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BACKGROUND: Previous studies showed that the perimenstrual window is associated with an increased susceptibility to migraine attacks without aura, but had conflicting results regarding attacks with aura. METHODS: We performed a longitudinal E-diary study among 526 premenopausal women with migraine. Differences in occurrence of perimenstrual migraine attacks between women with migraine with aura and without aura were assessed using a mixed effects logistic regression model. Additionally, participants completed a questionnaire about the influence of hormonal milestones on migraine frequency. RESULTS: Prevalence of menstrual migraine did not differ between women with migraine without aura and migraine with aura (59% versus 53%, p = 0.176). The increased risk of migraine attacks without aura during the perimenstrual window was similar for women with migraine without aura (OR[95%CI]:1.53 [1.44-1.62]) and those with migraine with aura (1.53 [1.44-1.62]). The perimenstrual window was not associated with increased risk of migraine aura attacks (1.08 [0.93-1.26], p = 0.314). Women with migraine with aura more often reported increased migraine frequency during pregnancy and breastfeeding compared to women with migraine without aura, but not during hormonal contraception use. CONCLUSION: Sex hormone levels seem to differently affect the trigeminovascular system (migraine headache) and the susceptibility to cortical spreading depolarization (aura). Exclusively migraine attacks without aura should be interpreted as perimenstrual attacks.

Objective: In this prospective cohort study, characteristics of perimenstrual and non-perimenstrual migraine attacks in women were compared with migraine attacks in men. Background: Women report longer migraine attacks and more accompanying symptoms than men in cross-sectional questionnaire studies, but this has not been confirmed in longitudinal studies. Supposed differences could result from different characteristics specific to perimenstrual migraine attacks, or of attacks in women in general. Methods: This cohort study was performed among patients with migraine who were treated at the Leiden Headache Clinic. We assessed differences in migraine attack characteristics between men and women who were prospectively followed by a previously validated electronic headache diary. The primary outcome was “attack” duration. Differences between perimenstrual (Days −2 to +3 of the menstrual cycle) and non-perimenstrual attacks in women versus attacks in men were corrected for age, chronic migraine, and medication overuse headache. Results: A total of 1347 women and 284 men were included, reflecting the preponderance of women in migraine prevalence. Crude median (first and third quartile [Q1−Q3]) attack duration in men was 32.1 [17.7–53.6] h, compared to 36.7 [21.9–62.4] h for non-perimenstrual migraine attacks and 44.4 [17.9–79.0] h for perimenstrual migraine attacks in women. After correction for confounding, perimenstrual migraine attacks were 1.62 (95% confidence interval [CI] 1.47–1.79; p < 0.001) and non-perimenstrual 1.15 (95% CI 1.05–1.25; p = 0.003) times longer compared to migraine attacks in men. The mean relapse percentage in men was 9.2%, compared to 12.6% for non-perimenstrual migraine attacks, and 15.7% for perimenstrual migraine attacks. Relapse risk was greater for perimenstrual (odds ratio [OR] 2.39, 95% CI 1.93–2.95; p < 0.001), but not for non-perimenstrual (OR 1.18, 95% CI 0.97–1.45; p = 0.060) attacks. Migraine attacks in women were more often a

Background: Cyclic hormonal fluctuations influence migraine incidence and severity. Previously, we described reduced menstrual cyclicity in estradiol levels and dermal blood flow reaction to capsaicin in female migraineurs. It is unclear whether pain perception in women with migraine is influenced by the menstrual cycle. Methods: Women with menstrually-related migraine (n = 14), healthy age-matched controls (n = 10) and postmenopausal women (n = 15) were asked to grade trigeminal and non-trigeminal painful stimuli on a numeric pain rating scale on menstrual cycle day 19–21 (mid-luteal) and day 1–2 (early follicular). Results: In women with menstrually-related migraine, trigeminal pain remained low throughout the cycle. Controls showed increased trigeminal pain during the mid-luteal phase compared to the early follicular phase. Changes throughout the cycle were significantly different between women with MRM and controls. Conclusion: The compromised menstrual cyclicity of pain perception in women with menstrually-related migraine parallels our earlier findings on estradiol levels and dermal blood flow.

Aim: To examine the effect of sex on migraine trigger factors. Methods: Prevalence of 11 frequently reported trigger factors was determined in a cross-sectional study among migraine patients from a validated migraine database (n = 5725 females and n = 1061 males). Female-to-male odds ratios were calculated for each trigger, using a logistic regression model with attack frequency and migraine subtype (with or without aura) as covariates. Additionally, the effect of sex on total number of triggers per individual was determined. Results: The top three most reported triggers in women were menstruation (78%), stress (77%), and bright light (69%). Men reported stress (69%), bright light (63%), and sleep deprivation (60%) most frequently as provoking factors. The following triggers were more often reported by women than men: Bright light (odds ratio 1.29 [95% CI 1.12–1.48]; p = 0.003), stress (1.47 [1.27–1.69]; p < 0.001), skipping a meal (1.24 [1.09–1.42]; p = 0.015), sleep deprivation (1.37 [1.20–1.57]; p < 0.001), high altitudes (1.70 [1.40–2.09]; p < 0.001), and weather changes (1.35 [1.18–1.55]; p < 0.001). Women reported more triggers than men, even when menstruation was disregarded (mean ± SD: 4.6 ± 2.3 and 4.3 ± 2.3; p < 0.001). Conclusion: Women report migraine trigger factors to be provocative of their attacks more frequently than men, which may be related to a lower migraine threshold due to sex hormonal changes.

BACKGROUND AND OBJECTIVES: Endogenous and exogenous female sex hormones are considered important contributors to migraine pathophysiology. Previous studies have cautiously suggested that perimenstrual migraine attacks have a longer duration and are associated with higher disability compared to nonperimenstrual attacks, but they showed conflicting results on acute therapy efficacy, pain intensity, and associated symptoms. We compared perimenstrual and nonperimenstrual migraine attack characteristics and assessed premenstrual syndrome (PMS) in women with migraine. METHODS: Women with migraine were invited to complete a headache e-diary. Characteristics of perimenstrual attacks and nonperimenstrual attacks were compared. The primary outcome was attack duration. Secondary outcomes were headache intensity, accompanying symptoms, acute medication intake, and pain coping. Mixed effects models were used to account for multiple attacks within patients. PMS was assessed in patients without hormonal contraceptives. Subgroup analyses were performed for women with menstrually related migraine (MRM) and nonmenstrually related migraine (non-MRM) and women with a natural menstrual cycle and women using hormonal contraceptives. RESULTS: A representative group of 500 participants completed the e-diary for at least 1 month. Perimenstrual migraine attacks (n = 998) compared with nonperimenstrual attacks (n = 4097) were associated with longer duration (20.0 vs 16.1 hours, 95% confidence interval 0.2-0.4), higher recurrence risk (odds ratio [OR] 2.4 [2.0-2.9]), increased triptan intake (OR 1.2 [1.1-1.4]), higher headache intensity (OR 1.4 [1.2-1.7]), less pain coping (mean difference -0.2 [-0.3 to -0.1]), more pronounced photophobia (OR 1.3 [1.2-1.4]) and phonophobia (OR 1.2 [1.1-1.4]), and less aura (OR 0.8 [0.6-1.0]). In total, 396/500 women completed the diary for ≥3 consecutive menstrual cycles, of whom 56% (221/396) fulfilled MRM criteria. Differences in attack characteristics be

Aim: To determine whether our E-diary can be used to diagnose migraine and provide more reliable migraine-related frequency numbers compared to patients’ self-reported estimates. Methods: We introduced a self-developed E-diary including automated algorithms differentiating headache and migraine days, indicating whether a patient has migraine. Reliability of the E-diary diagnosis in combination with two previously validated E-questionnaires was compared to a physician’s diagnosis as gold standard in headache patients referred to the Leiden Headache Clinic (n = 596). In a subset of patients with migraine (n = 484), self-estimated migraine-related frequencies were compared to diary-based results. Results: The first migraine screening approach including an E-headache questionnaire, and the E-diary revealed a sensitivity of 98% and specificity of 17%. In the second approach, an E-migraine questionnaire was added, resulting in a sensitivity of 79% and specificity of 69%. Mean self-estimated monthly migraine days, non-migrainous headache days and days with acute medication use were different from E-diary-based results (absolute mean difference ± standard deviation respectively 4.7 ± 5.0, 6.2 ± 6.6 and 4.3 ± 4.8). Conclusion: The E-diary including algorithms differentiating headache and migraine days showed usefulness in diagnosing migraine. The use emphasised the need for E-diaries to obtain reliable information, as patients do not reliably recall numbers of migraine days and acute medication intake. Adding E-diaries will be helpful in future headache telemedicine.