Breast pain, also called mastalgia, is one of the most common complaints in breast surgery clinics and the prevalence of mastalgia varies between 41% and 80% among women. 123 Breast pain can be mild or severe, as well as cyclical or noncyclic. The most recent literature stresses that cyclic mastalgia is the most common form and is associated with menstruation. The aetiology of cyclical mastalgia addresses a disturbance in hormonal balance between oestrogen, progesterone, prolactin, and the responsiveness of target organs to these hormones. Therefore, hormonal treatments such as antiestrogen agents, danazol, and LHRH analogue are recommended in the treatment of pain. 3456 On the other hand, some women struggle with severe non-cyclic mastalgia, which affects their daily activities. The underlying physiopathology of non-cyclic pain is less obvious than cyclic mastalgia and this hinders the effectiveness of the management of the treatment. 57 Mastalgia is thought to have a connection with psychosomatic disorders because there is no clear organic cause identified in its aetiology. It was mentioned for the first time in 1949 that mastalgia may be related to a psychological problem. 8 This idea has gained considerable support when an association has been shown between treatment resistant mastalgia and psychological symptoms such as anxiety, depression and somatization. 9101112 In addition, mastalgia has a connection with psychosocial problems. Professional, social and psychological lives of women are negatively affected due to this pain. 8 Despite the widespread belief that psychological and social factors affect breast pain, empirical evidence is very limited.

Research has demonstrated that regional disparities, such as differences in socioeconomic composition, have a major impact on health. 1314 Turkey has regional inequalities; hence employment rates, education levels, welfare and economic structure are affected. There is a large East-West distinction in the development of agriculture and industry, in working and earning conditions, in public or private investment potential, and in the direction of migration flows. 15 The present study aims to illuminate the differences in psychological symptoms and health related quality of life (HRQL) between Eastern and Western Turkey in patients with mastalgia.

The current study was carried out in Istanbul University, Istanbul Faculty of Medicine, Department of General Surgery and Diyarbakır Ergani Hospital, General Surgery Clinic. The study, approved by the Ethical Committee of Istanbul University, Istanbul Faculty of Medicine and Ergani Hospital, was conducted in accordance with the guidelines of the 1975 Declaration of Helsinki and signed informed consent was obtained from all patients. Women who were suffering from breast pain for at least 3 months were offered the opportunity to participate in the study. Patients with a history of an organic breast disease such as cancer, abscess or known breast pathology, or a history of previous breast surgery were not included in the study. Pregnant, breastfeeding women and patients who could not complete the questionnaires were excluded from the study. Routine radiological breast screening was carried out via mammography or/and ultrasonography according to patient age and clinical findings. The Breast Imaging-Reporting and Data System (BI-RADS) 1 and BI-RADS 2 were included in the study. A score of four or greater on a breast-pain survey with pain scores from 1 to 10 (10 being worst pain) was also required. In addition, patients with a score of over 30 (maximum 78) in the McGill Pain Questionnaire were included in the study. The psychological findings of the patients were evaluated using SLR-90-R. Turkey's western (Istanbul University, Istanbul Faculty of Medicine) and eastern (Diyarbakır Ergani Hospital) regions were compared. Seventy-four patients who were admitted to general surgery clinics of Diyarbakır Ergani Hospital (n=39) and Istanbul Faculty of Medicine (n=35) were included in the study. The psychological findings of the patients were evaluated by the symptom checklist-90-revised (SCL-90-R) and HRQL was evaluated by the short-form health survey (SF-36) scale.

The SCL-90-R is a validated scoring index for assessing a broad range of psychopathological problems and symptoms. 1617 This psychiatric evaluation index contains 90 questions that are scored on a 5-point scale (1-5) ranging from "not at all" to "extremely," reflecting the occurrence rate of symptoms during the time reference. The questionnaire covers the previous week, and includes the current day. It measures symptom intensity on nine different subscales: somatisation, obsessivecompulsive behaviour, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid thinking and psychoticism. Higher scores show increased psychological adversity. The total score is evaluated as the Global Severity İndex (GSI). This checklist comprises 90 questions with five response options: 0=not at all, 1=a little bit, 2=moderately, 3=quite a bit, 4=extremely. 18 GSI is found by dividing the scores obtained from clinical subtests by the total number of questions. Make general judgment depending on the general symptom average of GSI. If the average is greater than one, it indicates a psychological problem. If the average is less than 0.5, it indicates that there is no psychological problem.

The SF-36 scale is a self-reported scale which consists of 36 items comprising 8 subscales, including physical functioning, role limitations due to physical health or emotional problems, bodily pain, general health, vitality (energy), social function and mental health. The SF-36 scale is scored over 100, and the obtained scores vary between 0 and 100 scores for each subscale. In this scale, while higher scores indicate good health, the lower scores demonstrate deterioration in health. 1920 In addition, SF-36 is a commonly used instrument for measuring HRQL.

Data were analysed using SPSS v.21.0 for Windows. The clinical characteristics of the patients were evaluated using descriptive statistics including means, medians and standard deviation. Since the data showed a normal distribution, independent sample t test was used for the statistical comparison of two patient groups. In addition, Spearman's rho correlation test was used for determining the relationship between psychological findings. Significance was accepted at P<0.05.

Seventy-four patients were included in the current study and the median age of the patients was 31.81±9.6 (18-70) years. The median age of the patients from the General Surgical Clinic of Diyarbakır Ergani Hospital (Eastern group) (n=39, 52.7%) was 27.54 (18-39) years and 35.57 years for the patients from Istanbul University, Istanbul Faculty of Medicine, Department of General Surgery (Western group) (n=35, 47.3%). The difference between median ages of the groups was statistically significant (t=-4.585, P<0.0001). There was no statistically significant difference between age and other variables.

Psychopathological findings were compared using SCL-90-R scales. The results are shown in Table 1.

Average GSI scores of the eastern group were statistically significantly higher than those of the western group (P<0.01). In addition, the average of all subscale scores of the eastern group, except for phobic anxiety, was over one. On the other hand, in the western group, somatization and obsessivecompulsive subscales averages were found to be above one. When the SCL-90-R values of the eastern and western groups were compared, somatization, interpersonal sensitivity, phobic anxiety, psychoticism, depression and anxiety in the eastern group were statistically higher than what was observed in the western group. No statistically significant difference was found between age and SCL-90-R subscales. Average GSI scores of the eastern group were statistically significantly higher than those of the western group (P<0.01). In addition, the average of all subscale scores of the eastern group, except for phobic anxiety, was over one. On the other hand, in the western group, somatization and obsessivecompulsive subscales averages were found to be above one. When the SCL-90-R values of the eastern and western groups were compared, somatization, interpersonal sensitivity, phobic anxiety, psychoticism, depression and anxiety in the eastern group were statistically higher than what was observed in the western group. No statistically significant difference was found between age and SCL-90-R subscales.

HRQL between groups were compared using SF-36 scales and results are presented in Table 2. According to SF-36 results, the average points of physical, physical role difficulty and social functions were found to be lower in the eastern group than in the western group (respectively P= 0,029, P= 0.002, P<0.001).

Studies have shown that regional inequalities, such as differences in socioeconomic areas, have an impact on health. 1314 There are differences between Eastern and Western Turkey. On average, Istanbul, Ankara, and Izmir constitute 52% of Turkey's GDP. On the other hand, the contribution of the East to GDP is 1.28%. 21 The rate of illiterate women is 6.30% in Marmara region (Istanbul zone), whereas 34.08% in Southeast regions. 22 Sozmen et al. indicated that inequalities in self-assessed adult health which is well known as an important predictor of morbidity, mortality and health services utilisation, has been mainly related to educational level, household wealth and geographical area. 23 The Eastern group's average SCL-90-R scores were statistically significantly higher than those of the Western group (P<0.01). These results may show us that the underlying psychosocial problems in women with breast pain may be affected by regional and socioeconomic factors. When looking at the sub-scales, somatization and obsessive-compulsive scores were over one in both groups, this means that obsessive-compulsive and somatization symptoms are dominant findings in mastalgia patients. In addition, some studies have even suggested that mastalgia is one of the somatization signs of fibromyalgia syndrome. 24 There are many studies that analyze the interaction between mastalgia and psychological stress and psychological symptoms. 9101112 Our results are similar in many respects to those from previous studies on mastalgia and psychological symptoms such as anxiety, depression and somatization. When the mean age of mastalgia patients in the east and west was compared, it was found that patients in the east area were statistically younger than those in the west (P<0.0001). Further research is needed to improve our understanding of the underlying causes of the age difference. However, this may be due to the early marriage and childbirth and taking the responsibility of the family as a woman at such a young age (mainly before 18 years).

Colgrave et al. compared psychological characteristics of women presenting to a breast clinic for mastalgia and they found that, in addition to anxiety, depression and somatization symptoms, a history of emotional abuse was associated with mastalgia. 11 In the current study, the scores of all subscales except paranoid thinking were significantly higher in the eastern group (somatization, obsessivecompulsive, interpersonal sensitivity, hostility, phobic anxiety, psychoticism, additives, depression and anxiety). This increase may be related to the role of the woman in the eastern region in the social and cultural environment. Women's desire to be more valuable in their environment and families may lead to somatization of pain as mastalgia. This is because the woman may have a belief that her family and especially her husband will love her more when she gets sick. Otherwise, the woman has only the role of childcare, doing the household chores and cooking and that's why she wants to change her current position in the home.

Research has raised an important point that severe mastalgia in women's daily life may be related to the fear of breast cancer. 2425 Physical examination, ultrasonography examination may affect the psychological state of the patient and reduce the patient's pain and anxiety. 25 In the west part of Turkey, women are more educated than the east part of Turkey. Therefore, women in the west may have higher psychological satisfaction rates after normal radiological imaging and doctor examinations.

Professional, social and psychological lives of women are negatively affected due to breast pain. 826 We used SF-36 scales to compare HRQL and the results showed that the physical function, physical role difficulty, and social functions were affected significantly in the eastern part. While the pain scores in the two groups were similar, the effect of pain on social life and physical functions were more strongly felt in the eastern group. This means that women's daily life activities and social functions are limited due to breast pain. However, whether this limitation is a result of psychology or chronic pain is not clear. It has been shown that chronic breast pain may also be associated with other chronic pain syndromes and this will lead to more negative effects on the sociopsychological life of the woman. 1227 The limitation of our study is that other chronic pain syndromes such as fibromyalgia and chronic pelvic pain were not questioned in detail in patients with long-term breast pain.

Following DER, LRP1 expression was associated positively with SRD5A2 (r=0.78, P=0.008), which, in turn, was associated negatively with HSD17B12. The finding is relevant because SRD5A2 encodes the 5α-reductase 2, the enzyme that catalyzes the conversion of androstenedione (the direct precursor of testosterone) into the less potent androgen androstenedione, following the so-called androgen alternative pathway.22 On the one hand, such a conversion reduces the amount of testosterone available to be converted directly into estradiol by aromatase and, on the other hand, the amount of androstenedione to be aromatized into estrone which will be, in turn, converted into estradiol by HSD17B12. These two effects will concur in reducing the estradiol production and the subsequent proliferative stimulus on epithelial cells.

Regarding the abdominal adipose tissue, the most remarkable finding is that, compared to breast epithelium, the substantial decrease in the expression level of HSD17B12 was not associated with a change in the correlation with LRP1 and SRD5A2. The negative association of HSD17B12 with LRP1 was weak and not statistically significant (r=-0.42, P=0.226), and the association with SRD5A2 disappeared. Conversely, a negative association between HSD17B12 and CYP19A1 (r=-0.60, P=0.065) was observed following DER, suggesting the cellular attempt to restore the local estradiol by increasing testosterone aromatization.

Undoubtedly, the small number of subjects who participated in the study, mainly caused by the invasiveness of the sampling procedure that required repeated biopsies in both breasts and the abdominal adipose tissue of healthy women, may represent a potential concern about the reliability of the results. That was overcome, at least in part, by the homogeneity for weight, age, and parity of the subjects, 11 which resulted in an almost superimposable gene expression profile of baseline and repeat biopsies of the breast epithelium or abdominal adipose tissue in the control subgroup. Furthermore, the stringent criteria adopted in the statistical analysis allowed us to identify only the genes differentially expressed in response to DER.

The etiology of mastalgia is still not fully understood. This study shows that psychological symptoms in a patient with breast pain differ between the east and west of Turkey. This may indicate that socio-economic differences may also have effects on psychological symptoms. Adding SCL-90-R to the diagnosis and treatment of resistant mastalgia patients could help provide a more accurate and reliable treatment. Further investigations are necessary for detailed evaluation of psychosocial effects on mastalgia and the results of psychological therapies in the treatment of mastalgia.