Perimenstrual Headache: Migraine without Aura or Premenstrual Syndrome Symptom?

Background/Aim. Definition of menstrual migraine as a specific clinical entity or, maybe, migraine headache with menstrually related occurring, still remains unresolved question. The aim of this study was to investigate if perimen-strual headache in our patients fulfills diagnostic the International Classification of Headache Disorders (ICHD) criteria for migraine without aura or represents a different type of headache which is the symptom of premenstrual syndrome (PMS). Methods. The study included 50 women with headache in perimenstrual period in at least two out of three menstrual cycles, during the last year or longer. Two questionnaires, a questionnaire for headache and a questionnaire for PMS, were used. Results. The majority of all the examined women, 29 of them, had migraine and PMS and 9 women had migraine without PMS. Headache in 38 (76.0%) patients fulfilled diagnostic criteria for menstrual migraine, (26 and 12 women had pure menstrual migraine and menstrually related migraine respectively). Intensity of PMS was not different in a groups of women with different types of headache (p = 0.184): a total number of PMS symptoms was 8.2 ± 4.6 in the group with pure menstrual migraine, 10.8 ± 3.9 in the group with menstrually related migraine and 10.8 ± 6.3 in the group with non-migraine headache. Conclusion. This study shows that headache, occuring in perimenstrual period, is not always migraine, but could fulfill criteria for tension-type headache, as well. Specific characteristics of perimenstrual headache, which could distinguish it as a symptom of PMS, were not found. Expected relation in time of headache onset and menarche was not confirmed.


Introduction
Migraine is а type of headache with recurrent attacks of unilateral, pulsating pain of high intensity which aggravate with physical activity and is accompanied by photo-and/or phonophobia and nausea and/or vomiting.Menstruation is claimed to be one of the trigger factors for migraine attack in more than half of in-hospital examined patients with migraine and, according to population based studies, in more than a quarter of women with migraine 1 .Headache gets worsen in 60% of women with migraine during the perimenstrual period, e.g. two days before and the first three days of menstrual bleeding, and some women, in smaller pеrcent, report the headache attacks occurring exclusively in this period 2, 3 .Menstrual migraine exists as a pure menstrual and menstrually related migraine 4 .Patients with pure menstrual migraine report migraine attacks exclusively two days before or during the first three days of menstrual bleeding, and women with menstrually related migraine have additional pain attacks in other time of menstrual cycle, in at least two out of three menstrual cycles, for both diagnosis.
Premenstrual syndrome (PMS), according to the American College for Gynecology and Obstetristics, consists of phsysical and psychological symptoms and signs, occurring during at least five days before menstrual bleeding and completely resolving in four days after the bleeding onset, in at least three consecutive menstrual cycles 5 .More than 50% of women with PMS has headache as one of the symptoms 6 , but, exact clinical characterisation of type of this headache was not given.
There is no enough data which explain if menstrual migraine is specific type of headache, or simply migraine without aura, occurring in menstrual period.Also, there is none specific biomarker which can be used for differentiation menstrual and other types of migraine.
The aim of this study was to investigate if perimenstrual headache in our patients corresponds with diagnostic the International Classification of Headache Disrders (ICHD) criteria for migraine without aura or represents a different type of headache which is the symptom of PMS.

Methods
This study included 50 women with headache in perimenstrual period in at least two out of three menstrual cycles, during the last year or longer.All the patients were recruited in the Headache Center, Institute of Neurology, Belgrade, in the period from January 2006 to January 2008.Exclusion criteria for this study were pregnancy, ongoing hormonal or prophylactic therapy of migraine.Cases of symptomatic headache were excluded by neurological examination, laboratory blood testing, ophthalmological examination, electroencephalography (EEG), computed tomography (CT) and nuclear magnetic resonance (NMR) brain examinations.Two questionnaires, a questionnaire for headache and a questionnaire for PMS, were used.
Clinical characteristics of perimenstrual headache were estimated by, for this survey designed, the original Question-naire for Headache (Attachment 1), and diagnosis of migraine without aura was given according to IHC diagnostic criteria.Frequency of headache attacks was recorded in perimenstrual period, but in other time of menstrual cycle as well and quantified as number of days with headache in one month period.Intensity of pain was estimated using the verbal analog scale (VAS, with 0 for notification of total absence of pain, and 10 for the pain with maximum of its intensity) (Attachment 2).According to data recorded using the Questionnaire for Headache, all patients were divided into three groups: women with pure menstrual migraine, with menstrually related migraine and with non-migraine headache.In these groups, we analysed the intensity of PMS and demographic features of patients.
Diagnosis of PMS was given using the Questionnaire for PMS, modification of the Moos's Menstrual Distress Questionnaire 7 .Using this questionnaire, we recorded phsysical and psychological symptoms and signs, occurring during at least five days before menstrual bleeding, persisting or vanishing during menstruation and completely resolving in four days after the bleeding onset, in at least three consecutive menstrual cycles.Intensity of PMS was quantified as a sum of points given for every symptom and sign.A maximum of points was 28.Diagnosis of severe PMS was given to patients with more than 20 points, of moderate PMS to those with 11 to 20 points, of mild PMS to those with 6 to 10 points, and a sum of less than 6 points indicated that a patient did not have PMS.According to the results of this questionnaire, all the examined women were divided into two groups: women with and without PMS.In these groups we analysed clinical characteristics of headache and demographic features of patients.
Statistical analyses of data was done in SPSS v. 16.0.pmprogramme, using Student's t-test, ANOVA and χ 2 test.Test value p < 0.05 was considered to be statistically significant.

Results
According to diagnosis of migraine without aura nad PMS, four groups have been formed: women with migraine and PMS, with migraine and without PMS, and with nonmigraine headache and PMS, and with non-migraine headache and without PMS.The majority of examined women, 29 of them, had migraine and PMS, and 9 patients had migraine without PMS.Non-migraine headache with PMS was present in 10 women, and non-migraine headache without PMS was recorded in only two cases.Demographic features of patients and the clinical characteristics of headache in these groups are given in Table 1.
Demographic features of patients and characteristics of headache were not significantly different in the groups of patients with perimenstrual headache (Table 1).
In 38 (76.0%) of all the examined women, headache fulfilled the IHC diagnostic criteria for menstrual migraine, with diagnosis of pure menstrual migraine in 26, and menstrually related migraine in 12 of them.Demographic features of patients and the clinical characteristics of headache in women with menstrual migraine are given in Compared with women with menstrually related migraine, women with pure menstrual migraine were older at the time of examination and at the time of headache onset, as well.Age at the time of menarche was similar in all the examined women.Age at the time of headache onset and menarche in women with menstrual migraine is given in Figure 1.
Characteristics of headache (duration of attack and frequency), intensity of PMS and education level were not significantly different in the examined groups, but the percent of women not having children at the time of examination was higher in the group with menstrually related migraine (Table 2).Intensity of PMS was not different in the groups of women with different types of headache (p = 0.184): total number of PMS symptoms was 8.2 ± 4.6 in the group with pure menstrual migraine, 10.8 ± 3.9 in the group with menstrually related migraine and 10.8 ± 6.3 in the group with non-migraine headache.

Discussion
Since ICHD 4 does not recognize menstrual migraine as separate entity, the Appendix to ICHD, as a suggestion for the next revision of classification, gives diagnostic criteria for two types of menstrual migraine, pure menstrual and menstrually-related migraine.Diagnoses of specific types of headache in this study were put according to these diagnostic criteria.In the patients with perimenstrual headache which fulfills diagnostic criteria for migraine without aura, more than 60% had pure menstrual, and about one third of them had menstrually related migraine.Results of several studies [8][9][10][11][12][13] suggest that in population of women with migraine without aura, menstrually related migraine has higher frequency of 35% to 54%, and pure menstrual migraine is reported in 4% to 21% cases.Predomination of pure menstrual migraine in our results can be explained by a specific selection of patients in the Headache Center, as a third level health care center.Secondly, using inclusion criteria of having headache in perimenstrual period, we got the results of predomination of pure menstrual migraine in patients with migraine in perimenstrual period, while previous investigation's subject was general population of women with migraine without aura.
The majority of women, two third of them, had migraine without aura, and one third had non-migraine headache.There is no sufficient data indicating that headache occuring in perimenstrual period has to be migraine without aura only.In the last edition of ICHD, only one type of primary headaches is related to perimenstrual period, migraine without aura with its two forms: pure menstrual and menstrually related migraine.Time relation of perimenstrual period and headache attacks in patients with tension type headache and cluster headache has been reported as a result of only few studies 14,15 .In this study, women with headache attacks not fulfilling ICHD diagnostic criteria for migraine without aura were classified in the group with non-migraine headache.In that way, non-migraine headache attacks fulfilled ICHD diagnostic criteria for tension type headache, given in the ICHD as a negation of migraine criteria, and the conclusion is that one third of women in this study had, in fact, tension type headache in perimenstrual period.In the study which examined 45 women with headache and PMS, 60% of them had migraine without aura, and about 30% had tension type headache 16 .This data are in accordance with suggestions of some authors that menstrual tension type headache exists as a separate entity and because of that deserves its place and definition in ICHD 14 .
Most of women with perimenstrual headache had mild PMS.Different types of headache were not related to intensity of PMS, meaning that PMS was not more severe in women with non-migraine headache comparing to those with migraine.Only few studies investigated if some specific type of headache in perimenstrual period is dominant in patients with PMS, so, the contribution of our study is the data that migraine without aura, as the most frequent type of headache in perimenstrual period, is not dependent on intensity of PMS.
Women with pure menstrual migraine, comparing to women with menstrually related migraine, were older at the time of first examination.This data suggests that women with headache occurring not only in the perimenstrual period, but additionally in other time of menstrual cycle, are more disabled by a high frequency of headache attacks, have lower quality of life and contact doctor for help earlier.Also, women with pure menstrual migraine were older at the time of headache onset, while age of menarche was similar in all women.According to the present knowledge, authors of this paper are not able to give explanation for this result.Time gap between age at the time of menarche and age at the time of headache onset in women with menstrual migraine, is not reported by other authors.Hershey 17 reports time relation between first attack of menstrual migraine and menarche, but Kröner-Herwig and Vath 18 do not find a connection between menarche and increased frequency of headache in girls in puberty.There is a lack of explanation for even more significant time gap between menarche and headache onset in women with pure menstrual migraine, comparing to those with menstrually related migraine.
A significantly higher percent of women with pure menstrual migraine already had children at the time of examination, what can be connected to age at the time of first examination.

Conclusion
This study shows that headache occurring in perimenstrual period is not always migraine, but could fulfill diagnostic criteria for tension-type headache, as well.Specific characteristics of perimenstrual headache, which could distinguish it as a symptom of PMS, were not found.An expected relation in time of headache onset and menarche was not confirmed in this study.

Fig. 1 -
Fig. 1 -Age at the time of headache onset and menarche in women with pure menstrual and menstrually related migraine

Table 1 Demographic features and clinical characteristics of headache in women with perimenstrual headache according to diagnosis of migraine and PMS
M -migraine; NM -non-migraine headache; PMS -premenstrual syndrome; p < 0.05 -statistically significant