The biological basis of headache.

This article covers the remarkable recent decades as clinicians and scientists have grappled with understanding headache. It is a challenge to understand how a 'normal' brain can become dysfunctional, incapacitating an individual, and then become 'normal' again. Does the answer lie in the anatomy, electrical pathways, the chemistry or a combination? How do the pieces fit together? The components are analyzed in this article. Animal models have provided potential answers. However, these processes have never been proven in man. The dynamic imaging of pain and headache is rapidly evolving and providing new insights and directions of research.

Treatment response and tolerability of frovatriptan in patients reporting short- or long-duration migraines at baseline.

OBJECTIVES: Compare migraine duration with frovatriptan (versus baseline) in migraineurs reporting long- (24-72 h) or short-duration (<24 h) migraines at baseline. METHODS: Post hoc analysis of two postmarketing surveillance studies of migraineurs in German primary care clinics using frovatriptan (2.5 mg) to treat a single migraine attack. Using case-report forms, physicians recorded migraine characteristics at baseline (aura, duration, frequency, severity) and with frovatriptan (duration, severity, and recurrence). Patients and physicians rated frovatriptan effectiveness and tolerability versus previous therapy; physicians recorded adverse reactions. The primary analysis was change in migraine duration with frovatriptan versus baseline. RESULTS: At baseline, 44.2% (7178/16 253) and 55.8% (9075/16 253) of patients reported short- and long-duration migraines, respectively; long-duration migraines were more often frequent (> or =3/months; 55.5% [4893/8811] vs. 30.6% [2132/6973]; p < 0.001; 95% CI, 23.5-26.5%), severe (61.7% [5584/9047] vs. 33.9% [2427/7156]; p < 0.001; 95% CI, 26.3-29.3%), and accompanied by aura (46.8% [4199/8977] vs. 31.3% [2215/7088]; p < 0.001; 95% CI, 14.0-17.0%). Mean (SD) onset of frovatriptan effect was <1 h; 72.3% (11 592/16 040) of patients required only one frovatriptan tablet. With frovatriptan, patients were 26.8-fold more likely to experience decreased versus increased headache duration (p < 0.001; 95% CI, 23.5-30.2) and 76.5% of patients reporting long-duration migraines at baseline experienced short-duration migraines. Most patients (87-90%) and physicians (70-75%) rated frovatriptan more effective and tolerable than previous therapies. CONCLUSION: Patients with more severe migraine characteristics at baseline were more likely to have attacks lasting > or =24 h. When using frovatriptan, patients were 26.8-fold more likely to experience decreased versus increased headache duration. Frovatriptan might be a good option for patients with long-duration or recurrent migraine attacks. The post hoc design and analysis of a single migraine attack are possible study limitations.

Review of frovatriptan in the treatment of migraine.

Triptans are recommended for the acute treatment of moderate to severe migraine or failure to respond to other acute migraine treatments. Seven triptans are available providing a wide range of choices. These triptans are more similar than dissimilar but patients do note differences in effectiveness and in tolerance. Also migraine situations may differ from attack to attack, providing the opportunity to exploit the uniqueness of a particular triptan. Frovatriptan has a uniquely long-half life, five times that of other triptans. This provides the opportunity to use frovatriptan in mini-prophylaxis such as in menstrual-related migraine and other situations, as well as use in long-lasting or recurrent migraine.

The broad treatment expectations of migraine patients.

The objective was to define the overall treatment expectations of migraineurs. Many studies have defined the expectations of patients regarding their acute migraine treatment but little information is available regarding overall expectations. During routine first visits to the author's headache clinic patients were asked about their expectations of treatment as well as demographics and headache characteristics. Demographics were recorded and expectations were compared between different forms of migraine and between females and males. One thousand seven hundreds and fifty patients were diagnosed with ICHD-II 1.1, 1.2, 1.5.1 and 1.6, 1207 with migraine and 543 with probable migraine. A percentage of 27.8 expected a cure from their treatment, 79.7% to be symptom free, 95.2% a reduction in frequency of headaches, 95.6% a reduction in severity of headaches and 95.5% an improved quality of life. Males had greater expectations for reduction in severity of migraines than females. Patients with migraine were more likely to expect a cure and a reduction in headache severity than patients with probable migraine. Patients with aura with every headache were more likely to expect reduced frequency of headache than patients with no aura. Some patients did expect a cure for their headaches and knowing patients' expectations may facilitate headache management and education, and achieve more realistic outcomes.

Using patient-centered endpoints to determine the cost-effectiveness of triptans for acute migraine therapy.

The objective of this study was to use the patient-centered efficacy measurements of sustained pain free and sustained pain free with no adverse events to compare the relative cost-effectiveness of 6 oral triptans in the treatment of acute migraine. Adverse event and sustained pain-free rates were obtained from a comprehensive meta-analysis of 53 clinical trials of oral triptans. Efficacy and tolerability were assumed to be independent. Average wholesale prices were in US dollars as of May 10, 2004. The meta-analysis of oral triptans reported that almotriptan 12.5 mg (Axert) exhibited the highest sustained pain-free rate (25.9%), with the lowest rate associated with eletriptan 20 mg (Relpax) (10.6%). In addition, almotriptan 12.5 mg possessed the lowest overall absolute adverse event rate (14.2%), with the highest adverse event rate exhibited by eletriptan 80 mg (53.9%). To attain 100 sustained pain-free patients, almotriptan 12.5 mg and rizatriptan 10 mg (Maxalt) proved to be the most cost-effective triptans, costing $7120 and $7427, respectively; the least cost-effective were naratriptan 2.5 mg (Amerge) ($13,736) and eletriptan 20 mg ($16,104). To attain 100 sustained pain-free with no adverse events patients, almotriptan 12.5 mg was the most cost-effective triptan ($8298) and the least cost-effective were eletriptan 20 mg ($25,521) and eletriptan 80 mg ($29,614). At average wholesale prices as of May 10, 2004, almotriptan 12.5 mg achieved the highest level of cost-effectiveness using either sustained pain free or sustained pain free with no adverse events as endpoints.

Migraine changes with age: IMPACT on migraine classification.

OBJECTIVE: To establish if criteria for the diagnosis of migraine change with age and to document the influence of age on the full spectrum of migraine features. Also to define the clinical spectrum and provide a prognostic profile of migraine stratified by age. BACKGROUND: Few studies have formally analyzed migraine characteristics stratified by age in a large cohort of patients. METHODS: One thousand nine consecutive patients meeting ICHD-2, 1.1, 1.2, and 1.5.1 at their initial office visit were studied. Patients were stratified by age into 3 groups: group I, 16 to 29, group II, 30 to 49, and group III, 50 years or older. Variables studied included gender, headache duration in years, prodrome, aura, postdrome, headache triggers, headache characteristics, associated symptoms, headache location, headache frequency, headache days, and disability. Ordinal variables were graded from 0 to 3 but only grades greater than grade 1 (more than occasional) were used in the study. RESULTS: A total of 86.3% patients were female and mean age was 37.7 years +/- 11.7 years (range 16 to 80), headache duration 15.0 years, and headache frequency 10 headaches per month. STUDY RESULTS: No significant age differences were seen in gender, or frequency of prodrome, aura, or postdrome. In patients with aura the percentage of headaches with aura significantly decreased with age. Headache triggers, in general, showed no age differences; specific triggers showed statistical differences: stress as a trigger decreased with age; alcohol, smoke, and neck pain triggers increased with age, while in women hormones as a trigger peaked markedly in the 30- to 49-year-old age group compared with the other ages. Exercise, food, not eating, heat, lights, perfume, sex, sleep disturbance, sleeping late, and weather triggers showed no significant differences in age. Headache location showed no differences except for neck location, which significantly increased with age. Associated symptoms of photophobia, phonophobia, dizziness decreased with age and running of the nose/tearing of the eyes increased with age. Nausea, vomiting, osmophobia, taste abnormalities, and diarrhea showed no significant differences. Headache quality showed decreasing throbbing, pressure, and stabbing with age, but aching showed no statistical difference. Being forced to sleep or rest with headache showed a significant decrease with age, but no significant differences were seen in other acute migraine characteristics, including choose to sleep or rest with headache, function during headache, average intensity and duration of headache, recurrence rate of headache, headache aggravation by activity, response to acute medication, and acute medication satisfaction. The 50+ age group tended to have less dizziness, photophobia, phonophobia, nausea, vomiting, temporal location, throbbing, pressure, stabbing, headache days, moderate days, severe days, aggravation of headache by activity, and recurrence but tended to have more mild days, greater ability to function during headache, and greatest response to acute medication. Despite no difference from other groups in headache intensity and duration of headache, these findings taken together seem to reflect a "lesser migraine" in the 50+ age group. CONCLUSIONS: This study highlights specific age differences in migraineurs, in most instances showing an age decline in frequency of variables, such as stress as a trigger, photophobia, phonophobia, dizziness, throbbing, pressure, stabbing, and being forced to sleep or rest with headache. Hormones as a trigger peaked in women in the 30- to 49-year-old age group. Increases with age were seen with alcohol, smoke, and neck pain triggers, neck location, and running of the nose/tearing of the eyes. The 50+ age group showed trends suggesting a "lesser acute migraine attack." These findings support the concept of lessening features of migraine over time resulting in a lower prevalence of migraine in older patients.

Pain characteristics of the acute migraine attack.

OBJECTIVES: This study describes the pain characteristics of the acute migraine attack, including time of onset, time to peak, duration, intensity, quality, aggravation by activity, as well as recurrence frequency and time to recurrence, in a tertiary care practice. BACKGROUND: The literature documenting the characteristics of the pain of the acute attack of migraine is sparse. METHODS: A total of 1,283 migraine patients (ICHD 1.1, 1.2, 1.5.1, and ICHD 1.6 [total migraine population]) were evaluated at first visit. Headache character (throbbing, aching, pressure, stabbing scaled grade 0 to 3; 0 = none; 1 = mild; 2 = moderate; 3 = severe), intensity (for average, minimum, and maximum intensity headaches, scaled 0 to 10), lifetime duration, frequency per month, duration in minutes (for average, minimum, maximum duration headaches), time of onset of headache (morning, afternoon, evening, night, anytime), aggravation of headache with activity (scaled 0 to 3), percentage recurrence, time to recurrence, were recorded. Patients were stratified into different groups; ICHD 1.1, 1.2, and 1.5.1 (migraine) ICHD 1.1 and 1.2 (episodic migraine), ICHD 1.5.1 (chronic migraine), and ICHD 1.6 (probable migraine). Patients with unremitting daily headache were excluded. DEMOGRAPHICS: A total of 84.3% patients were female, and the mean age was 37.7, ranging from 13.0 to 80.5 years. Eight hundred seventy-four patients were classified as ICHD 1.1, 1.2, and 1.5.1 (migraine), 524 with ICHD 1.1 and 1.2 (episodic migraine), 350 with ICHD 1.5.1 (chronic migraine), and 409 with ICHD 1.6 (probable migraine). STUDY RESULTS: Time of onset of headache was mostly in the morning in 18.7%, afternoon 13.5%, evening 4.0%, during night 9.4%, and "anytime" 54.3%, with minor differences seen in different headache types, gender, presence of aura, and headache frequency. The median time to peak of the headache was greater in migraine than probable migraine (90 minutes vs. 60 minutes; P < .01). Headache duration medians were reported as minimum of 12 hours, maximum of 48 hours with an average of 24 hours, females being greater than males in average headache (24.0 vs. 12.0; P < .01), minimum (24.0 vs. 8; P < .05), and maximum (48.0 vs. 24.0; P < .01). Only the minimum duration differed between migraine and atypical migraine (12.0 vs. 4.0; P < .01). Headache intensity medians were as follows: average intensity 7/10, minimum 4/10, and maximum 10/10, with no differences in migraine versus probable migraine, gender, or headache frequency. Headache intensity median was consistently greater in migraine episodic than chronic migraine (average 8.0 vs. 6.5, minimum 4.5 vs. 3.0, maximum 10.0 vs. 9.0, all P < .05). Headache character (greater than grade 1) was throbbing (73.5%), aching (73.8%), pressure (75.4%), and stabbing (42.6%) with significantly more throbbing in migraine than in probable migraine (73.5% vs. 63.2%; P < .01) and more aching in chronic than in episodic migraine (65.4% vs. 63.1%; P < .05). Headache increased by activity was present in 90.2% of patients, grade 1 in 13.8%, grade 2 in 30.8%, and grade 3 in 45.5% of patients. The presence of activity aggravating headache was more likely to be associated with headache triggers, maximum headache severity, longer time to 50% reduction of headache, and longer time to absent headache with triptans, and more headache-associated symptoms, and longer postdrome duration (all P < .05). Recurrence rate was 43.8% with the median time to recurrence being 8 hours. Significantly less recurrence occurred with episodic than chronic migraine (30.0% vs. 50.0%; P < .01). CONCLUSIONS: This study provides an in-depth description of pain features in the acute migraine attack. It was found that a significant number of patients need to be provided with the means of treating headache rapidly in at least some of their headaches and that headache recurrence needs to be addressed in a large number of patients.

Validation of the classification of migraine without aura (IHS A1.1) proposed in ICHD-2.

OBJECTIVE: This study attempts to validate the alternative criteria for classification of migraine without aura (International Headache Society [IHS] A1.1) proposed in the appendix of The International Classification of Headache Disorders, 2nd edition. This method uses at least two of the associated symptoms (nausea, vomiting, photophobia, phonophobia, and osmophobia) in category D of the IHS classification. BACKGROUND: In the appendix of The International Classification of Headache Disorders, 2nd edition, an alternative method of classification of migraine without aura is proposed. This method of classification has never been validated. METHODS: A total of 1480 consecutive headache patients in a tertiary care setting were evaluated at first visit. Headache-associated features, such as intensity, lifetime duration, frequency per month, duration, triggers, prodrome, percentage recurrence, and postdrome frequency, were recorded. In addition, medication satisfaction, acute and monthly disability, grading of headache days, sleep normality, mood, and habits were documented. RESULTS: Of the 1480 patients, 901 were initially classified as having migraine IHS 1.1. Using the proposed alternative method (IHS A1.1), 885 (98.2%) of these patients were reclassified as having migraine. The remaining 16 (1.8%) patients not classified had only nausea and none of the other specified associated symptoms. They also exhibited different characteristics from the IHS migraine population as a whole regarding their headache and other features. CONCLUSIONS: This classification of migraine in a headache center population shows that the proposed use of any two of nausea, vomiting, photophobia, phonophobia, and osmophobia in category D of the classification may be a valid alternative method of classification. This study also demonstrates that the standard IHS methodology includes a very small group of patients who appear to be different from other migraine patients.

Migraine pain location: a tertiary care study of 1283 migraineurs.

OBJECTIVES: This study of headache location in migraine was performed (1) to document the location of pain in a large group of migraine patients and (2) to assess the impact of different types of migraine, gender, aura, and headache features on the location of the headache. BACKGROUND: The literature documenting the location of the pain of acute attack of migraine is sparse. METHODS: A total of 1283 migraine patients (ICHD, 2004, 1.1, 1.2, 1.5.1, and 1.6) were evaluated at the 1st visit. Headache location and character were graded on a scale of 0 to 3 with 0 being none and 3 the most. Triggers were graded on a frequency scale of 0 to 3; 0 = none; 1 = less than 1/3 of time; 2 = between 1/3 and 2/3 of time; 3 = greater than 2/3 of time. Other headache features and medication responsiveness, were also recorded. Patients were stratified by migraine type and headache frequency. Combined and isolated locations, and the impact of age, gender, headache frequency, migraine types, and aura were addressed. Unremitting headache was excluded. RESULTS: Migraine patients reported that the highest location frequencies were in the eyes (67.1%), temporal (58.0%), and frontal (55.9%). The lowest were diffusely (17.5%) and vertex (24.1%). The intermediate were in the occipital (39.8%) and neck areas (39.7%). Other migraine types were remarkably similar. Hemi-cranial location was present in 66.6% of patients, 71.2% in episodic migraine and 61.4% in chronic migraine, 67.2% in females and 63.2% in males, 59.7% in migraine without aura and 68.9% in migraine with aura 100% of the time. Headaches were reported on the right side in 27.3%, left side 24.3%, both sides 23.7%, either side 15.0%, and in the middle of the head in 4.6% of cases. Significant differences in headache location were seen only within migraine and not other migraine types. Headache location was not correlated with lifetime duration of migraine, prodrome, response to triptan, intensity, time to peak of headache, recurrence frequency, and time to recurrence. CONCLUSIONS: This study provides a detailed documentation of headache location in a large cohort of patients. The commonest locations are the orbital, frontal, and temporal areas and least common sites being diffuse and the vertex. A single location is infrequent. Hemi-cranial location is present in two thirds of subjects and a quarter each are on the left side, right side, and both sides. The locations of the headache are very similar in different migraine types, but there are some differences. Under age 21 and older patients tended to show some differences in location and side. Location differences are seen with gender, headache frequency, and aura. Location shows many correlations with triggers and headache features.

Headache and sleep: examination of sleep patterns and complaints in a large clinical sample of migraineurs.

OBJECTIVES: This study characterized sleep parameters and complaints in a large clinical sample of migraineurs and examined sleep complaints in relation to headache frequency and severity. BACKGROUND: The relationship between headache and sleep has been documented at least anecdotally in medical literature for well over a century and clinical texts allude to the importance of sleep as a headache precipitant. A small number of empirical studies have emerged, but the precise nature and magnitude of the headache/sleep association and underlying mechanisms remain poorly understood. METHODS: In this investigation, 1283 migraineurs were drawn from 1480 consecutive headache sufferers presenting for evaluation to a tertiary headache clinic. Patients underwent a physical examination and structured interview assessing a variety of sleep, headache, and demographic variables. Migraine was diagnosed according the IHS criteria (1.1 to 1.6 diagnostic codes). Migraineurs were 84% female, with a mean age of 37.4 years. Groups were formed based on patient's average nocturnal sleep patterns, including short, normal, and long sleep groups, and were compared on headache variables. RESULTS: Sleep complaints were common and associated with headache in a sizeable proportion of patients. Over half of migraineurs reported difficulty initiating and maintaining sleep at least occasionally. Many in this sample reported chronically shortened sleep patterns similar to that observed in persons with insomnia, with 38% of patients sleeping on average 6 hours per night. Migraines were triggered by sleep disturbance in 50% of patients. "Awakening headaches" or headaches awakening them from sleep were reported by 71% of patients. Interestingly, sleep was also a common palliative agent for headache; 85% of migraineurs indicated that they chose to sleep or rest because of headache and 75% were forced to sleep or rest because of headache. Patients with chronic migraine reported shorter nightly sleep times than those with episodic migraine, and were more likely to exhibit trouble falling asleep, staying asleep, sleep triggering headache, and choosing to sleep because of headache. Short sleepers (ie, average sleep period 6 hours) exhibited significantly more frequent and more severe headaches than individuals who slept longer and were more likely to exhibit morning headaches on awakening. CONCLUSIONS: These data support earlier research and anecdotal observations of a substantial sleep/migraine relationship, and implicate sleep disturbance in specific headache patterns and severity. The short sleep group, who routinely slept 6 hours per night, exhibited the more severe headache patterns and more sleep-related headache. Sleep complaints occurred with greater frequency among chronic than episodic migraineurs. Future research may identify possible mediating factors such as primary sleep and mood disorders. Prospective studies are needed to determine if normalizing sleep times in the short sleeps would impact headache threshold.

Osmophobia and taste abnormality in migraineurs: a tertiary care study.

OBJECTIVES: This study assesses osmophobia and taste abnormality for the first time in a large sample of migraine patients. METHODS: Seven hundred and twenty seven migraineurs were evaluated. Osmophobia, taste abnormality, and perfume or odor trigger were graded from 0 to 3. RESULTS: In patients with data, 24.7% of 673 patients complained of osmophobia (12.5% occasional, 7% frequent, and 5.2% very frequent) and 24.6% of 505 of taste abnormality (13.5% occasional, 6.1% frequent, and 5.0% very frequent). Perfume or odor trigger of acute migraine occurred in 45.5% of 724 patients (22.7% occasional, 10.2% frequent, and 12.6% very frequent). Perfume or odor trigger was associated with osmophobia in 61.5% and taste abnormality 62.1%. Osmophobia without taste abnormality occurred in 28.3% and taste abnormality without osmophobia in 40.3%. A greater percentage of females than males had osmophobia (25.7 vs. 17.5), taste abnormality (25.4 vs. 17.9), and perfume or odor trigger (49.3 vs. 22.1), all P<.0001. CONCLUSIONS: Osmophobia and taste abnormality occur in about one quarter of migraineurs during an acute migraine attack while perfume or odor trigger migraine in almost 50% of patients. Osmophobia and taste abnormality in the acute migraine attack, as well as perfumes or odor as a migraine trigger, are more common in females than in males.

The premonitory symptoms (prodrome): a tertiary care study of 893 migraineurs.

OBJECTIVES: This study of premonitory symptoms in migraine was performed to document the frequency, duration, and types of symptoms in a large group of migraine patients. BACKGROUND: Prodrome importance continues to be debated. Intervention early in the migraine attack is assuming more importance and necessitates better knowledge of the prodrome. METHODS: A total of 893 migraine patients (IHS 1.1-1.7) were evaluated at first visit. Prodrome frequency, duration, and characteristics were analyzed in the total migraine population IHS 1.1-1.7 and IHS 1.1-1.6 migraine. RESULTS: A total of 32.9% of IHS migraine 1.1-1.6 patients reported prodrome symptoms with an average of 9.42 hours. IHS 1.1-1.7 migraine reported 29.7% and 6.8 hours, respectively. The most commonest symptoms were tiredness, mood change, and gastrointestinal symptoms; all three of these symptoms were present together in 17% of the patients with prodrome. The duration of prodrome was less than 1 hour in 45.1%, 1-2 hours in 13.6%, 2-4 hours in 15.0%, 4-12 hours in 13.1%, and greater than 12 hours in 13.2%. IHS 1.1-1.7 patients showed similar findings. IHS 1.1-1.6 patients with prodrome differed from patients without prodrome in having more triggers as a whole (P <.01), more individual triggers including alcohol (P <.01), hormones (P <.01), light (P <.001), not eating (P <.05), perfume (P <.01), stress (P <.01), and weather changes (P <.05), a longer duration of aura (P <.05), longer time between aura and headache (P <.05), more aura with no headache (P <.05), longer time to peak of headache (P <.05), longer time to respond to triptan (P <.05), longer maximum duration of headache (P <.05), and more headache associated nausea (P <.05), more headache associated running of the nose or tearing of the eyes (P <.05), more postdrome syndrome (P <.05), and longer duration of postdrome syndrome (P <.001). CONCLUSIONS: This study provides a portrait of prodrome in a large cohort of patients. It highlights differences between patients with prodrome and patients not having prodrome, and it draws attention to the potential of preventing the headache phase of the acute migraine attack.

Women's issues of migraine in tertiary care.

OBJECTIVES: To document the frequency and types of symptoms of migraine in a large group of female migraineurs in tertiary care. Background.-Hormonal changes remain a significant accompaniment in the life cycle of the female migraineur. Little is documented on the relationship of women's issues to other features of migraine or to the lives of patients with migraine. Successful management of migraine mandates attention to women's issues from menarche to beyond menopause. The more information available to this end, the more confidently the clinician can prognosticate, guide, and treat the female patient. METHODS: Women's issues were evaluated in 504 women with migraine diagnosed according to the criteria of the International Headache Society (codes 1.1 and 1.2). The variables graded on a scale of 0 to 3 at the initial visit included premenstrual syndrome, menopausal symptoms, use of birth control pills, use of hormone replacement therapy, hormonal triggering of headaches, worsening of headaches with birth control pills or hormone replacement therapy, headaches with menses only, headaches with menses and at other times, headaches in pregnancy, headaches unchanged in pregnancy, headaches worse in pregnancy, and headaches better in pregnancy. These variables were stratified by age and headache diagnosis. RESULTS: Premenstrual syndrome was reported in 68.7% of patients, menopausal symptoms in 29.0%, and headaches attributed to birth control pills or hormone replacement therapy in 24.4% of patients. Sixty-four point nine percent of women had headaches with menses as well as at other times, while 3.4% of women had headaches exclusively with menses. A pregnancy was reported in 61.3% of the women; 20.4% did not experience headache in pregnancy. Of the 79.6% who did experience headache, 17.8% reported that headaches improved in pregnancy, 27.8% reported headaches to be unchanged, and 34% reported a worsening of headaches. Hormone replacement therapy or birth control pills triggered headaches in 64% of the study group. Patients with 100% aura were significantly different from patients with 0% aura, being less likely to have headaches worsening with birth control pills or hormone replacement therapy (P <.01) and more likely to have headaches occurring during pregnancy (P <.05). When patients with 100% aura were matched for age, headache frequency, use of birth control pills or hormone replacement therapy, and use of prophylactic medications with patients having 0% aura, the former were significantly less likely to have menopausal symptoms (P <.05), less likely to have headaches worsening with birth control pills or hormone replacement therapy (P <.01), and more likely to have headaches occurring only during pregnancy (P <.05). CONCLUSIONS: This study provides a documentation of women's issues in a large cohort of patients. Stratification by headache type, presence of aura, and age refine the study.