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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 (

To ensure reproducibility in research quantifying episodic migraine attacks, and identifying attack onset, a sound theoretical model of a migraine attack, paired with a uniform standard for counting them, is necessary. Many studies report on migraine frequencies—e.g. the fraction of migraine-days of the observed days—without paying attention to the number of discrete attacks. Furthermore, patients’ diaries frequently contain single, migraine-free days between migraine-days, and we argue here that such ‘migraine-locked days’ should routinely be interpreted as part of a single attack. We tested a simple Markov model of migraine attacks on headache diary data and estimated transition probabilities by mapping each day of each diary to a unique Markov state. We explored the validity of imputing migraine days on migraine-locked entries, and estimated the effect of imputation on observed migraine frequencies. Diaries from our patients demonstrated significant clustering of migraine days. The proposed Markov chain model was shown to approximate the progression of observed migraine attacks satisfactorily, and imputing on migraine-locked days was consistent with the conceptual model for the progression of migraine attacks. Hence, we provide an easy method for quantifying the number and duration of migraine attacks, enabling researchers to procure data of high inter-study validity.

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 Migraine affects 80.8 million people in Western Europe and is the first cause of disability among people between ages 15 and 49 worldwide. Despite being a highly prevalent and disabling condition, migraine remains under-diagnosed and poorly managed. Methods An international, online survey was conducted among 201 general practitioners (GPs) from 5 European countries (France, Germany, Italy, Spain and the UK) who are experienced in the management of headache disorders. Results The majority of GPs (82%) did not refer patients with chronic migraine (CM) to migraine specialists. Among those patients, the participants estimated that around 55% received preventive medication. Some differences between countries were observed regarding referral rate and prescription of preventive treatment. Most GPs (87%) reported a lack of training or the need to be updated on CM management. Accordingly, 95% of GPs considered that a migraine anamnesis guide could be of use. Overall, more than 95% of GPs favoured the use of a patient diary, a validated diagnostic tool and a validated scale to assess impact of migraine on patients’ daily life. Similarly, 96% of the GPs considered that the inclusion of warning features (red flags) in an anamnesis guide would be useful and 90% favoured inclusion of referral recommendations. Conclusions The results from this survey indicate that more education on diagnosis and management of CM is needed in primary care. Better knowledge on the recognition and management of migraine in primary care would improve both prognosis and diagnosis and reduce impact of migraine on patients’ lives, healthcare utilization and societal burden.

Additional file 1. Online questionnaire. 32-item questionnaire run online among GPs.

Additional file 2. Profile of patients attended by GPs in 1 week, on average.

Additional file 1. Online questionnaire. 32-item questionnaire run online among GPs.

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.

AimThis review summarises the available data on the disadvantages of the 7-day contraceptive-free interval (CFI) of combined oral contraceptives (COCs), in contrast to shorter CFIs or continuous use – including flexible regimens – and provides recommendations for practice.MethodsRelevant papers were identified by Medline and PubMed. The final reference list was generated on the basis of relevance to the review, with priority given to systematic reviews and randomised controlled trials.ResultsThere is considerable inter- and intra-individual variation in the absorption and metabolism of COCs. Even with perfect use, the loss of endocrine suppression during the standard 7-day CFI allows follicular development with the risk of escape ovulation in a vulnerable minority. This risk increases in typical users whenever the CFI is prolonged: late restarts are a common reason for pill omissions. Shortening or eliminating the CFI improves contraceptive efficacy using the lowest doses available, without evidence to date of compromised safety.ConclusionsThere is no scientific evidence to support a 7-day CFI and it should be replaced either by a continuous flexible regimen, or extended regimens with a shortened CFI, prescribed first-line. In women preferring a monthly ‘bleed’, a 4-day CFI similarly provides a greater safety margin when pills are omitted.

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.

Migraine is a common headache disorder, particularly in women. It usually starts during the teens and twenties, a time when many women are seeking contraception advice. Migraine without aura is the most prevalent type of migraine, affecting up to 70% of people with migraine, while the remainder experience attacks with and/or without aura. Aura is a phase of focal neurological symptoms, typically visual. An increasing body of evidence identifies aura as a marker of increased risk of ischaemic stroke and its presence is a contraindication to the use of combined hormonal contraception (CHC). However, aura is often confused with more generalised premonitory visual symptoms of migraine that may precede attacks of migraine with and without aura, which are not associated with stroke risk. Diagnostic confidence is needed so that CHC is not withheld unnecessarily.

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.

Migraine is known to be affected by sex hormones, with the higher prevalence in women during the reproductive years considered to be due to the effects of oestrogen. Hence, migraine is likely to be affected by hormones used for transgender treatment. Of the very limited data available, the prevalence of migraine increases in transgender women using oestrogen and reduces in transgender men using testosterone. The increased prevalence of migraine aura in transgender women may be associated with high oestrogen dosing, particularly of oral oestrogen. Risks can be reduced by using transdermal hormones, which result in stable physiologic levels. In patients with aura, modifiable risk factors for stroke should be managed, particularly smoking cessation. Otherwise migraine management should follow national guidelines.

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.

Background Methysergide has been as an effective treatment for migraine and cluster headache for over 50 years but has recently been investigated by the European Medicines Agency due to safety concerns. Methods To assess the need for continuing availability of methysergide, the International Headache Society performed an electronic survey among their members. Results The survey revealed that 71.3% of all respondents had ever prescribed methysergide and 79.8% would prescribe it if it were to become available. Respondents used it more in cluster headache than migraine, and reserved it for use in refractory patients. Conclusion The vast majority of headache experts in this survey regarded methysergide a unique treatment option for specific populations for which there are no alternatives, with an urgent need to continue its availability. This position was supported by the International Headache Society.

Following the publication of this article [1], the authors noticed that they incorrectly reported the Absolute risk of ischemic stroke in women aged 20 to 44 years in relation to the use of hormonal contraception and migraine status due to a miscalculation. They apologize for this misreported result.

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.

This issue provides a clinical overview of migraine, focusing on risk, prevention, diagnosis, treatment, follow-up, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers.

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.

The prevalence of migraine is highest during the peak reproductive years and many women report its association with their menstrual periods. In this review, Professor MacGregor discusses the diagnosis, pathophysiology and management of menstrual migraine. Copyright © 2011 Wiley Interface Ltd

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.

In Pregnancy is a series of reviews focusing on the management of women with psychiatric and neurological conditions during pregnancy. In this article, Dr MacGregor discusses the effect of pregnancy on migraine and the treatment choices available to women during pregnancy and lactation. Copyright © 2009 Wiley Interface Ltd

Migraine is a neurovascular condition that is influenced by the hormonal milieu. The risk of a migraine attack is increased among women migraineurs during a 5-day perimenstrual window that starts 2 days before the onset of menses and continues through the first 3 days of menstruation. Evidence suggests that the increased risk results from estrogen withdrawal in the concurrent late luteal/early follicular phase. For some women with menstrual migraine, headaches that occur at this time are more severe, are of longer duration, and are more disabling. If patients have regular menses, short-term prevention strategies may provide relief for women whose headaches are not responsive to acute treatment. Clinical trials designed to assess short-term prevention with estrogen supplements and with triptans have demonstrated efficacy in this setting and have provided new insights into the mechanisms underlying menstrual migraine. This review will summarize the implications of these data for the treatment of women with menstrual migraine.

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 is prevalent in women during the reproductive years and attacks are likely to continue during pregnancy. As medication is usually necessary to control symptoms effectively, management during pregnancy and lactation can be a cause of concern to both the woman and her healthcare providers. There is often confusion regarding which medicines are safe to use, leading many women to suffer unnecessarily. Migraine starting for the first time during pregnancy, particularly if associated with aura must be evaluated to exclude secondary causes. This paper reviews the diagnosis as well as management of migraine, which is similar to the nonpregnant state, with a few exceptions.

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.