Clinical Factors Associated With Anxiety and Depression in Korean Women With Abnormal Uterine Bleeding

Background: Abnormal uterine bleeding (AUB) is dened as an abnormality in menstrual bleeding and is common gynecological problem in premenopausal women. Anxiety and depressive disorders were frequently observed in patients with AUB. This study was conducted to investigate the prevalence and the relationship of anxiety and depression in Korean women with AUB. Methods: The study was a questionnaire study of 124 Korean women aged 15–55 who admitted a single university hospital due to AUB between September 2015 and December 2019. Anxiety, depression were assessed using the Korean Beck Anxiety Inventory (K-BAI), the Korean Beck Depression Inventory-II (K-BDI-II). The obstetrical and clinical data were analyzed to assess the association of anxiety and depression with AUB. Results: Out of 124 patients, 47 (37.9%) met the criteria for anxiety, and 24 (19.5%) met the criteria for depression. The most common menstrual problems seen were heavy menstrual bleeding (80.7%), followed by irregular bleeding (62.9%), dysmenorrhea (55.7%), and irregular menstrual cycles (33.9%). More women with AUB in our study had anxiety as measured by the K-BAI and depression as measured by the K-BDI-II. A history of abortion and cesarean section were related with anxiety, whereas a history of minor surgery was related to depression. Anxiety and depression (r = 0.629, p < 0.001) were correlated with AUB. Conclusions: Anxiety and depression are underdiagnosed and undertreated in Korean women with AUB symptoms. Screening and appropriate mental health management are needed for women with AUB for women’s health.

problems and heighten awareness of mental health and women's health [9]. Understanding the characteristics that predict anxiety and depression may help a clinician identify patients at risk for anxiety or depressive disorders.
To the best of our knowledge, no studies have yet examined the association of anxiety and depression with AUB in Korean women. The purpose of this study was to identify correlations between anxiety and depression in Korean women with AUB. The goals were to identify 1) the general characteristics and menstrual problems, 2) the prevalence and risk of anxiety, depression, and 3) the correlations of anxiety and depression with AUB.

Methods
The study was conducted with 124 consecutive patients who admitted the Department of Obstetrics and Gynecology with complaints of menstrual problems and who were diagnosed according to the FIGO classi cation system (PALM-COEIN) with AUB between September 2015 and December 2019.
The inclusion criteria were age between 15 and 55 years, premenopausal women and menstrual irregularities continuing for at least three months. The exclusion criteria of the study were the use of psychotropic drugs, such as antidepressants, anxiolytics, or antipsychotics, for any reason in the last six months; a diagnosis of gynecologic cancer; current oral contraceptives or any hormonal therapy, and pregnancy. The ow chart in Fig. 1 indicates the inclusion and exclusion criteria for the patients. This study was obtained from the local ethics committee (The Catholic University of Korea Catholic Medical Center, HC15QISI0078).
The de nition of menstrual regularity has changed from one where the shortest to the longest variation was up to 20 days, to a variation of seven to nine days. For practical purposes, this normal variation in cycle length can be alternatively expressed as ± 4 days. Clinically included is the term HMB, a symptom (not a diagnosis), that has been de ned (in clinical situations) by the National Institute for Health and Clinical Excellence as "excessive menstrual blood loss, which interferes with a woman's physical, social, emotional and/or material quality of life" [10][11][12].
After the survey, the patients were followed-up and treated medically or surgically. Major surgery included total hysterectomy, myomectomy, and ovarian surgery. Minor surgery included endobiopsy, dilatation and curettage, and hysteroscopy.

Measurements
The Korean Beck Anxiety Inventory (K-BAI) and Korean Beck Depression Inventory-II (K-BDI-II) were used to diagnose anxiety and depression.
The BAI is a 21-item instrument measuring the severity of anxiety symptoms [13]. The total scores range from 0 to 63, with higher scores indicating more severe anxiety symptoms. We used K-BAI that showed excellent internal consistency and good discriminant validity for anxiety disorders [6]. The normal range is 0-7 points (minimal), 8-15 points is mild, 16-25 points is moderate, and 26-63 points is severe. The presence of anxiety was determined based on the K-BAI score, and the subjects were classi ed into normal subjects (K-BAI score range: 0-15) and subjects with anxiety (K-BAI score range: 16-63).
The BDI was originally developed by Beck in 1961 [14] and revised to BDI-II in 1996 in response to changes in the DSM-IV criteria for the diagnosis of depressive symptoms [15]. The total score ranges from 0 to 63, with higher scores indicating more severe depressive symptoms. The normal range is 0-3 points, 4-19 points is mild depression, 20-28 points is moderate, and 29-63 points is severe on the K-BDI-II [16]. The presence of depression was determined based on the K-BDI-II score and the subjects were classi ed as either normal subjects (BDI score range: 0-19) or depressed subjects (BDI score range: 20-63) in our study.

Statistical analysis
All statistical analyses were performed using SAS software ver. 9.4 (SAS Institute Inc., Cary, NC, USA). The Kolmogorov Smirnov test was applied to data that conformed to a normal distribution. For continuous variables that were not normally distributed, the signi cance of the differences between the groups was tested using the Wilcoxon rank-sum test. The categorical variables were analyzed using the chi-squared test. Pearson's correlation and Spearman's rank correlation were used to analyze the distribution of the anxiety and depression scores. The association between anxiety and depression and clinical data were analyzed by univariable and multivariable logistic regression (anxiety score ≥ 16, depression score ≥ 20). Multivariable logistic regression was conducted using p-values of < 0.05 in the univariate analysis. For depression, only one variable with statistical signi cance was not used to perform the multivariable analysis. A p-value of 0.05 was considered signi cant.

Results
General characteristics of the women From September 1, 2015, to December 30, 2019, a total of 131 women with AUB participated in the survey. Seven patients with psychiatric problems con rmed in the past were excluded, and the nal research was conducted on 124 women with AUB. Informed consent was obtained from 131 women, the questionnaires were completed, and demographic data and comorbidities were collected from the medical records.
The most common menstrual problems seen in our study were HMB (n = 100, 80.7%), followed by dysmenorrhea (n = 69, 55.7%) and irregular menstruation (n = 42, 33.9%; Table 1). In the obstetrical and gynecological history, parity, menstrual irregularity, dysmenorrhea, and HMB did not affect the anxiety and depressive state. In the treatment aspect, anxiety and depression were not associated with oral contraceptives use, history of hospitalization due to AUB, transfusion history, or iron supplementation. Anxiety and depression scores did not differ according to underlying disease, and hemoglobin and hematocrit levels at the time of the examination ( Table 1).
The average number of abortions in the women was 0.9 ± 1.3 (range, 0-8), and 65 (52.4%) women had not had abortions history. In the anxiety group with a K-BAI score of 16 or higher, higher scores were seen in women with AUB and a history of abortion (p = 0.014; Table 1).
Among women who delivered, history of Cesarean section (C/sec) was 54 (43.6%) women, and anxiety was higher than in the women without C/sec history (p = 0.041). There were 73 women (58.9%) with AUB and a history of minor surgery and the degree of depression measured by the K-BDI-II was higher than in AUB women who had a history of minor surgery (p = 0.028). History of abortion and C/sec were associated with anxiety disorder, whereas a history of minor surgery was related to depressive disorder (  When the relationship between anxiety and depression was analyzed, Pearson's correlation coe cient was r = 0.675 (p < 0.001) and Spearman's rank correlation coe cient was r = 0.629 (p < 0.001), showing a moderately positive correlation (Fig. 2).
In this study, we performed univariable and multivariable logistic regression of the K-BAI scores, K-BDI-II scores, and clinical and gynecological data (cutoffs: anxiety score ≥ 16, depression score ≥ 20). Age, BMI, marriage, parity, delivery mode, menstrual regularity, dysmenorrhea, HMB, and history of admission with AUB were not associated with anxiety and depression.
The odds ratio ((OR) = 2.48 (1.18-5.23), p = 0.017) for the anxiety scores in univariable logistic regression in the patients with past abortions was high, and the OR was low for anxiety (OR = 0.47 (0.22-0.9), p = 0.047) in patients with a history of C/sec. The OR for depression in AUB patients with a history of minor surgery was high (OR = 2.96 (1.05-8.33), p = 0.04, Table 3). The worldwide impact of AUB in the reproductive years is noteworthy, with a prevalence of approximately 3-30% among reproductive-aged women. Many of the published studies are restricted to estimates of the prevalence of the symptoms of HMB. When other symptoms, particularly those of irregular and intermenstrual bleeding are included, the prevalence rises to 35% or higher [17]. AUB not only gives discomfort and anxiety to women, but it can be accompanied by depression when there is persistent AUB.
In AUB patients who visit the hospital with anxiety and depression, proper management is necessary, but the importance of psychological and risk evaluations has been underestimated.
Menstrual-related problems are associated with substantial psychological distress, a nding that con rms results reported in clinical cases and strongly supports the claim that menstrual-related problems pose important public health implications [18,19]. Mood and anxiety disorders, particularly major depression (15.6%), generalized anxiety disorder (18.8%), and obsessive-compulsive disorder (22.9%) were frequently observed in patients with AUB [1].
Strine et al. [4] suggested that menstrual-related problems in women pose considerable public health implications as they were reported by nearly 19% of U.S. women. Additionally, those with menstrualrelated problems are between 1.7 and 3.0 times more likely to report insomnia, sleepiness, recurrent pain, sadness, nervousness, restlessness, hopelessness, and worthlessness.
The lifetime prevalence of mental illness in Koreans is known to be 25.4%. According to an epidemiological survey of mental disorders in Korea conducted by the Ministry of Health and Welfare, the estimated lifetime prevalence of anxiety disorders for Korean adults was 9.3% (male 6.7%, female 11.7%) and the 1-year prevalence of anxiety disorders in Korean adults was 5.7% (male 3.8%, female 7.5%) [20].
The prevalence of major depression is quite wide and ranges between 8.2 and 67%. According to the level of mental health among Koreans, the rate of experience of depression was 13%, and the prevalence of depression was 5.0% [1,20].
More women with AUB in our study had anxiety as measured by the K-BAI (7.5% in the general population and 37.9% in this study) and depression as measured by the K-BDI-II (5% in the general population and 19.5% in this study). Our study found that the prevalence of anxiety and depression was higher in AUB patients.
Mood and anxiety disorders associated with irregular menstruation may also be associated with different etiologies. It is well-documented that depression is seen more frequently in women during premenstrual, postnatal, and menopausal periods due to the uctuations in hormonal levels during these periods [21]. However, it is di cult to clearly con rm the relationship between psychological aspects and physical symptoms.
When all factors are taken into consideration, a bidirectional relationship between AUB and psychiatric disorders may be observed. Kayhan et al. [1] reported that psychiatric disorders play a more important role than AUB because the latter frequently occurs together with stressful events and psychiatric disorders, but once these events or disorders are resolved, the menstrual cycle becomes regular again.
Although the relationship between AUB and anxiety, depression is di cult to know clearly, research on the association has important implications for women's health.
We hypothesized that age, BMI, obesity, abortion history, surgery-related delivery or gynecologic problems, menstruation cycles, dysmenorrhea, anemia, and medical disorders may be associated with anxiety and depression in the presence of AUB, but there was no clear relationship in our study.
In this study, anxiety and depression showed a moderately positive correlation with AUB, indicating that it is necessary to closely monitor and manage whether anxiety or depression accompany women with AUB.
Women with past mood disorders were more likely to report heavy bleeding symptoms, independent of known risk factors for heavy bleeding, such as high BMI, broids, early perimenopause, and mood disorders, occurring simultaneously with heavy bleeding. Mood disorder has been shown to be a risk factor for the subsequent development of important health disorders, such as diabetes, cardiovascular disease, pain, backache, and dizziness [3,22].
In the case of AUB, anxiety increased with a history of abortion, and anxiety scores were low in women with a history of C/sec. Although it is di cult to know the relationship clearly, it seems that anxiety increases when a loss is experienced, such as abortion, and sensitivity to anxiety decreases when a major operation such as C/sec has already been performed. However, it seems that parity, irregular menstruation, and dysmenorrhea did not signi cantly affect anxiety, especially in the presence of AUB in our study.
The degree of depression was increased in women with a history of minor surgery, which seemed to be because it affected patient mood in the presence of AUB. However, minor surgery did not appear to affect anxiety.
There were several limitations to our study. We were unable to determine if psychological distress and adverse health behaviors were related to AUB, and unable to exactly identify where during the menstrual cycle the psychological and behavioral associations were more evident. The K-BAI and K-BDI-II were not originally developed as diagnostic tools. Our study could not conclude a causal relationship between menstrual-related problems, emotional well-being, and psychological problems.
The women who participated in the survey are likely to have sampling bias error because AUB symptoms interfere with daily life and all participated women were admitted hospital due to management of AUB.
Due to a lack of other similar studies in the literature, an analysis of the di culties and limitations of the current study in comparison to other studies was not possible.

Conclusions
In Korean women, AUB seems to increase the risk of anxiety and depression. Although anxiety and depression were assessed through the K-BAI, K-BDI-II, respectively, this is a meaningful study by suggesting that anxiety and depression can be severe in women with AUB. Thus, including an assessment of AUB as part of the standard evaluation of women may better enable healthcare providers to recognize and treat potential manifestations of these symptoms.