Pain Medicine 2015; 16: 1426–1432 Wiley Periodicals, Inc.
HEADACHE & FACIAL PAIN SECTION Original Research Article Menstrual-Cycle and Menstruation Disorders in Episodic vs Chronic Migraine: An Exploratory Study
*Division of Craniofacial Pain, Headache, and Sleep, Department of Oral Pathology, Oral Medicine, and Craniofacial Pain, Tufts University School of Dental Medicine; †Headache & Face Pain Program, Department of Neurology, Tufts Medical Center, Boston, Massachusetts, USA Reprint requests to: Egilius L.H. Spierings, MD, PhD, Craniofacial Pain Center, One Kneeland Street, Boston, MA 02111, USA. Tel: 617-636-6817; Fax: 617-636-3831; E-mail: [email protected].
cycle, and the menstruation disorders, dysmenorrhea and menorrhagia, in episodic vs chronic migraine. Results. The prevalence of menstrual-cycle disorders in general (41.2 vs 22.2%) and dysmenorrhea (51.0 vs 28.9%) was statistically significantly higher in the women with chronic migraine than in those with episodic migraine (P £ 0.05)(not corrected for multiple comparisons). Whether the migraine was menstruation sensitive, that is, the headaches consistently occurred or worsened with menstruation, did not impact the prevalence of menstrual disorders.
Disclosure: The study was conducted without external funding and neither author has conflicts of interest to report.
Conclusion. We conclude that chronic migraine is possibly more often than episodic migraine associated with menstrual-cycle disorders in general and dysmenorrhea, without impact on menstruation sensitivity of the headaches.
Abstract
Key Words. Migraine; Episodic Migraine; Chronic Migraine; Menstruation-Sensitive Migraine; Menstruation; Menstrual Disorders; Oligomenorrhea; Polymenorrhea; Irregular Cycle; Dysmenorrhea; Menorrhagia; Hypothyroidism
Objective. Migraine is a chronic condition of recurring moderate-to-severe headaches that affects an estimated 6% of men and 18% of women. The highest prevalence is in those 18–49 years of age, generally when women menstruate. It is divided into episodic and chronic migraine depending on the total number of headache days per month being 14 or less or 15 or more, respectively. Migraine has been associated with menorrhagia, dysmenorrhea, and endometriosis, the latter particularly in chronic migraine. Methods. We conducted a questionnaire survey of 96 women with migraine, 18–45 years old, to determine the occurrence of the menstrual-cycle disorders, oligomenorrhea, polymenorrhea, and irregular 1426
Introduction Migraine is a condition of recurring headaches, with the headaches sometimes preceded by transient focal neurological symptoms, also known as aura symptoms. The headaches are generally moderate or severe in intensity, unilateral in location, throbbing in quality, worsened by routine physical activity, and associated with nausea, vomiting, photophobia, and/or phonophobia. It is a common condition that, in the United States, affects an estimated 6% of men and 18% of women, with the highest prevalence in the age range of 18–49 years, generally when women menstruate [1]. It is divided into episodic and chronic migraine depending on the total number of headache days per month, which is 14 days
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Egilius L.H. Spierings, MD, PhD,*,† and Aliya Padamsee, BA*
Menstrual Disorders in Migraine or less in episodic migraine and 15 days or more in chronic migraine [2]. Chronic migraine accounts for approximately 8% of the migraine burden and its prevalence in the general population has been mostly reported in the range of 1.4–2.2% [3].
Hypothyroidism, in turn, has been associated with menstrual disorders, in particular menorrhagia [8]. In a study of 171 hypothyroid patients and 214 age- and bodymass-index-matched controls, menstrual disorders occurred in 23.4% of the hypothyroid patients and in 8.4% of the controls (P < 0.001). Oligomenorrhea was common in both groups (42.5% and 67%, respectively), while menorrhagia was almost three times more common in the hypothyroid group (30 vs 11%). Treatment of the hypothyroid patients with levothyroxine brought the rate of menstrual disorders in that group down to 9.3%, which is similar to that observed in the control group (8.4%). We have had a long-standing interest in the role of hypothyroidism in headache, including migraine [9]. Hence, we conducted this study based on the relatively strong, above-mentioned association of chronic migraine, in comparison to episodic migraine, with hypothyroidism and, in turn, the association of hypothyroidism with menstrual disorders. In the study, we further explored the association of chronic migraine, in comparison to episodic migraine, with the menstrual-cycle disorders, oligomenorrhea, polymenorrhea, and irregular cycle, and the menstruation disorders, dysmenorrhea and menorrhagia. We also looked at menstruationsensitive in comparison to non-menstruation-sensitive migraine and the association with menstrual disorders. Menstruation-sensitivity was defined as headaches consistently occurring (episodic migraine) or consistently worsening (chronic migraine) with menstruation. The menstruation-sensitivity issue was looked at because a study of 168 women with menstrual or menstruallyrelated migraine, in comparison to 121 women with migraine unrelated to the menstrual cycle, showed the former group to be statistically significantly more often anemic due to iron deficiency (38.5 vs 22.9%; P 5 0.008), possibly indicating a higher prevalence of menstrual disorders associated with increased blood loss, that is, polymenorrhea and menorrhagia (hypermenorhea) [10].
Patients The study was based on a convenience sample of 173 female patients with migraine aged 18–45 years old, inclusive, from the private practice of the first author, a neurologist with fellowship training in headache management. He had previously evaluated the patients in his practice and diagnosed them with episodic or chronic migraine, according to the criteria as published by the International Headache Society [2]. The patients were contacted by mail and sent a 42-point questionnaire; review-board approval was not obtained for this noninterventional, private-practice survey. Of the questionnaires, 31 (18%) were undeliverable due to change of address and inability to contact the addressees by telephone and/or e-mail. Of the 142 questionnaires that were delivered, 96 were returned to us completed, generating a response rate of 68%. Questionnaire The questionnaire was specifically developed for the study because validated questionnaires to collect the information required for the study were not available. It was not validated because of the exploratory nature of the study and, therefore, its psychometric properties are unknown. The questionnaire consisted of two major sections: headache-related and menstruation-related questions. To confirm that the women did, in fact, still have migraine and to differentiate between episodic and chronic migraine, they were queried about the onset, current intensity, frequency, and duration, as well as about the following headache features and associated symptoms: nausea, vomiting, photophobia, phonophobia, laterality, throbbing, and worsening by routine physical activity. Those with episodic migraine were also queried about headaches consistently occurring with menstruation, while those with chronic migraine were queried about headaches consistently worsening with menstruation. The menstruation-related questions retrieved both quantitative and qualitative responses, where necessary, to obtain numerical data and to gauge how the woman perceived any menstrual abnormality. Quantitative questions included age of menarche, duration of periods, intervals between periods, number of pads/tampons required on worst day(s), and the number of days for which the indicated intensity of flow and level of abdominal pain persist. Qualitative questions addressed the woman’s perception of the length of the periods (normal, short, or long), the length of the interval between the periods (normal, short, or long), and their regularity. The intensity of flow and of abdominal pain was indicated as mild, moderate, or severe. It was also inquired whether the migraine began at menarche or following the use of hormonal birth control or pregnancy/nursing [11]. Lastly, the women were requested to indicate previous diagnoses of polycystic ovary syndrome (PCOS), endometriosis, infertility, hyperthyroidism, and hypothyroidism. 1427
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Migraine has been associated with menorrhagia, dysmenorrhea, and endometriosis, the latter particularly in chronic migraine [4,5]. Chronic migraine, in comparison to episodic migraine, has been associated with asthma (odds ratio: 2.4; P 5 0.03), allergies (odds ratio: 3.5; P 5 0.0001), hypertension (odds ratio: 6.9; P < 0.0001), and hypothyroidism (odds ratio: 8.4; P 5 0.0004) [6]. In another study, in terms of comorbidities, psychiatric disorders, insomnia, gastrointestinal disorders, musculoskeletal disorders, hypertension, and genitourinary disorders were significantly more common in 150 patients with chronic migraine than in 100 patients with episodic migraine [7].
Materials and Methods
Spierings and Padamsee Data Processing/Analysis Upon receipt of the questionnaires, menstrual abnormalities were divided into menstrual-cycle and menstruation disorders, using the following criteria: oligomenorrhea defined as intervals 35 days, polymenorrhea defined as intervals 24 days, irregular cycle defined as inconsistent intervals between the periods, dysmenorrhea defined as abdominal pain with menstruation indicated as severe, and menorrhagia (hypermenorrhea) defined as requiring five or more fully soaked pads/tampons per day on the heaviest day(s) of the periods.
Results Patients The average age of the respondents was 34.0 6 8.0 (S.D.) years; their body mass index (BMI) was 27.5 6 8.3 kg/m2. They reported the average age of onset of their migraine to be 17.6 6 7.6 years, which translates into an average migraine suffering of 16.4 6 9.4 years. Forty-five women (46.9%) reported the onset of the migraine to have occurred within 1 year of menarche, with menarche occurring at an average age of 12.5 6 1.6 years. Ten of the women (10.4%) related the onset of their migraine to the use of hormonal birth control and 9 (9.4%) following pregnancy/nursing. Of the women, 45 (46.9%) had episodic migraine and 51 (53.1%) chronic migraine at the time of questionnaire completion. Headaches The current intensity of the headaches was described as moderate by 49.0% of the women and as severe by 51.0%. The headaches were reportedly associated with nausea in 85.4% of the women and with vomiting in 21.9%. They were described as unilateral in 43.8%, throbbing in 89.6%, and aggravated by routine physical activity in 67.7%. Eighty of the women (83.3%) described the headaches as consistently occurring with menstruation (episodic migraine) or consistently worsening with menstruation (chronic migraine). In 63.8% of the 80 women, this occurred before menstruation with an average of 2.8 6 1.4 days, in 31.2% during menstruation, and in 5% after menstruation. Menstruation Disorders Of the 96 women, 35 (36.5%) used hormonal birth R , MirenaV R IUD, control (oral contraceptive, NuvaRingV R ), 17 (17.7%) for contraceptive purDepo-ProveraV poses, 16 (16.7%) for the relief of menstrual symp1428
Menstrual-Cycle Disorders Of the women, 16 (16.7%) reported the intervals between their periods to vary and, therefore, had irregular cycle. Of the remainder, 11 (11.5%) considered the interval between their periods to be short and 14 (14.6%) long. We diagnosed 7 (7.3%) of the women as having polymenorrhea and 8 (8.3%) with oligomenorrhea. Hence, 31 (32.3%) of the 96 women had a menstrual-cycle disorder and 11 (11.5%) a menstruation disorder. The menstrual disorders were reported by 19 (61.3%) of the 31 women to have started at menarche (primary) and by 11 (35.5%) after pregnancy/nursing (secondary). Miscellaneous Four (4.2%) of the 96 women had been diagnosed with PCOS, 5 (5.2%) with infertility, and 9 (9.4%) with endometriosis; additionally, 1 (1.0%) was diagnosed with hyperthyroidism and 11 (11.5%) with hypothyroidism. Episodic vs Chronic Migraine On the basis of headaches occurring 14 days or less per month or 15 days or more, we divided the women into those with episodic and those with chronic migraine. Comparing the two groups of women, we diagnosed the women with chronic migraine statistically significantly more often with menstrual-cycle disorders in general (41.2 vs 22.2%; P 5 0.05) and found them to have dysmenorrhea statistically significantly more often (51.0 vs 28.9%; P 5 0.04) (Table 1). As 26 tests were performed for Table 1, any kind of Bonferroni adjustment would have left both differences nonsignificant. Menstruation-Sensitive vs Non-Menstruation-Sensitive Migraine On the basis of headaches consistently occurring (episodic migraine) or worsening with menstruation (chronic migraine), we divided the women into those with menstruation-sensitive and those with nonmenstruation-sensitive migraine and found the prevalence of menstrual-cycle and menstruation disorders not statistically significantly different between the two groups (Table 2).
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SPSS software was used for data entry and analysis and in the analysis, a P value of 0.05 was considered indicating a statistically significant difference. The statistical tests used were the two-tailed Student t-test, which assumes a normal distribution, and the two-tailed Fisher exact test, which does not rely on approximation to a chi-squared distribution.
toms, and 5 (5.2%) for migraine relief. Disregarding the use of hormonal birth control, 12 (12.5%) of the 96 women reported their periods to be short and 31 (32.3%) long, not otherwise defined. The flow was described by 26 (27.1%) as moderate and by 42 (43.8%) as severe, requiring 5.6 6 2.4 pads/tampons per day on the heaviest day(s). The periods were described as moderately painful by 24 women (25.0%) and as severely painful by 39 (40.6%); the intensity of the pain was experienced for an average of 2.5 6 2.0 days. On the basis of these results, we diagnosed 56 (58.3%) of the women as having menorrhagia and 39 (40.6%) with dysmenorrhea.
Menstrual Disorders in Migraine
Table 1
Episodic migraine vs chronic migraine Chronic Migraine (N 5 51)
P Value
33.6 6 8.1 26.7 6 7.7 12.4 6 1.4 16.4 6 7.3
34.4 6 8.8 28.1 6 8.7 12.5 6 1.8 18.7 6 7.7
0.69 0.49 0.99 0.20
22 (48.9%) 23 (51.1%)
25 (49.0%) 26 (51.0%)
1.00 1.00
38 (84.4%) 6 (13.3%)
44 (86.3%) 15 (29.4%)
1.00 0.08
22 (48.9%) 42 (93.3%) 31 (68.9%)
20 (39.2%) 44 (86.3%) 34 (66.7%)
0.41 0.33 0.83
23 (51.1%) 2 (4.4%) 4 (8.9%)
22 (43.1%) 8 (15.7%) 5 (9.8%)
0.54 0.09 1.00
16 (35.6%)
28 (54.9%)
0.07
32 (71.1%)
37 (72.5%)
1.00
29 (64.4%)
35 (68.6%)
0.67
8 (17.8%) 10 (22.2%)
17 (33.3%) 21 (41.2%)
0.10 0.05
13 (28.9%) 23 (51.1%)
26 (51.0%) 33 (64.7%)
0.04 0.22
1 2 2 1 5
Discussion Limitations The limiting factors of this study are its retrospective nature, its sample size, the non-validated nature of the questionnaire used, its response rate, and, possibly, a report bias. Our sample size consisted of 173 women with migraine of child-bearing potential but on account of undeliverable mailing addresses, the sample size was reduced to 142 women, of whom 96 responded (68% response rate). While the episodic and chronic migraine subgroups were comparable in size (45 and 51, respectively), the menstruation-sensitive and non-
(2.2%) (4.4%) (4.4%) (2.2%) (11.1%)
3 7 3 0 6
(5.9%) (13.7%) (5.9%) (0%) (11.8%)
0.62 0.17 1.00 0.47 1.00
menstruation-sensitive migraine groups were very unequal in size (80 and 16, respectively). The numbers indicate 83.3% of our population of female migraineurs to have menstruation-sensitive migraine while a review of the literature suggests 40–70% of women to report an association between migraine and menstruation [12]. Report bias likely influenced this outcome as those with menstrually-related migraine were probably more inclined to respond to the survey and complete the questionnaire. However, it should also be noted that our definition was broader than that generally applied, including consistent worsening of headaches with menstruation in the women with chronic migraine as well. 1429
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General Age Body mass index Age of menarche Age at migraine onset Migraine-headache intensity Moderate Severe Migraine-associated symptoms Nausea Vomiting Migraine-headache features Unilateral Throbbing Worsened by routine activity Migraine onset Within 1 year of menarche Related to use of hormonal birth control Following pregnancy Perception of period duration Short/long Perception of period flow Moderate/severe Perception of period pain Moderate/severe Perception of period intervals Short/long Menstrual-cycle disorder (oligomenorrhea, poly-menorrhea, irregular cycle) Menstruation disorder Dysmenorrhea Menorrhagia Miscellaneous diagnoses Polycystic Ovary Syndrome Endometriosis Infertility Hyperthyroidism Hypothyroidism
Episodic Migraine (N 5 45)
Spierings and Padamsee
Table 2
Menstruation-sensitive vs non-menstruation-sensitive migraine Non-Menstruation-Sensitive Migraine (N 5 16)
P Value
34.4 6 7.9 27.5 6 8.9 12.5 6 1.6 17.5 6 8.0
32.1 6 8.8 27.0 6 4.0 12.3 6 1.9 18.3 6 5.6
0.35 0.72 0.70 0.65
36 (45.0%) 44 (55.0%) 10.1 6 6.3 1.6 6 1.3
7.9 6 3.9 1.4 6 1.0
0.79 0.79 0.16 0.58
38 (47.5%) 42 (52.5%)
8 (50.0%) 8 (50.0%)
1.00 1.00
71 (88.8%) 19 (23.8%)
11 (68.8%) 2 (12.5%)
0.05 0.51
37 (46.3%) 73 (91.3%) 57 (71.3%)
5 (31.3%) 13 (81.3%) 8 (50.0%)
0.41 0.36 0.14
39 (48.8%) 9 (11.3%) 7 (8.8%)
5 (31.3%) 1 (6.3%) 2 (12.5%)
0.27 1.00 0.64
39 (48.8%)
5 (31.3%)
0.27
60 (75.0%)
9 (56.3%)
0.22
54 (67.5%)
10 (62.5%)
0.77
21 (26.3%) 27 (33.8%)
3 (18.8%) 4 (25.0%)
0.75 0.57
35 (43.8%) 49 (61.3%)
4 (25.0%) 7 (43.8%)
0.26 0.27
4 8 4 1 10
0 1 1 0 1
1.00 1.00 1.00 1.00 0.68
(5.0%) (10.0%) (5.0%) (1.3%) (12.5%)
Episodic vs Chronic Migraine Comparing the women with episodic migraine to those with chronic migraine, the statistically significant findings, not corrected for multiple comparisons, were both menstrually related: Menstrual-cycle disorders in general and the specific menstruation disorder of dysmenorrhea were found to be associated with chronic rather than
1430
8 (50.0%) 8 (50.0%)
(0%) (6.3%) (6.3%) (0%) (6.3%)
with episodic migraine (41.2 vs 22.2% and 51.0 vs 28.9%, respectively). Menstrual-Cycle Disorders Regarding the prevalence of menstrual disorders, a systematic review by the World Health Organization (WHO), published in 2004, provides this information for
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General Age Body mass index Age of menarche Age at migraine onset Migraine type Episodic Chronic Features of episodic migraine Frequency (attacks/month) Duration (days) Migraine-headache intensity Moderate Severe Migraine-associated symptoms Nausea Vomiting Migraine-headache features Unilateral Throbbing Worsened by routine activity Migraine onset Within 1 year of menarche Related to use of hormonal birth control Following pregnancy Perception of period duration Short/long Perception of period flow Moderate/severe Perception of period pain Moderate/severe Perception of period intervals Short/long Menstrual-cycle disorder (oligomenorrhea, poly-menorrhea, irregular cycle) Menstruation disorder Dysmenorrhea Menorrhagia Miscellaneous diagnoses Polycystic Ovary Syndrome Endometriosis Infertility Hyperthyroidism Hypothyroidism
Menstruation-Sensitive Migraine (N 5 80)
Menstrual Disorders in Migraine developing countries [13]. The reviewers utilized population-based surveys related to at least 15 distinct studies, obtaining menstrually-related prevalence data from 20 countries. One of their conclusions was that the prevalence rates in developing countries are broadly comparable to those observed in developed countries, allowing for comparisons with the data we obtained. In regard to menstrual-cycle disorders, the WHO found the prevalence of oligomenorrhea to be 8–22% and that of irregular cycle to be 5–16%. Although our goal was not to study prevalence, 8.3 and 16.7% of our total migraine population reported oligomenorrhea and irregular cycle, respectively. Both percentages are in line with the above-quoted population ranges, suggesting from this perspective our sample to be representative of the general population.
In regard to menstruation disorders, 25–58% of women in the WHO review self-reported menstrual pain, while 3–18% indicated severe pain or pain that kept a woman from her work or daily activities. In our study, 40.6% of women reported severe pain with menstruation, diagnosed by us as dysmenorrhea, 28.9% of those with episodic migraine and 51.0% of those with chronic migraine (P 5 0.04). Menorrhagia, defined as blood loss of at least 80 mL, had prevalence rates of 11% in the Philippines, 12% in Nigeria, and 20% in China. On the basis of reporting at least five fully soaked pads/tampons on the heaviest day(s) (;80 mL), we diagnosed 51.1% of the women with episodic migraine to have menorrhagia and 64.7% of those with chronic migraine (P 5 0.22). Affecting approximately 30% of women, menorrhagia is reportedly the foremost reason for gynecological referral, accounting for two-thirds of all hysterectomies and most endometrial ablations. A questionnaire study, published in 2006, evaluated the frequency of menorrhagia and endometriosis in female migraineurs (N 5 50), as compared with age-matched migraine-free women (N 5 52) [4]. The authors found menorrhagia, defined as at least three consecutive heavy periods, to be statistically significantly more common in the migraineurs than in the control group (63 vs 37%; P 5 0.009). The study also found that endometriosis was more common in the migraineurs (30 vs 4%; P 5 0.001), with all but one of the women with endometriosis having a history of menorrhagia. Endometriosis Endometriosis has been estimated to affect at least 5.5 million women in the United States, corresponding to approximately 10% of women. A cross-sectional study of women with migraine (N 5 171) and healthy, nonmigraine controls (N 5 104) examined endometriosis and related comorbidities [5]. The study reported 60% of its subjects to be diagnosed with episodic migraine, which makes us assume that the remaining 40% had
Conclusion Chronic migraine is possibly more often than episodic migraine associated with menstrual-cycle disorders in general and dysmenorrhea, without impact of menstruation sensitivity. We do not believe that this finding relates to the association of chronic migraine, in comparison to episodic migraine, with hypothyroidism because it did not include menorrhagia, the menstruation disorder associated with hypothyroidism [8], and because we observed hypothyroidism to be equally common in both groups, affecting 11.1% of the women with episodic migraine and 11.8% of those with chronic migraine. The latter finding, in our opinion, also sheds doubt on the claimed role of hypothyroidism in the chronification of migraine [6], as does the study by Ferrari et al. [7]. Clinical Implication The difference between episodic and chronic migraine may be much more profound than the distinction on the basis of the number of headache days per month suggests. Chronic-migraine patients seem to be much more than their episodic-migraine counterparts troubled by comorbidities, which remarkably span the entire gamut of body systems: neurological, psychiatric, musculoskeletal, cardiovascular, respiratory, gastroenterological, genitourinary, endocrine, and immunological. In this study, we provided potential, additional support for the genitourinary system to be differentially involved in episodic vs chronic migraine. There is probably no significance to the involvement of a single body system in episodic vs chronic migraine, including the genitourinary system studied here, either in the development or in the presentation of chronic migraine. However, the bigger picture begs the question as to whether with the arbitrary, numerical distinction between episodic and chronic migraine, we have not uncovered a deeper feature of migraine not hitherto considered, that is, its systemic nature. We know that during the headaches of episodic migraine, the body derails in its functioning, both as a whole and in its parts. With the incessant occurrence of headaches as is the case in chronic migraine, this may have become the newly acquired status of the body, resulting in the array of comorbidities 1431
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Menstruation Disorders
chronic migraine. One finding was that 22% of the women in the migraine group had been diagnosed with endometriosis, as opposed to 9.6% in the control group (P < 0.01). The study also found that 64% of the women with chronic migraine, as opposed to 36% of those with episodic migraine, had been diagnosed with endometriosis (P 5 0.002). Additionally, 54% of the migraineurs had a history of dysmenorrhea, as compared with 23% of the control group (P < 0.05), and 68% had a history of menorrhagia, as compared with 43% of the control group (P < 0.05). The findings in migraineurs are similar to our results, with 40.6% of the women diagnosed by us with dysmenorrhea and 58.3% with menorrhagia, providing confirmatory support of our study results.
Spierings and Padamsee that this particular migraine presentation seems riddled with.
References 1 Stewart WF, Lipton RB, Celentano DD, Reed ML. Prevalence of migraine headache in the United States. J Am Med Assoc 1992;267:64–9. 2 Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders, 2nd edition. Cephalalgia 2004;24(suppl 1):1–160.
4 Tietjen GE, Conway A, Utley C, Gunning WT, Herial NA. Migraine is associated with menorrhagia and endometriosis. Headache 2006;6:422–8. 5 Tietjen GE, Bushnell CD, Herial NA, et al. Endometriosis is associated with prevalence of comorbid conditions in migraine. Headache 2007;47:1069–78. 6 Bigal ME, Sheftell FD, Rapoport AM, Tepper SJ, Lipton RB. Chronic daily headache: Identification of factors associated with induction and transformation. Headache 2002;42:575–81.
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8 Krassas GE, Pontikides N, Kaltsas T, et al. Disturbances of menstruation in hypothyroidism. Clin Endocrinol 1999;50:655–9. 9 Spierings ELH. Daily migraine with visual aura associated with an occipital arteriovenous malformation. Headache 2001;41:193–7. 10 Vukovic´-Cvetkovic´ V, Plavec D, Lovrencˇic´-Huzjan A, et al. Is iron deficiency anemia related to menstrual migraine?—Post hoc analysis of an observational study evaluating clinical characteristics of patients with menstrual migraine. Acta Clin Croatia 2010;49: 389–94. 11 Karpouzis KM, Spierings ELH. Circumstances of onset of chronic headache in patients attending a specialty practice. Headache 1999;39:317–20. 12 Mannix L. Menstrual-related pain conditions: Dysmenorrhea and migraine. J Women’s Health 2008; 17:879–91. 13 Harlow SD, Campbell OMR. Epidemiology of menstrual disorders in developing countries: A systematic review. Int J Obstet Gynaecol 2004;111:6–16.
Downloaded from http://painmedicine.oxfordjournals.org/ by guest on March 21, 2016
3 Schwedt TJ. Chronic migraine. Br Med J 2014;348: g1416.
7 Ferrari A, Leone S, Vergoni AV, et al. Similarities and differences between chronic migraine and episodic migraine. Headache 2007;47:65–72.
HEADACHE & FACIAL PAIN SECTION Original Research Article Menstrual-Cycle and Menstruation Disorders in Episodic vs Chronic Migraine: An Exploratory Study
*Division of Craniofacial Pain, Headache, and Sleep, Department of Oral Pathology, Oral Medicine, and Craniofacial Pain, Tufts University School of Dental Medicine; †Headache & Face Pain Program, Department of Neurology, Tufts Medical Center, Boston, Massachusetts, USA Reprint requests to: Egilius L.H. Spierings, MD, PhD, Craniofacial Pain Center, One Kneeland Street, Boston, MA 02111, USA. Tel: 617-636-6817; Fax: 617-636-3831; E-mail: [email protected].
cycle, and the menstruation disorders, dysmenorrhea and menorrhagia, in episodic vs chronic migraine. Results. The prevalence of menstrual-cycle disorders in general (41.2 vs 22.2%) and dysmenorrhea (51.0 vs 28.9%) was statistically significantly higher in the women with chronic migraine than in those with episodic migraine (P £ 0.05)(not corrected for multiple comparisons). Whether the migraine was menstruation sensitive, that is, the headaches consistently occurred or worsened with menstruation, did not impact the prevalence of menstrual disorders.
Disclosure: The study was conducted without external funding and neither author has conflicts of interest to report.
Conclusion. We conclude that chronic migraine is possibly more often than episodic migraine associated with menstrual-cycle disorders in general and dysmenorrhea, without impact on menstruation sensitivity of the headaches.
Abstract
Key Words. Migraine; Episodic Migraine; Chronic Migraine; Menstruation-Sensitive Migraine; Menstruation; Menstrual Disorders; Oligomenorrhea; Polymenorrhea; Irregular Cycle; Dysmenorrhea; Menorrhagia; Hypothyroidism
Objective. Migraine is a chronic condition of recurring moderate-to-severe headaches that affects an estimated 6% of men and 18% of women. The highest prevalence is in those 18–49 years of age, generally when women menstruate. It is divided into episodic and chronic migraine depending on the total number of headache days per month being 14 or less or 15 or more, respectively. Migraine has been associated with menorrhagia, dysmenorrhea, and endometriosis, the latter particularly in chronic migraine. Methods. We conducted a questionnaire survey of 96 women with migraine, 18–45 years old, to determine the occurrence of the menstrual-cycle disorders, oligomenorrhea, polymenorrhea, and irregular 1426
Introduction Migraine is a condition of recurring headaches, with the headaches sometimes preceded by transient focal neurological symptoms, also known as aura symptoms. The headaches are generally moderate or severe in intensity, unilateral in location, throbbing in quality, worsened by routine physical activity, and associated with nausea, vomiting, photophobia, and/or phonophobia. It is a common condition that, in the United States, affects an estimated 6% of men and 18% of women, with the highest prevalence in the age range of 18–49 years, generally when women menstruate [1]. It is divided into episodic and chronic migraine depending on the total number of headache days per month, which is 14 days
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Egilius L.H. Spierings, MD, PhD,*,† and Aliya Padamsee, BA*
Menstrual Disorders in Migraine or less in episodic migraine and 15 days or more in chronic migraine [2]. Chronic migraine accounts for approximately 8% of the migraine burden and its prevalence in the general population has been mostly reported in the range of 1.4–2.2% [3].
Hypothyroidism, in turn, has been associated with menstrual disorders, in particular menorrhagia [8]. In a study of 171 hypothyroid patients and 214 age- and bodymass-index-matched controls, menstrual disorders occurred in 23.4% of the hypothyroid patients and in 8.4% of the controls (P < 0.001). Oligomenorrhea was common in both groups (42.5% and 67%, respectively), while menorrhagia was almost three times more common in the hypothyroid group (30 vs 11%). Treatment of the hypothyroid patients with levothyroxine brought the rate of menstrual disorders in that group down to 9.3%, which is similar to that observed in the control group (8.4%). We have had a long-standing interest in the role of hypothyroidism in headache, including migraine [9]. Hence, we conducted this study based on the relatively strong, above-mentioned association of chronic migraine, in comparison to episodic migraine, with hypothyroidism and, in turn, the association of hypothyroidism with menstrual disorders. In the study, we further explored the association of chronic migraine, in comparison to episodic migraine, with the menstrual-cycle disorders, oligomenorrhea, polymenorrhea, and irregular cycle, and the menstruation disorders, dysmenorrhea and menorrhagia. We also looked at menstruationsensitive in comparison to non-menstruation-sensitive migraine and the association with menstrual disorders. Menstruation-sensitivity was defined as headaches consistently occurring (episodic migraine) or consistently worsening (chronic migraine) with menstruation. The menstruation-sensitivity issue was looked at because a study of 168 women with menstrual or menstruallyrelated migraine, in comparison to 121 women with migraine unrelated to the menstrual cycle, showed the former group to be statistically significantly more often anemic due to iron deficiency (38.5 vs 22.9%; P 5 0.008), possibly indicating a higher prevalence of menstrual disorders associated with increased blood loss, that is, polymenorrhea and menorrhagia (hypermenorhea) [10].
Patients The study was based on a convenience sample of 173 female patients with migraine aged 18–45 years old, inclusive, from the private practice of the first author, a neurologist with fellowship training in headache management. He had previously evaluated the patients in his practice and diagnosed them with episodic or chronic migraine, according to the criteria as published by the International Headache Society [2]. The patients were contacted by mail and sent a 42-point questionnaire; review-board approval was not obtained for this noninterventional, private-practice survey. Of the questionnaires, 31 (18%) were undeliverable due to change of address and inability to contact the addressees by telephone and/or e-mail. Of the 142 questionnaires that were delivered, 96 were returned to us completed, generating a response rate of 68%. Questionnaire The questionnaire was specifically developed for the study because validated questionnaires to collect the information required for the study were not available. It was not validated because of the exploratory nature of the study and, therefore, its psychometric properties are unknown. The questionnaire consisted of two major sections: headache-related and menstruation-related questions. To confirm that the women did, in fact, still have migraine and to differentiate between episodic and chronic migraine, they were queried about the onset, current intensity, frequency, and duration, as well as about the following headache features and associated symptoms: nausea, vomiting, photophobia, phonophobia, laterality, throbbing, and worsening by routine physical activity. Those with episodic migraine were also queried about headaches consistently occurring with menstruation, while those with chronic migraine were queried about headaches consistently worsening with menstruation. The menstruation-related questions retrieved both quantitative and qualitative responses, where necessary, to obtain numerical data and to gauge how the woman perceived any menstrual abnormality. Quantitative questions included age of menarche, duration of periods, intervals between periods, number of pads/tampons required on worst day(s), and the number of days for which the indicated intensity of flow and level of abdominal pain persist. Qualitative questions addressed the woman’s perception of the length of the periods (normal, short, or long), the length of the interval between the periods (normal, short, or long), and their regularity. The intensity of flow and of abdominal pain was indicated as mild, moderate, or severe. It was also inquired whether the migraine began at menarche or following the use of hormonal birth control or pregnancy/nursing [11]. Lastly, the women were requested to indicate previous diagnoses of polycystic ovary syndrome (PCOS), endometriosis, infertility, hyperthyroidism, and hypothyroidism. 1427
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Migraine has been associated with menorrhagia, dysmenorrhea, and endometriosis, the latter particularly in chronic migraine [4,5]. Chronic migraine, in comparison to episodic migraine, has been associated with asthma (odds ratio: 2.4; P 5 0.03), allergies (odds ratio: 3.5; P 5 0.0001), hypertension (odds ratio: 6.9; P < 0.0001), and hypothyroidism (odds ratio: 8.4; P 5 0.0004) [6]. In another study, in terms of comorbidities, psychiatric disorders, insomnia, gastrointestinal disorders, musculoskeletal disorders, hypertension, and genitourinary disorders were significantly more common in 150 patients with chronic migraine than in 100 patients with episodic migraine [7].
Materials and Methods
Spierings and Padamsee Data Processing/Analysis Upon receipt of the questionnaires, menstrual abnormalities were divided into menstrual-cycle and menstruation disorders, using the following criteria: oligomenorrhea defined as intervals 35 days, polymenorrhea defined as intervals 24 days, irregular cycle defined as inconsistent intervals between the periods, dysmenorrhea defined as abdominal pain with menstruation indicated as severe, and menorrhagia (hypermenorrhea) defined as requiring five or more fully soaked pads/tampons per day on the heaviest day(s) of the periods.
Results Patients The average age of the respondents was 34.0 6 8.0 (S.D.) years; their body mass index (BMI) was 27.5 6 8.3 kg/m2. They reported the average age of onset of their migraine to be 17.6 6 7.6 years, which translates into an average migraine suffering of 16.4 6 9.4 years. Forty-five women (46.9%) reported the onset of the migraine to have occurred within 1 year of menarche, with menarche occurring at an average age of 12.5 6 1.6 years. Ten of the women (10.4%) related the onset of their migraine to the use of hormonal birth control and 9 (9.4%) following pregnancy/nursing. Of the women, 45 (46.9%) had episodic migraine and 51 (53.1%) chronic migraine at the time of questionnaire completion. Headaches The current intensity of the headaches was described as moderate by 49.0% of the women and as severe by 51.0%. The headaches were reportedly associated with nausea in 85.4% of the women and with vomiting in 21.9%. They were described as unilateral in 43.8%, throbbing in 89.6%, and aggravated by routine physical activity in 67.7%. Eighty of the women (83.3%) described the headaches as consistently occurring with menstruation (episodic migraine) or consistently worsening with menstruation (chronic migraine). In 63.8% of the 80 women, this occurred before menstruation with an average of 2.8 6 1.4 days, in 31.2% during menstruation, and in 5% after menstruation. Menstruation Disorders Of the 96 women, 35 (36.5%) used hormonal birth R , MirenaV R IUD, control (oral contraceptive, NuvaRingV R ), 17 (17.7%) for contraceptive purDepo-ProveraV poses, 16 (16.7%) for the relief of menstrual symp1428
Menstrual-Cycle Disorders Of the women, 16 (16.7%) reported the intervals between their periods to vary and, therefore, had irregular cycle. Of the remainder, 11 (11.5%) considered the interval between their periods to be short and 14 (14.6%) long. We diagnosed 7 (7.3%) of the women as having polymenorrhea and 8 (8.3%) with oligomenorrhea. Hence, 31 (32.3%) of the 96 women had a menstrual-cycle disorder and 11 (11.5%) a menstruation disorder. The menstrual disorders were reported by 19 (61.3%) of the 31 women to have started at menarche (primary) and by 11 (35.5%) after pregnancy/nursing (secondary). Miscellaneous Four (4.2%) of the 96 women had been diagnosed with PCOS, 5 (5.2%) with infertility, and 9 (9.4%) with endometriosis; additionally, 1 (1.0%) was diagnosed with hyperthyroidism and 11 (11.5%) with hypothyroidism. Episodic vs Chronic Migraine On the basis of headaches occurring 14 days or less per month or 15 days or more, we divided the women into those with episodic and those with chronic migraine. Comparing the two groups of women, we diagnosed the women with chronic migraine statistically significantly more often with menstrual-cycle disorders in general (41.2 vs 22.2%; P 5 0.05) and found them to have dysmenorrhea statistically significantly more often (51.0 vs 28.9%; P 5 0.04) (Table 1). As 26 tests were performed for Table 1, any kind of Bonferroni adjustment would have left both differences nonsignificant. Menstruation-Sensitive vs Non-Menstruation-Sensitive Migraine On the basis of headaches consistently occurring (episodic migraine) or worsening with menstruation (chronic migraine), we divided the women into those with menstruation-sensitive and those with nonmenstruation-sensitive migraine and found the prevalence of menstrual-cycle and menstruation disorders not statistically significantly different between the two groups (Table 2).
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SPSS software was used for data entry and analysis and in the analysis, a P value of 0.05 was considered indicating a statistically significant difference. The statistical tests used were the two-tailed Student t-test, which assumes a normal distribution, and the two-tailed Fisher exact test, which does not rely on approximation to a chi-squared distribution.
toms, and 5 (5.2%) for migraine relief. Disregarding the use of hormonal birth control, 12 (12.5%) of the 96 women reported their periods to be short and 31 (32.3%) long, not otherwise defined. The flow was described by 26 (27.1%) as moderate and by 42 (43.8%) as severe, requiring 5.6 6 2.4 pads/tampons per day on the heaviest day(s). The periods were described as moderately painful by 24 women (25.0%) and as severely painful by 39 (40.6%); the intensity of the pain was experienced for an average of 2.5 6 2.0 days. On the basis of these results, we diagnosed 56 (58.3%) of the women as having menorrhagia and 39 (40.6%) with dysmenorrhea.
Menstrual Disorders in Migraine
Table 1
Episodic migraine vs chronic migraine Chronic Migraine (N 5 51)
P Value
33.6 6 8.1 26.7 6 7.7 12.4 6 1.4 16.4 6 7.3
34.4 6 8.8 28.1 6 8.7 12.5 6 1.8 18.7 6 7.7
0.69 0.49 0.99 0.20
22 (48.9%) 23 (51.1%)
25 (49.0%) 26 (51.0%)
1.00 1.00
38 (84.4%) 6 (13.3%)
44 (86.3%) 15 (29.4%)
1.00 0.08
22 (48.9%) 42 (93.3%) 31 (68.9%)
20 (39.2%) 44 (86.3%) 34 (66.7%)
0.41 0.33 0.83
23 (51.1%) 2 (4.4%) 4 (8.9%)
22 (43.1%) 8 (15.7%) 5 (9.8%)
0.54 0.09 1.00
16 (35.6%)
28 (54.9%)
0.07
32 (71.1%)
37 (72.5%)
1.00
29 (64.4%)
35 (68.6%)
0.67
8 (17.8%) 10 (22.2%)
17 (33.3%) 21 (41.2%)
0.10 0.05
13 (28.9%) 23 (51.1%)
26 (51.0%) 33 (64.7%)
0.04 0.22
1 2 2 1 5
Discussion Limitations The limiting factors of this study are its retrospective nature, its sample size, the non-validated nature of the questionnaire used, its response rate, and, possibly, a report bias. Our sample size consisted of 173 women with migraine of child-bearing potential but on account of undeliverable mailing addresses, the sample size was reduced to 142 women, of whom 96 responded (68% response rate). While the episodic and chronic migraine subgroups were comparable in size (45 and 51, respectively), the menstruation-sensitive and non-
(2.2%) (4.4%) (4.4%) (2.2%) (11.1%)
3 7 3 0 6
(5.9%) (13.7%) (5.9%) (0%) (11.8%)
0.62 0.17 1.00 0.47 1.00
menstruation-sensitive migraine groups were very unequal in size (80 and 16, respectively). The numbers indicate 83.3% of our population of female migraineurs to have menstruation-sensitive migraine while a review of the literature suggests 40–70% of women to report an association between migraine and menstruation [12]. Report bias likely influenced this outcome as those with menstrually-related migraine were probably more inclined to respond to the survey and complete the questionnaire. However, it should also be noted that our definition was broader than that generally applied, including consistent worsening of headaches with menstruation in the women with chronic migraine as well. 1429
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General Age Body mass index Age of menarche Age at migraine onset Migraine-headache intensity Moderate Severe Migraine-associated symptoms Nausea Vomiting Migraine-headache features Unilateral Throbbing Worsened by routine activity Migraine onset Within 1 year of menarche Related to use of hormonal birth control Following pregnancy Perception of period duration Short/long Perception of period flow Moderate/severe Perception of period pain Moderate/severe Perception of period intervals Short/long Menstrual-cycle disorder (oligomenorrhea, poly-menorrhea, irregular cycle) Menstruation disorder Dysmenorrhea Menorrhagia Miscellaneous diagnoses Polycystic Ovary Syndrome Endometriosis Infertility Hyperthyroidism Hypothyroidism
Episodic Migraine (N 5 45)
Spierings and Padamsee
Table 2
Menstruation-sensitive vs non-menstruation-sensitive migraine Non-Menstruation-Sensitive Migraine (N 5 16)
P Value
34.4 6 7.9 27.5 6 8.9 12.5 6 1.6 17.5 6 8.0
32.1 6 8.8 27.0 6 4.0 12.3 6 1.9 18.3 6 5.6
0.35 0.72 0.70 0.65
36 (45.0%) 44 (55.0%) 10.1 6 6.3 1.6 6 1.3
7.9 6 3.9 1.4 6 1.0
0.79 0.79 0.16 0.58
38 (47.5%) 42 (52.5%)
8 (50.0%) 8 (50.0%)
1.00 1.00
71 (88.8%) 19 (23.8%)
11 (68.8%) 2 (12.5%)
0.05 0.51
37 (46.3%) 73 (91.3%) 57 (71.3%)
5 (31.3%) 13 (81.3%) 8 (50.0%)
0.41 0.36 0.14
39 (48.8%) 9 (11.3%) 7 (8.8%)
5 (31.3%) 1 (6.3%) 2 (12.5%)
0.27 1.00 0.64
39 (48.8%)
5 (31.3%)
0.27
60 (75.0%)
9 (56.3%)
0.22
54 (67.5%)
10 (62.5%)
0.77
21 (26.3%) 27 (33.8%)
3 (18.8%) 4 (25.0%)
0.75 0.57
35 (43.8%) 49 (61.3%)
4 (25.0%) 7 (43.8%)
0.26 0.27
4 8 4 1 10
0 1 1 0 1
1.00 1.00 1.00 1.00 0.68
(5.0%) (10.0%) (5.0%) (1.3%) (12.5%)
Episodic vs Chronic Migraine Comparing the women with episodic migraine to those with chronic migraine, the statistically significant findings, not corrected for multiple comparisons, were both menstrually related: Menstrual-cycle disorders in general and the specific menstruation disorder of dysmenorrhea were found to be associated with chronic rather than
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8 (50.0%) 8 (50.0%)
(0%) (6.3%) (6.3%) (0%) (6.3%)
with episodic migraine (41.2 vs 22.2% and 51.0 vs 28.9%, respectively). Menstrual-Cycle Disorders Regarding the prevalence of menstrual disorders, a systematic review by the World Health Organization (WHO), published in 2004, provides this information for
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General Age Body mass index Age of menarche Age at migraine onset Migraine type Episodic Chronic Features of episodic migraine Frequency (attacks/month) Duration (days) Migraine-headache intensity Moderate Severe Migraine-associated symptoms Nausea Vomiting Migraine-headache features Unilateral Throbbing Worsened by routine activity Migraine onset Within 1 year of menarche Related to use of hormonal birth control Following pregnancy Perception of period duration Short/long Perception of period flow Moderate/severe Perception of period pain Moderate/severe Perception of period intervals Short/long Menstrual-cycle disorder (oligomenorrhea, poly-menorrhea, irregular cycle) Menstruation disorder Dysmenorrhea Menorrhagia Miscellaneous diagnoses Polycystic Ovary Syndrome Endometriosis Infertility Hyperthyroidism Hypothyroidism
Menstruation-Sensitive Migraine (N 5 80)
Menstrual Disorders in Migraine developing countries [13]. The reviewers utilized population-based surveys related to at least 15 distinct studies, obtaining menstrually-related prevalence data from 20 countries. One of their conclusions was that the prevalence rates in developing countries are broadly comparable to those observed in developed countries, allowing for comparisons with the data we obtained. In regard to menstrual-cycle disorders, the WHO found the prevalence of oligomenorrhea to be 8–22% and that of irregular cycle to be 5–16%. Although our goal was not to study prevalence, 8.3 and 16.7% of our total migraine population reported oligomenorrhea and irregular cycle, respectively. Both percentages are in line with the above-quoted population ranges, suggesting from this perspective our sample to be representative of the general population.
In regard to menstruation disorders, 25–58% of women in the WHO review self-reported menstrual pain, while 3–18% indicated severe pain or pain that kept a woman from her work or daily activities. In our study, 40.6% of women reported severe pain with menstruation, diagnosed by us as dysmenorrhea, 28.9% of those with episodic migraine and 51.0% of those with chronic migraine (P 5 0.04). Menorrhagia, defined as blood loss of at least 80 mL, had prevalence rates of 11% in the Philippines, 12% in Nigeria, and 20% in China. On the basis of reporting at least five fully soaked pads/tampons on the heaviest day(s) (;80 mL), we diagnosed 51.1% of the women with episodic migraine to have menorrhagia and 64.7% of those with chronic migraine (P 5 0.22). Affecting approximately 30% of women, menorrhagia is reportedly the foremost reason for gynecological referral, accounting for two-thirds of all hysterectomies and most endometrial ablations. A questionnaire study, published in 2006, evaluated the frequency of menorrhagia and endometriosis in female migraineurs (N 5 50), as compared with age-matched migraine-free women (N 5 52) [4]. The authors found menorrhagia, defined as at least three consecutive heavy periods, to be statistically significantly more common in the migraineurs than in the control group (63 vs 37%; P 5 0.009). The study also found that endometriosis was more common in the migraineurs (30 vs 4%; P 5 0.001), with all but one of the women with endometriosis having a history of menorrhagia. Endometriosis Endometriosis has been estimated to affect at least 5.5 million women in the United States, corresponding to approximately 10% of women. A cross-sectional study of women with migraine (N 5 171) and healthy, nonmigraine controls (N 5 104) examined endometriosis and related comorbidities [5]. The study reported 60% of its subjects to be diagnosed with episodic migraine, which makes us assume that the remaining 40% had
Conclusion Chronic migraine is possibly more often than episodic migraine associated with menstrual-cycle disorders in general and dysmenorrhea, without impact of menstruation sensitivity. We do not believe that this finding relates to the association of chronic migraine, in comparison to episodic migraine, with hypothyroidism because it did not include menorrhagia, the menstruation disorder associated with hypothyroidism [8], and because we observed hypothyroidism to be equally common in both groups, affecting 11.1% of the women with episodic migraine and 11.8% of those with chronic migraine. The latter finding, in our opinion, also sheds doubt on the claimed role of hypothyroidism in the chronification of migraine [6], as does the study by Ferrari et al. [7]. Clinical Implication The difference between episodic and chronic migraine may be much more profound than the distinction on the basis of the number of headache days per month suggests. Chronic-migraine patients seem to be much more than their episodic-migraine counterparts troubled by comorbidities, which remarkably span the entire gamut of body systems: neurological, psychiatric, musculoskeletal, cardiovascular, respiratory, gastroenterological, genitourinary, endocrine, and immunological. In this study, we provided potential, additional support for the genitourinary system to be differentially involved in episodic vs chronic migraine. There is probably no significance to the involvement of a single body system in episodic vs chronic migraine, including the genitourinary system studied here, either in the development or in the presentation of chronic migraine. However, the bigger picture begs the question as to whether with the arbitrary, numerical distinction between episodic and chronic migraine, we have not uncovered a deeper feature of migraine not hitherto considered, that is, its systemic nature. We know that during the headaches of episodic migraine, the body derails in its functioning, both as a whole and in its parts. With the incessant occurrence of headaches as is the case in chronic migraine, this may have become the newly acquired status of the body, resulting in the array of comorbidities 1431
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Menstruation Disorders
chronic migraine. One finding was that 22% of the women in the migraine group had been diagnosed with endometriosis, as opposed to 9.6% in the control group (P < 0.01). The study also found that 64% of the women with chronic migraine, as opposed to 36% of those with episodic migraine, had been diagnosed with endometriosis (P 5 0.002). Additionally, 54% of the migraineurs had a history of dysmenorrhea, as compared with 23% of the control group (P < 0.05), and 68% had a history of menorrhagia, as compared with 43% of the control group (P < 0.05). The findings in migraineurs are similar to our results, with 40.6% of the women diagnosed by us with dysmenorrhea and 58.3% with menorrhagia, providing confirmatory support of our study results.
Spierings and Padamsee that this particular migraine presentation seems riddled with.
References 1 Stewart WF, Lipton RB, Celentano DD, Reed ML. Prevalence of migraine headache in the United States. J Am Med Assoc 1992;267:64–9. 2 Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders, 2nd edition. Cephalalgia 2004;24(suppl 1):1–160.
4 Tietjen GE, Conway A, Utley C, Gunning WT, Herial NA. Migraine is associated with menorrhagia and endometriosis. Headache 2006;6:422–8. 5 Tietjen GE, Bushnell CD, Herial NA, et al. Endometriosis is associated with prevalence of comorbid conditions in migraine. Headache 2007;47:1069–78. 6 Bigal ME, Sheftell FD, Rapoport AM, Tepper SJ, Lipton RB. Chronic daily headache: Identification of factors associated with induction and transformation. Headache 2002;42:575–81.
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8 Krassas GE, Pontikides N, Kaltsas T, et al. Disturbances of menstruation in hypothyroidism. Clin Endocrinol 1999;50:655–9. 9 Spierings ELH. Daily migraine with visual aura associated with an occipital arteriovenous malformation. Headache 2001;41:193–7. 10 Vukovic´-Cvetkovic´ V, Plavec D, Lovrencˇic´-Huzjan A, et al. Is iron deficiency anemia related to menstrual migraine?—Post hoc analysis of an observational study evaluating clinical characteristics of patients with menstrual migraine. Acta Clin Croatia 2010;49: 389–94. 11 Karpouzis KM, Spierings ELH. Circumstances of onset of chronic headache in patients attending a specialty practice. Headache 1999;39:317–20. 12 Mannix L. Menstrual-related pain conditions: Dysmenorrhea and migraine. J Women’s Health 2008; 17:879–91. 13 Harlow SD, Campbell OMR. Epidemiology of menstrual disorders in developing countries: A systematic review. Int J Obstet Gynaecol 2004;111:6–16.
Downloaded from http://painmedicine.oxfordjournals.org/ by guest on March 21, 2016
3 Schwedt TJ. Chronic migraine. Br Med J 2014;348: g1416.
7 Ferrari A, Leone S, Vergoni AV, et al. Similarities and differences between chronic migraine and episodic migraine. Headache 2007;47:65–72.
![[Progression from episodic migraine to chronic migraine].](/assets/img/hold.png)
