Migraine is a common condition that can cause intense headaches, often on one side of the head, along with symptoms like nausea and sensitivity to light and sound. These headaches can be triggered by various factors, including stress, changes in hormones, sleep disturbances, diet, and even gut health. Migraines are more frequent in women, particularly those under 45, and this may be linked to hormones. After age 45, this difference between men and women becomes less noticeable. Women tend to experience migraines that are more severe and last longer than men, with menstrual migraines affecting about 22% of women during nearly half of their menstrual cycles, and 7.6% of women with migraines. Treatments for migraines include medications, lifestyle changes, and alternative therapies, all of which aim to address the different ways migraines can affect people. This review explores these aspects in detail.

Migraine affects women three times more often than it does men, and various mechanisms may explain this incidence, including the key role of female sex hormones. Fluctuations in the levels of these hormones and their feedback control regulate the menstrual cycle, pregnancy, puerperium, perimenopause, and menopause. They can influence the occurrence and severity of migraine throughout the reproductive period. Of particular importance seems to be the perimenopausal period, which is associated with an increase in migraine, especially menstrual migraine, which is considered more disabling and less amenable to treatment than non-menstrual attacks. This article reviews the available evidence documenting the relationship between perimenopause, menopause, and migraine and diagnostic considerations in an attempt to determine the management of these periods of a woman's life. Special considerations, future directions, and unmet needs for perimenopausal and menopausal migraine are also discussed.

Migraine is a complex neurological disorder frequently associated with hypothalamic dysfunction. This brain region is essential for maintaining homeostasis due to its regulation of autonomic, endocrine, and circadian systems. While the pathophysiology of migraine remains incompletely understood, clinical features such as the cyclic nature of attacks and symptoms, including nausea, vomiting, yawning, irritability, and sensitivity to light, indicate a significant role for the hypothalamus. Further, potential triggers of migraine, such as stress and disruption to feeding habits, also impact hypothalamic mechanisms. The higher prevalence of migraine in women compared to men suggests a link to hormonal fluctuations involving estrogen, progesterone, and prolactin. These hormones interact with the hypothalamus, potentially influencing the onset and severity of migraine episodes. Additionally, the hypothalamus synthesizes neuropeptides such as orexins, neuropeptide Y, PACAP, oxytocin, and vasopressin, which are all implicated in migraine mechanisms. Understanding the interplay between the hypothalamus, sex hormones, and neuropeptides offers valuable opportunities for endogenous targeted migraine therapies. In this review we discuss hypothalamic contributions to migraine pathophysiology, highlighting the mechanisms affected by hypothalamic connections, neuropeptides, and hormones, and their role as migraine triggers, particularly focusing on factors like stress, fasting, and changes in sleep patterns.

The pituitary adenylate cyclase-activating peptide (PACAP) pathway is a critical focus in the pathophysiology of several headache disorders. PACAP influences headache pathophysiology through interactions with distinct receptors (PAC1, VPAC1, and VPAC2) and pathways linked to neurovascular and hormonal regulation. Evidence supports its role in the modulation of trigeminal and parasympathetic systems, implicated in cluster headaches and menstrual migraine, and its involvement in sensitizing pain pathways post trauma in post-traumatic headaches. Early clinical trials targeting PACAP signaling show promise, with one study demonstrating efficacy in migraine prophylaxis. This narrative review synthesizes current evidence while addressing gaps in understanding PACAP's precise mechanisms. Future research should prioritize expanding the scope of PACAP-focused investigations across diverse headache types, aiming to establish it as a therapeutic target for several headache disorders. Success in ongoing and future trials could redefine headache management for millions of underserved patients worldwide.

Objective: The objective of the current post hoc analysis is to evaluate whether the combination of acetaminophen, aspirin, and caffeine (AAC) is more effective than placebo in relieving the pain intensity for and improving the quality-of-life (QoL) of subjects with menstrual migraine (MM). Methods: This analysis evaluated the impact of AAC (n = 85) versus placebo (n = 100) in relieving the pain intensity for and improving the QoL of subjects with MM during baseline and at 0.5, 1, 2, 3, 4, and 6 h post treatment. Subjects reported their pain intensity using a 4-point scale and QoL using a 5-point scale. A lower score indicates reduced pain intensity and improved QoL. Results: A statistically significant difference between the AAC and placebo groups (p ≤ 0.001) was observed in pain relief after 1 h (40% vs. 14%), 2 h (56.5% vs. 24%), 3 h (63.5% vs. 31%), 4 h (65.9% vs. 34%), and 6 h (64.7% vs. 31%) post treatment. Similarly, a significantly higher proportion of subjects reported improved QoL at 1 h (48.2% vs. 28.0%; p ≤ 0.005), 2 h (61.2% vs. 40.0%; p ≤ 0.005), 3 h (68.2% vs. 44.0%; p ≤ 0.001), 4 h (67.9% vs. 39.0%; p ≤ 0.001), and 6 h (64.3% vs. 37.0%; p ≤ 0.001) post treatment. The mean pain intensity and QoL scores reduced, while the relative pain intensity and QoL (difference between the AAC and placebo groups) increased with time and was sustained for 6 h. Conclusions: The rapid onset and sustained effect of AAC make it a potential option for managing headaches and other symptoms, and to improve the QoL of subjects with MM.

Headache is one of the leading causes of disability in worldwide and in China, and the second most burden disease of the nervous system after stroke. We aimed to analyze the global trends in the burden of headache disorders, migraine and TTH among people in China in an international context.

Data were taken from the Global Burden of Disease (GBD) Study 2021 database to examine trends in the incidence, prevalence, and disability-adjusted life year of headache disorders.

In the context of a large scale in the world, headache is currently in a state of high incidence in China, and female middle-aged and young patients are the main body of this disease.

Need to focus on the vulnerable population in China, while formulating effective health policies and developing good treatment measures to reduce the incidence of headache disorders and improve the DALYs rate of headache.

Menstrual migraine (MM) is a common subtype of migraine that greatly affects a woman's quality of life. A number of different drugs are used to treat menstrual migraine, but it is not known which is more effective.

In this study, we searched all randomized controlled trials that satisfied the inclusion and exclusion criteria up to December 2023 on PubMed, Embase and Cochrane Library using a suitable search strategy. We constructed a suitable network model for analysis after evaluating the heterogeneity among the included direct, indirect and pooled evidence. Odds ratio (OR) and corresponding 95% confidence intervals (CI) were used as valid indicators for this network meta-analysis.

In the Bayesian network model we constructed, we found that lasmiditan (vs. placebo OR, 14; 95% CI 3.1-100) was better than rizatriptan (vs. placebo OR, 1.9; 95% CI 1.2-3.3) in terms of the rate of sustained freedom from pain. There was no statistically significant difference between lasmiditan and different triptans in terms of the rate of being pain-free at 2 h (2-h pain-free) and the rate of pain relief at 2 h (2-h pain relief). Regarding safety, the probability of adverse events was significantly higher for rizatriptan (OR, 2.7; 95% CI 1.1-7.3) than for placebo.

In terms of treatment efficacy for MM, lasmiditan was not worse than different triptans and was even better than some of the triptans in the rate of sustained freedom from pain. As an emerging treatment, lasmiditan is promising for the treatment of MM. However, more research needs to be carried out because of the lack of safety analysis for lasmiditan.

Women with endometriosis still have to seek the legitimacy of their disease from the medical community and often feel unheard. This scoping review aims to map the scientific literature to describe barriers and facilitators in the endometriosis management from both patients' and healthcare professionals' (HCPs') perspectives.

We searched the literature published between 2012 and 2023 in the Web of Science, PsychInfo, PubMed, CINAHL, Embase, and Cochrane Library databases. A total of 52 eligible studies were identified.

We observed several barriers in the endometriosis management: the perception of patients as challenging and psychosomatic; lack of awareness and medical knowledge; persistent taboos and biases; challenging communication about pain, pregnancy, and infertility; lack of empathy from HCPs; and barriers in diagnostic tools and healthcare accessibility. Key facilitators were HCPs and community awareness; taking patients' symptoms seriously; compassionate communication about fertility and pain; shared decision-making, encouraging patients to seek evidence-based information; and multidisciplinary support.

We were able to identify concrete barriers and facilitators to successful endometriosis management. Future research is now required to identify optimal ways to implement this evidence, and research the extent to which it applies to more diverse populations in non-Western setting, and to explore the impact of HCP demographic characteristics.

In recent years, headache diseases have spread throughout the world, causing great suffering and even severe disability to patients, and increasing the burden on health care systems. However, studies of specific regions are rare. The purpose of our study is to comprehensively analyze the current situation and trends of headache diseases in Asia between 1990 and 2021, to provide details of headache diseases in Asia, and to provide scientific data to support health development strategies.

Data from the Global Burden of Disease (GBD) 2021 database were used to calculate the incidence, prevalence and disability-adjusted life years (DALYs) of headache disorders in Asia from 1990 to 2021. Differences between years, ages, sexes and countries were also assessed, and we evaluated the correlation between epidemiological and sociodemographic indices (SDIs).

In 2021, there were approximately 683,514,637 cases of migraine in Asia. Meanwhile, there are now 1,130,221,326 cases associated with tension-type headache (TTH) in Asia. Specifically, the age-standardized DALYs (ASDR) [607 cases per 100,000 people (95% UI: 70 - 1,363)] for migraine were highest in Southeast Asia, and the ASDR [422 cases per 100,000 people (95% UI: 86-938)] was lowest in high-income countries of the Asia-Pacific region. ASDR [67 cases per 100,000 people (95% UI: 18-236)] was highest for TTH in Central Asia and lowest for ASDR [43 cases per 100,000 people (95% UI: 13-141)] in East Asia. In addition, women are the key population for migraine and TTH prevalence. In Asia, there were negative and positive correlations between migraine and TTH and SDI, respectively.

Headache disorders pose a serious threat to the quality of life and safety of patients in Asia, increasing the burden on society, and this impact will continue to grow. Our findings suggest that active public awareness, improved guidelines, and better disease management are necessary to expand the public and healthcare system's attention to headache disorders, and thereby gain a greater advantage in combating the burden of headache disorders in the future.

Transient Receptor Potential Melastatin 3 (TRPM3) channels are Ca2+ permeable ion channels that act as polymodal sensors of mechanical, thermal, and various chemical stimuli. TRPM3 channels are highly expressed in the trigeminovascular system, including trigeminal neurons and the vasculature. Their presence in dural afferents suggests that they are potential triggers of migraine pain, which is originating from the meningeal area. This area is densely innervated by autonomous and trigeminal nerves that contain the major migraine mediator calcitonin gene-related peptide (CGRP) in peptidergic nerve fibers. Co-expression of TRPM3 channels and CGRP receptors in meningeal nerves suggests a potential interplay between both signalling systems. Compared to other members of the TRP family, TRPM3 channels have a high sensitivity to sex hormones and to the endogenous neurosteroid pregnenolone sulfate (PregS). The predominantly female sex hormones estrogen and progesterone, of which the levels drop during menses, act as natural inhibitors of TRPM3 channels, while PregS is a known endogenous agonist of these channels. A decrease in sex hormone levels has also been suggested as trigger for attacks of menstrually-related migraine. Notably, there is a remarkable sex difference in TRPM3-mediated effects in trigeminal nociceptive signalling and the vasculature. In line with this, the relaxation of human isolated meningeal arteries induced by the activation of TRPM3 channels is greater in females. Additionally, the sex-dependent vasodilatory responses to CGRP in meningeal arteries seem to be influenced by age-related hormonal changes, which could contribute to sex differences in migraine pathology. Consistent with these observations, activation of TRPM3 channels triggers nociceptive sensory firing much more prominently in female than male mouse meninges, suggesting that pain processing in female patients with migraine may differ. Overall, the combined TRPM3-related neuronal and vascular mechanisms could provide a possible explanation for the higher prevalence and even the more severe quality of migraine attacks in females. This narrative review summarizes recent data on the sex-dependent roles of TRPM3 channels in migraine pathophysiology, the potential interplay between TRPM3 and CGRP signalling, and highlights the prospects for translational therapies targeting TRPM3 channels, which may be of particular relevance for women with migraine.

To assess the effect of modeling free water (FW) on the identification of white matter (WM) microstructure alterations using diffusion Magnetic Resonance Imaging (dMRI) in episodic migraine without aura patients compared with healthy controls.

Diffusion tensor imaging (DTI) studies examining WM in migraine patients previously overlooked the potential influence of FW partial volume effects. Correcting FW effects could offer a clearer understanding of WM changes in migraine. This study is the first to incorporate FW effects when evaluating alterations in WM tracts in migraine patients, offering a comparison to standard DTI analysis.

A group of 14 patients with low-frequency episodic menstrual-related migraine without aura and 15 healthy controls matched for the phase of the menstrual cycle were recruited and underwent dMRI acquisitions. FW partial volume fraction was estimated, the diffusion signal corrected and the diffusion parameters calculated from both FW-corrected and uncorrected signals. Tract-Based Spatial Statistics (TBSS) and WM skeleton regions of interest (ROI) analyses were used to compare between groups.

Comparisons between control subjects and migraine patients with TBSS and ROI analyses revealed significantly lower axial diffusivity (AD), both with and without FW correction, as well as altered FW values in migraine patients in some WM tracts. TBSS detected MD changes only after FW correction.

These findings suggest WM alterations in these migraine patients in comparison with control subjects, in accordance with other migraine studies. Differences in the diffusion parameters might point to inflammatory processes in migraine related to cellular swelling.

Changes in large-scale brain networks have been reported in migraine patients, but it remains unclear how these manifest in the various phases of the migraine cycle. Case-control fMRI studies spanning the entire migraine cycle are lacking, precluding a complete assessment of brain functional connectivity in migraine. Such studies are essential for understanding the inherent changes in the brain of migraine patients as well as transient changes along the cycle. Here, we leverage the concept of functional connectome (FC) fingerprinting, whereby individual subjects may be identified based on their FC, to investigate changes in FC and its stability across different phases of the migraine cycle.

We employ a case-control longitudinal design to study a group of 10 patients with episodic menstrual or menstrual-related migraine without aura, in the 4 phases of their spontaneous migraine cycle (preictal, ictal, postictal, interictal), and a group of 14 healthy controls in corresponding phases of the menstrual cycle, using resting-state functional magnetic resonance imaging (fMRI). We propose a novel multilevel clinical connectome fingerprinting approach to analyse the FC identifiability not only within-subject, but also within-session and within-group.

This approach allowed us to obtain individual FC fingerprints by reconstructing the data using the first 19 principal components to maximize identifiability at all levels. We found decreased FC identifiability for patients in the preictal phase relative to controls, which increased with the progression of the attack and became comparable to controls in the interictal phase. Using Network-Based Statistic analysis, we found increased FC strength across several brain networks for patients in the ictal and postictal phases relative to controls.

Our novel multilevel clinical connectome fingerprinting approach captured FC variations along the migraine cycle in a case-control longitudinal study, bringing new insights into the cyclic nature of the disorder.

Migraine is a common primary headache disorder, less frequently affecting men than women, and often regarded as predominantly a "women's disease." Despite this, migraine in men presents with unique characteristics in terms of symptoms, treatment responses, comorbidities, and pain perception. Historically, research has focused more on migraine in women, overlooking critical male-specific aspects.

This review delves into the epidemiology, clinical presentation, and particular challenges of diagnosing and managing migraine in men. It addresses sex-specific triggers, hormonal influences, and comorbid conditions affecting migraine prevalence and severity in men. Additionally, the review evaluates current therapeutic strategies, underscoring the necessity for individualized approaches. Men with migraine often exhibit atypical symptoms compared to the ICHD-3 criteria and are less likely to report common associated symptoms. They also tend to have fewer psychological comorbidities, respond more favorably to pharmacological treatments, yet are less likely to seek medical support. The reasons for these sex disparities are complex, involving biological, psychosocial, and cultural factors, such as brain structural differences, differences in functional responses to painful stimuli, hormonal effects, and behavioral influences like adherence to masculine norms and stigma.

Men are underrepresented in clinical migraine research. In contrast, preclinical studies often focus solely in male animals as a result of various misconceptions. This disparity necessitates greater focus on sex-specific aspects of migraine to enhance diagnosis, treatment, and research. Addressing stigma, increasing healthcare access, and ensuring balanced sex and gender representation in future studies is crucial for a comprehensive understanding and effective management of migraine for all patients.

Headaches are a common and often debilitating condition among youth. The Inflammatory Burden Index (IBI), a simple surrogate marker of systemic inflammation, has been linked to various diseases. However, evidence for its relationship with headaches, particularly in youth, is lacking. This study aimed to investigate the association between IBI and persistent headache in youth, with a focus on evaluating gender-specific responses to IBI exposure.

We analyzed data from 2,210 young people in the 2001-2004 National Health and Nutrition Examination Survey (NHANES). The association between IBI and frequent or severe headaches in the past year was investigated using weighted logistic regression models. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated, and threshold effect analyses were performed.

Youths in the highest IBI quartile (Q4) had a 46% higher risk of severe headaches compared to the lowest quartile (Q1) (OR: 1.46, 95% CI: 1.12-1.91, P = 0.0051). Gender-stratified analysis revealed a significant association between high IBI and headache risk in females (OR: 1.48; 95% CI: 1.03-2.11, P = 0.0324), but not in males. Threshold effect analysis identified an IBI breakpoint of 3.78, below which the headache risk increased significantly in females under 18 years (OR: 1.12, 95% CI: 1.01-1.25, P = 0.0385).

Our findings demonstrate a significant association between elevated IBI and increased headache risk in youth, particularly in females. This gender-specific effect suggests that inflammatory processes may play a more prominent role in headache pathophysiology among female youth. These results underscore the importance of considering inflammatory markers in the early identification and prevention of youth headaches, especially in females.

Calcitonin gene-related peptide (CGRP) is part of the calcitonin peptide family, which includes calcitonin (CT), amylin (AMY), and adrenomedullin (ADM). CGRP and its receptor are highly present in the trigeminovascular system (TVS). Recent research suggests that other members of the calcitonin family could be feasible therapeutic targets in the treatment of migraine. The present study aims to elucidate the distribution of ADM, AMY, CT, and their receptors in the rat TVS, and to explore potential sex differences in their expression.

Trigeminal ganglia (TG) were dissected from male and female adult rats. Protein and gene expression were assessed through immunohistochemistry and RT-qPCR. Additionally, the dura mater was isolated for further investigation of protein expression and fiber localization using immunohistochemistry.

Quantitative gene expression analysis revealed the presence of all genes in male and female TGs, except for calcitonin receptor (CTR). Notably, CGRP mRNA levels in TG were several folds higher than those of other genes. The receptor activity-modifying protein-1 (RAMP1) mRNA levels were significantly higher in female compared to male. No AMY or CT immunoreactivity was observed in the TVS. In contrast, immunoreactivity for ADM, CGRP, RAMP1, CTR, and calcitonin-like receptor (CLR) were observed in the cytoplasm of TG neurons. Immunoreactive Aδ-fibers storing RAMP1, ADM and CLR were also identified. RAMP2 and RAMP3 were expressed in nucleus of TG neurons and in satellite glial cells. Furthermore, RAMP1 and CLR were co-localized with CASPR in the nodes of Ranvier located in Aδ-fibers.

This study provides valuable insights into the distribution of the CGRP family of peptides and their receptors in the TVS. CGRP mRNA levels in the TG were markedly higher than those of other genes, demonstrating the key role of CGRP. The co-localization of CLR and RAMP1 on Aδ-fibers with CASPR suggests a potential role for this receptor in modulating trigeminal nerve function and neuronal excitability, with implications for migraine pathophysiology. Additionally, RAMP1 mRNA levels were significantly higher in female TG compared to males, indicating sex-specific differences in gene expression. These findings underscore the need for further research into the functional significance of gender-related variations.

The profiles of muscle and joint pain throughout the menopausal transition and the factors associated with these symptoms have not been determined. A total of 609 participants from a longitudinal cohort study conducted in an urban Chinese community were enrolled in this study. We assessed the prevalence of musculoskeletal symptoms at different menopausal stages and explored the factors associated with these symptoms. The prevalence and severity of muscle and joint pain increase as menopausal stages progress, and late menopausal transition may be a crucial timepoint that triggers the onset of musculoskeletal pain. The results of the multivariate analysis revealed that poor health status (OR = 2.245, 95% CI = 1.714-2.94, P < 0.001), body mass index (BMI) (OR = 1.046, 95% CI = 1.01-1.084, P = 0.011), the presence of anxiety (OR = 1.601, 95% CI = 1.211-2.117, P < 0.001), and depression (OR = 1.368, 95% CI = 1.143-1.639, P < 0.001) were independently associated with muscle and joint pain. In addition, the severity of musculoskeletal pain was related to poor health status (OR = 2.738, 95% CI = 1.91-3.924, P < 0.001) and depression (OR = 1.371, 95% CI = 1.095-1.718, P = 0.006). Musculoskeletal symptoms are frequent somatic symptoms experienced by Chinese middle-aged women. Women with poor health status, high BMI, anxiety, and depression were at heightened risk of experiencing musculoskeletal pain. The severity of pain increased over time.

Currently, neurological diseases has surpassed cardiovascular diseases as the primary cause of global disease burden. Among these, headache disorders are the most prevalent and have emerged as the main cause of disability in people under 50 years old in recent years. Since the release of GBD 2021, there has been no comprehensive systematic exposition on the burden of headache among individuals under 50 years old and a forecast for future burdens. This study aims to quantify the global, regional, and national burden of headache disorders among people under 50 from 1992 to 2021 and to predict future trends in order to provide policy makers with precise and effective epidemiological evidence.

This study extracted the incidence, prevalence, and DALYs data related to headache disorders in the 5-50 age group from the GBD 2021. After age-standardizing the data, we used joinpoint regression analysis and health inequity analysis to analyze the burden and temporal trend of headache disorders and predicted the future disease burden and changes based on the age-period-cohort model.

By 2021, the case number of global incidence, prevalence and DALYs have increased by 35, 39, and 41%, respectively, over the past 30 years. The incidence and prevalence of tension-type headache (TTH) are significantly higher than those of migraine, but migraine causes greater health burdens. The burden is higher for female than for male. In terms of age, youth aged 25-29 years had the highest incidence in 2021, with an age-standardized rate (ASR) of 13,454.64 (95%CI, 9,546.96-18,361.36) per 100,000 population. Nationally, the highest ASR of incidence and prevalence are found in Norway, and the most damaging to health is found in Belgium. Among the five sociodemographic index (SDI) categories, the middle SDI has the highest number of cases (190 million in 2021). It is worth noting that the forecast shows that by 2046 the three indicators will reach 680 million, 2.33 billion, and 41 million, respectively, indicating that the burden of headache disorders in this age group will continue to persist.

Globally, the burden of headache disorders in people under 50 years of age remains significant and has not improved over the past 30 years, especially in regions with high SDI. Headache problems will continue to pose a serious public health challenge for this age group for some time to come. This study reveals the burden and distribution of headache disorders in this age group, providing important basis for governments and policymakers to accurately and effectively allocate health care resources, strengthen prevention and management strategies, and respond to this global health problem.

Varied responses to acute migraine medications have been observed, with over one-third (34.5%) of patients reporting insufficient headache relief. Sumatriptan-naproxen sodium, a single, fixed-dose combination tablet comprising sumatriptan 85 mg and naproxen sodium 500 mg, was developed with the rationale of targeting multiple putative mechanisms involved in the pathogenesis of migraine to optimise acute migraine care.

A narrative review of clinical trials investigating sumatriptan-naproxen sodium for both adults and adolescents was performed in March 2024.

Across a total of 14 clinical trials in nine publications, sumatriptan-naproxen sodium offered greater efficacy for 2-h pain freedom (14/14) and sustained pain-free response up to 24 h (13/14) compared with monotherapy and/or placebo for both adult and adolescent study participants with an acceptable and well-tolerated adverse effect profile. Clinical trial data also demonstrates the effectiveness of sumatriptan-naproxen sodium in participants with allodynia, probable migraine, menstrual-related migraine and those with poor responses to acute, non-specific, migraine medication.

Multi-mechanistic therapeutic agents offer an opportunity to optimise acute medications by targeting multiple mediators involved in the pathogenesis of migraine. Sumatriptan-naproxen sodium resulted in greater initial and sustained pain freedom, compared with either sumatriptan, naproxen-sodium and/or placebo, for the treatment of single or multiple attacks of migraine across both adult and adolescent study populations.

This study reviewed migraine prevalence and disability gathered through epidemiologic survey studies in the United States conducted over the past three decades. We summarized these studies and evaluated changing patterns of disease prevalence and disability.

We conducted a systematic review of US studies addressing the prevalence, disability, and/or burden of migraine, including both episodic migraine (EM) and chronic migraine (CM). A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol was used in conjunction with the PubMed search engine. Eligible studies were published before February 2022, were conducted in the United States, included representative samples, and used a case definition of migraine based on the International Classification of Headache Disorders (ICHD). The primary measure of disease burden was the Migraine Disability Assessment Scale (MIDAS). The MIDAS measures days lost due to migraine over 3 months in three domains and defines groups with moderate (Grade III) or severe disability (Grade IV) using cut-scores.

Of the 1609 identified records, 26 publications from 11 US population-based studies met eligibility criteria. The prevalence of migraine in the population has remained relatively consistent for the past 30 years: ranging from 11.7% to 14.7% overall, 17.1% to 19.2% in women, and 5.6% to 7.2% in men in the studies reviewed. CM prevalence is 0.91% (1.3% among women and 0.5% of men) in adults and 0.8% in adolescents. The proportion of people with migraine and moderate-to-severe MIDAS disability (Grades III-IV), has trended upward across studies from 22.0% in 2005 to 39.0% in 2012, to 43.2% in 2016, and 42.4% in 2018. A consistently higher proportion of women were assigned MIDAS Grades III/IV relative to men.

The prevalence of migraine in the United States has remained stable over the past three decades while migraine-related disability has increased. The disability trend could reflect changes in reporting, study methodology, social and societal changes, or changes in exacerbating or remediating factors that make migraine more disabling, among other hypotheses. These issues merit further investigation.

Menstrual-related headache (MRH) is the most prevalent health condition among young females that limits productivity and social life. However, the magnitude of the problem and its characteristics have not been studied in Ethiopia.

This study aimed to assess the prevalence, characteristics, and treatment of MRH among undergraduate female students at the College of Health Sciences, Addis Ababa University, Ethiopia.

A cross-sectional study was conducted among undergraduate female students from May to June 2023. A random sample of 1000 females were approached who fulfilled the eligibility criteria using the online electronic method. Descriptive statistics were used to summarize participant characteristics. Multivariate logistic regression analysis was performed to identify factors associated with the severity of pain. All statistical analyses were performed using SPSS version 26. A p-value ≤ 0.05 was considered statistically significant.

Of the 1000 students who approached online, 757 were included in the final analyses. The prevalence of MRH was (86, 11.4%) and 32.6% of them has experienced the headache before two to three days of menses. The median number of days of missed social activities and reduced productivity was three and one day, respectively. Being single was 6.24 times more likely to have severe MRH (AOR = 6.24, 95% CI: 2.73-14.26, p=0.001) and pharmacy students were less likely (AOR = 0.31, 95% CI: 0.16-0.61, p = 0.001) to have severe pain.

Our findings illustrated that MRH among young female students adversely affects students' productivity and social life. This demands interventions to reduce the impact and should pay attention in the future, particularly to create awareness to enhance screening and rendering various treatment options for the target population.

Migraine, a frequent and debilitating neurological disease, shows gender-specific differences in prevalence and severity. Pregnancy is associated with numerous unique features in terms of migraine course, treatment options and differential diagnoses.

How does pregnancy influence the course of migraine? What are the possible treatment options during pregnancy? Which differential diagnoses should be considered?

Narrative review with summary and discussion of relevant studies and guidelines on migraine in pregnancy.

During pregnancy up to three quarters of women experience improvement of their migraine; however, there may be a renewed increase in frequency after childbirth. Choosing an appropriate treatment during pregnancy requires a careful risk-benefit assessment. It is important to consider secondary causes of headache as these can occur more frequently during pregnancy and some can be life-threatening.

Consideration of specific aspects of migraine in pregnancy is crucial to be able to develop the best possible treatment strategies for affected patients.

We evaluated galcanezumab for migraine prevention in patients who met International Classification of Headache Disorders, 3rd edition criteria for menstrually related migraine (MRM).

Patients were identified post hoc from three double-blind, randomized, phase 3 clinical trials in patients with episodic migraine. Patients completed a 1-month prospective baseline period and up to 6 months (EVOLVE-1 and -2, studies pooled) of double-blind treatment with galcanezumab (120 mg/month) or placebo. Menses and headache information were recorded by electronic daily diary. Patients with a migraine attack starting during the 5-day perimenstrual interval (first day of bleeding ± 2 days) for ≥2 of their first three diary-recorded menstrual cycles were categorized as having MRM. The primary efficacy measure was mean change in monthly migraine headache days from baseline, averaged over Months 4 through 6. Response rates, change in monthly perimenstrual migraine headache days, monthly non-perimenstrual migraine headache days, and quality of life were also assessed.

Post hoc MRM analysis criteria were met by 462/1133 women (41%). Mean (standard deviation) baseline monthly migraine headache days were 9.7 (±3.1; n = 146) for galcanezumab-treated patients and 9.6 (±2.8; n = 316) for placebo-treated patients. The mean change (standard error [SE]) in migraine headache days over Months 4 through 6 was -5.1 days (±0.39) for galcanezumab versus -3.2 (±0.35) for placebo (p < 0.001). The mean change (SE) in perimenstrual migraine headache days over Months 4 through 6 was -0.75 days (±0.08) for galcanezumab versus -0.49 (±0.07) for placebo (p = 0.004). For migraine headache days outside the perimenstrual period, the mean change in migraine headache days was -4.6 (±0.38) for galcanezumab and -2.8 (±0.33) for placebo (p < 0.001). Improvements in response rates and the Migraine-Specific Quality of Life Questionnaire were also observed over Months 4 through 6.

Galcanezumab was effective for migraine prevention in women with MRM.

Menstrual migraine (MM) is widely recognized among the scientific community, with diagnostic criteria included in the appendix of the third edition of the International Headache Classification. However, this classification does not include other primary headaches that may occur during menstruation. Previous retrospective studies suggest the existence of menstrual tension-type headache. Our objective is to prospectively determine the existence of this type of headache and to determine its frequency relative to that of MM.

This is a descriptive, cross-sectional (case series), prospective, observational study, conducted in a hospital neurology department, using a previously validated ad hoc questionnaire. Participants were recruited by consecutive sampling, applying inclusion and exclusion criteria among women accompanying neurology outpatients, and classified into five groups: pure menstrual tension-type headache, menstrual-related tension-type headache, pure menstrual migraine, menstrual-related migraine and unclassifiable.

Ninety-five women (median age of 38.50 years, IQR: 13) were included, with the following group distribution: 13 (13.6%) pure menstrual tension-type headache, 14 (14.7%) menstruation-related tension-type headache, 23 (24.2%) pure menstrual migraine, 44 (46.3%) menstrual-related migraine and 1 unclassifiable. Of these patients, 23% did not treat menstrual headache, but this figure rose to 30.8% in the case of pure menstrual tension-type headache.

The results confirm the existence of pure menstrual tension-type headache among women who do not seek medical care for this condition. The frequency of this headache is lower than that of MM. This reduced incidence, together with its generally mild nature, may explain the lack of prior recognition.

Migraine is a common health condition in both men and women. Premenstrual syndrome (PMS) affects many women during their menstrual cycle, with around 50-60% of women with migraine attacks experiencing menstrual headaches. Most have mild symptoms, but 5-8% suffer from moderate to severe symptoms, causing distress and functional issues. Pure menstrual migraine (PMM) occurs in about 50% of women with migraine, and it can be debilitating in terms of frequency and severity. This information is crucial for Saudi Arabian medical professionals to provide better care and support, improving the quality of life for women with PMS and menstrual migraine (MM) attacks.

To estimate the prevalence of MM in women, to evaluate the severity and frequency of MM in women with PMS, and to identify potential risk factors aggravating MM in women with PMS in Saudi Arabia.

A cross-sectional community-based study was conducted on reproductive-aged (18-50 years) women who had regular menstrual cycles and were diagnosed with PMS, using a self-administered questionnaire between December 2022 to May 2023 in Saudi Arabia.

Out of the 2130 female participants, 397 (18.6%) had migraine. Among these 397 migraine sufferers, 230 (57.9%) experienced MM, while 167 (42.1%) had non-MM. In reproductive women in general, MM occurred in 10.7% of cases, while non-MM was observed in 7.8%. There is a correlation between increasing BMI and an increased incidence of MM. About one-third of the participants experienced moderate disability due to migraine attacks, with 134 (33.8%) individuals affected. Additionally, most MM sufferers missed at least 3 days of work in the last 3 months due to their condition.

Migraine attacks occurring during the menstrual cycle impair the ability to engage in social, physical, household, and academic activities, often hindering the fulfillment of professional commitments. To gain a deeper understanding of menstrual and non-menstrual migraine attacks, it is essential to conduct extensive prospective studies aimed at developing effective management strategies.

Migraine is a common disorder, particularly affecting women during their reproductive years. This female preponderance has been linked to exposure to female sex hormones.

We used self-reported data from women born in 1943-1965 enrolled in the Norwegian Women and Cancer Study to examine the differences between women with migraine and women without migraine in a prospective design with respect to both endogenous and exogenous female sex hormone exposure.

In total, 62,959 women were included in the study, of whom 24.8% reported previous migraine (n = 15,635). Using a Cox proportional hazards model, we found that higher age at menarche reduced the risk of migraine (hazards ratio (HR) = 0.96, 95% confidence interval (CI) = 0.95-0.98) and that oral contraceptive use and parity increased the risk of migraine (HR = 1.12, 95% CI = 1.06-1.18 and HR = 1.37, 95% CI = 1.29-1.46, respectively).

Older age at menarche appears to reduce migraine risk, whereas oral contraceptive use and having children appear to increase the risk. Further research is required to investigate the causality of these associations.

Menstrually related migraine is a disabling condition affecting 35% to 54% females with migraine during their fertile years. The International Headache Classification distinguishes menstrually related migraine from pure menstrual migraine based on the occurrence of the attacks even outside the perimenstrual periods. Hormonal fluctuations are the main driver for the disease in subjects with genetic susceptibility and alterations of brain structures and connectivity. Menstrually related attacks are often particularly severe and disabling requiring proper management. Acute treatment mainly consists of nonsteroidal anti-inflammatory drugs (NSAIDs), recommended in patients also suffering from dysmenorrhea, and triptans. Prevention is specifically indicated in women with high monthly headache frequency or burdensome attacks during perimenstrual periods. Trials proved the efficacy of short-term prevention with triptans and NSAIDs but did not evaluate possible long-term effectiveness and tolerability. Evidence of prevention using hormonal treatments is poor, but extended-cycle treatments might be suitable for women requiring hormonal replacement for concomitant conditions. Few data are available on treatments targeting CGRP, among whom gepants are the most promising because of their utility both in migraine acute and preventive treatment. A greater recognition of disease and a deep knowledge of patients' comorbidities are essential to its proper management.

Migraine, a neurovascular headache disorder, is a leading cause of disability worldwide. Within the multifaceted pathophysiology of migraine, hormonal fluctuations play an evident triggering and exacerbating role, pointing toward the need for identification and proper usage of both existing and new hormonal targets in migraine treatment.

With a threefold higher incidence of migraine in women than in men, the authors delve into sex hormone-related events in migraine patients. A comprehensive overview is given of existing hormonal therapies, including oral contraceptives, intrauterine devices, transdermal and subcutaneous estradiol patches, gnRH-agonists, oral testosterone, and 5α reductase inhibitors. The authors discuss their effectiveness and risks, noting their suitability for different patient profiles. Next, novel evolving hormonal treatments, such as oxytocin and prolactin, are explored. Lastly, the authors cover hormonal conditions associated with migraine, such as polycystic ovary syndrome, endometriosis, and transgender persons receiving gender affirming hormone therapy, aiming to provide more personalized and effective solutions for migraine management.

Rigorous research into both existing and new hormonal targets, as well as the underlying pathophysiology, is needed to support a tailored approach in migraine treatment, in an ongoing effort to alleviate the impact of migraine on individuals and society.

Migraine has been considered a chronic neuronal-based pain disorder characterized by the presence of cortical hyperexcitability. The Contingent Negative Variation (CNV) is the most explored electrophysiological index in migraine. However, the findings show inconsistencies regarding its functional significance. To address this, we conducted a review in both adults and children with migraine without aura to gain a deeper understanding of it and to derive clinical implications. The literature search was conducted in the PubMed, SCOPUS and PsycINFO databases until September 2022m and 34 articles were retrieved and considered relevant for further analysis. The main results in adults showed higher CNV amplitudes (with no habituation) in migraine patients. Electrophysiological abnormalities, particularly focused on the early CNV subcomponent (eCNV), were especially prominent a few days before the onset of a migraine attack, normalizing during and after the attack. We also explored various modulatory factors, including pharmacological treatments-CNV amplitude was lower after the intake of drugs targeting neural hyperexcitability-and other factors such as psychological, hormonal or genetic/familial influences on CNV. Although similar patterns were found in children, the evidence is particularly scarce and less consistent, likely due to the brain's maturation process during childhood. As the first review exploring the relationship between CNV and migraine, this study supports the role of the CNV as a potential neural marker for migraine pathophysiology and the prediction of pain attacks. The importance of further exploring the relationship between this neurophysiological index and childhood migraine is critical for identifying potential therapeutic targets for managing migraine symptoms during its development.

Migraine is an evolving, and sometimes lifelong disorder. The prevalence of episodic migraine peaks among individuals aged in their late 30s, implying a tendency for the disorder to remit with increasing age thereafter, whereas chronic migraine is more likely to persist into later life. Diagnosis and treatment of migraine in older adults, defined as individuals aged 60 years or older, is rendered more complex by increasing probabilities of atypical clinical features and comorbidities, with patients' comorbidities sometimes limiting their therapeutic options. However, the changing clinical presentation of migraine over an individual's lifespan is not well characterised. The neurobiological basis of remission in older adults remains unclear, although vascular, neuronal, and hormonal changes are likely to be involved. Long-term longitudinal studies of individuals with migraine would be particularly informative, with the potential not only to suggest new research directions, but also to lead to the identification of novel therapeutic agents. Although several novel migraine medications are becoming available, their effectiveness, tolerability, and safety often remain uncertain in older adults, who have commonly been excluded from the evaluation of these agents in randomised controlled trials, or who constitute only a small proportion of study populations. There is a need to recognise these limitations in the available evidence, and the specific, and often unmet, clinical needs of older adults with migraine, not least because older adults constitute an increasing proportion of populations worldwide.

To explore and critically appraise the evidence supporting the role of estrogen withdrawal in menstrual migraine.

Menstrual migraine, impacting about 6% of reproductive-age women, manifests as migraine attacks closely related to the menstrual cycle. The estrogen withdrawal hypothesis posits that the premenstrual drop in estrogen levels serves as a trigger of migraine attacks. Despite its wide acceptance, the current body of evidence supporting this hypothesis remains limited, warranting further validation. Estrogen is believed to exert a modulatory effect on pain, particularly within the trigeminovascular system - the anatomic and physiologic substrate of migraine pathogenesis. Nevertheless, existing studies are limited by methodologic inconsistencies, small sample sizes, and variable case definitions, precluding definitive conclusions. To improve our understanding of menstrual migraine, future research should concentrate on untangling the intricate interplay between estrogen, the trigeminovascular system, and migraine itself. This necessitates the use of robust methods, larger sample sizes, and standardized case definitions to surmount the limitations encountered in previous investigations.

Further research is thus needed to ascertain the involvement of estrogen withdrawal in menstrual migraine and advance the development of effective management strategies to address unmet treatment needs.

To evaluate the efficacy and safety of ubrogepant for the acute treatment of perimenstrual migraine (pmM) attacks.

Ubrogepant is an oral calcitonin gene-related peptide receptor antagonist approved for the acute treatment of migraine in adults.

After completing one of two phase 3 trials, participants could enroll in a phase 3, 52-week, open-label, long-term safety extension trial and were re-randomized 1:1:1 to usual care, ubrogepant 50 mg, or ubrogepant 100 mg. This post hoc analysis evaluated the efficacy of ubrogepant in a subset of women who treated ≥1 pmM or non-pmM attack with ubrogepant. A pmM attack started on or between 2 days before and the first 3 days of menstrual bleeding. Mean (standard deviation [SD]) percentages of ubrogepant-treated attacks achieving 2-h pain freedom and pain relief were reported, with outcomes weighted equally by participant.

Of 734 women in the modified intent-to-treat population, 354 reported ≥1 menstrual cycle start date and a ubrogepant-treated headache day in the same month. A qualifying pmM and non-pmM attack was reported by 278 and 716 women, respectively. Pain freedom at 2 h was achieved in a mean (SD) of 28.7% (37.4) of pmM attacks and 22.1% (26.9) of non-pmM attacks treated with ubrogepant 50 mg (p = 0.054) and 29.7% (35.2) versus 25.3% (26.3) of attacks treated with ubrogepant 100 mg (p = 0.757). No difference was found in the mean percentage of ubrogepant-treated pmM and non-pmM attacks that achieved 2-h pain relief with ubrogepant 50 mg (64.8% [39.9] vs. 65.2% [32.4]; p = 0.683) and with 100 mg (67.1% [37.4] vs. 68.4% [30.2]; p = 0.273). Treatment-related treatment-emergent adverse events were reported by 8.8% (12/137) and 12.8% (18/141) in the ubrogepant 50 and 100 mg pmM subgroups, respectively.

Ubrogepant demonstrated similar efficacy for the treatment of pmM and non-pmM attacks. No new safety signals were identified.

Menstrually-related migraine (MM) is a primary migraine in women of reproductive age. The underlying neural mechanism of MM was still unclear. In this study, we aimed to reveal the case-control differences in network integration and segregation for the morphometric similarity network of MM. Thirty-six patients with MM and 29 healthy females were recruited and underwent MRI scanning. The morphometric features were extracted in each region to construct the single-subject interareal cortical connection using morphometric similarity. The network topology characteristics, in terms of integration and segregation, were analyzed. Our results revealed that, in the absence of morphology differences, disrupted cortical network integration was found in MM patients compared to controls. The patients with MM showed a decreased global efficiency and increased characteristic path length compared to healthy controls. Regional efficiency analysis revealed the decreased efficiency in the left precentral gyrus and bilateral superior temporal gyrus contributed to the decreased network integration. The increased nodal degree centrality in the right pars triangularis was positively associated with the attack frequency in MM. Our results suggested MM would reorganize the morphology in the pain-related brain regions and reduce the parallel information processing capacity of the brain.

Migraine is a leading cause of disability in young adults. It occurs more frequently in females, often comorbidly with stress disorders, suggesting an association with hypothalamic sex and stress hormonal function and a likely interaction with autonomic nervous system activation. Thus, this study aimed to meta-analyse current literature pertaining to female and male sex hormones (estrogen, progesterone and testosterone concentration), hypothalamic-pituitary-adrenal axis (HPA axis) cortisol responses and heart rate variability (HRV) in migraineurs and controls aged 13-65 years. A systematic search of MEDLINE, Embase, PsycINFO, PubMed, CINAHL and Web of Science databases on 29/08/2022 identified 29 studies for meta-analysis (encompassing 719 migraineur and 592 control participants) that met inclusion and NHLBI risk of bias criteria. Results demonstrated that estrogen concentrations of female migraineurs were reduced (g = -.60, 95% CI [-.91, -.29], p < .001) in the luteal phase of the menstrual cycle, compared to controls. No differences were found in progesterone levels overall in female migraineurs, nor in testosterone levels in male migraineurs compared to controls. Further, early diurnal cortisol concentrations were elevated (g = .32, 95% CI [.00, .63], p = .036) in female and male migraineurs compared to controls, though no differences were found in HRV of female or male migraineurs compared to controls. These findings of dysregulation of estrogen in females and cortisol dysregulation in female and male migraineurs indicate perturbed hypothalamic function and highlight the association of migraine with stress and the need for further rigorous investigation of hypothalamic neuroendocrine functions in migraineurs of both sexes.

Migraine is a leading cause of disability in more than one billion people worldwide, yet it remains universally underappreciated, even by individuals with the condition. Among other shortcomings, current treatments (often repurposed agents) have limited efficacy and potential adverse effects, leading to low treatment adherence. After the introduction of agents that target the calcitonin gene-related peptide pathway, another new drug class, the ditans - a group of selective serotonin 5-HT_1F receptor agonists - has just reached the international market. Here, we review preclinical studies from the late 1990s and more recent clinical research that contributed to the development of the ditans and led to their approval for acute migraine treatment by the US Food and Drug Administration and the European Medicines Agency.

Menstrual migraine is a subtype of migraine disease that is typically more disabling, longer-lasting, and more challenging to treat. The purpose of this network meta-analysis (NMA) is to compare the relative efficacy of treatments for menstrual migraine.

We systematically searched databases, including PubMed, EMBASE, and Cochrane, and included all eligible randomized controlled trials in the study. We conducted the statistical analysis using Stata version 14.0, based on the frequentist framework. We used the Cochrane Risk of Bias tool for randomized trials version 2 (RoB2) to assess the risk of bias of the included studies.

This network meta-analysis included 14 randomized controlled trials with 4601 patients. For short-term prophylaxis, frovatriptan 2.5 mg twice daily had the highest probability of effectiveness [OR = 1.87 (95% CI: 1.48 to 2.38)] compared to placebo. For acute treatment, the results showed that sumatriptan 100 mg [OR = 4.32 (95% CI: 2.95 to 6.34)] was the most effective treatment compared to placebo.

These findings suggest that frovatriptan 2.5 mg twice daily was best for short-term prevention, sumatriptan 100 mg were best for acute treatment. More high-quality randomized trials are required to determine the most effective treatment.

Migraine is one of the leading causes of disability worldwide, affecting work and social life. It has been estimated that sales of migraine medicines will reach 12.9 billion USD in 2027. To reduce social impact, migraine treatments must improve, and the ATP-sensitive potassium (K_ATP) channel is a promising target because of the growing evidence of its implications in the pathogenesis of migraine. Strong human data show that opening of the K_ATP channel using levcromakalim is the most potent headache and migraine trigger ever tested as it induces headache in almost all healthy subjects and migraine attacks in 100% of migraine sufferers. This review will address the basics of the K_ATP channel together with clinical and preclinical data on migraine implications. We argue that K_ATP channel blocking, especially the Kir6.1/SUR2B subtype, may be a target for migraine drug development, however translational issues remain. There are no human data on the closure of the K_ATP channel, although blocking the channel is effective in animal models of migraine. We believe there is a good likelihood that an antagonist of the Kir6.1/SUR2B subtype of the K_ATP channel will be effective in the treatment of migraine. The side effects of such a blocker may be an issue for clinical use, but the risk is likely only moderate. Future clinical trials of a selective Kir6.1/SUR2B blocker will answer these questions.

There is a need for better recognition and more extensive research into menstrual migraine (MM) in the general population, and a revision of the diagnostic criteria for MM is warranted to move the field forward. Increased understanding of MM is crucial for improving clinical care, diagnosis, and therapy for MM.

To assess the clinical characteristics of MM, including severity and treatment response, and to propose new diagnostic criteria for pure MM and menstrually related migraine.

This is a case-control study of Danish individuals with migraine. All individuals completed a 105-item validated diagnostic migraine questionnaire, sent via the Danish electronic mailing system (e-Boks) between May and August 2020, allowing diagnosis of pure MM and menstrually related migraine by the International Classification of Headache Disorders, Third Edition (ICHD-3). Data analysis was performed from September 2021 to November 2022.

Diagnosis of migraine.

Clinical characteristics of women with MM and women with nonmenstrual migraine (non-MM) were compared using the ICHD-3 diagnostic criteria. A simulation of the risk of randomly misclassifying MM was based on number of migraine attacks during 3 menstrual cycles (3 × 28 days), and simulation analyses were performed using 100 000 permutations of random migraine attacks in migraine patients.

A total of 12 618 individuals, including 9184 women, with migraine participated in the study. Among the women with migraine, the prevalence of MM was 16.6% (1532 women), and the prevalence of non-MM was 45.9% (4216 women). The mean (SD) age was 38.7 (8.7) years for women with MM and 37.0 (9.2) years for women with non-MM. Of the 1532 women with MM, 410 (26.8%) fulfilled ICHD-3 diagnostic criteria for pure MM, 1037 (67.7%) fulfilled ICHD-3 diagnostic criteria for menstrually related migraine, and 152 (9.9%) fulfilled proposed diagnostic criteria for rare pure MM. MM was associated with a higher frequency of migraine-accompanying symptoms (odds ratio [OR], 1.98; 95% CI, 1.71-2.29), more frequent (OR, 7.21; 95% CI, 5.77-9.03) and more severe (OR, 1.17; 95% CI, 1.13-1.21) migraine attacks, lower frequency of nonmigraine headache (OR, 0.31; 95% CI, 0.18-0.49), an overall greater response to treatment with triptans (OR, 1.66; 95% CI, 1.24-2.24), better improvement of migraine attacks during late pregnancy (OR, 5.10; 95% CI, 2.17-14.00), and faster reappearance of migraine attacks post partum (OR, 3.19; 95% CI, 2.40-4.25). Hormonal contraceptive-related MM was associated with a higher prevalence of migraine without aura than migraine related to spontaneous menstruation (OR, 1.82; 95% CI, 1.62-2.06). Otherwise, no differences between hormonal and spontaneous MM were observed. The risk of random diagnostic misclassification of ICHD-3 menstrually related migraine in women with high frequency episodic migraine was 43%. This risk was reduced to 3% when applying the proposed criteria for menstrually related migraine.

In this case-control study, MM in the general population had clinical characteristics that were quantitively different from those of non-MM. Detailed descriptive data and suggested improved diagnostic criteria for pure MM and menstrually related migraine were provided.

Headaches are one of the most frequent reasons people visit the neurology department. In 2019, headache issues ranked as the 14th most common cause of disability-adjusted life years globally. According to the International Headache Society, migraine is a particular type of headache that is unilateral, frequently throbbing, associated with vertigo, and sensitive to light, sound, and head movement. A migraine has four stages: premonitory, aura, headache, and postdrome. Migraine is the type of discomfort that most frequently complicates the pregnancy. A migraine is more common in women than in men. Migraines are influenced by increased levels of estrogen during pregnancy and a sharp decrease in those levels during puerperium. Untreated migraine can result in premature labor, hypertension, and low birth weight babies. Menstrual-related events occurred more frequently in migraine sufferers than in non-migraine sufferers. We have explained the relation of sex hormones that trigger migraine. We have also reviewed the therapeutic approach, such as pharmacological and non-pharmacological approaches, for migraine in pregnancy and breastfeeding. A migraine episode during menstruation was slightly more severe and complicated than a headache that wasn't a migraine. Breastfeeding is not prohibited by migraines. The steady estrogen levels brought on by lactating women's lack of menstruation may function as a protective factor. In addition to any required drug therapy, nonpharmacological techniques should always be used as the first line of treatment. Preconception counseling is an essential part of providing headache patients with safe therapy during pregnancy. Supplemental estrogen should not be used by any women who have an aura or who are 35 years of age or older because there is inadequate proof to support any long-term adverse effects. Paracetamol is advised for use in acute therapy during pregnancy. Mothers who used acetaminophen during pregnancy are more likely to have children with hyperkinetic disorders and characteristics resembling attention-deficit/hyperactivity disorder. Menstrual migraine can be treated in a variety of ways, including acute therapy, non-pharmacological therapy, and preconception counseling. Similar tactics are used to treat migraines during pregnancy, but it's important to take the medications' safety rating into account. Migraines and menstrual problems go together. A safeguarding element is a constant estrogen level during pregnancy and breastfeeding. The preferred method of treatment for migraine is non-pharmacological therapy, followed by prenatal counseling. Sumatriptan and acetaminophen are both effective treatments for transient migraine attacks that occur during pregnancy or breastfeeding.

Approximately 60% of female migraineurs experience menstrual migraine (MM). Whether MM is a distinct clinical entity with more severe migraine attacks and a worse prognosis than nonmenstrual migraine (nMM) is still under debate. We conducted a systematic review and meta-analysis to investigate clinical differences between MM and nMM patients.

A systematic literature search was performed to identify observational studies comparing MM and nMM patients' clinical characteristics. Quality of evidence grades of the synthesized effect estimates for each outcome were determined following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines.

Of 1837 identified studies, 16 were eligible for inclusion. MM patients had more migraine attacks per month (MD 0.65, 95% CI 0.05-1.24) than nMM patients; however, the quality of evidence was "low" according to the GRADE assessment. They also had more headache days (MD 0.86, 95% CI 0.12-1.60) per month, a higher rate of family history of migraine (OR 1.41 95% CI 1.12-1.78), migraine aggravation with physical activity (OR 1.60, 95% CI 1.35-1.89), a younger age at migraine onset (MD - 0.99, 95% CI - 1.78 to - 0.19), and a higher risk of accompanying symptoms (OR 2.31, 95% CI 1.72-3.10) than nMM patients; however, the quality of evidence was "very low".

There were differences between MM and nMM, showing that MM patients have a worse profile than nMM patients, but the quality of evidence is too low to draw definite conclusions on the separation/unification of the two clinical entities.

To systemically review clinical studies investigating the role of prolactin and its receptors in headache and migraine.

Migraine prevalence is more common in women compared to men. As prolactin is a crucial regulator of the hypothalamus-pituitary-gonadal axis, prolactin and its receptors might contribute to signaling mechanisms underlying migraine.

In this systematic review, we searched PubMed and EMBASE with the terms: prolactin, hyperprolactinemia, macroprolactinemia, hypoprolactinemia, migraine, headache, head pain and trigeminal pain pathway for clinical studies investigating prolactin signaling in headache and migraine. Two reviewers independently screened 841 articles for population, intervention, comparison, outcome, and study design. Studies were restricted to the English language and were excluded if they had a nonexperimental methodology.

Nineteen clinical studies met the inclusion criteria and were included in the qualitative and quantitative analysis. The main findings were that serum prolactin levels were found to be higher in individuals with migraine compared to healthy controls, and prolactinomas (prolactin-secreting pituitary adenomas) were correlated with higher incidence of headache in otherwise healthy individuals and migraine attacks in individuals with migraine.

Considerable evidence suggests a key role of prolactin and its receptors in migraine pathophysiology. Further randomized and placebo-controlled clinical studies targeting prolactin signaling are needed to further clarify influences of prolactin in migraine attack initiation.