Comparing Perimenstrual and Nonperimenstrual Migraine Attacks Using an e-Diary

BackgroundEndogenous 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 non-perimenstrual attacks, but they showed conflicting results on acute therapy efficacy, pain intensity, and associated symptoms.ObjectivesTo compare perimenstrual and non-perimenstrual migraine attack characteristics and assess premenstrual syndrome (PMS) in women with migraine.MethodsWomen with migraine were invited to complete a headache E-diary. Characteristics of perimenstrual attacks and non-perimenstrual 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 those without hormonal contraceptives. Subgroup analyses were performed for women with menstrually related migraine (MRM) and non-menstrually related migraine (non-MRM), and women with a natural menstrual cycle and women using hormonal contraceptives.ResultsA representative group of n=500 participants completed the E-diary for at least one month. Perimenstrual migraine attacks (n=998) compared with non-perimenstrual attacks (n=4097) were associated with longer duration (20.0 vs 16.1 hours, 95%CI [0.2-0.4]), higher recurrence risk (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- -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 became more pronounced when focusing on women with MRM and women using hormonal contraceptives. Prevalence of PMS was not different for women with MRM compared to non-MRM (11% vs. 15%).DiscussionThe longer duration of perimenstrual migraine attacks in women (with MRM) is associated with higher recurrence risk and increased triptan use. This may increase the risk of medication overuse and emphasizes the need to develop female-specific prophylactic treatment.

Prevalence of menstrually-related migraine in a population of students from a municipal university center in the interior of Brazil

ObjectiveTo identify the prevalence of migraine associated to menstruation in a population of students at a college in Brazil’s inland.MethodsThe students were recruited and submitted to the Test for the Identification of Women with Menstrual Period-Related Headache based on the ID-MigraineTM and Menstrual Migraine Assessment Tool questionnaires. Migraine diagnosis was made according to ICHD-3 criteria.ResultsOf the 424 students, 312 (73.5%) answered affirmatively in at least two of the four questions in the first part of the questionnaire and in the following 216 (69.2%) of these reported having migraine related to their menstrual period in the majority of the months.ConclusionsMenstrual migraine is a prevalent public health problem that deserves attention in order to ensure a better quality of life for women affected by such a condition.

Comparison of pregnenolone sulfate, pregnanolone and estradiol levels between patients with menstrually-related migraine and controls: an exploratory study

Background Neurosteroids affect the balance between neuroexcitation and neuroinhibition but have been little studied in migraine. We compared the serum levels of pregnenolone sulfate, pregnanolone and estradiol in women with menstrually-related migraine and controls and analysed if a correlation existed between the levels of the three hormones and history of migraine and age. Methods Thirty women (mean age ± SD: 33.5 ± 7.1) with menstrually-related migraine (MM group) and 30 aged- matched controls (mean age ± SD: 30.9 ± 7.9) participated in the exploratory study. Pregnenolone sulfate and pregnanolone serum levels were analysed by liquid chromatography-tandem mass spectrometry, while estradiol levels by enzyme-linked immunosorbent assay. Results Serum levels of pregnenolone sulfate and pregnanolone were significantly lower in the MM group than in controls (pregnenolone sulfate: P = 0.0328; pregnanolone: P = 0.0271, Student’s t-test), while estradiol levels were similar. In MM group, pregnenolone sulfate serum levels were negatively correlated with history of migraine (R2 = 0.1369; P = 0.0482) and age (R2 = 0.2826, P = 0.0025) while pregnenolone sulfate levels were not age-related in the control group (R2 = 0.04436, P = 0.4337, linear regression analysis). Conclusion Low levels of both pregnanolone, a positive allosteric modulator of the GABAA receptor, and pregnenolone sulfate, a positive allosteric modulator of the NMDA receptor, involved in memory and learning, could contribute either to headache pain or the cognitive dysfunctions reported in migraine patients. Overall, our results agree with the hypothesis that migraine is a disorder associated with a loss of neurohormonal integrity, thus supporting the therapeutic potential of restoring low neurosteroid levels in migraine treatment.

Menstrual Migraine : How Hormones Impact Migraine

Menstrual Migraine is divided into 2 subtypes: Menstrually Related Migraine (MRM) and Pure Menstrual Migraines (PMM). In PMM symptoms do not occur outside the menstrual cycle while MRM, symptoms can occur at other times apart from the menstrual cycle. The occurrence of menstrual migraines is related to the female hormones cycle in the form of the decrease in estrogen levels which usually occurs a week before the onset of menstruation. The mechanism is unclear, but it is thought that a decrease in estrogen levels can trigger decrease in serotonin levels, causing cranial vasodilation and sensitization of the trigeminal nerve. Keywords: menstrual migraine, hormones

Pain perception in women with menstrually-related migraine

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.

Brain structural and functional differences between pure menstrual migraine and menstrually-related migraine

The pathophysiological differences between menstrually-related migraine (MRM) and pure menstrual migraine (PMM) are largely unclear. The aim of this study was to investigate the potential differences in brain structure and function between PMM and MRM. Forty-eight menstrual migraine patients (32 MRM; 16 PMM) were recruited for this study. Voxel-based morphometry (VBM) was applied on structural magnetic resonance imaging (sMRI), and the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) in resting state functional MRI (rsfMRI) were calculated. No significant between-group difference was observed in the grey matter volume (GMV). MRM patients exhibited lower ALFF values at the dorsolateral prefrontal cortex (DLPFC) and medial prefrontal cortex (mPFC) than PMM patients. Moreover, the MRM group showed significantly higher ReHo values in the DLPFC. Higher values in the mPFC were related to higher expression of calcitonin gene-associated peptide (CGRP) in the PMM group (r = 0.5, P = 0.048). Combined ALFF and ReHo analyses revealed significantly different spontaneous neural activity in the DLPFC and mPFC, between MRM and PMM patients, and ALFF values in the mPFC were positively correlated with CGRP expression, in the PMM group. This study enhances our understanding of the relationship between neural abnormalities and CGRP expression in individuals with PMM.

Serum levels of allopregnanolone, progesterone and testosterone in menstrually-related and postmenopausal migraine: A cross-sectional study

Background Reduced blood or cerebrospinal fluid levels of allopregnanolone are involved in menstrual cycle-linked CNS disorders, such as catamenial epilepsy. This condition, like menstrually-related migraine, is characterized by severe, treatment-resistant attacks. We explored whether there were differences in allopregnanolone, progesterone and testosterone serum levels between women with menstrually-related migraine (MM, n = 30) or postmenopausal migraine without aura who had suffered from menstrually-related migraine during their fertile age (PM, n = 30) and non-headache control women in fertile age (FAC, n = 30) or post-menopause (PC, n = 30). Methods Participants were women with migraine afferent to a headache centre; controls were female patients’ acquaintances. Serum samples obtained were analyzed by HPLC-ESI-MS/MS. Results In menstrually-related migraine and postmenopausal migraine groups, allopregnanolone levels were lower than in the respective control groups (fertile age and post-menopause) ( p < 0.001, one-way analysis of variance followed by Tukey-Kramer post-hoc comparison test) while progesterone and testosterone levels were similar. By grouping together patients with migraine, allopregnanolone levels were inversely correlated with the number of years and days of migraine/3 months ( p ≤ 0.005, linear regression analysis). Conclusion Decreased GABAergic inhibition, due to low allopregnanolone serum levels, could contribute to menstrually-related migraine and persistence of migraine after menopause. For the management of these disorders, a rise in the GABAergic transmission by increasing inhibitory neurosteroids might represent a novel strategy.

Headache

Migraine is a common disorder that affects women of menstruating age, and it is frequently the chief complaint of women presenting in the neurology clinic. The prevalence of menstrually related migraine can range from 20–60%, while pure menstrual migraine occurs in less than 10% of women. In addition to utilizing non–gender-specific abortive and preventative strategies, understanding migraine and its relationship to hormones, particularly estrogen, can have clinical implications for optimal treatment. This chapter seeks to provide insight into diagnosing menstrually related migraine, the role of decreased estrogen just prior to menstrual cycle onset and migraine, as well as the therapeutic options that are available to treat and possibly prevent menstrual migraine attacks.