This retrospective epidemiologic study analyzed data from almost 25 000 individuals aged over 18 who were diagnosed with migraine up to 2022. During this period, we observed a steady increase in migraine prevalence, from 4.5% in 2017 to 5.2% in 2022, underscoring a growing disease burden. Migraine was more prevalent among women (8.0% vs. 2.4% in men), and the mean age of migraine patients was 46.8 years, with the highest prevalence observed in individuals in their third and fourth decades of life. Using our highly specific criteria for migraine, the annual incidence in 2022 was 3.6 cases per 1000 individuals, with approximately 75% of new cases occurring in women, whose mean age was 36.5 years.

Interestingly, despite the introduction of new migraine-specific treatments and increased awareness efforts by medical societies and pharmaceutical companies, the number of new migraine cases declined from 2035 in 2017 to 1686 in 2022. This decrease may be attributed to several factors. First, the COVID-19 pandemic likely discouraged some individuals from seeking healthcare services, impacting diagnosis rates [19]. Second, the relatively low percentage of LHS members with complementary insurance (70.9% vs. 79% in the general population in 2020) may have limited access to new-generation migraine treatments, as complementary insurance is the primary means for obtaining these therapies. Patients without access to these newer treatments might be less likely to seek or receive a formal migraine diagnosis. Additionally, most migraine awareness activities have been concentrated in central Israel, where a smaller proportion of citizens are LHS-insured, possibly impacting awareness and diagnosis rates in other regions.

The observed increase in migraine prevalence from 2017 to 2022 aligns with global trends reported from 1990 to 2019 [20]. This upward trend may be attributed to improvements in diagnostic procedures and an increased tendency for patients to seek medical care for migraine symptoms. Despite this increase, the prevalence rate in our study remains relatively low compared to other recent local and global data. Globally, the prevalence of migraine is estimated to be around 14.0% [21], and a recent study from southern Israel reported a prevalence of 7.65% (11.43% in women and 3.75% in men)[22]. This discrepancy may be explained by the lower percentage of middle-aged individuals insured with LHS, as this age group constitutes a substantial proportion of migraine patients, as well as the stringent criteria we used to identify migraine [23]. Indeed, nearly two-thirds of migraine patients identified using the stringent criteria of this study were diagnosed by neurologists, while only 19% were diagnosed by family physicians. This contrasts with previous studies, where migraine diagnoses were more commonly made by general practitioners [24].

The higher prevalence of migraine in females aligns with findings from previous studies conducted in the US, Spain, Japan, and Italy [15, 25, 26]. The mean age of patients in our migraine cohort was 47.6 years, slightly higher than the previously reported mean of 40.3 years. This difference may be attributed to the fact that migraine diagnoses sometimes remain in electronic health records even after symptoms have subsided [15]. The mean age of migraine diagnosis in our cohort, around 36.5 years, is consistent with the previously reported age of 38.2 years [27]. The annual incidence of migraine reported in a United Kingdom database study was 3.69 cases per 1000 [28], similar to the 3.6 cases per 1000 observed in our study for 2022.

Anti CGRP MAB's (Monoclonal Antibodies) were approved by the US Food and Drug Administration (FDA) in 2018 for the preventive treatment of migraine and their use in Israel began in 2019–2020 [29]. The prevalence of CGRP inhibitor use increased from 0.1% in 2020 to 1% in 2022. The higher cost of CGRP inhibitors compared to triptans may have limited their use [30]. However, CGRP inhibitor usage has gradually increased, which could be attributed to their favorable safety and tolerability profile [31] especially the aging population. A previous study suggested that CGRP inhibitors are associated with fewer side effects in older patients and in those with comorbidities and concurrent medication use [32].

To identify risk factors, we compared physical measurements and laboratory test results between individuals with migraine and matched controls. We found that patients with migraine had a lower BMI, a decreased rate of obesity, higher diastolic blood pressure (BP), higher hemoglobin levels, lower glucose levels, a higher rate of normal HbA1c (below 6.5), and lower rates of microalbuminuria compared to the control cohort. These findings align with a recent meta-analysis by Ha et al. (2024), which reported a reverse association between diabetes and migraine, further supporting the observed differences in HbA1c and glucose levels in our study [33].

Research suggests that both underweight (BMI ≤ 18) [34] and overweight (BMI ≥ 30) [35,36,37] are associated with an increased risk of migraine. In this study, individuals with clinically significant migraine had a higher prevalence of normal weight (BMI 18.5–24.9) and overweight (BMI 25–29.9), while obesity (BMI > 30) was more common in the control cohort. These findings underscore the complex relationship between BMI and migraine risk, highlighting the importance of addressing body weight as a modifiable factor in the diagnosis and management of migraine [38].

Previous studies have highlighted associations between migraine and hypoglycemia (low blood glucose) [39], and hypertension [40], findings that were confirmed by our study. Additionally, while past research has linked migraine with low hemoglobin (particularly in patients with iron-deficiency anemia) [41], our study found a higher average hemoglobin level among individuals with migraine.

The laboratory differences observed in this study suggest potential risk factors that may influence migraine risk in the population and could provide valuable directions for future research.

This study has several strengths, including the use of high-quality data from the electronic health records (EHR) of a national health provider in Israel, encompassing a comprehensive review of patient medical records and pharmacy purchases. The study benefits from long-term follow-up, well-ascertained outcomes, and the use of relatively recent data, enabling a robust analysis of clinically significant migraine epidemiology. Additionally, the inclusion of diverse populations, such as Arab and Ultra-Orthodox Jewish communities and individuals from medium-to-low socioeconomic status (SES) groups, ensures that subpopulations at higher risk of health disparities are adequately represented.

However, several limitations should be considered when interpreting these results. First, as a retrospective and observational study, it shares the inherent limitations of such a design, including potential confounding and bias. Second, the study lacks data on the severity and frequency of migraine symptoms, as well as information on private medication purchases made outside LHS pharmacies, which may have influenced treatment patterns. Third, crude estimates were used instead of standardized estimates, meaning that demographic differences could be confounded by the LHS population characteristics. Consequently, caution is advised when interpreting ethnic, socioeconomic, and geographical disparities.

Furthermore, while our descriptive approach provides valuable insights into migraine epidemiology, this study did not utilize regression models to investigate the associations between socio-demographics, clinical variables, and migraine prevalence. Although we mitigated potential confounding effects through careful matching of cases and controls on key variables, the absence of regression analysis limits our ability to explore these relationships in greater depth. Future studies are planned to build on these findings by using multivariable regression models to gain a deeper understanding of these associations and their potential influence on incidence trends.

Lastly, the cohort reflects migraine patients within LHS, one of four health maintenance organizations in Israel. LHS has a stronger presence in the country’s periphery and a smaller representation in central Israel, where most migraine awareness activities have been concentrated in recent years, compared to other health funds. This may limit the generalizability of the observed prevalence and incidence trends to other healthcare settings or regions.