Sex differences in the epidemiology, clinical features, and pathophysiology of migraine
TL;DR: Although migraine is often recognised in women, it is underdiagnosed in men, resulting in suboptimal management and less participation of men in clinical trials.
Abstract: 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.
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Valery L. Feigin1, Amanuel Alemu Abajobir2, Kalkidan Hassen Abate3, Foad Abd-Allah4 +267 more•Institutions (138)
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors (GBD) study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions as discussed by the authors.
Abstract: Summary Background Comparable data on the global and country-specific burden of neurological disorders and their trends are crucial for health-care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions. In this systematic analysis, we quantified the global disease burden due to neurological disorders in 2015 and its relationship with country development level. Methods We estimated global and country-specific prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) for various neurological disorders that in the GBD classification have been previously spread across multiple disease groupings. The more inclusive grouping of neurological disorders included stroke, meningitis, encephalitis, tetanus, Alzheimer's disease and other dementias, Parkinson's disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, medication overuse headache, brain and nervous system cancers, and a residual category of other neurological disorders. We also analysed results based on the Socio-demographic Index (SDI), a compound measure of income per capita, education, and fertility, to identify patterns associated with development and how countries fare against expected outcomes relative to their level of development. Findings Neurological disorders ranked as the leading cause group of DALYs in 2015 (250·7 [95% uncertainty interval (UI) 229·1 to 274·7] million, comprising 10·2% of global DALYs) and the second-leading cause group of deaths (9·4 [9·1 to 9·7] million], comprising 16·8% of global deaths). The most prevalent neurological disorders were tension-type headache (1505·9 [UI 1337·3 to 1681·6 million cases]), migraine (958·8 [872·1 to 1055·6] million), medication overuse headache (58·5 [50·8 to 67·4 million]), and Alzheimer's disease and other dementias (46·0 [40·2 to 52·7 million]). Between 1990 and 2015, the number of deaths from neurological disorders increased by 36·7%, and the number of DALYs by 7·4%. These increases occurred despite decreases in age-standardised rates of death and DALYs of 26·1% and 29·7%, respectively; stroke and communicable neurological disorders were responsible for most of these decreases. Communicable neurological disorders were the largest cause of DALYs in countries with low SDI. Stroke rates were highest at middle levels of SDI and lowest at the highest SDI. Most of the changes in DALY rates of neurological disorders with development were driven by changes in YLLs. Interpretation Neurological disorders are an important cause of disability and death worldwide. Globally, the burden of neurological disorders has increased substantially over the past 25 years because of expanding population numbers and ageing, despite substantial decreases in mortality rates from stroke and communicable neurological disorders. The number of patients who will need care by clinicians with expertise in neurological conditions will continue to grow in coming decades. Policy makers and health-care providers should be aware of these trends to provide adequate services. Funding Bill & Melinda Gates Foundation.
2,995 citations
01 Nov 2017
1,173 citations
Tulane University1, Cedars-Sinai Medical Center2, National Institutes of Health3, University of Arizona4, Karolinska Institutet5, Brigham and Women's Hospital6, Georgia State University7, University of Colorado Denver8, Washington University in St. Louis9, Johns Hopkins University10, University of Modena and Reggio Emilia11, University of Illinois at Chicago12, University of Texas Health Science Center at Houston13, University of Zurich14, Charité15, Georgetown University16, Duke University17, Veterans Health Administration18
TL;DR: Clinicians and researchers are guided to consider sex and gender in their approach to diagnosis, prevention, and treatment of diseases as a necessary and fundamental step towards precision medicine, which will benefit men's and women's health.
781 citations
TL;DR: The cumulative evidence reviewed indicates sex-specific patterns of disease manifestation as well as sex differences in the rates of cognitive decline and brain atrophy, suggesting that sex is a crucial variable in disease heterogeneity.
Abstract: Alzheimer disease (AD) is characterized by wide heterogeneity in cognitive and behavioural syndromes, risk factors and pathophysiological mechanisms. Addressing this phenotypic variation will be crucial for the development of precise and effective therapeutics in AD. Sex-related differences in neural anatomy and function are starting to emerge, and sex might constitute an important factor for AD patient stratification and personalized treatment. Although the effects of sex on AD epidemiology are currently the subject of intense investigation, the notion of sex-specific clinicopathological AD phenotypes is largely unexplored. In this Review, we critically discuss the evidence for sex-related differences in AD symptomatology, progression, biomarkers, risk factor profiles and treatment. The cumulative evidence reviewed indicates sex-specific patterns of disease manifestation as well as sex differences in the rates of cognitive decline and brain atrophy, suggesting that sex is a crucial variable in disease heterogeneity. We discuss critical challenges and knowledge gaps in our current understanding. Elucidating sex differences in disease phenotypes will be instrumental in the development of a 'precision medicine' approach in AD, encompassing individual, multimodal, biomarker-driven and sex-sensitive strategies for prevention, detection, drug development and treatment.
475 citations
University of Pavia1, University Hospital Bonn2, Mayo Clinic3, Thomas Jefferson University4, Albert Einstein College of Medicine5, University of Copenhagen6, Allen Institute for Brain Science7, University of Calgary8, Leiden University Medical Center9, National Institute for Health Research10, Autonomous University of Barcelona11, Taipei Veterans General Hospital12
TL;DR: The present update is intended to optimize the design of controlled trials of preventive treatment of chronic migraine in adults, and its recommendations do not apply to trials in children or adolescents.
Abstract: Background Quality clinical trials form an essential part of the evidence base for the treatment of headache disorders. In 1991, the International Headache Society Clinical Trials Standing Committee developed and published the first edition of the Guidelines for Controlled Trials of Drugs in Migraine. In 2008, the Committee published the first specific guidelines on chronic migraine. Subsequent advances in drug, device, and biologicals development, as well as novel trial designs, have created a need for a revision of the chronic migraine guidelines. Objective The present update is intended to optimize the design of controlled trials of preventive treatment of chronic migraine in adults, and its recommendations do not apply to trials in children or adolescents.
215 citations
Cites background from "Sex differences in the epidemiology..."
...As a result, efforts should be made to recruit male subjects in proportions that reflect the sex ratio in epidemiologic studies (29,30)....
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Theo Vos1, Amanuel Alemu Abajobir, Kalkidan Hassen Abate2, Cristiana Abbafati3 +775 more•Institutions (305)
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016.
10,401 citations
TL;DR: The International Classification of Headache Disorders, 3 edition (beta version), may be reproduced freely for scientific, educational or clinical uses by institutions, societies or individuals as mentioned in this paper. But the authors require the permission of the International Headache Society.
Abstract: The International Classification of Headache Disorders, 3 edition (beta version), may be reproduced freely for scientific, educational or clinical uses by institutions, societies or individuals. Otherwise, copyright belongs exclusively to the International Headache Society. Reproduction of any part or parts in any manner for commercial uses requires the Society’s permission, which will be granted on payment of a fee. Please contact the publisher at the address below. International Headache Society 2013. Applications for copyright permissions should be submitted to Sage Publications Ltd, 1 Oliver’s Yard, 55 City Road, London EC1Y 1SP, United Kingdom (tel: þ44 (0) 20 7324 8500; fax: þ44 (0) 207 324 8600) (www.sagepub.co.uk). Translations
6,519 citations
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) as discussed by the authors was used to estimate the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015.
5,050 citations
TL;DR: The calculations indicate that the disability attributable to tension-type headache is larger worldwide than that due to migraine, which would bring headache disorders into the 10 most disabling conditions for the two genders, and into the five most disabling for women.
Abstract: This study, which is a part of the initiative 'Lifting The Burden: The Global Campaign to Reduce the Burden of Headache Worldwide', assesses and presents all existing evidence of the world prevalence and burden of headache disorders. Population-based studies applying International Headache Society criteria for migraine and tension-type headache, and also studies on headache in general and 'chronic daily headache', have been included. Globally, the percentages of the adult population with an active headache disorder are 46% for headache in general, 11% for migraine, 42% for tension-type headache and 3% for chronic daily headache. Our calculations indicate that the disability attributable to tension-type headache is larger worldwide than that due to migraine. On the World Health Organization's ranking of causes of disability, this would bring headache disorders into the 10 most disabling conditions for the two genders, and into the five most disabling for women.
2,067 citations
TL;DR: The prevalence, sociodemographic profile, and the burden of migraine in the United States in 1999 and to compare results with the original American Migraine Study, a 1989 population‐based study employing identical methods are described.
Abstract: Objective.—To describe the prevalence, sociodemographic profile, and the burden of migraine in the United States in 1999 and to compare results with the original American Migraine Study, a 1989 population-based study employing identical methods.
Methods.—A validated, self-administered questionnaire was mailed to a sample of 20 000 households in the United States. Each household member with severe headache was asked to respond to questions about symptoms, frequency, and severity of headaches and about headache-related disability. Diagnostic criteria for migraine were based on those of the International Headache Society. This report is restricted to individuals 12 years and older.
Results.—Of the 43 527 age-eligible individuals, 29 727 responded to the questionnaire for a 68.3% response rate. The prevalence of migraine was 18.2% among females and 6.5% among males. Approximately 23% of households contained at least one member suffering from migraine. Migraine prevalence was higher in whites than in blacks and was inversely related to household income. Prevalence increased from aged 12 years to about aged 40 years and declined thereafter in both sexes. Fifty-three percent of respondents reported that their severe headaches caused substantial impairment in activities or required bed rest. Approximately 31% missed at least 1 day of work or school in the previous 3 months because of migraine; 51% reported that work or school productivity was reduced by at least 50%.
Conclusions.—Two methodologically identical national surveys in the United States conducted 10 years apart show that the prevalence and distribution of migraine have remained stable over the last decade. Migraine-associated disability remains substantial and pervasive. The number of migraineurs has increased from 23.6 million in 1989 to 27.9 million in 1999 commensurate with the growth of the population. Migraine is an important target for public health interventions because it is highly prevalent and disabling.
2,012 citations