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1.  Migraine, vascular risk, and cardiovascular events in women: prospective cohort study 
Objectives To evaluate whether the association between migraine with aura and increased risk of cardiovascular disease is modified by vascular risk groups as measured by the Framingham risk score for coronary heart disease.
Design Prospective cohort study.
Setting Women’s health study, United States.
Participants 27 519 women who were free from cardiovascular disease at baseline with available information on the Framingham risk score and migraine status.
Main outcome measures Time to major cardiovascular disease event (non-fatal myocardial infarction, non-fatal ischaemic stroke, death from ischaemic cardiovascular disease), myocardial infarction, and ischaemic stroke.
Results At baseline, 3577 (13.0%) women reported active migraine, of whom 1418 (39.6%) reported migraine with aura. During 11.9 years of follow-up, there were 697 cardiovascular disease events. We stratified participants based on 10 year risk of coronary heart disease estimated from the Framingham risk score (≤1%, 2-4%, 5-9%, and ≥10%). Compared with women without migraine, the age adjusted hazard ratios in women with active migraine with aura were 1.93 (95% confidence interval 1.45 to 2.56) for major cardiovascular disease, 1.80 (1.16 to 2.79) for ischaemic stroke, and 1.94 (1.27 to 2.95) for myocardial infarction. When stratified by Framingham risk score, the association between migraine with aura and major cardiovascular disease was strongest in the lowest risk score group. There was a diametric association pattern for ischaemic stroke and myocardial infarction. Compared with women without migraine, the age adjusted hazard ratios in women who reported migraine with aura in the lowest Framingham risk score group were 3.88 (1.87 to 8.08) for ischaemic stroke and 1.29 (0.40 to 4.21) for myocardial infarction. Hazard ratios in women with migraine with aura in the highest Framingham risk score group were 1.00 (0.24 to 4.14) for ischaemic stroke and 3.34 (1.50 to 7.46) for myocardial infarction. Women with migraine without aura were not at increased risk of ischaemic stroke or myocardial infarction in any of the Framingham risk score groups.
Conclusion The association between migraine with aura and cardiovascular disease varies by vascular risk status. Information on history of migraine and vascular risk status might help to identify women at increased risk for specific future cardiovascular disease events.
Trial registration Clinical trials NCT00000479.
doi:10.1136/bmj.a636
PMCID: PMC2505092  PMID: 18687721
2.  Migraine and risk of incident diabetes in women: prospective study 
Background
Previous cross-sectional studies evaluating the relationship between diabetes prevalence and migraine status have found conflicting results. We examined the relationship between migraine and incident type 2 diabetes (T2D) in a cohort of adult women.
Methods
Prospective cohort study conducted among participants in the Women’s Health Study who provided information on migraine and did not have diabetes at baseline. Our four exposure groups were migraine with aura, migraine without aura, past history of migraine and no history of migraine. Cox proportional hazards models were used to determine the hazard ratio for incident T2D.
Results
Among the 38,620 women included in this study, 5062 (13.1%) women had migraine, of whom 2014 (39.8%) reported migraine with aura, and 2,087 (5.4%) women had a past history of migraine. During a mean of 14.6 years of follow-up, there were 3,032 cases of incident T2D. After adjustment for confounders, the hazard ratio (95% confidence interval) for developing diabetes was 1.06 (0.91–1.24) for women with migraine with aura, 1.01 (0.89–1.16) for women with migraine without aura, 1.13 (0.98–1.30) for women with a past history of migraine compared to women with no history of migraine.
Conclusion
Results of this prospective study in women do not support an association between migraine and incident T2D.
doi:10.1177/0333102412453954
PMCID: PMC3460043  PMID: 22807568
migraine; diabetes; epidemiology
3.  Migraine and Functional Outcome from Ischemic Cerebral Events in Women 
Circulation  2010;122(24):2551-2557.
Background
Studies have linked migraine with aura to an increased risk of ischemic stroke, particularly among women. Data on the relationship of migraine and functional outcome from ischemic cerebral events are sparse.
Methods and Results
Prospective cohort study among 27,852 women enrolled in the Women’s Health Study for whom we had information on migraine and measured cholesterol values and who had no prior stroke or transient ischemic attack (TIA). Migraine was classified into no history of migraine, active migraine with aura, active migraine without aura, and past history of migraine. Possible functional outcomes were no stroke or TIA, TIA, and stroke with modified Rankin Scale (mRS) score 0–1, mRS 2–3, and mRS 4–6. We used multinomial logistic regression to evaluate the relationship of migraine with functional outcomes after ischemic stroke. During a mean of 13.5 years of follow-up, 398 TIAs and 345 ischemic strokes occurred. Compared with women without history of migraine and who did not experience a TIA or stroke, women who reported migraine with aura had adjusted relative risk (95% confidence interval) of 1.56 (1.03–2.36) for TIA, 2.33 (1.37–3.97) for stroke with mRS 0–1, 0.82 (0.30–2.24) for mRS 2–3, and 1.18 (0.28–4.97) for mRS 4–6. The risk of any outcome was not significantly elevated for women who experienced migraine without aura or who had a past history of migraine.
Conclusion
Results of this large prospective cohort suggest that women with migraine with aura are at increased risk of experiencing TIA or ischemic stroke with good functional outcome.
doi:10.1161/CIRCULATIONAHA.110.977306
PMCID: PMC3058846  PMID: 21126968
Migraine; stroke; epidemiology; women
4.  Migraine, Headache and the Risk of Depression: Prospective Cohort Study 
Background
While cross-sectional studies have shown associations between migraine and depression, few studies have been able to evaluate the association between migraine and incident depression.
Methods
Prospective cohort study among 36,016 women without a history of depression enrolled in the Women’s Health Study who provided information about migraine and headache at baseline. Women were classified as either having non-migraine headache, migraine with aura, migraine without aura, past history of migraine or no history of headache. Cox proportional hazards models were used to evaluate the association between migraine and headache status and incident depression.
Results
At baseline, 5115 women reported a history of non-migraine headache, 1805 reported migraine with aura, 2723 reported migraine without aura and 1896 reported a past history of migraine. During 13.8 mean years of follow-up, 3833 new cases of depression occurred. The adjusted relative risks of incident depression were 1.44 (95% CI: 1.32, 1.56) for non-migraine headache, 1.53 (95% CI: 1.35, 1.74) for migraine with aura, 1.40 (95% CI: 1.25, 1.56) for migraine without aura and 1.56 (95% CI: 1.37, 1.77) for past history of migraine compared to no history of headache.
Conclusions
Middle-aged women with migraine or non-migraine headache are at increased risk of incident depression.
doi:10.1177/0333102413483930
PMCID: PMC3720737  PMID: 23588795
Migraine; depression; epidemiology
5.  Migraine and risk of haemorrhagic stroke in women: prospective cohort study 
Objectives To examine the association between migraine and migraine aura status with risk of haemorrhagic stroke.
Design Prospective cohort study.
Setting Women’s Health Study, United States.
Participants 27 860 women aged ≥45 who were free from stroke or other major disease at baseline and had provided information on self reported migraine, aura status, and lipid values.
Main outcome measures Time to first haemorrhagic stroke and subtypes of haemorrhagic stroke.
Results At baseline, 5130 (18%) women reported any history of migraine; of the 3612 with active migraine (migraine in the previous year), 1435 (40%) described having aura. During a mean of 13.6 years of follow-up, 85 haemorrhagic strokes were confirmed after review of medical records. Compared with women without a history of migraine, there was no increased risk of haemorrhagic stroke in those who reported any history of migraine (adjusted hazard ratio 0.98, 95% confidence interval 0.56 to 1.71, P=0.93). In contrast, risk was increased in women with active migraine with aura (2.25, 1.11 to 4.54, P=0.024). The age adjusted increased risk was stronger for intracerebral haemorrhage (2.78, 1.09 to 7.07, P=0.032) and for fatal events (3.56, 1.23 to 10.31, P=0.02). Four additional haemorrhagic stroke events were attributable to migraine with aura per 10 000 women per year. Women who reported active migraine without aura had no increased risk for haemorrhagic stroke.
Conclusion Migraine with aura might, in addition to ischaemic events, also be a risk factor for haemorrhagic stroke. The relatively low number of events and attributable risk should caution against definitive conclusions and call for further confirmation of these observations.
doi:10.1136/bmj.c3659
PMCID: PMC2927695  PMID: 20736268
6.  Association between polymorphisms in the β2-adrenoceptor gene and migraine in women 
Headache  2008;49(2):235-244.
Objective
To investigate the role of three common polymorphisms in the β2 adrenoceptor gene in migraine.
Background
Migraine has been associated with increased risk of cardiovascular disease and asthma in which β2 adrenoceptors play an important role; β adrenoceptor antagonists are used in migraine prevention. However, the role of variants in the β2 adrenoceptor gene in migraine is unclear.
Methods
Association study among 23,753 white women, participating in the Women’s Health Study, for whom we had information on migraine at baseline and genotype status of the polymorphisms rs1042713 (Gly16Arg), rs1042714 (Gln27Glu), rs1800888 (Thr164Ile). Migraine was self-reported and we distinguished between any history of migraine, active migraine with and without aura, and prior migraine (history of migraine but not active migraine) in our analyses.
Results
At baseline 4,339 women reported any history of migraine. Of these 3,041 had active migraine (1,221 migraine with aura, 1,820 migraine without aura) and 1,298 prior migraine. No migraine was reported by 19,414 women. Genotype- and haplotype-based analyses did not show an association of any of the gene variants tested with any history of migraine. The multivariable-adjusted odds ratios (ORs) (95% confidence intervals) for any history of migraine in the additive model were 1.0 (0.96–1.05) for rs1042713, 1.0 (0.95–1.05) for rs1042714, and 0.84 (0.68–1.05) for rs1800888. In the haplotype analysis the ORs ranged from 0.83 (0.67–1.03) to 1.01 (0.94–1.07) with Gly16-Glu27-Thr164 as the reference. We also did not find associations in the genotype- and haplotype-based analyses within migraine-specific subgroups.
Conclusions
Our results do not support a role of three investigated polymorphisms in the β2 adrenoceptor gene in migraine pathophysiology.
doi:10.1111/j.1526-4610.2008.01207.x
PMCID: PMC2644736  PMID: 18647184
migraine; β2 adrenoceptor; ADRB2; women
7.  Structural Brain Changes in Migraine 
Context
A previous cross-sectional study showed an association of migraine with a higher prevalence of magnetic resonance imaging (MRI)–measured ischemic lesions in the brain.
Objective
To determine whether women or men with migraine (with and without aura) have a higher incidence of brain lesions 9 years after initial MRI, whether migraine frequency was associated with progression of brain lesions, and whether progression of brain lesions was associated with cognitive decline.
Design, Setting, and Participants
In a follow-up of the 2000 Cerebral Abnormalities in Migraine, an Epidemiological Risk Analysis cohort, a prospective populationbased observational study of Dutch participants with migraine and an age- and sexmatched control group, 203 of the 295 baseline participants in the migraine group and 83 of 140 in the control group underwent MRI scan in 2009 to identify progression of MRI-measured brain lesions. Comparisons were adjusted for age, sex, hypertension, diabetes, and educational level. The participants in the migraine group were a mean 57 years (range, 43–72 years), and 71% were women. Those in the control group were a mean 55 years (range, 44–71 years), and 69% were women.
Main Outcome Measures
Progression of MRI-measured cerebral deep white matter hyperintensities, infratentorial hyperintensities, and posterior circulation territory infarctlike lesions. Change in cognition was also measured.
Results
Of the 145 women in the migraine group, 112 (77%) vs 33 of 55 women (60%) in the control group had progression of deep white matter hyperintensities (adjusted odds ratio [OR], 2.1; 95%CI, 1.0–4.1; P=.04). There were no significant associations of migraine with progression of infratentorial hyperintensities: 21 participants (15%) in themigraine group and 1 of 57 participants (2%) in the control group showed progression (adjusted OR, 7.7; 95% CI, 1.0–59.5; P=.05) or new posterior circulation territory infarctlike lesions: 10 of 203 participants (5%) in the migraine group but none of 83 in the control group (P=.07). There was no association of number or frequency of migraine headaches with progression of lesions. There was no significant association of high vs nonhigh deep white matter hyperintensity load with change in cognitive scores ( 3.7 in the migraine group vs 1.4 in the control group; 95% CI, 4.4 to 0.2; adjusted P=.07).
Conclusions
In a community-based cohort followed up after 9 years, women with migraine had a higher incidence of deep white matter hyperintensities but did not have significantly higher progression of other MRI-measured brain changes. There was no association of migraine with progression of any MRI-measured brain lesions in men.
doi:10.1001/jama.2012.14276
PMCID: PMC3633206  PMID: 23150008
8.  Polymorphisms in the Renin-Angiotensin System and Migraine in Women 
Headache  2008;49(2):292-299.
Background
Recent findings suggest an association between the renin-angiotensin system and migraine. However, genetic studies are scarce and controversial.
Objective
To investigate the association between the AGTR1 1166A>C and AGT Met235Thr polymorphisms with migraine and migraine aura status.
Methods
We performed an association study among 25,000 Caucasian U.S. women, participating in the Women's Health Study, with information on the AGTR1 1166A>C and AGT Met235Thr polymorphisms. Migraine and migraine aura status were self-reported. We distinguished between any history of migraine, active migraine with aura, active migraine without aura, and prior migraine (history of migraine, but not in the year prior to baseline). We used logistic regression to investigate the genotype-migraine association.
Results
At baseline, 4,577 (18.3%) women reported any history of migraine; 39.5% of the 3,226 women with active migraine indicated aura. The polymorphisms were not associated with migraine or migraine specific subgroups. We also did not find a significant interaction between the polymorphisms.
Conclusions
Data from this large cohort of Caucasian women do not suggest an association of polymorphisms in the renin-angiotensin system with migraine or aura status. Future studies should focus on haplotype analyses and additional gene-gene as well as gene-environment interactions.
doi:10.1111/j.1526-4610.2008.01287.x
PMCID: PMC2644741  PMID: 19178574
migraine; renin-angiotensin system; polymorphism; women
9.  Anatomical Alterations of the Visual Motion Processing Network in Migraine with and without Aura 
PLoS Medicine  2006;3(10):e402.
Background
Patients suffering from migraine with aura (MWA) and migraine without aura (MWoA) show abnormalities in visual motion perception during and between attacks. Whether this represents the consequences of structural changes in motion-processing networks in migraineurs is unknown. Moreover, the diagnosis of migraine relies on patient's history, and finding differences in the brain of migraineurs might help to contribute to basic research aimed at better understanding the pathophysiology of migraine.
Methods and Findings
To investigate a common potential anatomical basis for these disturbances, we used high-resolution cortical thickness measurement and diffusion tensor imaging (DTI) to examine the motion-processing network in 24 migraine patients (12 with MWA and 12 MWoA) and 15 age-matched healthy controls (HCs). We found increased cortical thickness of motion-processing visual areas MT+ and V3A in migraineurs compared to HCs. Cortical thickness increases were accompanied by abnormalities of the subjacent white matter. In addition, DTI revealed that migraineurs have alterations in superior colliculus and the lateral geniculate nucleus, which are also involved in visual processing.
Conclusions
A structural abnormality in the network of motion-processing areas could account for, or be the result of, the cortical hyperexcitability observed in migraineurs. The finding in patients with both MWA and MWoA of thickness abnormalities in area V3A, previously described as a source in spreading changes involved in visual aura, raises the question as to whether a “silent” cortical spreading depression develops as well in MWoA. In addition, these experimental data may provide clinicians and researchers with a noninvasively acquirable migraine biomarker.
A structural abnormality in the network of motion-processing areas could account for, or be the result of, the cortical hyperexcitability seen in people who have migraine.
Editors' Summary
Background.
Migraine is a disabling brain disorder that affects more than one in ten people during their lifetimes. It is characterized by severe, recurrent headaches, often accompanied by nausea, vomiting, and light sensitivity. In some migraineurs (people who have migraines), the headaches are preceded by neurological disturbances known as “aura.” These usually affect vision, causing illusions of flashing lights, zig-zag lines, or blind spots. There are many triggers for migraine attacks—including some foods, stress, and bright lights—and every migraineur has to learn what triggers his or her attacks. There is no cure for migraine, although over-the-counter painkillers can ease the symptoms and doctors can prescribe stronger remedies or drugs to reduce the frequency of attacks. Exactly what causes migraine is unclear but scientists think that, for some reason, the brains of migraineurs are hyperexcitable. That is, some nerve cells in their brains overreact when they receive electrical messages from the body. This triggers a local disturbance of brain function called “cortical spreading depression,” which, in turn, causes aura, headache, and the other symptoms of migraine.
Why Was This Study Done?
Researchers need to know more about what causes migraine to find better treatments. One clue comes from the observation that motion perception is abnormal in migraineurs, even between attacks—they can be very sensitive to visually induced motion sickness, for example. Another clue is that aura are usually visual. So could brain regions that process visual information be abnormal in people who have migraines? In this study, the researchers investigated the structure of the motion processing parts of the brain in people who have migraine with aura, in people who have migraine without aura, and in unaffected individuals to see whether there were any differences that might help them understand migraine.
What Did the Researchers Do and Find?
The researchers used two forms of magnetic resonance imaging—a noninvasive way to produce pictures of internal organs—to examine the brains of migraineurs (when they weren't having a migraine) and healthy controls. They concentrated on two brain regions involved in motion processing known as the MT+ and V3A areas and first measured the cortical thickness of these areas—the cortex is the wrinkled layer of gray matter on the outside of the brain that processes information sent from the body. They found that the cortical thickness was increased in both of these areas in migraineurs when compared to healthy controls. There was no difference in cortical thickness between migraineurs who had aura and those who did not, but the area of cortical thickening in V3A corresponded to the source of cortical spreading depression previously identified in a person who had migraine with aura. The researchers also found differences between the white matter (the part of the brain that transfers information between different regions of the gray matter) immediately below the V3A and MT+ areas in the migraineurs and the controls but again not between the two groups of migraineurs.
What Do These Findings Mean?
This study provides new information about migraine. First, it identifies structural changes in the brains of people who have migraines. Until now, it has been thought that abnormal brain function causes migraine but that migraineurs have a normal brain structure. The observed structural differences might either account for or be caused by the hyperexcitability that triggers migraines. Because migraine runs in families, examining the brains of children of migraineurs as they grow up might indicate which of these options is correct, although it is possible that abnormalities in brain areas not examined here actually trigger migraines. Second, the study addresses a controversial question about migraine: Is migraine with aura the same as migraine without aura? The similar brain changes in both types of migraine suggest that they are one disorder. Third, the abnormalities in areas MT+ and V3A could help to explain why migraineurs have problems with visual processing even in between attacks. Finally, this study suggests that it might be possible to develop a noninvasive test to help doctors diagnose migraine.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030402.
The MedlinePlus encyclopedia has several pages on migraine
The US National Institute of Neurological Disorders and Stroke offers patient information on migraine and other headaches
The NHS Direct Online contains patient information on migraine from the UK National Health Service
MAGNUM provides information from The US National Migraine Association
The Migraine Trust is a UK charity that supports research and provides support for patients
The Migraine Aura Foundation is a site about aura that includes a section on art and aura
doi:10.1371/journal.pmed.0030402
PMCID: PMC1609120  PMID: 17048979
10.  Selectivity in Genetic Association with Sub-classified Migraine in Women 
PLoS Genetics  2014;10(5):e1004366.
Migraine can be sub-classified not only according to presence of migraine aura (MA) or absence of migraine aura (MO), but also by additional features accompanying migraine attacks, e.g. photophobia, phonophobia, nausea, etc. all of which are formally recognized by the International Classification of Headache Disorders. It remains unclear how aura status and the other migraine features may be related to underlying migraine pathophysiology. Recent genome-wide association studies (GWAS) have identified 12 independent loci at which single nucleotide polymorphisms (SNPs) are associated with migraine. Using a likelihood framework, we explored the selective association of these SNPs with migraine, sub-classified according to aura status and the other features in a large population-based cohort of women including 3,003 active migraineurs and 18,108 free of migraine. Five loci met stringent significance for association with migraine, among which four were selective for sub-classified migraine, including rs11172113 (LRP1) for MO. The number of loci associated with migraine increased to 11 at suggestive significance thresholds, including five additional selective associations for MO but none for MA. No two SNPs showed similar patterns of selective association with migraine characteristics. At one extreme, SNPs rs6790925 (near TGFBR2) and rs2274316 (MEF2D) were not associated with migraine overall, MA, or MO but were selective for migraine sub-classified by the presence of one or more of the additional migraine features. In contrast, SNP rs7577262 (TRPM8) was associated with migraine overall and showed little or no selectivity for any of the migraine characteristics. The results emphasize the multivalent nature of migraine pathophysiology and suggest that a complete understanding of the genetic influence on migraine may benefit from analyses that stratify migraine according to both aura status and the additional diagnostic features used for clinical characterization of migraine.
Author Summary
Migraine is among the most common and debilitating neurological disorders. Diagnostic criteria for migraine recognize a variety of symptoms including a primary dichotomous classification for the presence or absence of aura, typically a visual disturbance phenomenon, as well as others such as sensitivity to light or sound, and nausea, etc. We explored whether any of 12 recently discovered genetic variants associated with common migraine might have selective association for migraine sub-classified by aura status or nine additional migraine features in a population of middle-aged women including 3,003 migraineurs and 18,180 non-migraineurs. Five of the 12 genetic variants met the most stringent significance criterion for association with migraine, among which four had selective association with sub-classified migraine, including one that was selective for migraine without aura. At suggestive significance, all of the remaining genetic variants were selective for sub-classifications of migraine although no two variants showed the same pattern of selectivity. The selectivity patterns suggest very different contributions to migraine pathophysiology among the 12 loci and their implicated genes. Further, the results suggest that future discovery efforts for new migraine susceptibility loci would benefit by considering associations with sub-classified migraine toward the ultimate goals of more specific diagnosis and personalized treatment.
doi:10.1371/journal.pgen.1004366
PMCID: PMC4031047  PMID: 24852292
11.  Migraine and Cognitive Decline in the Population-Based EVA Study 
Background
Previous studies on migraine and cognition have shown mixed results. However, many could not assess the relationship between migraine and change in cognitive function or only used a limited number of cognitive tests.
Methods
Prospective cohort study among 1170 participants of the Epidemiology of Vascular Aging Study who provided information about migraine status and completed cognitive testing. Participants were classified as having no severe headache, non-migraine headache and migraine. Cognitive functioning was measured at up to four time points using nine different cognitive functioning tests. Linear mixed effects models were used to evaluate the relationship between migraine status and change in cognitive function.
Results
Of the 1170 participants, 938 had no severe headache, 167 had migraine, and 65 had non-migraine headache. After adjusting for age, gender, education, and smoking status, people with migraine or non-migraine headache did not experience a greater rate of cognitive decline than those without headache or migraine in any domain (for the MMSE, p-values were 0.68 for the non-migraine headache and time interaction and 0.85 for the migraine and time interaction) during 4-5 years of follow-up. For the Wechsler, those with migraine declined less over time (p-value=.02).
Conclusion
Migraine was not associated with faster cognitive decline over time.
doi:10.1177/0333102411417466
PMCID: PMC3175294  PMID: 21816772
Migraine; cognitive function; epidemiology
12.  A Candidate Gene Association Study of 77 Polymorphisms in Migraine 
Population-based studies have established an association between migraine and cardiovascular disease (CVD). We sought to investigate whether genetic variants implicated in CVD are associated with migraine. We performed an association study among 25,713 women, participating in the Women’s Health Study, with information on 77 previously characterized polymorphisms. Migraine and migraine aura status were self-reported. We used logistic regression to investigate the genotype-migraine association. At baseline, 4,705 (18.3%) women reported history of migraine; 39.6% of the 3,306 women with active migraine indicated aura. Regarding any history of migraine, the multivariable-adjusted odds ratios (95% confidence intervals) for TNF rs673 were 0.52 (0.30-0.89), for TGFB1 rs1800469 0.93 (0.89-0.98), and for CCR2 rs1799864 1.12 (1.03-1.21). Among active migraine with aura the odds ratios (95% confidence intervals) were 1.35 (1.0-1.81) for TNF rs1800750, 1.13 (1.02-1.26) for TNF rs1800629, and 1.22 (1.07-1.40) for CCR2 rs1799864; among active migraine without aura 0.9 (0.84-0.97) for TGFB1 rs1800469, 1.13 (1.01-1.27) for NOS3 rs3918226, and 1.12 (1.02-1.24) for IL9 rs2069885. After correction for multiple testing using the false discovery rate, none of the results remained significant. Our data suggest an association of polymorphisms implicated in inflammatory pathways and migraine in women. TNF, CCR2, TGFB1, NOS3, and IL9 warrant further investigation.
Perspective
This article presents results from an association study of 77 polymorphisms, implicated in CVD, and migraine. Variants in TNF, CCR2, TGFB1, NOS3, and IL9 were found to be associated with migraine, but did not remain significant after adjustment for multiple testing. Variations in these genes warrant further investigation.
doi:10.1016/j.jpain.2009.01.326
PMCID: PMC2704575  PMID: 19559392
epidemiology; genetics of migraine; polymorphisms; cardiovascular disease
13.  Increase in self-reported migraine prevalence in the Danish adult population: a prospective longitudinal population-based study 
BMJ Open  2012;2(4):e000962.
Objective
It is uncertain whether migraine prevalence has increased in modern society. The aim of this study was to assess any change in migraine prevalence over an 8-year period among the adult population in Denmark.
Design
Prospective longitudinal population-based study.
Setting
30 000 twin individuals were invited to participate in two cross-sectional questionnaire surveys containing validated questions to diagnose migraine in 1994 and 2002. The twins are representative of the Danish population with regard to migraine and other somatic diseases.
Participants
The 1994 cohort comprised 28 571 twin individuals aged 12–41 years and the 2002 cohort 31 865 twin individuals aged 20–71 years.
Outcome measures
Sex-, age- and subtype-specific incidence and lifetime prevalence as well as 1-year prevalence of migraine.
Results
1-year prevalence in 2002 was 12.3% for migraine, 4.1% for migraine with aura and 8.2% for migraine without aura. Lifetime prevalence of migraine was 16.1% in 1994 (aged 12–41 years) and 25.2% in 2002 (aged 20–71 years). Lifetime prevalence of migraine for age 20–41 was increased from 1994 to 2002 (18.5% vs 24.5%) by 32.2% (95% CI 27.0% to 37.3%; p<0.001). The difference was primarily seen in the population older than 32 years. The increase was especially evident in migraine with aura (5.6% vs 9.4%, p<0.001) but also a significant increase in migraine without aura was found (13.0% vs 15.1%, p<0.001). Eight-year period incidence rate of migraine was 0.141 corresponding to an average annual incidence rate of 17.6 per 1000 person-years.
Conclusions
Lifetime prevalence of migraine in Denmark increased substantially from 1994 to 2002. Part of the increase may be due to increased medical consultation resulting in increased rate of physician diagnosis or awareness due to previously participation in the 1994 survey. It is pertinent to study the environmental causes of the increase and to implement preventive measures.
Article summary
Article focus
Has migraine prevalence increased in modern society?
Key messages
Self-reported migraine prevalence increased substantially in the Danish young adult population.
Sex- and age-specific prevalence and incidence of migraine and its subtypes were estimated in a large population-based sample.
Strengths and limitations of this study
Large sample size made it possible to differentiate between migraine with aura and migraine without aura using the validated diagnostic questions and furthermore subdivide between men and women and to distinguish between age groups.
The validation of the two questions used to identify migraine cases showed that self-reported migraine was only correct in 74.5% of cases, and furthermore, approximately 23.8% of the migraine patients were not identified. Thus, our estimates would tend to be conservative.
doi:10.1136/bmjopen-2012-000962
PMCID: PMC3391377  PMID: 22761284
14.  Migraine and cardiovascular disease: systematic review and meta-analysis 
Objective To evaluate the association between migraine and cardiovascular disease, including stroke, myocardial infarction, and death due to cardiovascular disease.
Design Systematic review and meta-analysis.
Data sources Electronic databases (PubMed, Embase, Cochrane Library) and reference lists of included studies and reviews published until January 2009.
Selection criteria Case-control and cohort studies investigating the association between any migraine or specific migraine subtypes and cardiovascular disease.
Review methods Two investigators independently assessed eligibility of identified studies in a two step approach. Disagreements were resolved by consensus. Studies were grouped according to a priori categories on migraine and cardiovascular disease.
Data extraction Two investigators extracted data. Pooled relative risks and 95% confidence intervals were calculated.
Results Studies were heterogeneous for participant characteristics and definition of cardiovascular disease. Nine studies investigated the association between any migraine and ischaemic stroke (pooled relative risk 1.73, 95% confidence interval 1.31 to 2.29). Additional analyses indicated a significantly higher risk among people who had migraine with aura (2.16, 1.53 to 3.03) compared with people who had migraine without aura (1.23, 0.90 to 1.69; meta-regression for aura status P=0.02). Furthermore, results suggested a greater risk among women (2.08, 1.13 to 3.84) compared with men (1.37, 0.89 to 2.11). Age less than 45 years, smoking, and oral contraceptive use further increased the risk. Eight studies investigated the association between migraine and myocardial infarction (1.12, 0.95 to 1.32) and five between migraine and death due to cardiovascular disease (1.03, 0.79 to 1.34). Only one study investigated the association between women who had migraine with aura and myocardial infarction and death due to cardiovascular disease, showing a twofold increased risk.
Conclusion Migraine is associated with a twofold increased risk of ischaemic stroke, which is only apparent among people who have migraine with aura. Our results also suggest a higher risk among women and risk was further magnified for people with migraine who were aged less than 45, smokers, and women who used oral contraceptives. We did not find an overall association between any migraine and myocardial infarction or death due to cardiovascular disease. Too few studies are available to reliably evaluate the impact of modifying factors, such as migraine aura, on these associations.
doi:10.1136/bmj.b3914
PMCID: PMC2768778  PMID: 19861375
15.  Migraine and Restless Legs Syndrome in Women 
Cephalalgia  2012;32(5):382-389.
Background
Few clinic-based studies report an association between migraine and restless legs syndrome (RLS); however, population-based data are unavailable.
Methods
Cohort study among 31,370 women participating in the Women’s Health Study. We had detailed self-reported information on migraine, including aura status, and RLS. RLS was ascertained at the 9-year follow-up. We calculated odds ratios (OR) and 95% confidence intervals (CI) for the association between migraine and RLS. We investigated any indication of migraine until RLS ascertainment as well as migraine with and without aura at baseline, prior migraine before baseline, and new reports of migraine during follow-up.
Results
At baseline or during follow-up 6,857 (21.9%) women reported any migraine. These women had an increased risk for RLS (multivariable-adjusted OR=1.22; 95%CI 1.13–1.32). Further analyses indicated a similar association for migraine with aura (multivariable-adjusted OR=1.27; 95%CI 1.10–1.48) and migraine without aura (multivariable-adjusted OR=1.24; 95%CI 1.09–1.40) as well as for new reports of migraine during follow-up (multivariable-adjusted OR=1.30; 95%CI 1.10–1.54). Prior migraine did not appear to be associated with RLS.
Conclusions
Our data suggest an association between migraine and RLS at the population level. The association is similar for migraine with and without aura and for new reports of migraine during follow-up.
doi:10.1177/0333102412439355
PMCID: PMC3334395  PMID: 22395798
migraine; restless legs syndrome; cohort study; association
16.  Associations of socioeconomic status with migraine and non-migraine headache 
Cephalalgia  2011;32(2):159-170.
Background
Migraine has been linked with several measures of socioeconomic status (SES). However, results are inconsistent and data on the association between SES and non-migraine headache, migraine subtypes and migraine frequency are sparse.
Methods
We conducted a cross-sectional study among 36,858 participants in the Women’s Health Study. As proxy for SES, we calculated an SES index using annual household income and education. Migraine, migraine aura, and non-migraine headache were self-reported with good validation rates. Multinomial logistic regression models were used to evaluate the association between SES index and the various headache forms.
Results
12,140 (32.9%) women reported any history of headache, 6,801 women (18.4%) reported any history of migraine and 5,339 (14.5%) reported non-migraine headache. Women with low SES had an increased risk for all headache forms. The multivariable-adjusted OR (95% CI) were 1.22 (1.10–1.36) for non-migraine headache, 1.40 (1.28–1.54) for any migraine, 1.44 (1.23–1.69) for migraine with aura, and 1.38 (1.21–1.58) for migraine without aura. Among active migraineurs, low SES was associated with an increased OR for ≥weekly attack frequency (1.77, 1.26–2.49).
Conclusions
In this large cohort of female health professionals, low SES was associated with an increased prevalence for all headache forms and an increased migraine attack frequency.
doi:10.1177/0333102411430854
PMCID: PMC3266434  PMID: 22174348
Migraine; non-migraine headache; migraine frequency; socioeconomic status
17.  Migraine frequency and risk of cardiovascular disease in women 
Neurology  2009;73(8):581-588.
Background:
Migraine has been associated with risk of cardiovascular disease (CVD). Data on the association between migraine frequency and CVD are sparse.
Methods:
Prospective cohort study of 27,798 US women aged ≥45 years, who were free of CVD, and for whom we had information on lipids and migraine frequency. We categorized migraine frequency as < monthly, monthly, and ≥ weekly. Incident CVD was confirmed after medical record review.
Results:
Of the 3,568 women with active migraine at baseline, 75.3% reported a migraine frequency of < monthly, 19.7% monthly, and 5.0% ≥ weekly. During 11.9 years of follow-up, 706 CVD events occurred. Compared with women without migraine, the multivariable-adjusted hazard ratios (HRs) (95% confidence intervals) among active migraineurs for CVD were 1.55 (1.22–1.97), 0.65 (0.31–1.38), and 1.93 (0.86–4.33) for an attack frequency of < monthly, monthly, and ≥ weekly, respectively. The association between migraine frequency and CVD was only apparent among migraineurs with aura. Among those, the multivariable-adjusted HRs for women with a migraine frequency < monthly ranged from 1.81 (1.30–2.50) for coronary revascularizations to 2.43 (1.58–3.74) for myocardial infarction. For women with active migraine with aura and migraine frequencies of ≥ weekly, we only found significant increased risk of ischemic stroke (HR = 4.25 [1.36–13.29]).
Conclusions:
In our data, the association between migraine and cardiovascular disease varies by migraine frequency. Significant associations were only found among women with migraine with aura. Ischemic stroke was the only outcome associated with a high-attack frequency while a low-attack frequency was associated with any vascular event. Low number of outcome events should caution the interpretation.
GLOSSARY
= confidence interval;
= cardiovascular disease;
= hazard ratio;
= myocardial infarction;
= Women’s Health Study.
doi:10.1212/WNL.0b013e3181ab2c20
PMCID: PMC2731618  PMID: 19553594
18.  Migraine, Migraine Features, and Cardiovascular Disease 
Headache  2010;50(6):1031-1040.
Background
— Many studies support an association between migraine and cardiovascular disease (CVD). This association appears particularly in migraine with aura and is also modified by additional factors.
Objective
— We sought to investigate whether the association between migraine and CVD in addition to aura status is affected by certain migraine features.
Methods
— Cohort study among 27,840 women, participating in the Women’s Health Study. We had detailed self-reported information on migraine and migraine features among women with active migraine (migraine during the year prior to baseline). Incident CVD events were confirmed after medical record review. We used Cox proportional hazards models to evaluate the association between migraine and incident CVD. The results have been presented in part before. We ran additional analyses according to migraine features.
Results
– At baseline, 5,125 (18.4%) women reported history of migraine; 39.7% of the 3,610 women with active migraine indicated aura. During a mean of 11.9 years of follow-up, 708 CVD events occurred. Migraine with aura doubled the risk for CVD, ischemic stroke, and myocardial infarction. With regard to ischemic stroke, this association seemed stronger in the absence than in the presence of migraine features. This was most pronounced in the absence (HR=3.27; 95% CI=1.93–5.51; p<0.0001) than in the presence of nausea/vomiting (HR=0.91; 95% CI=0.43–1.93; p=0.80). In contrast, the association with myocardial infarction did not reveal a certain pattern.
Conclusions
— These data suggest that the association between migraine with aura and ischemic stroke may differ by absence or presence of migraine features.
doi:10.1111/j.1526-4610.2009.01609.x
PMCID: PMC2891199  PMID: 20100297
migraine; migraine features; cardiovascular disease; cohort study
19.  Migraine, weight gain and the risk of becoming overweight or obese: prospective cohort study 
Background
Some cross-sectional studies have suggested an association between migraine and increased body weight. However, prospective data on the association are lacking.
Methods
We conducted a prospective cohort study among 19,162 participants in the Women’s Health Study who had a body mass index (BMI) of 18.5–<25kg/m2 at baseline. Migraine was self-reported by standardized questionnaires. Main outcome measures were: incident overweight (BMI ≥25kg/m2), incident obesity (BMI ≥30kg/m2), and mean weight change. Age- and multivariable-adjusted hazard ratios were calculated for the association between migraine and incident overweight and obesity. Differences in weight change were evaluated by ANCOVA.
Results
3,483 (18.2%) women reported any migraine history. After 12.9 years of follow-up, 7,916 incident overweight and 730 incident obesity cases occurred. Migraineurs had multivariable-adjusted HRs (95%CI) of 1.11 (1.05–1.17) for becoming overweight and 1.00 (0.83–1.19) for becoming obese. These associations remained stable after censoring for chronic diseases and were similar according to migraine aura status. Multivariable-adjusted mean weight change from baseline to the end of study was +4.7kg for migraineurs and +4.4kg for women without migraine (P=0.02).
Conclusion
Results of this large prospective study of middle-aged women do not indicate a consistent association between migraine and incident overweight, obesity, or relevant weight gain.
doi:10.1177/0333102412455708
PMCID: PMC3460066  PMID: 22875879
Migraine; body mass index; overweight; obesity; prospective study
20.  Association Between Intimate Partner Violence, Migraine and Probable Migraine 
Headache  2010;51(2):208-219.
Objective
Intimate partner violence (IPV) among women is a global public health problem. The association between childhood maltreatment and migraine is well established, but not the association between IPV and migraine. The aim of this cross-sectional study was to evaluate the relationship between type and severity of IPV and migraine in a large cohort of Peruvian women.
Methods
Women who delivered singleton infants (N=2,066) at the Instituto Nacional Materno Perinatal, Lima, Peru were interviewed during their post-partum hospital stay. Participants were queried about their lifetime experiences with headaches and migraine, and with physical and sexual violence. The International Classification of Headache Disorders (ICHD-2) diagnostic criteria were used to classify participants according to their migraine status. Questions on physical and sexual violence were adapted from the protocol of Demographic Health Survey Questionnaires and Modules: Domestic Violence Module and the World Health Organization (WHO) Multi-Country Study on Violence against Women. Depressive symptoms were assessed using the nine-item Patient Health Questionnaire Depression Subset. Logistic regression was used to estimate multivariate adjusted odds ratios (aOR) and 95% confidence intervals (CI).
Results
Compared with women without a history of violence, women with experiences of lifetime physical or sexual violence (aOR=1.44, 95% CI 1.19–1.75), physical violence only (aOR=1.36, 95% CI 1.10–1.68), sexual violence only (aOR=1.76, 95% CI 0.97–3.21) and both physical and sexual violence (aOR=1.61, 95% CI 1.12–2.31) had increased odds of any migraine after adjusting for maternal age, parity and access to basic foods. There was no gradient of increased odds of any migraine with severity of physical violence. The relationship between IPV and any migraine was strongest among women with depressive symptoms. The odds of any migraine was increased 2.25-fold (95% CI 1.75–2.28) among abused women who also had depressive symptoms compared with non-abused and non-depressed women. Associations from sensitivity analyses that segregated women according to probable migraine (ICHD-2 category 1.6.1) and migraine (ICHD-2 category 1.1) diagnoses were of similar magnitudes as those reported here for women with any migraine diagnoses. IPV, particularly sexual violence, appears to be a risk factor for migraine.
Conclusion
Our findings suggest the potential importance of considering a history of violence among migraineurs.
doi:10.1111/j.1526-4610.2010.01777.x
PMCID: PMC3662491  PMID: 20946432
21.  Visual migraine aura with or without headache: association with right to left shunt and assessment following transcutaneous closure 
Video abstract
Video
Background
Right to left shunting, usually caused by a patent foramen ovale (PFO), is associated with migraine and visual aura. It is unknown if patients who present with visual aura without headache behave similarly to those experiencing typical migraine headache with aura. The purpose of this study was to assess the prevalence of right to left shunting in patients who present with migraine aura without headache and evaluate the response to PFO closure.
Methods
The records of patients referred to the Interventional Cardiology program at the University of California at Los Angeles for suspected intracardiac right to left shunt were reviewed. Individuals with visual auras with or without migraine headaches were divided into three groups: group A (aura + migraine), migraine aura during or within 60 minutes of headache; group B (migraine aura unrelated to headache), migraine aura and headache temporally unrelated; and group C (migraine aura only), isolated migraine visual aura without a history of headaches. The presence of right to left shunt was assessed using transcranial Doppler with an agitated saline test. PFO closure was performed in 80 patients. Residual headache and migraine visual aura were assessed 3 and 12 months after the procedure. The control group consisted of 200 patients referred for diagnostic cardiac catheterization.
Results
Of 590 referred patients, 225 had migraine visual aura with or without headache. The prevalence of right to left shunt was similar (P = 0.66) in groups B (21/29, 72%) and C (14/21, 67%). Group A patients had a higher prevalence of right to left shunt (168/175, 96%) due to selection bias. The prevalence of right to left shunt in the control group was significantly (P < 0.0001) lower (36/200, 18%) than in groups A, B, and C. At 12 months after PFO closure, visual aura was resolved in 52%, 75%, and 80% of patients in groups A, B, and C, respectively (difference not statistically significant).
Conclusion
There is an increased prevalence of PFO among patients with migraine aura without headache. The closure of PFO correlates with improvement of the visual aura, suggesting a causative association between the presence of PFO and both visual aura and migraine headaches. Ophthalmologists should be aware of the association of right to left shunts with visual aura.
doi:10.2147/OPTH.S30999
PMCID: PMC3413347  PMID: 22888208
visual aura without headache; right to left shunt; patent foramen ovale
22.  ACE D/I polymorphism, migraine, and cardiovascular disease in women 
Neurology  2009;72(7):650-656.
Background:
Interrelationships among the ACE deletion/insertion (D/I) polymorphism (rs1799752), migraine, and cardiovascular disease (CVD) are biologically plausible but remain controversial.
Methods:
Association study among 25,000 white US women, participating in the Women’s Health Study, with information on the ACE D/I polymorphism. Migraine and migraine aura status were self-reported. Incident CVD events were confirmed after medical record review. We used logistic regression to investigate the genotype-migraine association and proportional hazards models to evaluate the interrelationship among genotype, migraine, and incident CVD.
Results:
At baseline, 4,577 (18.3%) women reported history of migraine; 39.5% of the 3,226 women with active migraine indicated aura. During 11.9 years of follow-up, 625 CVD events occurred. We did not find an association of the ACE D/I polymorphism with migraine or migraine aura status. There was a lack of association between the ACE D/I polymorphism and incident major CVD, ischemic stroke, and myocardial infarction. Migraine with aura doubled the risk for CVD, but only for carriers of the DD (multivariable-adjusted relative risk [RR] = 2.10; 95% CI = 1.22–3.59; p = 0.007) and DI genotype (multivariable-adjusted RR = 2.31; 95% CI = 1.52–3.51; p < 0.0001). The risk was not significant among carriers of the II genotype, a pattern we observed for myocardial infarction and ischemic stroke.
Conclusions:
Data from this large cohort of women do not suggest an association of the ACE deletion/insertion (D/I) polymorphism with migraine, migraine aura status, or cardiovascular disease (CVD). The increased risk for CVD among migraineurs with aura was only apparent for carriers of the DD/DI genotype. Due to limited number of outcome events, however, future studies are warranted to further investigate this association.
GLOSSARY
= angiotensin-converting enzyme;
= confidence interval;
= cardiovascular disease;
= deletion/insertion;
= hazard ratios;
= International Headache Society;
= myocardial infarction;
= odds ratio;
= Women’s Health Study.
doi:10.1212/01.wnl.0000342517.97178.f6
PMCID: PMC2644823  PMID: 19221299
23.  ACE D/I Polymorphism, Migraine, and Cardiovascular Disease in Women 
Neurology  2009;72(7):650-656.
Background
Interrelationships between the ACE D/I polymorphism (rs1799752), migraine, and cardiovascular disease (CVD) are biologically plausible but remain controversial.
Methods
Association study among 25,000 white U.S. women, participating in the Women's Health Study, with information on the ACE D/I polymorphism. Migraine and migraine aura status were self-reported. Incident CVD events were confirmed after medical record review. We used logistic regression to investigate the genotype-migraine association and proportional hazards models to evaluate the interrelationship between genotype, migraine, and incident CVD.
Results
At baseline, 4,577 (18.3%) women reported history of migraine; 39.5% of the 3,226 women with active migraine indicated aura. During 11.9 years of follow-up, 625 CVD events occurred. We did not find an association of the ACE D/I polymorphism with migraine or migraine aura status. There was a lack of association between the ACE D/I polymorphism and incident major CVD, including ischemic stroke and myocardial infarction. Migraine with aura doubled the risk for CVD (multivariable-adjusted RR=2.07; 95%CI=1.53-2.79; p<0.0001), but only for carriers of the DD/DI genotype. The risk was not significant among carriers of the II genotype (multivariable-adjusted RR=1.47; 95%CI=0.71-3.03), a pattern we observed for myocardial infarction and ischemic stroke.
Conclusions
Data from this large cohort of women do not suggest an association of the ACE D/I polymorphism with migraine, migraine aura status, or CVD. The increased risk for CVD among migraineurs with aura was only apparent for carriers of the DD/DI genotype. Due to limited number of outcome events, however, future studies are warranted to further investigate this association.
doi:10.1212/01.wnl.0000342517.97178.f6
PMCID: PMC2644823  PMID: 19221299
[101] migraine; ACE D/I polymorphism; [2] cardiovascular disease; [54] cohort study
24.  Interrelationships Between the MTHFR 677C>T Polymorphism, Migraine, and Cardiovascular Disease 
Neurology  2008;71(7):505-513.
Background
Interrelationships between the MTHFR 677C>T polymorphism (rs1801133), migraine, and cardiovascular disease (CVD) are plausible but remain controversial.
Methods
Association study among 25,001 white U.S. women, participating in the Women’s Health Study, with information on MTHFR 677C>T polymorphism. Migraine and migraine aura status were self-reported. Incident CVD events were confirmed after medical record review. We used logistic regression to investigate the genotype-migraine association and proportional hazards models to evaluate the interrelationships of genotype and migraine on incident CVD.
Results
At baseline, 4,577 (18.3%) women reported history of migraine; 39.5% of the 3,226 women with active migraine indicated aura. During a mean of 11.9 years of follow-up, 625 CVD events occurred. Our results suggest a modestly reduced risk for migraine with aura in carriers of the TT genotype. The multivariable-adjusted relative risk (RR) in the recessive model was 0.79 (95%CI=0.65–0.96; p=0.02). The TT genotype did not increase the risk for CVD. In contrast, migraine with aura doubled the risk for CVD (multivariable-adjusted RR=2.06; 95%CI=1.53–2.78; p<0.0001). Co-existence of migraine with aura and the TT genotype selectively raised this risk (RR=3.66; 95%CI=1.69–7.90; p=0.001). This pattern was driven by a 4-fold increased risk for ischemic stroke (multivariable-adjusted RR=4.19; 95%CI=1.38–12.74; p=0.01) and not apparent for myocardial infarction.
Conclusions
Data from this large cohort of women suggest a modest protective effect of the MTHFR 677TT genotype on migraine with aura. The increased risk for CVD among migraineurs with aura was magnified for TT genotype carriers, which was driven by a substantially increased risk of ischemic stroke.
doi:10.1212/01.wnl.0000316198.34558.e5
PMCID: PMC2562562  PMID: 18672474
[101] migraine; MTHFR polymorphism; [2] cardiovascular disease; [54] cohort study
25.  Migraine: is it related to hormonal disturbances or stress? 
Background
Common neurological syndrome (migraine without aura) is more common among women than men. Migraine is among the top 20 causes of disability. Menstruation is known to be a powerful trigger for migraine, and so is stress, but the presentation of headache is similar in both. Also, women are more vulnerable to stress as well as migraine, and this makes a complex relationship of menstruation, stress, and migraine.
Objective
This study was done to understand the association of hormonal fluctuation in menstruation and stress with common migraine.
Materials and methods
A cross-sectional comparative study was conducted in 40 young adult females, of whom 20 participants were cases of migraine without aura (18–35 years old), and the remaining 20 participants were age-matched controls. The study was done in Maulana Azad Medical College, New Delhi. Study participants were selected on the basis of International Headache Society (ICHD-IIA1.1) (2004) classification. Study participants with neurological disorders, chronic diseases, and disease suggestive of any hormonal disturbances were excluded. Clinically diagnosed migraine cases were asked to maintain a headache diary and to fill in the Depression Anxiety Stress Scales questionnaire. Biochemical assessment of hormonal status for thyroid-stimulating hormone, triiodothyronine, thyroxine, estrogen, follicle-stimulating hormone, luteinizing hormone, and prolactin was also done on the second day of their menstrual cycle. We used the Mann–Whitney U test to compare hormonal levels and the χ2 test to compare anxiety- or depression-related stress among the migraine and nonmigraine groups.
Results
Significantly higher values of prolactin were observed in cases (mean ± standard deviation, 152.7 mIU/L±30.5) compared to controls (76.1 mIU/L±8.7), with a P-value <0.001. There was no statistically significant difference observed in levels of thyroid-stimulating hormone (P=0.081), estrogen (P=0.086), luteinizing hormone (P=0.091), or follicle-stimulating hormone (P=0.478). Also, anxiety with stress or depression with stress was significantly higher among the migraine group than the controls (P=0.002). Odds of any stress in migraine were higher in the migraine group than in the nonmigraine group (odds ratio 12, 95% confidence interval 2.7–53.33).
Conclusion
Migraine, particularly without aura, in women is mainly associated with stress-related anxiety or depression, and are more susceptible to stress in the premenstrual period.
Video abstract
doi:10.2147/IJWH.S62922
PMCID: PMC4216045  PMID: 25368535
migraine; menstruation; stress

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