to investigate the prevalence of PMM and MRM in the general population in Norway. The survey included 15,000 women, 30–44 years old, residing in the eastern part of Norway. They received a postal questionnaire containing six questions about migraine, headache frequency and the relation of migraine and menstruation. The study included 11,123 women. The questionnaire response rate was 77%. The prevalence of self-reported migraine was 34.8%. Of the migraineurs, 21% reported migraine related to menstruation in at least two of three menstrual cycles, of which 7.7% were considered to have PMM and 13.2% MRM. This corresponds to the prevalence of PMM and MRM in the general population of 2.7 and 4.6%, respectively. Thus, self-reported menstrual migraine among women aged 30–44 years appears to be common in the general population in Norway. Published Open Access with SpringerOpen.

Menstrual migraine is prevalent but it is only recently that research has specifically addressed the pathophysiology and management of this disabling condition.For many years, menstrual migraine was a loose term used to describe an undefined association between migraine and menstruation. The introduction of recognized criteria has improved the diagnosis and enabled the study of a more homogenous population of women with this condition. As a consequence, studies have addressed putative mechanisms, particularly the association between oestrogen 'withdrawal' and migraine. It is recognised that other mechanisms have yet to be identified. Studies have confirmed the efficacy of perimenstrual prophylaxis with triptans and physiological doses of oestrogen. Despite robust data from randomized placebo-controlled studies, no treatments are licensed specifically for this indication at the time of writing.Recognition of menstrual migraine as a specific entity has resulted in improved diagnosis and increased research into the condition. However, our understanding of the pathophysiology and the consequent development of effective management strategies remain limited.

Migraine attacks are often associated with menstruation in many, but not all, women with migraine. To date, no hormonal abnormalities have been identified in these women and it appears that normal hormonal fluctuations are associated with an abnormal central nervous system response. Diagnosis of migraine and confirmation of menstrual association is clinical, based on headache history and review of diary cards. Tests of hormone levels are rarely useful. Standard drugs to treat the acute symptoms suffice for the majority of women with monthly attacks. If acute therapy alone is inadequate, pre-emptive treatment of the expected menstrual headache with perimenstrual estradiol, triptans or non-steroidal anti-inflammatory drugs (NSAIDs) may be effective. Suppression of the menstrual cycle with anovulatory contraceptive agents is an additional option, particularly for women who also require contraception. A variety of other treatments have been studied, but the quality of evidence for their use is generally poor.

Migraine is most prevalent in women during their reproductive years. An understanding of the effects of menstruation and menopause on migraine can enable neurologists to provide targeted and appropriate medical and hormonal strategies, enabling their patients to achieve better control of migraine and reduced disability. This article reviews the effects of hormonal events on migraine and summarizes the evidence-based options available for management.Estrogen "withdrawal" during the late luteal phase of the natural menstrual cycle and the hormone-free interval of combined hormonal contraceptives has long been implicated in the pathophysiology of menstrual migraine. However, more recent research suggests that other independent mechanisms may be relevant. Prostaglandin inhibitors used for management of dysmenorrhea are effective for associated menstrual migraine, suggesting a common pathophysiology. The interplay between serotonin and estrogen also deserves further research.Menstrual and perimenopausal migraine can be managed effectively using a variety of strategies, the choice of which depends on the efficacy of acute treatment, predictability and regularity of menstruation, use of contraception, and presence of menstrual disorders or perimenopausal vasomotor symptoms.

Heart disease is the leading cause of maternal mortality in the UK. There is therefore a need to disseminate amongst the medical profession accurate information about contraception and pre-pregnancy counselling for women with heart disease. The risk of pregnancy depends on the specific disease and the individual patient. For example the risk of maternal death is up to 50% for those with pulmonary arterial hypertension but there is no anticipated extra risk for those with mild pulmonary stenosis compared to women without heart disease. Similarly although certain contraceptive methods are associated with unacceptable increases in risk for specific cardiac conditions it is not the case that "most structural heart disease" is an absolute contraindication for use of the combined oral contraceptive (COC). (excerpt)

To determine which medications UK migraineurs have access to and assess the usage of these products in a 'real-life' setting.Data were collected using an online questionnaire, which subjects were directed to by advertisements in pharmacies, a UK national newspaper, on the internet and information on the Migraine Action Association website and newsletters. Respondents were eligible for inclusion if attacks fulfilled International Headache Society criteria for migraine and/or if previously diagnosed by a physician as having migraine.Respondents were asked to specify which products had been prescribed or purchased for migraine treatment. The pattern of use of these products was determined, including the reasons why respondents chose particular products to treat attacks.Of 3072 eligible respondents, the majority had purchased a variety of over-the-counter (OTC) medicines for treatment of attacks. Eighty-seven per cent had been diagnosed by a physician and were prescribed multiple products (average 1.68); 45% received triptans, but 26% were still prescribed products that were also available OTC. Over half (52%) of respondents initially used an OTC medicine to treat the last migraine attack. However, 73% required a second dose/product, mainly as a result of lack of efficacy of the first dose/product. Respondents using triptans were less likely to require a second dose/product than those not using triptans (52% vs. 78%, respectively). The two main reasons for choosing a triptan to treat an attack were the need for quick control and the severity of the attack. Satisfaction with regard to migraine medication was higher among triptan-users than nontriptan users.Medicines that are available OTC are often used as first-line therapy for migraine despite many migraineurs having access to prescription therapies such as triptans. Many migraineurs require a second dose/product, possibly indicating sub-optimal treatment efficacy. Physicians should consider the range of migraine-specific treatments available, including triptans, in order to develop a treatment plan that is based on the patient's needs and preferences.

Objective The objective of this article is to compare clinical characteristics of menstrual and non-menstrual attacks of migraine without aura (MO), prospectively recorded in a headache diary, by women with and without a diagnosis of menstrual migraine without aura (MM) according to the International Classification of Headache Disorders (ICHD). Material and methods A total of 237 women from the general population with self-reported migraine in ≥50% of their menstrual periods were interviewed and classified by a physician according to the criteria of the ICHD II. Subsequently, all participants were instructed to complete a prospective headache diary for at least three menstrual cycles. Clinical characteristics of menstrual and non-menstrual attacks of MO were compared by a regression model for repeated measurements. Results In total, 123 (52%) women completed the diary. In the 56 women who were prospectively diagnosed with MM by diary, the menstrual MO-attacks were longer (on average 10.65 hours, 99% CI 3.17–18.12) and more frequently accompanied by severe nausea (OR 2.14, 99% CI 1.20–3.84) than non-menstrual MO-attacks. No significant differences between menstrual and non-menstrual MO-attacks were found among women with MO, but no MM. Conclusion In women from the general population, menstrual MO-attacks differ from non-menstrual attacks only in women who fulfil the ICHD criteria for MM.

Objectives The objective of this article is to compare the diagnosis of menstrual migraine without aura (MM) from a clinical interview with prospective headache diaries in a population-based study. Material and methods A total of 237 women with self-reported migraine in at least half of menstruations were interviewed by a neurologist about headache and diagnosed according to the International Classification of Headache Disorders II (ICHD II). Additionally, the MM criteria were expanded to include other types of migraine related to menstruation. Subsequently, all women were asked to complete three month prospective headache diaries. Results A total of 123 (52%) women completed both clinical interview and diaries. Thirty-eight women were excluded from the analyses: Two had incomplete diaries and 36 women recorded ≤1 menstruation, leaving 85 diaries eligible for analysis. Sensitivity, specificity, positive and negative predictive value and Kappa for the diagnosis of MM in clinical interview vs. headache diary were 82%, 83%, 90%, 71% and 0.62 (95% CI 0.45–0.79). Using a broader definition of MM, Kappa was 0.64 (95% CI 0.47–0.83). Conclusion A thorough clinical interview is valid for the diagnosis of MM. When this is undertaken, prospective headache diaries should not be mandatory to diagnose MM but may be necessary to exclude a chance association.

A FACT is an up-to-date review of a subject relevant to the speciality, intended to help you fulfil your CPD requirements in your home or place of work. Whilst FACTs are edited and reviewed at various levels within the Faculty, the actual contents and views expressed are those of the authors and not the Faculty. More specifically, these reviews are not guidelines. The CEC is producing clinical guidelines separately. FACTs have three sections: a review, a true/false test, and discussion points. To use a FACT to earn CPD credits you should do the following

A home-use fertility monitor was used to time perimenstrual prophylaxis in 27 women with menstrual or menstrually related migraine. Cycle length variability was mostly caused by follicular phase variability; the postovulatory luteal phase was relatively constant. The monitor accurately identified ovulation in >90% of cycles, enabling prediction of menstruation and precise timing of perimenstrual prophylaxis. Ninety-seven percent of women found the monitor useful in predicting menstrual migraine attacks.

Aim To present data from a population-based epidemiological study on menstrual migraine. Material and methods Altogether, 5000 women aged 30–34 years were screened for menstrual migraine. Women with self-reported menstrual migraine in at least half of their menstrual cycles were invited to an interview and examination. We expanded the International Classification of Headache Disorders III beta appendix criteria on menstrual migraine to include both migraine without aura and migraine with aura, as well as probable menstrual migraine with aura and migraine without aura. Results A total of 237 women were included in the study. The prevalence among all women was as follows: any type of menstrual migraine 7.6%; menstrual migraine without aura 6.1%; menstrual migraine with aura 0.6%; probable menstrual migraine without aura 0.6%; probable menstrual migraine with aura 0.3%. The corresponding figures among female migraineurs were: any type of menstrual migraine 22.0%, menstrual migraine without aura 17.6%, menstrual migraine with aura 1.7%, probable menstrual migraine without aura 1.6% and probable menstrual migraine with aura 1.0%. Conclusion More than one of every five female migraineurs aged 30–34 years have migraine in ≥50% of menstruations. The majority has menstrual migraine without aura and one of eight women had migraine with aura in relation to their menstruation. Our results indicate that the ICHD III beta appendix criteria of menstrual migraine are not exhaustive.

Most women have used at least 1 method of contraception during their reproductive years, with the majority favoring combined oral contraceptives. Women are often concerned about the safety of their method of choice and also ask about likely effects on their pre-existing headache or migraine and restrictions on using their headache medication. While there should be no restriction to the use of combined hormonal contraceptives by women with migraine without aura, the balance of risks vs benefits for women with aura are debatable. Migraine with aura, but not migraine without aura, is associated with a twofold increased risk of ischemic stroke, although the absolute risk is very low in healthy, nonsmoking women. Although ethinylestradiol has been associated with increased risk of ischemic stroke, the risk is dose-dependent. Low-dose pills currently used are considerably safer than pills containing higher doses of ethinylestradiol but they are not risk-free. This review examines the evidence available regarding the effect that different methods of contraception have on headache and migraine and identifies strategies available to minimize risk and to manage specific triggers such as estrogen "withdrawal" headache and migraine associated with combined hormonal contraceptives. The independent risks of ischemic stroke associated with migraine and with hormonal contraceptives are reviewed, and guidelines for use of contraception by women with migraine are discussed in light of the current evidence.

Although more than 50% of women with migraine report an association between migraine and menstruation, menstruation has generally considered to be no more than one of a variety of different migraine triggers. In 2004, the second edition of the International Classification of Headache Disorders introduced specific diagnostic criteria for menstrual migraine. Results from research undertaken subsequently lend support to the clinical impression that menstrual migraine should be seen as a distinct clinical entity. This paper reviews the recent research and provides specific recommendations for consideration in future editions of the classification.

Objective.— To assess efficacy and tolerability of rizatriptan orally disintegrating tablet (ODT) for treatment of acute migraine in patients using topiramate for migraine prophylaxis. Background.— There are limited data from prospective controlled trials demonstrating the benefit of triptans in patients who experience migraine attacks while taking prophylactic medication. Methods.— This was a worldwide, randomized, placebo-controlled, double-blind, multiple-attack study in adults with a >1-year history of migraine taking a stable dose of topiramate for migraine prophylaxis and experiencing ≥2 moderate/severe attacks per month. Participants treated 3 moderate/severe attacks in crossover fashion (2 with rizatriptan 10-mg ODT, 1 with placebo) following random assignment to 1 of 3 treatment sequences. The primary end point was 2-hour pain relief. Results.— Two-hour pain relief was significantly greater with rizatriptan compared with placebo (55.0% vs 17.4%, P

This manuscript discusses sex-related differences in headache prevalence, the symptoms and natural history of migraine, associated disability, and co-morbid disorders. The role of sex hormones is discussed with reference to the effects of hormonal events across the reproductive years and the specific effects of the menstrual cycle on migraine. Differences between the sexes were identified across all parameters reviewed. Future research should ensure that data are analyzed separately for men and women to ensure that differences between the sexes are identified.

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.

Triptans are a recommended first-line treatment for moderate to severe migraine.Using clinical trial data, we evaluated the safety and tolerability of frovatriptan as acute treatment (AT) and as short-term preventive (STP) therapy for menstrual migraine (MM).Data from 2 Phase III AT trials (AT1: randomized, placebo controlled, 1 attack; AT2: 12-months, noncomparative, open label) and 3 Phase IIIb STP trials in MM (MMP1 and MMP2: randomized, placebo controlled, double blind, 3 perimenstrual periods; MMP3: open label, noncomparative, 12 perimenstrual periods) were analyzed. In AT1, patients treated each attack with frovatriptan 2.5 mg, sumatriptan 100 mg, or placebo. In AT2, they used frovatriptan 2.5 mg. In MMP1 and MMP2, women administered frovatriptan 2.5 mg for 6 days during the perimenstrual period, taking a loading dose of 2 or 4 tablets on day 1, followed by once-daily or BID frovatriptan 2.5 mg, respectively; in MMP3, they used BID frovatriptan 2.5 mg. In AT1, which was previously published in part, group differences in adverse events (AEs) were analyzed using the Fisher exact test, and response rates were compared using logistic regression. Post hoc analyses of sustained pain-free status with no AEs (SNAE) and sustained pain response with no AEs (SPRNAE) were performed using a 2-sample test for equality of proportions without continuity correction. For AT2 and the STP studies, data were summarized using descriptive statistics. Results of individual safety analyses for the STP studies were previously reported; the present report includes new results from a pooled analysis of MMP1 and MMP2 and a new analysis of MMP3 in which AEs were coded using Medical Dictionary for Regulatory Activities version 8.0.AT1 included 1206 patients in the safety group; AT2 included 496. In the STP studies, safety data were collected for 1487 women. In AT1 and AT2, 85.6% and 88.3%, respectively, of enrolled patients were women. Overall, AEs were generally mild to moderate (AT studies: 82.3%-90.0%; STP studies: 78.9%89.5%). In AT1, 27.3% (131/480) of frovatriptan patients, 33.4% (161/482) of sumatriptan patients, and 14.8% (36/244) of placebo patients experienced an AE considered possibly or probably related to treatment (P0.001 for either drug vs placebo).There were no significant differences between frovatriptan and sumatriptan in SNAE at 4 to 24 hours or in SPRNAE at 2 to 24 hours or at 4 to 24 hours. In randomized, controlled STP trials for MM, AEs were reported by 57.8% (166/287, BID) and 63.4% (210/331, once daily) of frovatriptan users versus 62.8% (216/344) of placebo recipients. There were no consistent differences in AEs reported by patients with potential cardiovascular risk or in AEs related to the use of estrogencontaining contraceptives (ECCs).In randomized controlled trials and 12-month open-label studies, frovatriptan was well tolerated in these women during AT and STP therapy for MM. Subgroup analyses provide preliminary evidence of tolerability in women using ECCs and in women with comorbidities that do not contraindicate triptan use but may be suggestive of cardiovascular risk.

Background Migraine is a common disorder that is highly co-morbid with psychopathological conditions such as depression and anxiety. Despite the extensive research and availability of treatment, migraine remains under-recognised and undertreated. The aim of this study was to design a short and practical screening tool to identify migraine for clinical and research purposes. Methods The structured migraine interview (SMI) based on the International Classification of Headache Disorders (ICHD) criteria was used in a clinical setting of headache sufferers and compared to clinical diagnosis by headache specialist. In addition to the validating characteristics of the interview different methods of administration were also tested. Results The SMI has high sensitivity (0.87) and modest specificity (0.58) when compared to headache specialist's clinical diagnosis. Conclusions Our study demonstrated that a structured interview based on the ICHD criteria is a useful and valid tool to identify migraine in research settings and to a limited extent in clinical settings, and could be used in studies on large samples where clinical interviews are less practical.

Objective.— To assess the safety and tolerability profile of the 5-HT1B/1D agonist frovatriptan (Frova®, Endo Pharmaceuticals Inc., Chadds Ford, PA, USA) when used as a 6-day regimen for the short-term prevention of menstrual migraine scheduled over multiple perimenstrual periods. Background.— Two randomized controlled trials have established the efficacy of a 6-day regimen of frovatriptan for reducing the incidence and severity of menstrual migraine over 1 to 3 perimenstrual periods; long-term data are needed to further assess the safety and tolerability profile of this regimen. Methods.— Two multinational trials were included in the analysis: Study 1 was a randomized, placebo-controlled double-blind parallel trial (3 perimenstrual periods treated) with an open-label extension (3 additional perimenstrual periods treated), and Study 2 was a long-term (12 perimenstrual periods treated over 12-15 months) open-label study. Enrolled women experienced menstrual migraine defined as predictable migraine attacks that started −2 days to +3 (Study 1) or +4 (Study 2) days relative to the first day of menses and that occurred in at least 2 out of 3 menstrual cycles. Frovatriptan or placebo was given 2 days before anticipated menstrual migraine and continued for 6 days. Adverse events, serious adverse events, vital signs, cardiovascular events, electrocardiograms, and laboratory parameters were assessed and recorded periodically and summarized using descriptive statistics. Adverse event data from Study 1 and Study 2 were compared using event rates. Results.— The demographic characteristics of the 2 study populations were similar: the mean age was approximately 38 years, ≥94% of participants were white, and 85% reported menstrual migraine began on days −2 to +1 of the menstrual cycle. The mean reported history of menstrual migraine was approximately 11 years. A large percentage of the respective safety populations completed each study or study period: 87% (362/416) and 88% (273/309) completed the double-blind period and open-label periods of Study 1, respectively, and 59% (308/525) completed treatment of 12 perimenstrual periods in Study 2. Major reasons for discontinuation in Study 1 included adverse events (5%, double-blind period) and “other” (10% double-blind period and 5% open-label period). In Study 2, major reasons for discontinuation included patient request (17.3%) and adverse event (10.2%). The most common treatment emergent adverse events in the double-blind period of Study 1 (placebo vs frovatriptan twice daily) were upper respiratory infection (9% vs 9%), nausea (6% vs 8%), dizziness (7% vs 7%), fatigue (4% vs 7%), dysmenorrhea (3% vs 7%), influenza (3% vs 6%), neck pain (4% vs 6%), and migraine (4% vs 4%). With the exception of migraine (which was reported using a different method in each study), prevalence rates for Studies 1 and 2 were numerically similar. The most frequently reported cardiovascular adverse events during double-blind treatment (placebo vs frovatriptan twice daily) were chest discomfort (2% and 3%), chest pain (2% and 2%), and hypertension (0 and 2%). The corresponding adverse event rates in Study 2 were 2% (chest pain), 3% (chest discomfort), and 3% (hypertension). In both studies, most adverse events were of mild or moderate intensity and their incidence numerically declined with each perimenstrual period/cycle, as did the incidence of menstrual migraine. The observed rate of intercurrent migraine in Study 2 over 12 perimenstrual periods was 1.5 per month, compared with 1.7 at baseline. There was no observable increase in the first occurrence of migraine in the 5 days following the perimenstrual period, indicating a lack of rebound headache. Conclusions.— During treatment of up to 12 perimenstrual periods over a 12- to 15-month period, the safety and tolerability of frovatriptan for short-term prevention of menstrual migraine was similar to that observed with acute use of triptans. Adverse events were generally mild or moderate in severity, there was no evidence of an increased risk of cardiovascular adverse events relative to acute treatment, and rebound headache was not evident. A short-term regimen with frovatriptan presents a safe and viable treatment option for preventing predictable migraine such as menstrual migraine.

Perimenopause marks a time of change in a woman's hormonal environment, which is apparent from the resultant irregular periods and vasomotor symptoms. These symptoms can start in the early 40s and continue through to the early 50s. Migraine is also affected by hormonal fluctuations, particularly the natural decline in estrogen in the late luteal phase of the menstrual cycle. This effect of estrogen "withdrawal" on migraine appears to become more predominant during perimenopause. Despite the increased prevalence of headache and migraine in women in their 40s, migraine is underdiagnosed in this population. In women attending with symptoms suggestive of perimenopause, it is important to ask about headache symptoms. Once diagnosed, a number of strategies can be used to manage both perimenopausal migraine and menopausal symptoms effectively, with the potential to reduce the associated morbidity.

Frovatriptan is a 5-HT(1B/1D) receptor agonist that belongs to the triptan therapeutic class. Relative to other triptans, frovatriptan has a long half-life (26 h) and a low incidence of migraine recurrence (17%). Frovatriptan is indicated for the acute treatment of migraine with or without aura, and has a relatively good safety and tolerability profile. Recent studies have also shown that a 6-day regimen of frovatriptan scheduled during the perimenstrual period significantly reduced the incidence and severity of menstrual migraine (MM; attacks that regularly start day -2 to +3 relative to menses). Prevention may be important because MM attacks have been characterized as being of longer duration, more severe and more refractory to treatment than non-MM attacks.

In contrast to the relatively stable hormone profile during the middle reproductive years, the perimenopause is marked by erratic fluctuations of oestrogen and progesterone. By the late perimenopause, oestrogen levels can reach high magnitudes.1 Given the association between migraine and oestrogen ‘withdrawal’ it is not surprising that this stage of life is often accompanied by worsening migraine, which persists until oestrogen levels plateau post-menopause. This paper reviews the effects that menopause and hormone replacement therapy (HRT) have on headache and migraine and considers the data on the risk of ischaemic stroke in HRT users with migraine. This evidence will be used to support practical guidance on the management of women with migraine wishing to use HRT.

Headache is a common condition affecting the majority of women at some time in their lives. Epidemiological studies of migraine also confirm that up to one-third of women will experience migraine particularly during their fertile years. Studies suggesting that migraine in young women is associated with an increased risk ischaemic stroke have led to particular concerns regarding the additional effect of other risk factors such as use of combined oral contraceptives (COCs). This paper reviews the effect that COCs have on headache and migraine and considers the data on the risk of ischaemic stroke in COC users with migraine. This evidence will be used to support practical guidance on the management of women with migraine wishing to use COCs. Whilst the evidence presented is based on studies of COCs there is no evidence to suggest that the effects of other combined hormonal contraceptives (CHCs) are any different. Until further data are available on the different routes of delivery the following recommendations apply to all CHCs. (excerpt)

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The prevalence of migraine peaks during the 40s and an increased association between migraine and menstruation is often noted. Migraine generally improves after the menopause. Although menstrual irregularity, hot flushes and other climacteric symptoms may warrant management with hormone replacement therapy (HRT), there has been some concern that HRT may aggravate migraine and potentially increase the risk of ischaemic stroke. This evidence-based review concludes that migraine is not a contraindication for HRT but continuous-release transdermal estrogen, in the lowest effective dose, is recommended.

Context Migraine in the pill-free interval of combined oral contraceptives is reported by many women, but there is little published information on possible mechanisms and treatments. Objective To determine whether the use of natural oestrogen patches affected the occurrence and severity of migraine during the pill-free interval. Design A double-blind, placebo-controlled, randomised, crossover study. Setting The City of London Migraine Clinic. Participants Fourteen women with migraine during the pill-free interval. Interventions 50 μg oestradiol patches (Evorel™) used during the pill-free interval for two cycles versus placebo for two cycles (total four cycles). Main outcome measures Number of pill-free intervals (zero, one or two) during which migraine occurred; number of days of migraine; severity of migraine; number of days of migraine accompanied by nausea, vomiting and/or photophobia. Results Complete data were available for 12 women and for two cycles for one woman. Use of 50 μg oestrogen patches during the pill-free interval showed a trend towards reducing the frequency and severity of migraine. Discussion These results were not as good as expected. However, we had originally aimed for 20 eligible women to participate in the trial, but only 14 were recruited and only 12 completed the study with full data for analysis. Conclusion The results of this pilot study suggest that use of 50 μg oestrogen patches during the pill-free interval may reduce the frequency and severity of migraine at that time. This study should be repeated with larger numbers of women and a higher dose of oestrogen.

Diary data from 155 women were analyzed using within-woman analysis. Compared with all other times of the cycle, migraine was 1.7 times more likely to occur during the 2 days before menstruation and 2.1 times more likely to be severe and 2.5 times more likely to occur during the first 3 days of menstruation and 3.4 times more likely to be severe. This confirms that migraine at menstruation is different from nonmenstrual attacks, even within individuals.

Summary During women's reproductive years, migraine is three times more common than in men of a similar age. Although this female preponderance is commonly assumed to be associated with the additional trigger of fluctuating sex hormones of the menstrual cycle, few studies have been done to confirm or refute this. This review is confined to the relation between oestrogen and attacks of migraine. The evidence for an association between oestrogen "withdrawal" and attacks of migraine without aura is presented, as well as evidence for an association between high oestrogen states and attacks of migraine with aura. Only clinical data are presented here.