Childhood maltreatment and migraine (part III). Association with comorbid pain conditions.

OBJECTIVE: To evaluate in a headache clinic population the relationship of childhood maltreatment on the prevalence of pain conditions comorbid with migraine. BACKGROUND: Childhood maltreatment is highly prevalent and has been frequently associated with recurrent headache. The relationship of maltreatment and pain has, however, been a subject of some debate. METHODS: Cross-sectional data on self-reported physician-diagnosed pain conditions were electronically collected from persons with migraine (diagnosed according to International Classification of Headache Disorders-2), seeking treatment in headache clinics at 11 centers across the US and Canada. These included irritable bowel syndrome (IBS), chronic fatigue syndrome (CFS), fibromyalgia (FM), interstitial cystitis (IC), arthritis, endometriosis, and uterine fibroids. Other information included demographics, migraine characteristics (frequency, headache-related disability), remote and current depression (The Patient Health Questionnaire-9), and remote and current anxiety (The Beck Anxiety Inventory). Patients also completed the Childhood Trauma Questionnaire regarding sexual, emotional, and physical abuse, and emotional and physical neglect under the age of 18 years old. Statistical analyses accounted for the survey design and appropriate procedures in SAS such as surveymeans, surveyfreq, and surveylogistic were applied to the weighted data. RESULTS: A total of 1348 migraineurs (88% women) were included in this study (mean age 41 years). Based on physician diagnosis or validated criteria, 31% had IBS, 16% had CFS, and 10% had FM. Diagnosis of IC was reported by 6.5%, arthritis by 25%, and in women, endometriosis was reported by 15% and uterine fibroids by 14%. At least 1 comorbid pain condition was reported by 61%, 2 conditions by 18%, and 3 or more by 13%. Childhood maltreatment was reported by 58% of the patients. Emotional abuse was associated with increased prevalence of IBS, CFS, arthritis, and physical neglect with arthritis. In women, physical abuse was associated with endometriosis and physical neglect with uterine fibroids. Emotional abuse, and physical abuse and neglect (P < .0001 for all) were also associated with increased total number of comorbid conditions. In ordinal logistic regression models, adjusted for sociodemographics and current depression (prevalence 28%) and anxiety (prevalence 56%), emotional abuse (odds ratios [OR] = 1.69, 95% confidence intervals [CI]: 1.224-2.33) and physical neglect (OR = 1.73, 95% CI: 1.22-2.46) were independently associated with an increased number of pain conditions. The cohort of women, similarly, had associations of emotional abuse (OR = 1.94, 95% CI: 1.40-2.72) and physical neglect (OR = 1.90, 95% CI: 1.34-2.68) with an increased number of pain comorbidities. CONCLUSION: The association of childhood maltreatment and pain was stronger in those reporting multiple pain conditions and multiple maltreatment types. This finding suggests that in migraineurs childhood maltreatment may be a risk factor for development of comorbid pain disorders.

Childhood maltreatment and migraine (part I). Prevalence and adult revictimization: a multicenter headache clinic survey.

OBJECTIVES: To examine the prevalence of childhood maltreatment and adult revictimization in migraineurs and the association with sociodemographic factors, depression and anxiety. BACKGROUND: Population and practice-based studies have demonstrated an association of childhood abuse and headache in adults, although further details on headache diagnoses, characteristics, and comorbid conditions are lacking. There are mounting data suggesting substantial impact of early maltreatment on adult physical and mental health. METHODS: Electronic surveys were completed by patients seeking treatment in 11 headache centers across the United States and Canada. Physicians determined the primary headache diagnoses based on the International Classification of Headache Disorders-2 criteria and average monthly headache frequency. Self-reported information on demographics (including body mass index), social history, and physician-diagnosed depression and anxiety was collected. The survey also included validated screening measures for current depression (Patient Health Questionnaire-9) and anxiety (The Beck Anxiety Inventory). History and severity of childhood (<18 years) abuse (sexual, emotional, and physical) and neglect (emotional and physical) was gathered using the Childhood Trauma Questionnaire. There were also queries regarding adult physical and sexual abuse, including age of occurrence. Analysis includes all persons with migraine with aura, and migraine without aura. RESULTS: A total of 1348 migraineurs (88% women) were included (mean age 41 years). Diagnosis of migraine with aura was recorded in 40% and chronic headache (>or=15 days/month) was reported by 34%. The prevalence of childhood maltreatment types was as follows: physical abuse 21%, sexual abuse 25%, emotional abuse 38%, physical neglect 22%, and emotional neglect 38%. Nine percent reported all 3 categories of childhood abuse (physical, sexual, and emotional) and 17% reported both physical and emotional neglect. Overlap between maltreatment types ranged between 40% and 81%. Of those reporting childhood abuse, 43% reported abuse in adulthood, but infrequently (17%) over the age of 30 years. In logistic regression models adjusted for sociodemographic variables, current depression was associated with physical (P = .003), sexual (P = .007), and emotional abuse (P < .001), and physical and emotional neglect (P = .001 for both). Current anxiety was also associated with all childhood abuse and neglect categories (P < .001 for all). A graded relationship was observed between the number of childhood maltreatment types and remote or current depression and anxiety. In adjusted logistic regression analysis, migraineurs reporting 3 or more categories of childhood trauma were more likely to have received diagnoses of both depression and anxiety (odds ratios [OR] = 6.91, 95% confidence interval [CI]: 3.97-12.03), or either depression or anxiety (OR = 3.66, 95% CI: 2.28-5.88) as compared with those without childhood abuse or neglect. CONCLUSION: Reports of childhood maltreatment, especially emotional abuse and neglect, are prevalent in outpatients with migraine. There is extensive overlap of maltreatment types and a high rate of revictimization in adulthood. All types of childhood abuse and neglect are strongly associated with remote and current depression and anxiety, and the relationship strengthens with an increasing number of maltreatment types.

Childhood maltreatment and migraine (part II). Emotional abuse as a risk factor for headache chronification.

OBJECTIVES: To assess in a headache clinic population the relationship of childhood abuse and neglect with migraine characteristics, including type, frequency, disability, allodynia, and age of migraine onset. BACKGROUND: Childhood maltreatment is highly prevalent and has been associated with recurrent headache. Maltreatment is associated with many of the same risk factors for migraine chronification, including depression and anxiety, female sex, substance abuse, and obesity. METHODS: Electronic surveys were completed by patients seeking treatment in headache clinics at 11 centers across the United States and Canada. Physician-determined data for all participants included the primary headache diagnoses based on the International Classification of Headache Disorders-2 criteria, average monthly headache frequency, whether headaches transformed from episodic to chronic, and if headaches were continuous. Analysis includes all persons with migraine with aura, and migraine without aura. Questionnaire collected information on demographics, social history, age at onset of headaches, migraine-associated allodynic symptoms, headache-related disability (The Headache Impact Test-6), current depression (The Patient Health Questionnaire-9), and current anxiety (The Beck Anxiety Inventory). History and severity of childhood (<18 years) abuse (sexual, emotional, and physical) and neglect (emotional and physical) was gathered using the Childhood Trauma Questionnaire. RESULTS: A total of 1348 migraineurs (88% women) were included (mean age 41 years). Diagnosis of migraine with aura was recorded in 40% and chronic headache (>or=15 days/month) was reported by 34%. Transformation from episodic to chronic was reported by 26%. Prevalence of current depression was 28% and anxiety was 56%. Childhood maltreatment was reported as follows: physical abuse 21%, sexual abuse 25%, emotional abuse 38%, physical neglect 22%, and emotional neglect 38%. In univariate analyses, physical abuse and emotional abuse and neglect were significantly associated with chronic migraine and transformed migraine. Emotional abuse was also associated with continuous daily headache, severe headache-related disability, and migraine-associated allodynia. After adjusting for sociodemographic factors and current depression and anxiety, there remained an association between emotional abuse in childhood and both chronic (odds ratio [OR] = 1.77, 95% confidence intervals [CI]: 1.19-2.62) and transformed migraine (OR = 1.89, 95% CI: 1.25-2.85). Childhood emotional abuse was also associated with younger median age of headache onset (16 years vs 19 years, P = .0002). CONCLUSION: Our findings suggest that physical abuse, emotional abuse, and emotional neglect may be risk factors for development of chronic headache, including transformed migraine. The association of maltreatment and headache frequency appears to be independent of depression and anxiety, which are related to both childhood abuse and chronic daily headache. The finding that emotional abuse was associated with an earlier age of migraine onset may have implications for the role of stress responses in migraine pathophysiology.

Migraine and biomarkers of endothelial activation in young women.

BACKGROUND AND PURPOSE: There is mounting evidence of endothelial activation and dysfunction in migraine. Our objectives were to determine in a population of premenopausal women whether endothelial activation markers are associated with migraine. METHODS: Women (18 to 50 years) with and without migraine and free from cardiovascular disease were evaluated with tests of coagulation (von Willebrand factor activity, prothrombin fragment), fibrinolysis (tissue-type plasminogen activator antigen), inflammation (high-sensitivity C-reactive protein), and oxidative stress (homocysteine, total nitrate/nitrite concentrations, thiobarbituric acid-reactive substances). RESULTS: Sixty-one participants had migraine with aura (MA), 64 had migraine without aura (MO), and 50 were controls. Compared with controls, women with migraine had higher adjusted odds ratios for elevated von Willebrand factor activity of 6.51 (95% CI, 1.94 to 21.83) in those with MA and of 4.59 (95% CI, 1.37 to 15.38) in those with MO, elevated high-sensitivity C-reactive protein of 7.99 (95% CI, 2.32 to 27.61) in those with MA and of 2.63 (95% CI, 0.73 to 9.45) in those with MO, and for lower nitrate/nitrite levels of 6.60 (95% CI, 2.06 to 21.16) in those with MA and of 3.03 (95% CI, 0.90 to 10.15) in those with MO. Within the migraine group, von Willebrand factor activity was correlated with tissue-type plasminogen activator antigen (P=0.035) and nitrate/nitrite (P=0.024). There was a trend with high-sensitivity C-reactive protein (P=0.09). CONCLUSIONS: In premenopausal women with migraine, particularly in those with MA, there is evidence of increased endothelial activation, a component of endothelial dysfunction.

Allodynia in migraine: association with comorbid pain conditions.

BACKGROUND: Cutaneous allodynia (CA) in migraine is a clinical manifestation of central nervous system sensitization. Several chronic pain syndromes and mood disorders are comorbid with migraine. In this study we examine the relationship of migraine-associated CA with these comorbid conditions. We also evaluate the association of CA with factors such as demographic profiles, migraine characteristics, and smoking status that may have an influence on the relationships of CA to pain and mood. METHODS: Data are from a cross-sectional multicenter study of comorbid conditions in persons seeking treatment in headache clinics. Diagnosis of migraine was determined by a physician based on the International Classification of Headache Disorders-II criteria. Participants completed a self-administered questionnaire ascertaining sociodemographics, migraine-associated allodynia, physician-diagnosed comorbid medical and psychiatric disorders, headache-related disability, current depression, and anxiety. RESULTS: A total of 1413 migraineurs (mean age = 42 years, 89% women) from 11 different headache treatment centers completed a survey on the prevalence of comorbid conditions. Aura was reported by 38% and chronic headache by 35% of the participants. Sixty percent of the study population reported at least one migraine-related allodynic symptom, 10% reported > or =4 symptoms. Symptoms of CA were associated with female gender, body mass index, current smoking, presence of aura, chronic headaches, transformed headaches, severe headache-related disability, and duration of migraine illness from onset. The prevalence of self-reported physician diagnosis of comorbid pain conditions (irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia) and psychiatric conditions (current depression and anxiety) was also associated with symptoms of CA. Adjusted ordinal regression indicated a significant association between number of pain conditions and severity of CA (based on symptom count). Adjusting for sociodemographics, migraine characteristics, and current depression and anxiety, the likelihood of reporting symptoms of severe allodynia was much higher in those with 3 or more pain conditions (odds ratio = 3.03, 95% confidence interval: 1.78-5.17), and 2 pain conditions (odds ratio = 2.67, 95% confidence interval: 1.78-4.01) when compared with those with no comorbid pain condition. CONCLUSION: Symptoms of CA in migraine were associated with current anxiety, depression, and several chronic pain conditions. A graded relationship was observed between number of allodynic symptoms and the number of pain conditions, even after adjusting for confounding factors. This study also presents the novel association of CA symptoms with younger age of migraine onset, and with cigarette smoking, in addition to confirming several previously reported findings.

Race differences in adherence to headache treatment appointments in persons with headache disorders.

PURPOSE: This research characterized patterns and predictors of adherence to headache treatment appointments in patients presenting at headache specialty treatment clinics throughout Ohio. BASIC PROCEDURES: Participants were 186 patients (118 white, 68 African Americans, 89% female) in headache treatment clinics in Cincinnati, Cleveland, Columbus and Toledo, OH. The study used a naturalistic longitudinal cohort design and assessed patients during four treatment visits (pretreatment, one-month follow-up, two-month follow-up and six-month follow-up). During the 30 days prior to initiating new headache treatments, patients used a daily diary to record data on headache severity, frequency and disability; headache treatment locus of control and headache management self-efficacy; social support; and demographic characteristics. The Primary Care Evaluation for Mental Disorders interview was administered to all patients at pretreatment to screen for psychiatric diagnoses. Patient attendance at the four treatment appointments was used to create a dichotomous measure of treatment appointment adherence (i.e., 0 = completed treatment; 1 = terminated treatment prematurely). MAIN FINDINGS: African Americans were more likely to be diagnosed with depression than whites and were more likely to prematurely terminate their headache treatment appointments regardless of their socioeconomic status (SES). White patients with SES values above the median reported the lowest rate of premature treatment termination. PRINCIPAL CONCLUSIONS: Higher SES enables whites (but not African Americans) to attend all headache treatment appointments. Interventions that enable African-American headache patients to complete their prescribed headache treatments are urgently needed.

Altered hemostasis in migraineurs studied with a dynamic flow system.

INTRODUCTION: Livedo reticularis (LR) refers to the violaceous netlike pattern of skin related to arteriopathy at the dermis-subcutis border. Livedo is associated with migraine, and among migraineurs, LR is more common in those with prior stroke. Other evidence of vascular perturbation in migraine comes from studies showing elevated von Willebrand factor (vWF). The purpose of this study is to evaluate global hemostasis in migraineurs, including the subset with LR, using a dynamic flow system simulating physiological conditions, and measuring vWF activity and antigen levels. MATERIALS AND METHODS: Patients with migraine were enrolled from the headache clinic and presence or absence of LR was noted. Age-matched healthy, non-migraine, LR-free individuals were recruited as controls. To evaluate hemostasis, we used the Clot Signature Analyzer (CSA) measuring platelet hemostasis time (PHT), collagen-induced thrombus formation (CITF), and clot time (CT). vWF activity and vWF antigen levels were also measured. RESULTS: The mean vWF activity level (142.7 vs. 103.4, p<0.01) and antigen level (132.1 vs. 104.5, p<0.05) were higher, and all three hemostasis parameters shorter in the episodic migraineurs than in the controls. The subset of migraineurs with LR had the highest vWF activity (155+/-59, p<0.05) and vWF antigen (141+/-43, p<0.05) levels, and the shortest PHT (3.7+/-1.6, p<0.05). In this subset there was a significant inverse correlation between vWF activity and PHT (r=-0.51, p=0.01). CONCLUSIONS: For migraineurs, the differences from controls in vWF and PHT are most robust in the LR subset, with the inverse correlation suggesting that endothelial perturbation may be causally related to the response of the platelets.

Do psychiatric comorbidities influence headache treatment outcomes? Results of a naturalistic longitudinal treatment study.

This study examined if the presence of one or more psychiatric disorders influences headache treatment outcomes in patients in headache specialty treatment centers. Using a naturalistic, longitudinal design, 223 patients receiving preventive therapy for headache disorders completed 30-day daily diaries that assessed headache days/month and severity at acute therapy baseline and 6-month evaluation and also provided data on headache disability and quality of life at acute therapy baseline, preventive therapy initiation, preventive therapy adjustment, and 6-month evaluation visits. Psychiatric diagnoses were determined using the Primary Care Evaluation for Mental Disorders (PRIME MDs). Of the 223 patients, 34% (n = 76) had no psychiatric disorder, 21% (n = 46) were diagnosed with Depression-Only; 13% (n = 29) were diagnosed with Anxiety-Only; and 32% (n = 72) were diagnosed with Depression-and-Anxiety. Prior to initiating new preventive therapy, patients with one or more psychiatric disorders reported more frequent and disabling headaches and poorer life quality compared to patients with no psychiatric disorders. Rates of improvement in headache days/month, disability, and quality of life were significant and comparable across the four groups. Contrary to clinical wisdom, patients with psychiatric disorders respond very favorably to contemporary headache treatments administered in headache specialty treatment centers.

Endometriosis is associated with prevalence of comorbid conditions in migraine.

OBJECTIVE: To examine the headache characteristics of women with migraine and endometriosis (EM), and differences in the prevalence of comorbid conditions between female migraineurs with EM, without EM and nonheadache controls. BACKGROUND: Migraine and EM are common conditions in women of reproductive age, and both are influenced by ovarian hormones. The comorbidity of migraine and EM is newly recognized, but reasons for the association are uncertain. METHODS: This is a cross-sectional study of female headache outpatients and healthy controls conducted at University of Toledo and Duke University in 2005 and 2006. After a headache specialist determined headache frequency and diagnosis (based on criteria of the second International Classification of Headache Disorders), patients completed a self-administered electronic survey with information on demographics, headache-related disability, menstrual disorders, premenstrual dysphoric disorder (PMDD), vascular event risk, and comorbid conditions, including irritable bowel syndrome (IBS), fibromyalgia (FM), chronic fatigue syndrome (CFS), interstitial cystitis (IC), depression, and anxiety. RESULTS: Study enrolled 171 women with migraine and 104 controls. EM was reported more commonly in migraineurs than in controls (22% vs 9.6%, P < .01). Frequency of chronic headache was higher in migraineurs with EM compared to without EM (P= .002) and median headache-related disability scores were also higher in the EM group (P= .025). Symptoms of PMDD were more common in migraineurs, but frequency did not differ by EM status. Migraineurs with EM reported more menorrhagia, dysmenorrhea, and infertility compared to the migraine cohort without EM and to controls. Depression, anxiety, IBS, FM, CFS, and IC were more common in migraine with EM group than in controls. Anxiety (OR = 2.2, 95% CI 1.0-4.7), IC (OR = 10.6, 95% CI 1.9-56.5), and CFS (OR = 3.6, 95% CI 1.1-11.5) were more common in migraine with EM group, than in the cohort with migraine without EM. CONCLUSION: Prevalence of EM is higher in women with migraine than in nonheadache controls. Migraineurs with EM have more frequent and disabling headaches, and are more likely to have other comorbid conditions affecting mood and pain, compared to migraineurs without EM.

Migraine comorbidity constellations.

OBJECTIVES: To identify distinct constellations of comorbid disorders occurring in migraineurs, and to examine differences in demographics, headache profiles, and psychosocial features between the comorbidity constellations. METHODS: This is a retrospective electronic chart review of consecutive new female outpatients diagnosed with migraine (n = 223) using International Classification of Headache Disorders (ICHD)-II criteria. Questionnaire collected information on comorbid diagnoses, current depression, somatic symptoms, psychosocial stressors, and antidepressant use, social and abuse history. Cluster analysis, based on nonheadache disorders, was performed and differences between the resulting groups were examined. RESULTS: We identified 3 groups. Group 1 (n = 55) was defined by hypertension, hyperlipidemia, diabetes mellitus, and hypothyroidism; Group 2 (n = 83) by depression, anxiety, and fibromyalgia; Group 3 (n = 85) by the absence of defining comorbidities. Group 1 had more males (22% vs 5% vs 12%, P < .05), was older (median years: 52 vs 36 vs 32, P < .01), and had later age of headache onset (median years: 22 vs 16 vs 18, P < .05). Group 2 had the greatest disability (P < .05), and the lowest quality of life (P < .001). Persons in Group 2 more commonly reported sexual abuse (OR = 2.7, 95% CI: 1.1 to 6.5), physical abuse (OR = 2.5, 95% CI: 1.2 to 5.1), and emotional abuse (OR = 4.3, 95% CI: 1.9 to 8.9). CONCLUSION: Within a headache clinic population, we identified 3 different migraine comorbidity constellations, with differing headache and psychosocial profiles, suggesting heterogeneity of genetic and environmental factors. This may have implications for diagnosis and disease management.

Depression and anxiety: effect on the migraine-obesity relationship.

OBJECTIVE: To discern the effects of depression and anxiety on the migraine-obesity relationship. BACKGROUND: Migraine and obesity are highly prevalent conditions and are both independently linked to psychiatric conditions, mainly depression and anxiety. METHODS: Data are from an ongoing cross-sectional multicenter study on comorbid conditions in clinic patients seeking treatment for headache. The diagnosis of migraine was determined by the examining physician based on the International Classification of Headache Disorders (ICHD)-II criteria. Participants completed a self-administered questionnaire with information on demographics, headache features, and physician-diagnosed comorbid medical and psychiatric disorders. The questionnaire included scales for measuring current depression (PHQ-9), anxiety (BAI), and headache-related disability (HIT-6). RESULTS: A total of 721 migraineurs (88% women) from 8 different headache treatment centers were included in this study (mean age = 42 years, SD = 12). Aura was reported in 45% and chronic headache (>or=15 headache days/month) in 35% of the participants. Prevalence of obesity in our population was 30% and only 38% had normal weight. Obesity was more common in men (P= .004), African Americans (P= .026), and in lower education (P= .05) and household income (P=.05) groups. Current depression (PHQ-9 score >or=10) was noted in 42% and current anxiety (BAI score >or=8) in 70% of the obese migraineurs. In ordinal logistic regression, obesity was associated with current depression (odds ratio [OR]= 1.86, 95% confidence interval [CI]: 1.25 to 2.78) and anxiety (OR = 1.58, 95% CI: 1.12 to 2.22). A significant effect of depression on the body mass index (BMI) and headache frequency relationship was noted. Obese migraineurs with depression were more likely to have higher headache frequency (OR = 4.16, 95% CI: 1.92 to 8.99) and headache-related disability (OR = 7.10, 95% CI: 2.69 to 18.77) compared to normal weight migraineurs without depression. Similarly, obese migraineurs with anxiety were more likely to have higher headache frequency (OR = 1.96, 95% CI: 1.07 to 3.61) and headache-related disability (OR = 3.59, 95% CI: 1.64 to 7.86) compared to normal weight migraineurs without depression. Compared to migraineurs with either current depression or anxiety, those with both these conditions were more likely to have higher headache frequency (OR = 3.18, 95% CI: 1.86 to 5.43) and headache disability (OR = 6.13, 95% CI: 2.58 to 14.59). CONCLUSION: Depression and anxiety were common in obese migraineurs. The relationship of obesity with migraine frequency and migraine-related disability is modified by depression and by anxiety, with the strongest effect observed in migraineurs with both depression and anxiety.

Migraine is associated with menorrhagia and endometriosis.

OBJECTIVE: To evaluate the frequency of menorrhagia and endometriosis in female migraineurs compared to age-matched women without headache. BACKGROUND: Migraine predominantly affects women of childbearing age and is often associated with the menstrual period, yet there is a paucity of data regarding the relationship of migraine and menstrual disorders. METHODS: Women diagnosed with migraine, using International Headache Society criteria and an age- and sex-matched control group, were administered a semistructured questionnaire regarding migraine and migraine-related disability, menstrual history, other bleeding history, vascular event history, and vascular risk factors. RESULTS: Fifty female migraineurs between the ages of 22 and 50 years and 52 age-matched women (mean age 37 years) were enrolled in the study. Similar proportions of women in each group reported using hormone contraceptives (30% vs. 33%, P = .77) and hormone replacement therapy (12% vs. 8%, P = .69). The proportions presently menstruating (64 % vs. 80%, P = .20) and status after hysterectomy were similar (24% vs. 14%, P = .84). Menorrhagia (defined as at least three consecutive heavy periods), both current and prior, was more commonly reported in migraineurs (63% vs. 37%, P = .009), with higher likelihood of staining clothes by menses (35% vs. 8%, P = .003), and significant impact of menses on activities of daily living (on a 10-point Likert scale) with work/school participation (P = .02), family activities (P < .0001), sleep (P = .003), life enjoyment (P = .001), mood (P = .02), and overall quality of life (P = .003). Endometriosis, which may be associated with menorrhagia, was also more commonly diagnosed in the migraineurs (30% vs. 4%, P = .001). The migraineurs more frequently described bruising (40% vs. 10%, P < .001) and rectal bleeding (18% vs. 2%, P = .017) but not more serious bleeding problems. Nonsteroidal anti-inflammatory drug (NSAID) use was more frequent in the migraine group (28% vs. 12%, P = .036), and significance for increased menorrhagia, endometriosis, menstrual interference, and bruising was maintained, even when controlling for the use of NSAIDs. With logistic regression, menorrhagia was significantly associated with migraine, adjusted odds ratio (OR) = 2.8 (95% CI 1.2 to 6.5), and with endometriosis, adjusted OR = 10.5 (95% CI 2.2 to 51.4). There were no differences in vascular events and risk factors, except for trends of increased hypertension (25% vs. 10%, P = .05), transient ischemic attack/stroke (10% vs. 2%, P = .08), and Raynaud's disease (10% vs. 2%, P = .08) in the migraineurs. CONCLUSION: Women with migraine have a higher frequency of menorrhagia, endometriosis, and associated psychosocial consequences. These findings suggest that there should be further study of factors influencing endometriosis and menstrual blood flow, such as eicosanoids and platelet function, in migraineurs.