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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.

Background and purpose: Anti-calcitonin gene-related peptide (CGRP) (receptor) antibodies effectively reduce overall migraine attack frequency, but whether there are differences in effect between perimenstrual and nonperimenstrual migraine days has not been investigated. Methods: We performed a single-arm study among women with migraine. Participants were followed with electronic E-diaries during one (pretreatment) baseline month and 6 months of treatment with either erenumab or fremanezumab. Differences in treatment effect on perimenstrual and nonperimenstrual migraine days were assessed using a mixed effects logistic regression model, with migraine day as dependent variable; treatment, menstrual window, and an interaction term (treatment × menstrual window) as fixed effects; and patient as a random effect. Results: There was no interaction between the menstrual window and treatment effect, indicating that the reduction in migraine days under treatment was similar during the menstrual window and the remainder of the menstrual cycle (odds ratio for treatment = 0.44, 95% confidence interval = 0.38–0.51). Conclusions: Our findings support prophylactic use of anti-CGRP (receptor) antibodies for women with menstrual migraine, as this leads to consistent reductions in number of migraine days during the entire menstrual cycle.

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

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

Background and purpose: New prophylactics for migraine, targeting calcitonin gene-related peptide (CGRP), have recently emerged. Real-world data are important for a comprehensive understanding of treatment response. We assessed the consistency of response to erenumab, a monoclonal CGRP receptor antibody, in a real-world setting, in order to determine which patients may be considered responders in clinical practice. Methods: All erenumab-treated patients (n = 100) completed a time-locked daily electronic diary, and an automated algorithm was used to monitor treatment response. Monthly migraine days (MMD), non-migrainous headache days, days of acute medication use (MAMD), well-being and coping with pain were assessed for a 6-month period. The primary outcome was reduction in MMD compared to baseline. Results: The numbers of MMD and MAMD decreased in all months, in both episodic and chronic migraine patients, compared to baseline (p < 0.001), while general well-being (p < 0.001) and coping with pain (p < 0.001) also improved. Of all patients, 36% had an MMD reduction of ≥50% in ≥3/6 months, and 6% had such a reduction in all 6 months. For a ≥30% MMD reduction, the figures were 60% and 24%, respectively. Almost 90% of patients with an average MMD reduction of ≥30% over the first 3 months had a sustained response in the last 3 months. In addition, 20% of patients without an initial response (average <30%), had a delayed response (average ≥30%) in the last 3 months. Conclusion: Erenumab was effective in migraine patients who were highly refractory to previous prophylactics. As a practical guideline, we propose that treatment be continued for at least 6 months and that patients with a ≥30% MMD reduction in at least half of the treatment period should be considered to be responders.

Following the publication of the original article [1], we were notified of a few corrections: 1. The corresponding author should be Gisela M. Terwindt, instead of Iris E. Verhagen. 2. In the Results section of the Abstract, the phrase “Responders were older compared to nonresponders and more likely to suffer from lifetime depression” should read “Responders were older compared to non-responders and less likely to suffer from lifetime depression”. 3. ICHD-II and ICHD-III were modified into ICHD-2 and ICHD-3. The original article has been corrected.

Background: To compare symptoms of clinical androgen deficiency between men with migraine, men with cluster headache and non-headache male controls. Methods: We performed a cross-sectional study using two validated questionnaires to assess symptoms of androgen deficiency in males with migraine, cluster headache, and non-headache controls. Primary outcome was the mean difference in androgen deficiency scores. Generalized linear models were used adjusting for age, BMI, smoking and lifetime depression. As secondary outcome we assessed the percentage of patients reporting to score below average on four sexual symptoms (beard growth, morning erections, libido and sexual potency) as these items were previously shown to more specifically differentiate androgen deficiency symptoms from (comorbid) anxiety and depression. Results: The questionnaires were completed by n = 534/853 (63%) men with migraine, n = 437/694 (63%) men with cluster headache and n = 152/209 (73%) controls. Responders were older compared to non-responders and more likely to suffer from lifetime depression. Patients reported more severe symptoms of clinical androgen deficiency compared with controls, with higher AMS scores (Aging Males Symptoms; mean difference ± SE: migraine 5.44 ± 0.90, p < 0.001; cluster headache 5.62 ± 0.99, p < 0.001) and lower qADAM scores (quantitative Androgen Deficiency in the Aging Male; migraine: − 3.16 ± 0.50, p < 0.001; cluster headache: − 5.25 ± 0.56, p < 0.001). Additionally, both patient groups more often reported to suffer from any of the specific sexual symptoms compared to controls (18.4% migraine, 20.6% cluster headache, 7.2% controls, p = 0.001). Conclusion: Men with migraine and cluster headache more often suffer from symptoms consistent with clinical androgen deficiency than males without a primary headache disorder.

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.