Health-Related Quality of Life and Associated Factors in Chinese Menstrual Migraine Patients

Menstrual migraine is a special form of migraine with signicant impact on quality of life for those women aicted. Presently, there is no study reported on quality of life in menstrual migraine patients. The study reported here aimed to assess the health-related quality of life and identify its associated factors among Chinese menstrual migraine patients. The cross-sectional study group consisted of 109 patients with menstrual migraine and the control group consisted of 397 female patients with non-menstrual migraine. In total, 506 patients completed questionnaires for demographic and clinical information, Self-rating Idea of Suicide Scale, Hamilton Depression Scale, Hamilton Anxiety Scale, Headache Impact Test-6, Perceived Social Support Scale, Pittsburgh Sleep Quality Index. Health-related quality of life was measured using the 36-Item Short Form Survey. HAMA, Hamilton Rating Scale for Anxiety; PSSS, Perceived social support scale; PSQI, Pittsburgh Sleep Quality Index; SIOSS, Self-rating Idea of Suicide Scale.MCS: mental component summary.


Results
Migraine is a common debilitating headache disorder that was ranked as the second highest cause of disability in the 2016 Global Burden of Disease study [1]. Menstrual migraine (MM) is a subclass of migraine that can be classi ed into two types: pure menstrual migraine and menstrually-related migraine [2], and the prevalence of MM in female migraine patients is nearly 60% [3]. Compared with nonmenstrual Migraine (NMM), MM is characterised by longer duration, greater frequency, less responsive to treatment, and may cause more severe disability and heavier life burden to patients [4,5].
Health-related quality of life is de ned as an individual's subjective perception of the impact of disease and treatment on physical, psychological, social and somatic domains of functioning and well-being [6]. HRQoL assessments could provide patients, researchers and policy makers with information about the status of a patient's health in an e cient manner [7]. Limited number of studies indicate a negative effect of migraine on quality of life [8,9]. In clinical practice, it has also been observed that a considerable proportion of MM patients suffer from anxiety and depression symptoms, sleep disorders and other unpleasant mental and physical experience, leading to decreased quality of life. Therefore, it is of great signi cance to actively search for and devote to improving controllable risk factors for MM patients.
Clinicians have found the contribution of that demographic factors such as age, clinical factors such as frequency and severity of pain, and psychological factors such as anxiety and depression symptom play an important role in decreasing the migraine patients' quality of life. However, studies on the quality of life and its associated factors in patients with MM are scarce. Based on the particularities of MM, further study of factors related to quality of life with MM is warranted.
The purpose of this cross-sectional study was to explore the HRQoL of MM versus NMM and to identify its associated factors among Chinese MM patients. It was hypothesized that (1) MM patients have lower HRQoL when compared with NMM; (2) Some clinical and psychological factors could affect the HRQoL of MM patients. Our research would provide a more comprehensive understanding of the HRQoL and associated factors among Chinese MM patients. Understanding these factors may help the development of individualized strategies for patients, thereby raising the HRQoL and reducing the nancial, social and psychological burden.

Method
Participants and study design A cross-sectional study was conducted from February 2019 to February 2020 at the neurology department of a hospital in western China. A total of 545 female migraine patients who met the diagnostic criteria were screened, and 39 persons who did not complete the HRQoL scale were excluded (3 with MM, 36 with NMM). A total of 506 female patients diagnosed with MM (n = 109) and NMM (n = 397) were included in this study, the inclusion criteria are in line with the International Classi cation of Headache Disorders, Third Edition (ICHD-3) developed by the Headache Classi cation Committee of the International Headache Society (Two experienced neurologists con rmed all diagnoses using ICHD-3 diagnostic criteria). Exclusion criteria: 1. Patients who had been diagnosed with psychiatric illness before the headache occurred, including anxiety disorder, depressive disorder, sleep disturbance, etc; 2. Patients with secondary headaches; 3. patients suffered from other disease that affect the quality of life; 4. patients who could not understand the content of questionnaire or did not complete the questionnaire; 5.
Patients who refuse to sign informed consent. All participants signed an informed consent, and this study was approved by the Survey Ethics Committee of the rst author's a liated institution. All authors had full access to all data.

Data Collection
Demographic and headache information Demographic variables include age, ethnicity (Han/minority), height (cm), weight (kg), body mass index (BMI), BMI is calculated as BMI = body mass (kg)/ (height (m))2. Headache related information include headache frequency (the average number of days with headache per month over the last 3 months), duration (<24h/24-72h/>72h), severity (mild/moderate/severe), with or without family History and with or without aura.
Health-related quality of life HRQoL was measured using the Mandarin version of 36-Item Short Form Survey (SF-36) which has been tested with satisfactory reliability and validity [10,11]. The SF-36 is a widely used survey of self-

Impact of Headache on daily life
We performed the Headache Impact Test-6 (HIT-6) to assess the impact of headache on daily life. The HIT-6 is a concise and reliable tool for measuring headache burden based on six domains with total score ranging from 36 to 78. The higher the score, the greater impact of headaches on daily activities [12].

Anxiety and depression symptoms
The severity of anxiety symptoms and depression symptoms of patients were assessed using the Hamilton Anxiety Scale (HAMA) and the Hamilton Depression Scale (HAMD) respectively. The higher the score, the more severe the anxiety or depression symptoms are [13,14].

Social support
Perceived Social Support Scale (PSSS) consists of 12 items, assessing perceived support from family, friends, and signi cant others. The total score ranges from 12-84, with higher scores representing higher perceived social support [15].

Sleep quality
We measured sleep quality of patients using the Pittsburgh Sleep Quality Index (PSQI), a questionnaire that assesses subjectively perceived sleep quality over the last month. The PSQI is a self-report instrument that consists of 7 components: subjective sleep quality, sleep latency, sleep duration, habitual sleep e ciency, sleep disturbances, use of sleeping medications, and daytime dysfunction. The total score ranges from 0-21, with higher scores indicating poorer sleep quality[16].

Suicidal ideation
Self-rating Idea of Suicide Scale (SIOSS) is a self-report tool in Chinese with 26 questions that evaluate the suicide ideation of patients. We use the sum of three factors (despair, sleep and optimism) to assess the level of suicidal ideation. The SIOSS has been shown to have good reliability and validity [17]. A higher score re ects a higher level of suicidal ideation.

Data quality control
All the data collectors including psychiatrists and neurologists have received special training about data collection and management to ensure uniformity in criteria evaluation.

Statistical methods
Statistical analyses were performed with IBM SPSS version 26.0 software. Measurement data was expressed as Mean (standard deviation (SD)) and t test was used to compare between two groups. Count data was presented as percentages (N, %), and chi-square test was used to compare between two groups.
Possible associated factors of PCS and MCS were analyzed using univariable logistic regression, stepwise multiple linear regression was performed on the factors with statistical signi cance in the univariate regression analyses to identify the independent factors that in uenced PCS and MCS. P < 0.05 was considered statistically signi cant.

Demographic and clinical characteristics
A total of 506 patients consented to participate in the study, including 109 MM patients and 397 NMM patients, with mean ages of 23.62 years (SD=7.59) and 21.48 years (SD=7.08), respectively. Table 1 presents the demographic and clinical characteristics about the participants and illustrates the differences between MM and NMM.
Health-related quality of life

Univariate analysis of factors associated with PCS and MCS
Univariate analysis showed that the PCS and MCS scores were both correlated with headache frequency, anxiety and depression symptoms, suicidal ideation, sleep quality and social support, while the impact of headache on daily life was only related to PCS scores. Detailed data are presented in Table 2. Step  Our study demonstrated that depression symptoms are independently associated with PCS and MCS, after adjusting the confounding factors. Depression is a common comorbidity in migraine patients, and HRQoL was reduced in patients who had both migraine and depression relative to migraine patients who were not depressed [20]. A recent study in the United States found that depression symptoms are a predictor of headache frequency and migraine-related disability [21]. Hence, it is not di cult to understand that depression symptoms are closely associated with physical and mental health. In agreement with the study nding in Brazil, we demonstrated that the severity of depression symptoms is a predictor of HRQoL among MM [22]. Pradeep et al. reported the presence of depression was noted to add to the magnitude of migraine-related disability and diminished the quality of life in migraine patients, which is similar to the results of our study [23]. This study [23] also found that anxiety had a negative impact on the quality of life of patients who suffer from migraine. In our study, although univariate analysis showed that anxiety symptoms may be a signi cant risk factor for HRQoL in MM patients, no signi cant difference was detected by multivariate analysis. At present it cannot be certain that anxiety symptoms are independently associated with HRQoL among MM patients.
MM patients who reported more frequent migraine attacks and greater impact of headaches on daily life could impair HRQoL by affecting their physical health. A downward trend in the quality of life of migraine was noted with the increased headache frequency [20]. Previous study has proved that the more frequent migraine attacks and greater impact of headaches on daily life were predictors of detrimental effects on quality of life in migraine patients [23], which is similar to our results. In a recent study, Irimia found that a positive linear association between headache frequency and the risk of anxiety, depression in migraine patients [24]. Patients with monthly headache days ≥ 3 days are at higher risk of anxiety, while those with ≥ 19 days are at risk of depression. Moreover, patients with monthly headache days ≥ 10 days are often accompanied by severe disability [24]. It is interesting to note that patients experiencing only one to six headaches per year still show a reduction in quality of life, it might be due to the unpredictability of attacks that magni es the effect of the few headache days on quality of life in a remarkable way [20].
Richard et al [25] examined the association between headache-free days and the disease burden of migraine, and found headache-related disability shows a decrease tendency with the headache-free days increasing [25].
Our research showed that the perception of social support is positively associated with MCS. An Italian study of chronic migraine patients with medication overuse found that social support is a predictor of the quality of life to some extent [26]. Moreover, a French study also found that the higher perceived social support was, the higher the probability of being an active consulter for migraine [27,28]. Such headache counseling allowed patients to actively take prevention and treatment strategies to minimize the burden of migraine and relieve adverse emotions, and thus engaged more in social activities and improved HRQoL, especially in mental health related HRQoL.
As the limitations of daily social and work-related activities caused by migraine, the mental health of patients was impacted, and severe cases may lead to suicidal ideation. Our research found that suicidal ideation can affect MCS and could consequently predict HRQoL of MM patients. Many scholars agreed that migraine patients are associated with a poor quality of life and a higher likelihood of suicidal ideation [8,9,29,30]. This study demonstrated, for the rst time to our knowledge, the correlation between HRQoL and suicidal ideation among MM patients. Providing psychological treatment to MM patients with suicidal ideation may help to reduce suicide risk, as can the application of active treatment, improving their mental health and HRQoL.
Sleep disturbance, as a clinical triggers for migraine, is associated with migraine, creating a vicious cycle [31]. Although sleep quality is associated with the PCS and MCS of patients with MM in the univariate analysis, it is no longer a signi cant associated factor after adjusting for the potential confounders in the multivariate model. Thus, we cannot consider sleep quality as a predictor for HRQoL in MM patients. In the current study, the evidence describing the relationship between sleep quality and HRQoL was still insu cient among migraine patients [32],and this result was in line with the previous study. There were some limitations to this study. The sample representativeness was limited because the sample was derived from the outpatient population of a hospital in southwest China. A multicenter study would be needed with a larger sample size and more associated factors to determine the factors that had an association with HRQoL of MM patients.

List Of Abbreviations
HRQoL

Consent for publication
Not applicable.

Availability of data and materials
The datasets used or analysed during the current study are available from the corresponding author on reasonable request.

Con icts of interest
The authors declare that they have no competing interests

Funding
The research received funding from the Bureau of Science and Technology and Intellectual Property of Nanchong City (No. NSMC20170420).

Authors' contributions
Material preparation, data collection and analysis were performed by Wenxiu Luo, Xing Cao and Jiaming Luo. The rst draft of the manuscript was written by Wenxiu Luo and Xing Cao, and all authors commented on previous versions of the manuscript. All authors read and approved the nal manuscript. All authors certify responsibility of the paper.