Others Section DOI : 10.7860/JCDR/2020/42703.13484
Year : 2020 | Month : Feb | Volume : 14 | Issue : 02 Page : OC10 - OC14

Menstrual Disorders and its Association with Migraine

Shahrzad Fakhraee1, Omid Hesami2, Zahra Soroureddin3

1 School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
2 Department of Neurology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
3 School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.


NAME, ADDRESS, E-MAIL ID OF THE CORRESPONDING AUTHOR: Zahra Soroureddin, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
E-mail: Leili_surur@yahoo.com
Abstract

Introduction

Migraine is a common disorder which can be seen in approximately 18% of women. The highest prevalence of this disorder has been reported vastly in the women of age between 18 and 49, when they are in the menstrual period and this is supposed to be associated with the same.

Aim

To study the menstrual disorders in women with and without migraine.

Materials and Methods

A case-control study was conducted with total population of 175 women (Jan 2018-Feb 2019), diagnosed with migraine, using International Headache Society criteria. Age and sex-matched control group was included in the present study. A semi-structured questionnaire about migraine and migraine-related disabilities, menstrual and headache history was conducted. All results were evaluated by SPSS version 22.0 statistical software; Independent t-test and to investigate the relationship between quantitative variables, Spearman’s correlation coefficient was used.

Results

In case group, 25.6% of women had menstrual cycle <24 days, and their population was significantly more than control group (10.1%). Also, in case group, 12.8% of women had menstrual cycle >38 days, which was significantly more than control group. The proportion of women with period lasting <4 days in case group (17.4%) was significantly more than that in control group (6.7%). In addition, the percentage of women with last period more than 8 days in case group was 12.8% and in control groups it was (6.7%) which was significantly high.

Conclusion

There is significant relation between period duration, oligomenorrhea, polymenorrhea and prevalence of migraine; however, there is no significant relation between other menstrual disorders such as dysmenorrhea and menstrual regularity with migraine. This study demonstrates no relation between severity and duration of headache and menstrual disorders.

Introduction

Menstruation is a vivid sign of a healthy body. After puberty, in order to keep hormonal balance, the body starts ovulation. However, sometimes imbalances of hormonal levels lead to menstrual abnormalities [1]. Menstrual disorders, an abnormal cycle length, such as amenorrhea, menorrhagia, dysmenorrhea, polymenorrhea, oligomenorrhea are the common issues in adolescents and young adult females which sometimes cause serious problems. Among these, dysmenorrhea is the most common form, reported in 60% to 90% of women [2-4]. Oligomenorrhea is defined as less than six to eight periods during a year. Dysmenorrhea is classified into two categories such as primary and secondary dysmenorrhea [5]. Menorrhagia is a heavy yet regular menstrual bleeding (loss of 80 mL blood per cycle) in a woman which is thought to be caused by disordered prostaglandin production and abnormal uterine [6]. Polymenorrhea is another type of abnormal uterine bleeding and defined as a menstrual length cycle which lasts less than 21 days [7].

Migraine is known as a common disorder, and according to the international headache society’s criteria, there are at least 5 episodes of headaches with the duration of 4-72 hours. Except for other secondary causes, minimum two of four causes should be involved in the headache’s quality; unilateral headache, from moderate to severe mood, interference with the daily physical activity. Moreover, one of these symptoms such as nausea, photophobia, phonophobia, vomiting should be present in migraine. Migraine is categorised by moderate to severe headaches and includes 18% of women over 18-49 ages as they are in the menstrual ages [8].

In clinical practices, the association between migraine and menstruation has been reported in 50% of women [9]. It has also been indicated that many women with menstrual disorders might show severe, longer, and fewer responses to the drugs against migraines compared to others in menstrual ages [10,11].

As per the International Headache Society (IHS) “The endogenous menstrual cycle results from complex hormonal changes in the hypothalamic, pituitary, ovarian axis resulting in ovulation suppressed using of combined oral contraceptives. Therefore researcher should separately work on the women using the hormonal treatment and those who not use hormonal treatment. Several diary card studies have assessed the clinical association between migraine and menstruation [12-14] whilst there has not been much research reported on the menstrual disorders in those who have suffered from migraine. This, therefore, motivated the present clinicians to conduct a study relation between menstrual disorders in women with migraine and without migraine.

Materials and Methods

This was a case-control study, conducted in one year (Jan 2018-Feb 2019) among women referring to neurological clinic at one of the academic hospitals in Iran. The study was based on a convenience sample of 175 female patients, aged 18-49 years old. This study received the Ethical Committee approval (IR.SBMU.MSP.REC.1395.55) and all the patients were enrolled after obtaining their consent.

According to International Headache Society (IHS) by a same neurologist, the subjects were separated in two groups; case and control groups and 86 women were put in case group that suffered from migraine, and 89 were put in control group without any signs of migraine. Women with a history of hysterectomy and HRT and the patients with history or suspicion for Polycystic Ovary Syndrome (PCOS), endometriosis, hyper/hypothyroidism were excluded from study.

A written questionnaire was filled by participants according to their vernacular language (Persian). The questionnaire was validated and reliability checked by mean alpha score 0.7 designed by Zandifar A et al., and consisted of two major sections: menstruations-related and headache-related questions [15]. The menstruation-related questions were involved in both quantitative and qualitative responses. Quantitative questions included the duration of periods; interval between periods, number of pad/tampons required on heavy flow day of menstruations, and the number of days that they feel intensity of menstrual blood flow is increased. In order to evaluate the menstrual blood loss, the Pictorial Blood Loss Assessment Chart (PBLAC) was used. PBLAC is a semi-quantitative method for evaluation of menstrual blood loss (score >100) defined by Higham JM and validated by Janssen CA et al., [16,17].

Qualitative questions addressed the woman’s perception of the length of periods (4-8 days, <4, >8), the length of the interval between the periods (24-38 days, <24, >38), and the regularity. The intensity of flow and abdominal pain was indicated as mild, moderate, severe, defined by WALIDD score [18]. The participants were also asked about the onset, current intensity, frequency, and duration, as well as about the following headache features and associated symptoms: vomiting, nausea, photophobia, phonophobia, laterality, aura, throbbing, worsening by routine physical activity.

Statistical Analysis

Descriptive statistics were utilised to characterise the study population. All results were expressed using the lowest, median, highest data, frequency and percentage. To control the effect of defaceable variables, statistical tests such as independent t test, was used. Logistic regression was used for effectiveness of migraine. The present authors also used Spearman coefficient of correlation for finding quantitative variables and chi-square test for comparison variables. All analysis was expressed as the mean±SEM at the level of 0.05 and all results were evaluated by SPSS version 22.00 statistical software.

Results

In the control group, 55 people (61.8%) were married while in the case group 62 (72.1%) women were married. There was no considerable difference in the level of education, and both groups had pre-university degrees (p=0.164) [Table/Fig-1].

Comparison of demographic characteristics between cases and controls.

VariableControl (n=89)Case (n=86)p-value
Age*31.07±7.63; (18,49)32.41±8.39; (18,49)0.271
BMI*24.05±4.03; (17.19,39.04)25.28±5.42; (16.42,45.84)0.091
Marital statusSingle34 (38.2)24 (27.9)0.148
Married55 (61.8)62 (72.1)
Medical problemHeart problem1 (1.1)6 (7)0.061
Aspiration2 (2.2)5 (5.8)0.272
Digestion7 (7.9)17 (19.8)0.022
Endocrine6 (6.7)3 (3.5)0.497
Haematology11 (12.4)3 (3.5)0.031
Psychiatry6 (6.7)8 (9.3)0.532
Allergy5 (5.6)6 (7.1)0.696
Urology4 (4.5)2 (2.3)0.682
EducationPrimary school/illiterate13 (14.6)24 (27.9)0.164
Diploma28 (31.5)29 (33.7)
Technician10 (11.2)6 (7)
B.S20 (22.5)12 (14)
MS/MD/PhD18 (20.2)15 (17.4)

*data are shown as mean±SD; median(min, max); data are shown as N (%)

Independent T-test; SPSS


The proportion of women with menstrual cycle <24 was 25.6% and 10.1% in case and control group in order (p=0.020). Also, the proportion of women with menstrual cycle >38 days’ in case group 12.8% vs 11.2% in control group which showed a significant relation, while the proportion of women with a duration of 24-38 days was 61.6% in case group vs 78.7% in control group [Table/Fig-2]. As in [Table/Fig-3], by controlling factors such as age, BMI and other variables, pictorial score was found to affect migraine in a way that the risk of getting migraine would increase to 1% just by increasing 1 unit of the scale (OR=1.01: p=0.031). The characteristics of headache in case group are illustrated in [Table/Fig-4].

Comparison of menstruation related history between cases and controls.

VariableControl n=89Case n=86p-value
Pictorial score90 (82.5); (7,400)99 (141.5); (5,310)0.166
Cycle durationLess than 24 days9 (10.1)22 (25.6)0.020
24-38 days70 (78.7)53 (61.6)
More than 38 days10 (11.2)11 (12.8)
Period regularityIrregular19 (21.3)18 (20.9)0.445
Regular, more than 5 days21 (23.6)51 (59.3)
Regular, less than 5 days49 (55.1)17 (19.8)
Menstrual durationLess than 4 days6 (6.7)15 (17.4)0.025
4-8 days77 (86.5)60 (69.8)
More than 8 days6 (6.7)11 (12.8)
Dysmenorrhea48 (53.9)35 (40.7)0.080
Any consumption of drugs related to menstruation0 (0)0 (0)
Delivery typeNone48 (53.9)36 (41.9)0.405
César17 (19.1)19 (22.1)
NVD18 (20.2)25 (29.1)
Both NVD and César6 (6.7)6 (7)
ContraceptiveNone37 (41.6)23 (26.7)0.139
Pill8 (9)16 (18.6)
Surgery5 (5.6)2 (2.3)
Withdrawal18 (20.2)19 (22.1)
Barrier14 (15.7)20 (23.3)
IUD7 (7.9)6 (7)
Amenorrhea0 (0)0 (0)
Parity numberNone48 (53.9)34 (39.5)0.047
One11 (12.4)12 (14)
Two16 (18)19 (22.1)
Three and more14 (15.7)21 (24.4)
Child numberNone49 (55.1)36 (41.9)0.078
One14 (15.7)17 (19.8)
Two20 (22.5)22 (25.6)
Three and more6 (6.7)11 (12.8)
AbortionNone75 (84.3)65 (75.6)0.326
One12 (13.5)19 (22.1)
Two or more2 (2.2)2 (2.3)

Independent T-test; SPSS


Logistic regression of migraine risk factors.

VariableBSEp-valueOR95% CI for OR
LowerUpper
Age-0.020.030.5030.980.931.04
BMI0.050.040.2091.050.971.14
Pictorial score0.010.0020.0311.011.001.01
Parity number0.210.180.2371.230.871.75
Cycle duration (ref: More than 38 days)
Less than 24 days)1.410.800.0754.090.8719.34
24-38 days0.220.590.7041.330.403.95
Menstrual duration (baseline: less than 4 days)
4-8 days-1.710.620.0060.180.050.61
More than 8 days-1.940.950.0410.140.020.92

logistic regression; SPSS V22


Charectristics of headache in case group.

VariableMean±SDMed (IQR); min-max
Age at onset23.6±5.3724 (9.5); 12-32
Headache timing15.47±17.738(17) 4-72
Pain severity7.42±1.588 (3) 1-10
Categorical variableLevelsN (%)
Pain relief number06 (7)
153 (61)
225 (29.1)
32 (2.3)
Pain durationFor months12 (14)
For years74 (86)
Pain frequencyonce a month19 (22.1)
once a week20 (23.3)
two times or more in a week42 (48.8)
daily5 (5.8)
Pain locationalternative63 (73.3)
one sided10 (11.6)
bilateral13 (15.1)
QualityPulsatile74 (86)
Tensional12 (14)
Auranone65 (75.6)
Visual14 (16.3)
Sensory4 (4.6)
olfactory2 (2.3)
visual and olfactory1 (1.2)
Pain provokerlight4 (4.7)
noise5 (5.8)
smell2 (2.3)
Daily activity 02 (2.3)
stress1 (1.2)
light and noise20 (23.3)
light and noise and daily activity41 (47.7)
light and noise and smell11 (12.8)
Associated symptomsnone10 (11.6)
Nausea54 (62.8)
Nausea and vomiting21 (24.4)
others1 (1.2)
Precipitating factornone51 (59.3)
menstruation35 (40.7)
Family history of migraine64 (74.4)

Moreover, there was no significant linear relationship among cycle duration, period regularity, and menstrual duration, dysmenorrhea, on severity and duration of headache [Table/Fig-5]. No significant relationships between any of variables such as, the number of births (r=0.15), number of children (r=0.18), pictorial score (0.04), age (r=0.02), age of onset of headache (r=0.01), BMI (r=-0.07) [Table/Fig-6].

Patients’ comparison of (headache) severity and headache timing according to the period history.

VariableHeadache severity(mean±SD; med (min, max))p-valueTiming of headache (hour)(mean±SD; med (min, max))p-value
Cycle Durationless than 24 days7.71±1.65; 8 (4,10)16.27±19.61; 8 (2,72)
24-38 days7.26±1.61; 7 (1,10)0.42916.17±18.41; 8 (4,72)0.800
more than 38 days7.64±1.29; 8 (6,9)9.27±6.53; 6 (5,24)
Period regularityIrregular7.41±1.5; 6 (6,10)17.72±21.15; 9.5 (2,72)
regular/more than 5 days7.07±1.59; 7 (4,9)0.58221.64±24.48; 8.5 (4,72)0.735
regular/less than 5 days7.52±1.61;8 (1,10)12.87±13.87; 7.5 (4,72)
Precipitating factorNone7.65±1.27; 8 (5,10)0.14918.53±21.36; 8(4,72)0.210
Menstruation7.11±1.90; 7 (1,10)11.31±9.89; 6 (4,48)
Menstrual durationless than 4 days6.71±2.02; 7 (1,9)12.80±17.38; 7 (2,72)
4-8 days7.57±1.40; 8 (5,10)0.34415.52±17.64; 7.5 (4,72)0.860
more than 8 days7.55±1.81; 8 (4,9)17.64±19.59; 10 (4,72)
DysmenorrheaNo7.63±1.36; 8 (5,10)0.30515.51±18.09; 8 (4,72)0.717
Yes7.12±1.84; 7 (1,9)15.03±17.33; 7 (2,72)
ContraceptiveNone6.87±1.87; 7 (1,9)9.74±7.54; 6 (4,24)
Pill7.813±1.22; 8 (5,9)14.25±8.13; 12.5 (4,24)
Surgery8±1.41; 8 (7,9)0.35039±46.67; 39 (6,72)0.476
Withdrawal7.16±1.74; 7 (4,10)14.84±17.71; 8 (4,72)
Barrier7.95±1.31; 8 (6,10)18.55±23.96; 6 (2,72)
IUD7.5±1.05; 7.5 (6,9)22.33±25.48; 14 (5,72)
AbortionNo7.44±1.59; 8 (1,10)0.81415.15±16.55; 8 (2,72)0.427
Yes7.38±1.57; 8 (4,10)15.81±21.26; 6 (4,72)

chi-square test


Correlation of (headache) severity and headache timing and patients characteristics.

Parity numChild numPictorial scoreAgeAge at onsetBMI
Headache severityrho0.150.180.040.020.01-0.07
p-value0.1590.1030.7140.8700.9030.543
Timing headacherho0.180.2450.020.070.080.06
p-value0.0950.0230.8500.5210.4810.605

Spearman correlation coefficient


Discussion

Following study considered the prevalence of migraine which is significantly higher among women with oligomenorrhea, polymenorrhea, also in women with abnormal menstrual duration (<24 or >38) [19]. This study was designed to compare women in reproductive age, as prior studies reported the prevalence of migraine among women in reproductive age is more than twice of men in the same age, there is a significant decline in rate of migraine after 65 years of age in both sexes [20,21]. Since menarche, hormonal changes affect the intensity and timing of migraine attacks in women. However, the present authors achieved no significant influence on the intensity or time duration of headache in the present study. Migraine in women in adolescent and reproductive age is more prolong and more resistant to treatment in comparison to women in non-productive ages.

In a case-control study by Tietjen GE et al., the frequency of menorrhagia was evaluated and it was defined by at least 3 severe consecutive menses and Endometriosis in migraine sufferers which finally resulted in no signs of episodes of migraine [10]. They enrolled 50 women who suffered from migraine at the age of 22-50. They were also diagnosed to have migraine, and based on the international headache society’s criteria; they all were compared with 52 healthy women. It has been revealed that the women with migraine are more susceptive to menorrhagia and endometriosis, as the amount of menorrhagia in women with migraine was measured (63% vs 37%) (p=0.009). The results of menorrhagia are similar to present study. In 2015, Spiering ELH and Padamse A, published a research during which the menstrual cycle abnormalities in acute and chronic migraine were investigated, and 96 women ageing 18-45 years were examined via questionnaire and they were separated into two different groups [22]; including episodic and chronic migraine. Data recorded menstrual cycle disorders consisted of oligomenorrhea, polymenorrhea, irregular cycles of dysmenorrhea, menorrhagia, and finally the prevalence of menstrual cycle disorders. It has been illustrated that the percentage of such features in group with chronic migraine was 2.41% vs 2.22% in other groups. Furthermore, the prevalence of dysmenorrhea was 51% vs 9.28% in women with chronic migraine showing the higher proportion rather than that in episodic ones (p≤0.05). The result of this study is in line with prior studies, which showed the higher number of chronic migraine between migrainous populations suffering from menstrual disorders.

Neurogenic inflammation is another hypothesis to explain migraine pain [23]. According to this theory, inflammation agents play a main role of sensitisation nociceptors and induce migraine headache. A common origin of pain signals is trigemino-vascular structure in the meninges which carry out pain to the cortex [24]. Trigemino-vascular activation causes the release of nociceptors neuropeptides such as Calcitonin Gene-Relatedpeptide (CGRP), prostaglandins, Vasoactive Intestinal Peptide (VIP), Somatostatin (SST), Substance p (SP). Release of these inflammatory agents induce a cascade mechanism which consist of dilation of cerebral arteries, increase cerebral blood flow, increase sensitisation of nociceptors and increase pressure and pain of migraine [23,25,26]. As a consequence of this theory, elevated CGPR and other nociceptors neuoropeptides which seems to be increasing in migraineous women during migraine attack [27-29] induced peripheral and central sensitisation, perceive as headache, photophobia, and phonophobia [30]. Menstrual migraine is a special type of migraine influenced by neuroendocrine fluctuation due to menstrual cycle. Reduction of oestrogen levels prior to luteal phase may induce menstrual migraine attacks more feasible in premenstrual period that triggered by oestrogen withdrawal after high oestrogen level [31]. MacGregor EA et al., investigated migraine prevalence among 38 migraineous women, comparison revealed that the incidence of period is raised with falling in oestrogen level during the late luteal or early follicular phase, in comparison to elevated oestrogen phase [32]. Further migraine occurring during menstruation bleeding is more severe than other times [33]. In a study by Granella F et al., assessed menstrual related migraine among 64 women, reported that, migraine attacks which occurred between 2 days prior to menstruation time to day 7 of menstruation cycle [34], last long and less responsive to drugs, also they have high recurrency rate as compared to other episodes of migraine [35]. Moreover, endometrial prostaglandins level increase from follicular phase to luteal phase and become much higher during timeframe. Releasing of the Prostaglandins as an inflammatory agent into blood circulation inducing neurogenic inflammation [36]. Prostaglandin indicated to be a related biochemical factor for menstrual disorders, but there are other correlated conditions such as oestrogen withdrawal may inevitably coordinate in migraine accuracy in subjects with menstrual disorders. Therefore migraine pain may impute to inflammation and similar biochemical changes [33].

Limitation(s)

Due to lack of resources, the present authors did not examine the mechanism of menstrual disorders and its effectiveness on migraine. However, this study could not found out any relation between severity and duration of headache with menstrual disorders.

Conclusion(s)

According to the finding of the present study, Migraine is more common among women with menstrual disorders. Further research is needed to find the exact mechanisms behind that.

*data are shown as mean±SD; median(min, max); data are shown as N (%)Independent T-test; SPSSIndependent T-test; SPSSlogistic regression; SPSS V22chi-square testSpearman correlation coefficient

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