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Comorbidity of headache and gastrointestinal complaints. The Head-HUNT Study
AH Aamodt, LJ Stovner, K Hagen & J-A Zwart
Norwegian National Headache Centre, Trondheim University Hospital, Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology, Norway

Aamodt AH, Stovner LJ, Hagen K & Zwart J-A. Comorbidity of headache and gastrointestinal complaints. The Head-HUNT Study. Cephalalgia 2008; 28:144– 151. London. ISSN 0333-1024 Associations between headache, including migraine, and gastrointestinal (GI) symptoms were studied in a large questionnaire-based cross-sectional study (the Head-HUNT Study). The headache questionnaire was completed by 43 782 individuals, who answered all the questions concerning nausea, reflux symptoms, diarrhoea and constipation. In the multivariate analyses, adjusting for age, sex, educational level, medication use, depression and anxiety, a higher prevalence of headache was found in individuals with much reflux [odds ratio (OR) 2.4, 95% confidence interval (CI) 2.2, 2.6], diarrhoea (OR 2.4, 95% CI 2.1, 2.8), constipation (OR 2.1, 95% CI 1.9, 2.4) and nausea (OR 3.2, 95% CI 2.6, 3.8) compared with those without such complaints. All the GI symptoms investigated seemed to be approximately as common among persons with non-migrainous headache as among migraine sufferers, but the association between headache and GI complaints increased markedly with increasing headache frequency. This may suggest that headache sufferers generally are predisposed to GI complaints. ᮀ Migraine, headache, gastrointestinal complaints, epidemiology, HUNT Anne Hege Aamodt, MD, Norwegian National Headache Centre, Trondheim University Hospital, Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology, N-7006 Trondheim, Norway. Tel. + 47 7257 6006, fax + 47 7257 5773, e-mail anne.hege.aamodt@ntnu.no Received 20 October 2006, accepted 12 July 2007

Both headaches and gastrointestinal (GI) symptoms such as nausea, acid regurgitation, diarrhoea and constipation are common in the general population and account for substantial healthcare utilization. However, the scientific literature about the comorbidity of headache and GI complaints is scant (1). Population-based studies have shown positive associations between migraine and irritable bowel syndrome (IBS) (2), colitis and peptic ulcer (3). However, in one study migraine has been associated with peptic ulcer only among smokers (4). Although a pathogenic role for Helicobacter pylori (Hp) infection in migraine has been suggested (5), most studies have not demonstrated any association between Hp infection and migraine (6, 7).

Coeliac disease has also been linked with migraine (8), but it remains to be confirmed by larger epidemiological studies. Clinic-based studies have demonstrated a higher prevalence of gastro-oesophageal reflux (9) and idiopathic dyspepsia (10) among migraineurs. However, in a recent clinic-based study on patients with dyspepsia referred for upper GI endoscopy, migraine prevalence was lower among patients with reflux-like/ulcer-like dyspepsia and higher only among those with dysmotility-like dyspepsia or nausea/vomiting (11). Furthermore, upper endoscopy and oesophageal pH monitoring in migraineurs have shown a low prevalence of abnormal findings (11, 12). As regards a possible association between nonmigrainous headache and GI symptoms, hardly any
© Blackwell Publishing Ltd Cephalalgia, 2007, 28, 144–151

Gastrointestinal complaints Q1 included questions about different GI symptoms such as: ‘have you suffered from nausea during the last 12 months?’. prognosis and choice of therapy (3).Comorbidity of headache and GI symptoms reports are available. (iii) during headache. 2007. 7–14 days/month and >14 days/month. were administered to the participants. Potential confounders such as gender. they were classified into two groups of either migraine or non-migrainous headache. cardiovascular medication. The Q1 included questions about GI complaints and the Q2 included 13 questions about headache (13). anxiety. 45 453 (88. or (b) photophobia and/or phonophobia. The target population. 145 Methods Study population All inhabitants aged Ն20 years in Nord-Trøndelag County in Norway were invited to participate in the Nord-Trøndelag Health Study between 1995 and 1997 (‘Helseundersøkelsen i Nord-Trøndelag’ = HUNT). © Blackwell Publishing Ltd Cephalalgia. (b) unilateral location. duration of education (Յ9 years. (ii) headache with at least one of the following three characteristics: (a) pulsating quality. and the subjects were asked to rate the intensity of these symptoms as ‘no’. has been described in detail previously (13). and the second (Q2) was filled in after a medical examination. vitamins. Heartburn and acid regurgitation are the cardinal symptoms of gastro-oesophageal reflux disease (16). diarrhoea and constipation. fish oil or other medicines) and how many months they had used it. cross-sectional health study. or (c) aggravation by physical activity. antasthmatics. Further knowledge about associations between headaches and GI complaints is important. 144–151 . The first questionnaire (Q1) was enclosed with the invitation letter. The aim of the present study was to investigate possible associations between GI complaints and headache in a large-scale. These questions were mainly designed to determine whether the person suffered from headache or not. The interaction coefficients were tested using Wald test statistics. ‘some’ or ‘much’. antidepressants. Medication use was based on questions in Q2: ‘Have you taken any medication daily or almost daily during the last 12 months?’ Those who answered ‘yes’ were asked about type of medication (analgesics. 64 560 (70%) participated. including participants and non-participants. sleep medications. Two questionnaires. Of these 51 383 individuals. at least one of the following symptoms: (a) nausea. Based on data from the subsequent 12 headache questions.5%) completed at least one question about GI complaints and 43 782 (85. iron supplement. The diagnoses were mutually exclusive. population-based. depression. Based on a question about headache frequency during the last year. and medication use were adjusted for. to determine frequency of headache and to diagnose migraine according to a modified version of the migraine criteria of the Headache Classification Committee of the International Headache Society (1988) (14). The HUNT study was approved by the Regional Committee for Medical Research Ethics and by the Norwegian Data Inspectorate. tranquillizer. of the 92 566 eligible individuals. headache frequency was divided in three categories: <7 days/month. 28. Persons were classified as migraineurs if they reported having migraine or fulfilled the following three criteria: (i) headache attacks lasting 4–72 h (<4 h was accepted for those who reported visual disturbances often before headache). Statistical analysis The association between headache and GI complaints was estimated using multiple logistic regression with odds ratio (OR) and 95% confidence intervals (CI). including >200 health-related questions. 10–12 years and Ն12 years). Briefly. Headaches that did not fulfil the criteria for migraine were classified as non-migrainous headache. age (10-year categories). The same kind of question was also asked about heartburn/acid regurgitation (reflux symptoms). Anxiety and depression were assessed by The Hospital Anxiety and Depression Scale (HADS) Headache diagnoses Subjects who answered ‘yes’ to the question ‘Have you suffered from headache during the last 12 months? ‘were classified as headache sufferers (13). as comorbidity may alter the clinical course of the disorder and the chance of correct diagnosis by affecting the time of detection. The classification of the subjects has been described in detail previously and has been validated by interview diagnoses (15).2%) completed all the questions about GI complaints. A total of 51 383 subjects completed the headache questionnaire Q2 and constituted the ‘head-HUNT’ study.

7% and 18.6%). much reflux 2.2 Headache-free (n = 31 541) 46.9% and 8.2 35.2 (15.9). 70 One-year headache prevalence (%) 60 50 40 30 20 10 0 20-29 30-39 40-49 50-59 60-69 ≥70 Age groups much reflux some reflux no reflux Figure 1 One-year prevalence of headache (%) related to age in those with no. There were more women than men in the headache groups compared with headache-free individuals.2 Migraine (n = 6209) 71. whereas reflux and diarrhoea were more equally distributed among men and women (reflux.146 AH Aamodt et al. OR for non-migrainous headache among men with some reflux 1.4.5 (1. and diarrhoea 16. 2007.5) 11. evaluating the probability of a linear relationship between headache frequency and reflux symptoms. the results in the multivariate analyses are shown for men and women together as there were no major gender differences. diarrhoea. Chicago. e.6%. and much reflux symptoms. 33. respectively. there were linear trends (P < 0. Other variables such as alcohol consumption.0 47. USA). 144–151 .8 52. There were also slight differences in the educational level between the groups. 2. 1. 2. female (%) Mean age (SD) Years of education (%) Ն13 10–12 Յ9 (17–19).8 41.6.0 (1. The ORs for the association between levels of headache frequency and different GI symptoms were performed for each headache diagnosis (migraine and non-migrainous headache) separately where headache-free individuals were used as the reference group. reflux was the most common in both genders. educational level. As shown in Fig.9 44. The corresponding ORs for women were 1. some.9% and 17. There was significant interaction by gender regarding non-migrainous headache for all GI complaints. the GI complaints were treated as single ordinal variables (categories 1.2) 11.6) and 1. respectively.0 (13.05. smoking and body mass index (BMI) were also evaluated as potential confounders. headache frequency categories were incorporated in a test for trend.5 Characteristics Sex.0 (SPSS Inc. IL. version 13. ‘much’) and were incorporated in a test for trend (approximately a c2 statistic with one degree of freedom) in the logistic analyses to evaluate the probability of a linear relationship between degree of GI complaints and headache (‘dose–response relation’). age.2 46. When appropriate.0%) than in men (respectively.8.g. constipation and nausea. and this was most pronounced for those with migraine. The mean age was higher in the group of headache-free individuals compared with the groups with migraine or non-migrainous headache. However.5. Differences between means were tested with one-way ANOVA and between categories with c2 test. 1. and 3. anxiety and depression.0001) of increasing prevalence of headache (both migraine and non-migrainous headache) with © Blackwell Publishing Ltd Cephalalgia. Among the GI symptoms. After adjusting for gender. ‘no’.3).8). age and educational level in the different diagnostic groups Non-migrainous headache (n = 13 633) 62. Table 1 Distribution of sex. ‘some’.7 (95% CI 1. 28. Results Table 1 presents the demographic data for the different headache groups.3% and 29.2%)..3 44. higher headache prevalence was found in all age groups among those with much reflux symptoms compared with those with some or no such complaints (unadjusted analyses). 1.7 (17. Likewise. with higher ORs for non-migrainous headache in men than women. 13. Constipation and nausea were more prevalent in women (respectively. Data analysis was performed with the Statistical Package for the Social Sciences.4 53. 1. medication use. The trend test was considered statistically significant at P < 0.8) 13.7 (1.5 42. 30.

5 (1.3. 1.7 (95% CI 5.0001) of higher prevalence ORs for all the GI complaints with increasing headache frequency (Table 3).8) among individuals with ‘much’ nausea compared with those without nausea (Table 2).4 (1.8.5 (1. 3. 2. 2007.0.2 (2.Comorbidity of headache and GI symptoms Table 2 Prevalence odds ratio (OR) of headache (dependent variable) among different groups with gastrointestinal complaints. 1.6. 144–151 Discussion In this large-scale. 1.3. 1. diarrhoea and constipation was increased more than two times for those with headache >14 days/ month compared with those without headache. diarrhoea. 3. 1.5 (95% CI 2. 1.5 (1.2 (1. cross-sectional study we found higher prevalence of headache in individuals with much reflux symptoms.0) 1.5) 1.8 (1. OR* (95% CI) Migraine (n = 6209) No. education.4 (1. The associations between headache and GI symptoms were reduced after adjustment for potential confounding by medication use.5. 2. other GI symptoms have not been validated and no further GI investigations were performed. However. For example. 1. 2. The OR for each of the symptoms reflux.9) 1.4. one would expect that functional GI disorders.6.9 (1.0) 1. 2.7.2 (1.1.5) for migraine and 4.0001 for all the variables.3.0 1. The corresponding OR was 2. (1. 1.3 (1.4) 1. © Blackwell Publishing Ltd Cephalalgia.7) for non-migrainous headache compared with those without headache.6) 1. increasing intensity of GI symptoms. 95% CI 2. 1.6) 1.2 (3. 1.6.8) 1.8) 1.0 3.6) 1.5) 1.7) 1.5.8) 1. population-based.6) *Odds ratio adjusted for sex.0 (1.8 (1. 3.8) 2. age and education. However.7 (1. 1. anxiety or depression.6) 2. This was most clearly demonstrated for nausea. there are several limitations to the study.4.1.0 1. 3.4) 1.1.4) 1.2.8) 3566 1763 441 439 4213 1175 191 630 3928 1368 351 630 4014 1431 153 611 1. 2. 2. 2. 2.6 (1. OR* (95% CI) 147 Variables Total number Non-migrainous headache (n = 13 633) No.3 (1. 2.8 (1.1. age.0 1.4 (2. Not all individuals answered all questions All headache types (n = 19 842) No.4.7) 1.6. OR* (95% CI) Reflux symptoms No 32 312 Some 12 215 Much 2 519 Missing 4 337 Diarrhoea No 37 692 Some 6 839 Much 922 Missing 5 930 Constipation No 35 729 Some 8 618 Much 1 936 Missing 5 930 Nausea No 39 312 Some 5 579 Much 587 Missing 5 905 11 201 5 630 1 356 1 655 13 397 3 593 563 2 289 12 587 4 139 1 074 2 289 13 476 3 717 405 2 244 1.0 1.5-1. so the reported complaints may have represented different disorders. 1.4 (2. 1.4 (2.0 2.6.0 1.1 (1.0.8) after adjusting for all the covariates. there were strong linear trends (P < 0.8 (95% CI 4.6 (1. 1. First.4) 3.6 (1.6 (1. In addition. being very prevalent in . 1.4. 1. 1. 1.4 (1. The strengths of the study were the large and unselected population and the use of validated headache diagnoses.8) 1. 3.7. 1.7) 1.4) after adjustment for only sex. depression. 22).4 (1.0 (95% CI 2.8 (1.0) 1.7 (1.8) 1.5) 1.6.0 1.0) 1.9. P-trend value <0. 28.0 1. 1.0 1. There were no major differences between migraine and non-migrainous headache regarding the association with GI complaints.2.1) 1.2. 1.5 (1.4.8 (1. anxiety and use of medication calculated in multiple logistic regression.3.5) 7635 3867 915 1216 9184 2418 372 1659 8659 2771 723 1659 9462 2286 252 1633 1.4 (1.6) 1.6) 1. the OR for all headache types in much diarrhoea was 3.6) 1.1) after adjustment for medication use in addition and 2. constipation or nausea than in those without such complaints. 2.7 (95% CI 2.2) 1. 2. The association between headache and GI complaints increased markedly with increasing headache frequency. 1.7.6. headache being more than three times more likely (OR 3.7) 2.0 1. For nausea the corresponding OR values were 6.9) 2.8 (1. The question on acid regurgitation/heartburn (reflux) has also been validated (20) and the use of questionnaires to assess these symptoms is well validated as a reliable measurement of the true occurrence of reflux (21.7 (1.8 (1. 1.

3) 2. 2. The fact that headache and GI complaints were among many other objectives of HUNT makes selective participation due to headache or GI complaints unlikely.6) Constipation (n = 46 283) No. 2. making the two groups more similar than they really were.2 (2. 28.1. 5711 3560 873 410 1094 380 131 2466 493 279 OR* (95% CI) 1. 3. 2.2 (3.7) Headache-free 32 965 All headache types <7 days/month 14 500 7–14 days/month 2 729 >14 days/month 1 189 Migraine <7 days/month 4 361 7–14 days/month 1 125 >14 days/month 350 Non-migrainous headache <7 days/month 10 139 7–14 days/month 1 604 >14 days/month 839 *Odds ratio adjusted for sex.6) 5.8. 3.5) 2. fibromyalgia and chronic fatigue syndrome (29–32). This is not surprising.0.) 1. 2. The bias caused by misclassification can either exaggerate or underestimate the true differences between headache groups. The GI symptoms investigated in this study seem to be approximately as common among persons with non-migrainous headache as among migraine sufferers.8) 2.2 (1. which was more prevalent among migraineurs (Table 3).0 (1. 2.7) 1. Our results seem to be in accordance with previous population-based and clinic-based studies concerning comorbidity of migraine and GI conditions (2. 2. 9.1.7) 2.4 (1. 3806 2973 669 313 921 280 106 2052 389 207 OR* (95% CI) 1.7) 4.0.8) 2.5. 2. 1.5. the questionnaire-based headache diagnoses were not optimal compared with the interview diagnoses (15). depression.6.4) 2.7. 2.8.5) 1.8. Furthermore.0.8 (1.9.1 (1.0) 3.9.2.) 2. 3.3) 1. In addition. 6.9) 2. The impact of nonparticipants has been discussed in more detail previously (13).7 (1. 2.2 (4. 3.8.1) 1. 2. 2007. 4.9 (3. P-trend value < (1.7 (1. age.6) 2.5. 1. 144–151 .8. 2. anxiety and use of medication calculated in multiple logistic regression. 1. headache frequency seems to have had a greater impact on the association with GI complaints than the headache diagnoses. the general population. 5. which has previously been linked to both headache and GI © Blackwell Publishing Ltd Cephalalgia. 11). 2.8. 35).8 (1.7) 2. 2.4 (3. education.9. Since the study is cross-sectional it cannot be determined whether frequent headache causes GI complaints or whether other risk factors or a shared susceptibility causes this association.6 (1. 8215 4886 1116 517 1450 469 165 3436 647 352 OR* (95% CI) 1.5. which may suggest that headache sufferers generally are predisposed to other pain syndromes and somatic complaints (33).6) 2.2 (1.2 (2. 4.7 (5.1 (1.7 (2. Table 3 Prevalence odds ratio (OR) of different gastrointestinal complaints (dependent variables) related to headache frequency and compared with headache-free subjects Reflux symptoms (n = 47 046) Variables Total No. 8. 36).5) 2. 1. as nausea is among the diagnostic criteria for migraine.4) 2.6 (4. An exception was nausea.0 (ref. Information bias should be considered as an explanation for the findings in the present study.4) Nausea (n = 45 478) No. the prevalence of migraine in the current population is consistent with data from other population-based studies in Western countries (23).3) 2.0 (ref. 2.7.8) 4.0.8) 2.0 (ref.2 (1.148 AH Aamodt et al. 9–11).3 (2.) 1. 1. 1.2.5. In studies on self-reported complaints the results may be influenced by a tendency to report different symptoms in some individuals (34.9.0 (ref. 2. In the present study. 1. 3.4) 2.3) 1.3 (2.5) 4.0.8) 2.5) 2. The gastrointestinal symptoms were considered to be present if there were some or many of the symptoms.7.6 (2.7 (2.7 (1. Furthermore. the findings in the present study were in line with other studies using different methods (2. Autonomic nervous system (ANS) dysfunction.3 (2. 2. headache has been reported as a significantly more frequent symptom in various unexplained clinical conditions such as IBS. are responsible for the described GI symptoms among the majority.0. 2. the prevalence of GI symptoms in the current population is comparable to that found in other studies (24–28).6.9.) 1.1 (1.0 (1. 2. due to diagnostic inaccuracy. This may create strong associations that are explained by personality traits rather than by biological mechanisms (34.4) Diarrhoea (n = 45 453) No. However.3 (2.0) 2.4 (1.5) 1.9) 2. 3. 5. 2262 2719 795 390 1013 375 144 1706 420 246 OR* (95% CI) 1. there were migraine patients in the group of non-migraineurs and vice versa. Most likely.4 (2. 1.8 (4.0.6) 3.0001 for all the variables. Furthermore.6.8 (1.0.6 (1. Those who report their headache complaints might be more likely to report other complaints such as GI symptoms.3) 6.

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