Gender and Migraine

This book focuses on the influence of sex and gender in migraine, presenting new insights in basic science as well as their clinical relevance.  As migraine is roughly three times more common in women than in men, and also highly depends on hormonal milestones – such as menarche, menstruation, pregnancy and menopause – particular attention is devoted to the role of female sex hormones in this disease. 

The first chapters present general data on gender-related differences in migraine such as epidemiology, comorbidities and related risks. Furthermore, while several chapters focus on the role of female sex hormones in migraine-triggering mechanisms at a basic scientific level (e.g. cranial circulation), ample attention is also paid to the clinical relevance of such mechanisms and to the best clinical treatment for migraine patients.

As the first book entirely devoted to this topic, it will be of interest to researchers and practitioners in the fields of neurology, internalmedicine, endocrinology, physiology and pharmacology.

• Language: English
• Publisher: Springer
• Release date: Feb 14, 2019
• ISBN: 9783030029883

Book preview

© Springer Nature Switzerland AG 2019

Antoinette Maassen van den Brink and E. Anne MacGregor (eds.)Gender and MigraineHeadachehttps://doi.org/10.1007/978-3-030-02988-3_1

1. Epidemiology of Migraine in Men and Women

Kjersti Grøtta Vetvik¹  

(1)

Department of Neurology, Akershus University Hospital, Lørenskog, Norway

Kjersti Grøtta Vetvik

Email: [e-mail]

Keywords

MigraineSexGenderEpidemiologyPrevalenceIncidenceMenWomenBurden

1.1 Introduction

Migraine is a primary headache disorder—a headache without underlying cause [1]. The diagnosis is based on the patients’ reported symptoms during attacks and can to date not be confirmed by any specific diagnostic tests, e.g., blood tests or radiological investigations.

The International Classification of Headache Disorders (ICHD) defines two major subtypes of migraine which may coexist; migraine without aura and migraine with aura [1]. The main feature of migraine without aura is a unilateral throbbing headache of moderate to severe intensity. Headache is often aggravated by routine physical activity and is accompanied by photo- and phonophobia, as well as nausea with or without vomiting. The migraine headache is thought to be a result of activation of trigeminovascular pathways, the brain stem, and diencephalic nuclei with subsequent release of neuropeptides and sensitization of second- and third-order central neurons [2].

Migraine with aura affects about one third of migraineurs and is characterized by one or more transient and fully reversible focal neurological symptoms developing gradually over minutes, of which each symptom lasts for up to an hour [1, 3, 4]. The most common aura symptoms are visual disturbances, followed by sensory symptoms and speech problems. In rare cases, the migraine aura can also include motor symptoms and retinal or brain stem symptoms. The migraine aura is in most cases followed, by or accompanied by, a headache that may or may not have migrainous features, but in fewer than 5%, no headache occurs [5]. A slowly propagating wave of neuronal depolarization, the so-called cortical spreading depression, is the anticipated underlying pathophysiological mechanism for the aura [6].

Migraine may also be subdivided into episodic and chronic migraine, depending on the total headache frequency per month. Chronic migraine is defined as headache occurring on 15 or more days per month for more than 3 months, which has the features of migraine headache on at least 8 days per month [1]. In episodic migraine, headache occurs less than 15 days per month.

The distinction between episodic and chronic migraine has mainly implications for the treatment, while the subclassification of migraine with and without aura additionally is relevant to comorbidity, assessment of risk factors (e.g., vascular diseases), and prognosis—especially in women.

1.2 Prevalence of Migraine

The prevalence of migraine is significantly influenced by age and sex. In prepubertal children, the prevalence is about 3–7% with no significant difference between boys and girls [7–11]. From the age of 10–14 years, and during all the following years, the prevalence is two to three times higher in women than in men. The maximum sex difference is between age 30 and 45 (Fig. 1.1) when the migraine prevalence peaks in both men and women [12–16]. After the age of 50 years, the prevalence declines in both sexes, most markedly for women. New onset of migraine after the age of 50 years is rare in both sexes [17].

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Fig. 1.1

Prevalence of migraine by age and sex. Data from the Global Burden of Disease Study 2016 (GBD 2016) [18]

The prevalence of migraine varies across continents with the highest figures in Australia, Europe, and North America and the lowest in Africa, Central/South America, and Southeast Asia (Fig. 1.2a, b). The male to female prevalence ratio is however consistently reported. Large population-based studies indicate that the 1-year prevalence and sex ratio are stable over time, with the numbers of men and women reporting migraine increasing in proportion to the population growth [12, 14, 16, 19].

../images/456838_1_En_1_Chapter/456838_1_En_1_Fig2a_HTML.jpg../images/456838_1_En_1_Chapter/456838_1_En_1_Fig2b_HTML.jpg

Fig. 1.2

(a) Global prevalence of migraine among men aged 15–49 years. (b) Global prevalence of migraine among women aged 15–49 years [18]

1.2.1 Subtypes of Migraine

In both men and women, migraine without aura occurs about twice as often as migraine with aura, and the prevalence of migraine with aura is two to three times higher in women than men. Among men, the 1-year prevalence is within the range 0.6–3.4% with corresponding figures for women 1.9–7.4% [4, 16, 20–24]. A Danish study reported slightly higher figures for the lifetime prevalence of migraine with aura: 3.6% for men and 7.5% for women [25].

Chronic migraine accounts for about 8% of all migraine cases with prevalence estimates typically in the range of 1.4–2.2% [26]. Similar to the total migraine prevalence, the prevalence of chronic migraine peaks in the 40s in both sexes [27]. Chronic migraine is 4.7 times more common in women than men among young adults aged <30 years [28]. Thereafter, the prevalence is two to three times higher in women than in men, mirroring the sex ratio of the total migraine prevalence [27–29]. However, in the general population, chronic migraine is more prevalent within the total male migraine population than within the total female migraine population. This becomes specifically evident after the age of 40 when chronic migraine accounts for 9.9–11.7% of all male migraine cases as compared to 7.3–8.4% of all female migraine cases [27].

1.2.2 Incidence and Age at Onset

Age- and sex-specific incidence rates for migraine have been presented in both longitudinal and cross-sectional studies, although there is a dearth of longitudinal studies among adults [21, 30–33]. Common to all studies are the significant higher annual and cumulative incidence rates of migraine in women.

In a 12-year longitudinal Danish population-based study of 673 adults aged 25–64 years, the annual incidence rate of migraine was 8.1 per 1000 person-years with a male to female ratio of 1:6 [30]. Among both sexes, the incidence decreased significantly by age. The highest incidence was found among participants aged 25–34 years, with annual incidence rates of 6.5 per 1000 person-years for men and 22.8 per 1000 person-years for women.

Cross-sectional studies from the USA consistently report an earlier peak incidence in men [17, 34, 35]. The American Migraine Prevalence and Prevention (AMPP) study included more than 160,000 participants aged ≥12 years [17]. Migraine incidence peaked between the ages of 20 and 24 years in women (18.2 per 1000 person-years) and 15 and 19 years in men (6.2 per 1000 person-years) [17]. The median age at migraine onset was 24 years in men and 25 years in women. More than 75% of new-onset cases in men and more than 85% of new-onset female cases occurred after age 14 years. The cumulative lifetime incidence for migraine was significantly higher in women than men (43% vs. 18%). Another USA-based study that included younger participants (10–29 years) reported earlier migraine onset in men than in women for both migraine with aura (<5 years vs. 12–13 years) and without aura (11–12 years vs. 14–17 years) [34]. In contrast to men, new onset of migraine was relatively common among women in their late 20s. In both sexes, the incidence of migraine with aura peaked 3–5 years earlier than the incidence for migraine without aura.

A 30-year longitudinal study from Switzerland found that the cumulative incidence of migraine in men levelled off at age 35, whereas that in women continued to increase to age 50 [21]. The cumulative incidence of migraine in this prospective study was higher than estimates from the AMPP study: 50.7% in women and 20.7% in men.

A Danish study including 1136 twin pairs with a mean age of 36.6 years reported a later onset of migraine without aura in women than men (21.5 years vs. 16.5 years), while onset of migraine with aura did not differ significantly (21.8 years vs. 20.8 years) [36].

1.3 Natural History/Prognosis

Migraine is a fluctuating condition with periods of remission interposed by relapse; only about 35% of young adults with migraine continue to have intermittent attacks, while 20% continue to develop chronic migraine over 30-year follow-up [21].

Prospective studies of children and adolescents with migraine report higher remission rates in boys than in girls from childhood to young adulthood. In the long term, this sex difference seems to disappear, indicating that the capacity to have migraine remains in both men and women, with men being more likely to experience longer periods with remission [37–39].

To date, the longest prospective cohort of children with migraine is a 40-year follow-up study including 73 Swedish school children aged 7–15 years at baseline [11]. Before the age of 25 years, significantly more boys (34.9%) than girls (15.0%) were migraine-free. However, when the cohort reached around 50 years of age, 46% were migraine-free with no differences between the sexes.

A Finnish 25-year longitudinal study included 1185 children from the general population. The cohort was studied at three different ages: the age of 7, 14, and 32 years. Among the 7-year-olds, 4.0% had migraine (girls 3.7%, boys 4.3%, p = 0.58). At the age of 14 years, significantly more girls than boys had migraine (15% of girls and 7% boys, p < 0.001), and this sex difference remained significant when the cohort had reached the age of 32 years (22% girls vs. 8% boys, p < 0.001) [40]. Childhood migraine persisted into adulthood (from age 7–32) in 65% of women and 21% of men, while new onset of migraine occurred in 17% of the women and only 7% of men after childhood.

A population-based study of 1155 Turkish school children attending to the second to fifth school grade found that female sex was a significant risk factor for both development and persistence of migraine 6 years later, when the cohort had reached a mean age of 15.5 years [41]. During the 6 years, migraine prevalence among girls had increased from 9.9% to 21.5%. Corresponding figures for boys were 7.9% and 15.8%.

Studies from clinic populations display similar trends. An Italian clinic population including 64 children and adolescents (mean age 11.4 years, range 4–18) found that significantly more girls than boys had enduring migraine at 8-year follow-up (67% vs. 33%, p < 0.05) [42]. Similarly, a German study including 140 children and adolescents with mean age 17.6 years (range 11–26) at the time of follow-up found that female sex was a predictor for increased headache frequency from baseline 6.6 years earlier (p = 0.04) [43].

Longitudinal studies of adults present conflicting results. A French longitudinal study of 1250 employees aged 30–54 years at inclusion reported that retention or acquisition of a migraine diagnosis was more common in women than in men at 10-year follow-up [37]. In contrast, a Danish population-based study including 549 participants aged 25–64 years at inclusion reported that sex was not associated with poor outcome 12 years later [44].

Whether the prognosis differs between migraine with and without aura is uncertain, but studies suggest that men are more likely to experience longer periods with remission of migraine with aura. In a 10–20-year follow-up of a clinic sample including 81 patients aged 11–63 years, more men than women were attack-free for at least 1 year (46% vs. 29%) and 5 years (30.8% vs. 13.6%) [39]. In another clinic sample of 53 patients aged 12–66 years, a nonsignificant trend toward higher cessation rates for migraine with aura was found among men after 16-year follow-up (55% men vs. 31% women, p = 0.17) [38].

Regarding chronic migraine, population-based longitudinal studies show a more favorable prognosis for women. A recent German study reported that female sex was associated with remission of chronic headache (OR 2.29, 1.03–5.10) over a period of 3 years [45]. Similarly, in a US study of 1134 people with chronic migraine, the likelihood of remission increased with age for women, but not for men [46].

1.4 Phenotype

Studies consistently show that women report a longer duration of their migraine attacks compared to men [47–58], which may partly be due to the prolonged duration of menstrual attacks in women [59–61]. Other characteristics, such as pain intensity and attack frequency, do not differ among sexes in most studies [15, 19, 47, 48, 51, 52, 55, 57, 58, 62], with a few exceptions [4, 48]. Conversely, no studies report that men have more painful, longer-lasting, and more disabling migraine attacks. The presence and severity of associated symptoms, such as photo- and phonophobia, nausea and vomiting, as well as cutaneous allodynia, are mostly reported to be more prevalent in women [15, 19, 48, 50, 52, 56, 63]. In women, the clinical features of migraine attacks vary significantly with age, while they show little alteration in men [48, 51, 56]. Sex differences in attack features have also been described in children aged 11.7 years, with girls reporting longer duration and higher frequency of migraine [64].

These findings must however be interpreted with caution since most of the studies are based on retrospective self-report and retrospectively recorded migraine symptoms may not correlate with those recorded prospectively. In addition, both men and women rate men as less willing to report pain [65, 66].

1.5 The Impact of Migraine

Migraine causes a substantial amount of burden both to the affected individual and to the society. The individual burden encompasses headache and associated symptoms, as well as limitations to activities at work and home and in social roles. The societal burden involves indirect costs due to lost work time, underemployment, and unemployment, as well as direct medical costs. The societal burden is further mediated by the high prevalence among working-age individuals.

The Global Burden of Disease (GBD) study 2016 ranks migraine as the fourth leading cause of years lived with disability (YLDs) among women and number five among men at all ages (Table 1.1). Among people aged 15–49, migraine is ranked as number two among women and number three among men. Within each age group, years lived with disability mirror the migraine prevalence and remain consistently higher in women than men (Fig. 1.3).

Table 1.1

Global ranking of years lived with disability (YLDs) by age and sex