Methodological considerations

Studies of headache progress generally from cross-sectional to longitudinal, from clinical to population-based, and from clinical case definition to standardized diagnostic criteria. Each study design has its own merits and flaws. Cross-sectional study is comparatively inexpensive and simple compared to its longitudinal counterpart. Cross-sectional studies have point-prevalence as the primary outcome measure. The prevalence can be incorrectly estimated in chronic and intermittent conditions, such as frequent tension-type headache or other chronic daily headache (42). When cross-sectional study is applied to examine the determinants of the disease, its results lead to problems in determining cause and effect from any observed associations. This is because the risks and outcomes are measured simultaneously. To overcome these limitations, studies of headache have been conducted longitudinally, for example, Zurich cohort study (65), Danish follow-up study (61), and American Migraine Prevention and Prevalence (AMPP) study (98).

Longitudinal study has incidence as the main outcome. Additionally, this type of study can determine the temporal sequence between risk factors and the occurrence of the disease. With this design, individuals are assessed at the beginning of the study and then reassessed after predetermined time intervals. Only longitudinal design can reliably determine the onset, the rate of remission, or relapse. For instance, a longitudinal study conducted by Stewart and colleagues found that cumulative lifetime incidence of migraine was approximately three times the prevalence (98). This can be explained by a considerably high rate of migraine remission.

Although longitudinal study offers a promising result in terms of the progress of the disease, it still requires cautious interpretation. Notably, aging and period effect can confound the longitudinal results as seen in patients with migraine whose symptoms change when they are older. Changes in socioeconomic or environmental factors can also change individuals’ pattern of disease. Longitudinal studies also have other limitations, such as a relatively high attrition rate (which may cause nonresponse bias) and high cost (which may compromise the way the study is conducted).

Samples selected for the study also influence the results. Generally, clinical-based studies constitute biased samples and can give a deceptively high prevalence of disease. However, if the aim of the study is to focus on rare diseases, such as cluster headache, it is hardly possible to obtain a reliable result from a population-based study. Clinical-based studies have, therefore, an advantage in investigating rare phenomena. Apart from such reasons, population-based studies have been almost always preferable in determining the prevalence or incidence of a disease or disorder. When comparing the magnitude of disorders, selection of samples must be considered.

Determining whether or not patients have headache is not simple, especially in primary headache and even more so for individuals in research. Until 1988, there was no consensus on the research definition of headache; therefore, the studies conducted before 1988 were not comparable. The International Classification of Headache Disorders (ICHD), following the first edition in 1988, has provided specific criteria for diagnosis of headaches for both clinicians and researchers (45). Most criteria are explicit; thus, interobserver reliability can be achieved. By using ICHD criteria, we are able to consistently compare results from various studies (45).

All primary headaches are, however, defined based on symptom-based criteria, similar to the way mental disorders are defined (02). These subjective criteria cannot provide adequate information for accurate diagnosis of a postulated disease. Thus, they lack specificity, and to distinguish one condition from another becomes difficult (48). For instance, primary headache has been found to overlap other symptom-based conditions, such as irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, and anxiety (114; 12; 78; 87).

Although case definition is well operationalized, case-finding instruments are still problematic. As most instruments are in forms of interview or self-completion questionnaires, they are prone to interviewer bias, recall bias, and acquiescence bias. Samples with and without disease condition tend to respond to measures differently. This may result in over- or underestimation of any associations being studied. We should, therefore, interpret results of epidemiological studies of headaches with caution.

The use of metaanalyses in order to establish more reliable evidence from epidemiological studies becomes more popular. Consideration on analyzed data from metaanalyses or systematic reviews has to be done with caution. Substantial difficulties can interfere the interpretation, including publication bias in each study (50). Complete protocol has to be explicitly shown in order to enlighten readers about how to statistically deal with these difficulties.

Classification

Classification is a major issue in the epidemiological study of headaches. Without a clear classification system and criteria, an epidemiological study is almost impossible, and information from different studies cannot be compared. In acknowledgement of this problem, the International Headache Society (IHS) established a Headache Classification Subcommittee in late 1980. In 1988, IHS published the first edition of the International Classification of Headache Disorders (ICHD-I), followed by the second edition (ICHD-II) in 2004. The third (ICHD-III) edition was published in 2018 (44).

The ICHD classification system has been universally accepted since its first edition. The existence of the operational diagnostic criteria described in this system has strong impact on both clinical and epidemiological studies of headache. In the ICHD system, headache disorders are primarily divided into three parts, namely (1) primary headaches, (2) secondary headaches, and (3) painful cranial neuropathies, other facial pains, and other headaches. The headache disorders are classified into major groups, and each group is then subdivided into headache types, subtypes, and subforms. A major change since the second edition is that all secondary headaches are described as “attributed to” another disorder whereas the first edition used the term “associated with.” This change reflects the well-established causal link between the underlying disorders and the headache disorders. A chapter for “Headache attributed to psychiatric disorder” has been included as one of the secondary headaches since the second edition. A major change for the third edition includes the reclassification of migraine with aura. The section on “medication-overuse headache and its subforms” of the ICHD-II was also revised in ICHD-III to include (i) medication-overuse headache attributed to multiple drug classes not individually overused, and (ii) medication-overuse headache attributed to unverified overuse of multiple drug classes. It is useful to notice medication-overuse headache in clinical practice, as its incidence is increasingly common, particularly in migraine patients. Successful rate of treatment is 50% to 70%, which is considerably high for such a chronic disease (27).

Epidemiology of primary headaches

Generally, primary headaches are far more common than secondary headaches. Due to vast variety of their etiology, accurately determining prevalence of secondary headaches is not possible. Therefore, this review focuses on the primary headaches of migraine, tension-type headache, chronic daily headache, and cluster headache; other primary headaches, such as primary stabbing headache and primary exercise headache are also described.

Migraine. Migraine is common. Data from a literature review of 357 population-based studies showed that the global “active migraine” prevalence, as defined by migraine currently present or that has presented within the last year, was 14.0% (males 8.6%, females 17.0%) (100). A similar trend was from a large-sized study in the United States demonstrating that age-adjusted 3-month period prevalence of migraine and severe headache was 15.3%, including 20.7% of women and 9.7 % of men, which was slightly higher than the global number and had been stable over a period of 19 years (17). A comprehensive review of literature of migraine prevalence studies in East Asian adults showed similar figures (101).

Although the study of migraine prevalence is common, the study in incidence rate and proportion of migraine is much less available. A longitudinal 12-year follow-up population-based study showed that the incidence rate was 8 per 1000 person-years, with a female-to-male ratio of approximately 6 to 1 (61). No significant age or sex differences were noted between migraine subtypes. Similar findings were seen in the United States. The American Migraine Prevention and Prevalence (AMPP) cohort study also reported that incidence peak was 18/1000 person-years in females of 20 to 24 years of age compared to 6/1000 person-years in males of 15 to 19 years of age. The estimated cumulative lifetime incidence from this study was as high as 43% in women and 18% in men. The median age of onset for both sexes was 25 to 34 years of age (98).

Unlike tension-type headache, migraine prevalence has remained stable across different regions and time periods. Tension-type headache was observed in approximately 6% of males and 14% of females globally. Migraine has the lowest prevalence in China (9% for overall prevalence) and the highest in Europe (up to 35%) (88). Taking ethnicity into consideration, it was found that whites had significantly higher prevalence than blacks (women, 17.3% vs. 13.7%; men, 5.7% vs. 4.1%) (59). Overall, it ranged from 1% to 25%. Compared to tension-type headache (see below), the range was narrow, taking into account the different methodologies employed in each study.

Migraine also affects children and adolescents. The global estimate, derived from a well-known international epidemiological study, Global Burden of Diseases (GBD) 2007 and 2017, stated that migraine represented approximately 10.5% of all-cause prevalence in both years among people aged 5 to 19, with a clear gender and age gradient as females and older subjects showing higher prevalence (56). In prepubertal period, headache rates were comparable between boys and girls, with estimated migraine prevalence ranging from 2.4% to 17% (55) whereas in adolescents, prevalence in males was lower—4.8% in males versus 9.1% in females (115). Migraine seems to decline with age. That is, the incidence of approximately 14/1000 person-years in the 25 to 34 years age group was down to less than 5/1000 in the 55 to 64 years age group for both sexes (61). However, female incidence was predominant in adulthood; even in the postmenopause group, incidence was around 2% to 3:1% (59). A 30-year follow-up study showed that incidence of migraine in men leveled off at the age of 35, whereas that in women continued to increase to the age of 50 (66).

Lyngberg and colleagues studied risk factors of migraine and found that young age, no vocational education, family history of migraine, and coincidence with frequent tension-type headache increased the likelihood of migraine occurrence (61). From the same study population, the results from the same study population showed overall prognosis of migraine was rather favorable. They found that 42% of subjects with migraine at baseline were in remission at follow-up. Only 20% experienced poor outcome, ie, having more than 14 days of migraine attack per year. A review of statistics from the United States also showed the inverse correlation between the prevalence of migraine and income, as well as educational attainment (95). The principle behind this finding probably lies on the social causation hypothesis which states that unpleasant factors such as poor diet or stressful lifestyle in low-income society could increase the rate of migraine onset (18).

Migraine has been found to overlap with other physical and mental disorders. Migraine was associated with an increased risk of ischemic stroke (adjusted RR 2.41 95% confidence interval [CI] 1.81 – 3.20) and transient ischemic attack (adjusted OR 2.76 95% CI 1.88 – 4.05) (06; 97). The risk is greater in those with migraine with aura. However, it is suggested that cerebrovascular events associated with migraine are small-vessel in origin. There is no significant association between migraine episodes, both with or without aura, and level of calcification of both intracranial and internal carotid arteries (106). With other symptom-based conditions, migraine was found to be associated with pain conditions, especially conditions involving the musculoskeletal system (75; 41; 107). Among surgical patients, postoperative pain and stroke were found to be more pronounced in patients with migraine (70). Prevalence of insomnia was higher in patients with migraine compared to non-headache controls (105). Migraine is also associated with obesity. Peterlin and colleagues showed that prevalence of episodic migraine was higher in an obese group compared to a normal weight group (OR 1.81; 95% CI 1.27 – 2.57; p = 0.001) (76). A number of studies have found that the incidence of patent foramen ovale (PFO) in migraine patients, especially migraines with aura, is higher than that in the general population, and the presence of right-to-left shunt in echocardiography finding increased the likelihood of aura attacks, suggesting the bidirectional causal relationship between patent foramen ovale and migraine (60).

Considering risk factors during earlier ages of migraine manifestation, some preschool episodic syndromes have long been stated as risk factors of developing migraine in later primary school age. Among these syndromes, abdominal migraine had the highest probability (RR 21.87; 95% CI 3.6 - 35.03). Recurrent gastrointestinal disturbances and somnambulism (sleepwalking) were also linked to later migraine (01). The concept of shared pathophysiology is believed to be the fundamental basis of this relationship.

The comorbidity of migraine and psychiatric disorders has long been consistently evident (65; 13; 14; 16; 15; 87). Major depression, bipolar disorder, panic disorder, and social phobia were all at least twice as prevalent in migraine (49). Of those, anxiety disorder was the most common mental disorder and affected approximately 44.5% of migraine sufferers compared to major depressive disorder, which affected only 18.8% (87). However, various studies establish variable prevalence rates of mood disorders in migraine due to differences in the inclusion criteria, geographical population, and scale used to diagnose and assess the severity (80).

Apart from anxiety and depression, association between migraine and bipolar disorder has also been documented. A longitudinal study conducted by Breslau and colleagues showed that patients with migraine had an increased risk of bipolar disorder at an odds ratio of up to 4.7 (95% CI 1.4, 15.4) (13). A cross-sectional hospital-based study found that, as compared to the patients without migraine, the patients with comorbid migraine had a higher frequency of bipolar II disorder (43% vs. 10%) and lower frequency of bipolar I disorder (11% vs. 33%) (29). Another hospital-based study showed the prevalence of coexistent somatoform disorder to be 30.1% (69).

The nature of the relationship between migraine and mental disorder, especially depression, was examined by Breslau and colleagues, who demonstrated that the association was bidirectional (14; 16). A newer investigation found that association of migraine and depression was substantially due to shared environmental factors that affect both diseases rather than a simple bidirectional association per se (67). In persons with migraine, the hazard ratio for the onset of major depression was 2.35 (95% CI 1.84 to 3.01), whereas the hazard ratio for the first occurrence of migraine in persons with prior major depression was 2.75 (95% CI 2.17 to 3.48). Moreover, a physician-based study in 48 countries showed that primary headaches cause one suicide per 1,000,000 population each year. Cluster headache and migraine account for 70% to 80% of the cases, with cluster headache entailing greater risk of suicide than migraine (103). Although psychiatric comorbidities are common in migraine patients, most problems usually remain untreated. Concerns about stigmatization may be an important factor that prevents patients from expressing their psychological symptoms, especially in patients with higher level of symptoms (52).

Migraine affects individuals, families, and also society. Most patients with migraine experience severe distress and impairment during migraine attacks. They have a substantially reduced health-related quality of life, comparable to hypertension, diabetes, and coronary heart disease (104). A review of global burden of headache suggested that migraine contributed to around 40% to 50% of the total disease burden (99). The total annual cost for migraine was around 14 billion dollars. Of that, 13 billion dollars was accounted for by indirect cost, which was secondary to missed workdays (43). The percentage of employed headache population in Brazil who missed at least one day of work in three months was 12.8% of overall population (71).

Tension-type headache. Tension-type headache is the most prevalent primary headache disorder. “Active tension-type headache” was present in 26.0% of the population (males 23.4%, females 27.1%) according to the narrative review of prevalence studies published until 2020 (100). In 2006, Russell and colleagues studied the prevalence of tension-type headache in 33,764 Danish twins 12 to 41 years of age (85). The 1-year prevalence was 83.5% (78.9% in men; 92.5% in women). A longitudinal 12-year follow-up population-based study showed that the incidence rate was 14.2 per 1000 person-years, with a female-to-male ratio of approximately 3 to 1 (61). Although the prevalence of tension-type headache has been acceptably high, the range varies across regions from 20% to 87%. Tension-type headache prevalence is less consistent than that of migraine. It was suggested that the prevalence was lower in Asia than in other regions, such as Europe or the United States (99). Illness behavior, that is, perception and attitude towards minor health conditions may explain this variation.

Most studies confirm prevalence of tension-type headache to be highest in the fourth decade of life. The prevalence is much lower in the younger age groups. The 1-year prevalence of tension-type headache of all subtypes in children ages 10 to 18 years was 21.6% according to a study in Austria (77). Another more detailed study in children aged 5 to 12 years old showed the prevalence of infrequent episodic tension-type headache to be 2.3% of the sample whereas prevalence of frequent episodic tension-type headache was 1.6% (03). Chronic tension-type headache is rare in early adolescence. Tension-type headache seems to decline with age; that is, the incidence of approximately 23/1000 person-years in the 25 to 34 years age group was down to less than 5/1000 in the 55 to 64 years age group for both sexes (61).

Lyngberg and colleagues studied risk factors of tension-type headache and found that poor general health, deficient sleep, and difficulty with relaxation after work increased the likelihood of tension-type headache occurrence (61). From the same study population, the results showed the prognosis of tension-type headache was rather favorable. They found that 45% of subjects with frequent tension-type headache or chronic tension-type headache at baseline were in remission at follow-up. Only 16% experienced poor outcome, ie, onset or continued chronic tension-type headache. Being single, having poor sleep habits, and suffering from migraine were among factors associated with poor outcome (62).

Tension-type headache has been found to overlap with other physical and mental disorders, especially those diagnosed by symptom-based criteria. Tension-type headache overlaps with other physical conditions, such as temporomandibular disorder, fibromyalgia, irritable bowel syndrome, chronic fatigue syndrome, and obstructive sleep apnea (30; 114; 78; 37; 23). A review of tension-type headache and psychiatric disorders showed that chronic tension-type headache had a higher frequency of psychiatric comorbidity than episodic tension-type headache (46). A population-based study conducted in Korea demonstrated the significantly higher prevalence of anxiety and depression in tension-type headache group than the control group (9.5% vs. 5.3% and 4.2% vs. 1.8%, respectively) (96). Anxiety disorder was the most common mental disorder and affected approximately 48% compared to 30% for depressive disorder in chronic tension-type headache. Most studies under review were, however, clinically based rather than population-based, and different measures were used. Therefore, comparison of the results had some limitations. The study also revealed that the prevalence of anxiety increases with the frequency of headache attacks. Moreover, tension-type headache is the most common headache disorder associated with sleep disturbances, including insomnia, and excessive daytime sleepiness (79).

Tension-type headache is less disabling but more common than migraine and is ranked as the second most common cause of chronic disease globally (GBD 2015 Disease and Injury and Prevalence Collaborators). According to the analysis for Global Burden of Diseases (GBD) Study 2017, tension-type headache had a much lower disability than migraine, with 7.1 million years of life lived with disability compared with 47.2 million for migraine globally (26). Individuals with tension-type headache also account for 4% to 12% of the missed work in one year; this was three times higher than the work hours lost because of migraine (81; 92).

Crossover between migraine and tension-type headache has been shown in a prospective 30-year follow-up study (66). Approximately 19% of migraine patients developed tension-type headache without migraine, whereas 22% of those with tension-type headache developed migraine alone across the follow-up period.

Trigeminal autonomic cephalalgias. Trigeminal autonomic cephalalgias refer to the group of headache disorders associated with autonomic features, especially cranial parasympathetic overactivity. This headache group comprises cluster headache, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT). Cluster headache is the most common and best-studied of the trigeminal autonomic cephalalgias. A meta-analysis of population-based studies showed the lifetime prevalence of 124 per 100,000 (confidence interval 101, 151) and a 1-year prevalence of 53 per 100,000 (confidence interval 26, 95) (31). The typical age of onset for cluster headaches is between 20 to 40 years old (64). However, 27.5% of the population affected by this condition also encounter a pediatric onset, occurring in individuals less than 20 years old (91). The overall male-to-female ratio was 4.3. Interestingly, the ratio was higher in chronic cluster headache (15.0) compared with episodic cluster headache (3.8). The overall ratio for episodic versus chronic cluster headache was 6.0. A 10-year follow-up study showed that about 13% of the baseline episodic cluster headache patients evolved to the chronic form (63). Predictors of progression included onset of cluster headache from the third decade of life onwards, greater than one annual cluster period, and short duration of remission periods (102). Compared to Western series, Asian patients were different in several aspects, including the very rare occurrence of chronic cluster headache and a low prevalence of restlessness and aura (58). Racial and geographical factors might contribute to the differences.

The information regarding the comorbidities of cluster headache is limited due to the low prevalence of this condition. The documented comorbidities include sleep disorders, tobacco use, history of head injuries, and mental disabilities. Association between cluster headache and sleep disorders, especially obstructive sleep apnea, has been observed. Using polysomnography, around 80% of cluster headache patients had an apnea–hypopnea index indicating at least mild obstructive sleep apnea (38). The association between tobacco use and cluster headache was so strong that some investigators considered tobacco use, specifically cadmium toxicity from cigarette smoke, to be involved in the pathogenesis of the disease (84). Second hand exposure to cigarette smoke appeared to initiate cluster headache at an earlier age (83). Few posttraumatic cluster headaches have been reported, but the cause-effect relationship is still unclear (54). Mood disorders especially anxiety and depression are strongly associated with cluster headache. Suicidal thought in persons living with cluster headache is significantly higher than in normal population (103).

Epidemiological data of other subtypes of trigeminal autonomic cephalalgias are less well-studied and lacks of accuracy and consistency. Prevalence of paroxysmal hemicrania was less than 0.5 in 1000 (28) whereas the number of SUNCT/SUNA ranged from 1 to 100 in 100,000 (25). Exact prevalence in population settings of hemicrania continua is unknown but in the clinic settings, the number was 1% to 2% of total headache patients (20). The age of onset of paroxysmal hemicrania and hemicrania continua were comparable, between 30 to 50 years of age (20; 72). Later age of onset from 40 to 70 years was the characteristic of SUNCT/SUNA (73). The pattern of male predominance, similar to cluster headache, was found only in SUNCT/SUNA with the ratio of 1.5:1 but not in paroxysmal hemicrania and hemicrania continua, which manifested as female predominance (11; 20).

Chronic daily headache. Chronic daily headache refers to headaches that occur 15 or more days per month for more than three months. The nomenclature of chronic daily headache has not been included in the ICHD-III and ICD-10. The four main subtypes of primary chronic daily headache of long duration (more than 4 hours per day) are chronic migraine, chronic tension-type headache, hemicrania continua, and new daily persistent headache.

Many population-based studies demonstrate the prevalence of chronic daily headache to be between 3% and 5% (89; 19; 109; 47). The prevalence is approximately three times higher in women (82). The prevalence remains consistent from mid-adolescence through adulthood and in the elderly. The majority of chronic daily headache sufferers have either chronic migraine or chronic tension-type headache. A systematic review showed the prevalence of chronic migraine to be 0% to 5.1% (68). Chronic migraine is approximately 7.7% of overall migraine cases. Women had higher chronic migraine prevalence than men (1.39% vs. 0.15%). A long-term follow-up study of a community-based adolescent cohort showed that presence of migraine, chronic daily headache onset at younger than 13 years of age, duration of more than two years, and medication overuse at baseline predicted poorer outcome (111).

Other forms of chronic daily headache are less prevalent compared to chronic migraine and chronic tension-type headache. Prevalence rates of new daily persistent headache in the general population have been reported at 0.03% to 0.1% (19; 39). This condition is more prevalent in younger age groups. New daily persistent headache has been estimated to occur in 1.7% to 10.8% of adults with chronic daily headache (10; 07) and in 13% to 35% of children with chronic daily headache (36; 51). Similar to other primary headaches, new daily persistent headache is more common in females, with the female-to-male ratio in adults at 2.5:1 and in children and adolescents at 1.8:1 (53).

Several studies have been conducted to determine the risk factors of chronic daily headache. Comorbid psychiatric conditions, especially depression and medication overuse, have been consistently reported to be associated with chronic daily headache. These factors are also independent predictors of persistence of chronic daily headache in adolescence (110). Overconsumption of abortive treatments may interfere with the endogenous pain control system and lead to chronic daily headache. A longitudinal population-based study showed that nausea, daily use of acute headache medications, and coexistent tension-type headache and migraine were significant predictors of chronic headache (04). A population-based study showed that individuals using barbiturate-containing compounds (OR 2.06, 95% CI 1.3 to 3.1) and opiates (OR 1.98, 95% CI 1.4 to 2.2) were at the greatest risk of chronic daily headache (09). Lower socioeconomic status has been reported to be a risk factor for chronic daily headache whereas age, gender, and race were not found to be risk factors (90). Health status scores were significantly lower among people with chronic headache in all socioeconomic statuses (112). Obesity is also an independent risk factor for incident chronic daily headache. Chronic daily headache prevalence was higher in obese (OR 1.3, 95% CI 1.1 to 1.6) and morbidly obese (6.8% OR 1.8, 95% CI 1.4 to 2.2) individuals (08). Fibromyalgia is present in 35% of chronic migraine patients and is associated with depression and insomnia (75). Hypertension prevalence is also higher in patients with chronic daily headache compared to those with migraine and episodic tension-type headache. However, its causal effect as a predictor of headache chronification is still unclear (35).

Chronic daily headache has strong impact on quality of life. A population-based study showed a significant decrease in each health-related concept of the short form-36 (SF-36) as compared with healthy subjects. The highest decreases were seen for physical role, bodily pain, vitality, and social functioning (40). Among chronic daily headache patients, the quality of life was lower in those with migraine features (05). Several studies consistently reported that patients with chronic daily headache had significantly higher disability, economic burden, impairment of quality of life, and poorer treatment outcome compared to those with episodic headache (24).

Other primary headaches. According to ICHD-III, other primary headaches consist of primary stabbing headache, primary cough headache, primary exercise headache (previously called primary exertional headache), primary headache associated with sexual activity, hypnic headache, primary thunderclap headache, and new daily persistent headache. Among these groups, primary stabbing headache is the most prevalent. Its prevalence in the population and in headache clinics was 2% to 35.2% and 13% respectively. The prevalence was higher in women, with a female-to-male ratio between 1.5 and 2.3 (94; 33; 108). The mean age of onset was around 28 years in the community-based study (94) and 48 years old in the clinic-based study (33). This condition was observed more often in patients with migraine.

The second most prevalent headache in this group is primary exercise headache. The reported prevalence in the population was 12.3% in adults (94) and 30.4% in adolescents (22). Its prevalence tends to decline with increasing age. Because primary exercise headache typically has time-limited course, it may be challenging to identify lifetime prevalence retrospectively due to recall issues (86). Gender predominance remains inconclusive, with some studies supporting higher prevalence in women, whereas others suggest otherwise. (86). Coexistence of primary exercise headache and migraine was observed in 46% of the patients (93).

Primary cough headache and primary headache associated with sexual activity have comparable prevalence of around 1% (32; 74; 21). Both conditions are male predominant. Primary headache associated with sexual activity was three to four times more common in men. The mean age of onset was between the 30th and 40th years of life. Orgasmic headache was more common than preorgasmic subtype.