Assessment of vitamin D level in women with abnormal uterine bleeding and chronic psychogenic stress

The objective: to study the level of vitamin D (25-hydroxycalciferol – (25(OH)D) in blood serum of women with abnor- mal uterine bleeding (AUB) and chronic psychogenic stress. Materials and methods. We examined 100 women of reproductive age with AUB and chronic psychogenic stress (basic group) and 50 patients with AUB without psychogenic chronic stress (comparison group). 30 women without AUB and chronic stress were included in the control group. AUB was diagnosis according to the Order No. 353 of the Ministry of Health of Ukraine dated April 13, 2016. The concentration of vitamin D was determined in blood serum in all the women using the ELISA method. Results. The concentration of vitamin D in the blood serum in patients with AUB and chronic psychogenic stress was on 28.01 % lower compared to the controls (p < 0.001), in the patients with AUB without psychogenic chronic stress – 13.94 % (p = 0.045). The number of individuals with optimal concentration of vitamin D in the control group (36.67 %) was in 2.29 times higher compared to the basic group (16.00 %; p=0.03) and in 1.41 times more compared to the comparison group (26.00 %). Suboptimal level of vitamin D had 53.33 % women in the control group, 43.00 % – basic and 58.00 % – comparison one. The rate of persons with deficiency of vitamin D among the patients with AUB and chronic psychogenic stress was in 4.56 times higher compared to the healthy women (41.00 % and 9.00 % individuals, respec- tively; p = 0.003), and in patients with AUB without chronic stress –1.78 time (16.00 % women). Conclusions. There is the insufficient vitamin D concentration in women with abnormal uterine bleeding which is more severe in the persons with chronic psychogenic stress.

A bnormal uterine bleeding (AUB) occurs in 30 % women in reproductive age [1]. Etiological factors are divided into structural (PALM: P -polyps, Aadenomyosis, L -leiomyoma, M -malignant tumors and endometrial hyperplasia) and non-structural (COEIN: C -coagulopathy, O -ovulation disorders, E -endometrial pathology, I -iatrogenic factors and N -unclassified causes) [2]. Currently, the course and severity of the pathology is often influenced by external factors, among which a special role is given to stress. There are stressdependent disorders of the menstrual cycle [3], which include luteal phase insufficiency [4], infertility [5], menstrual disorders [6].
However, in recent years, a special attention is paid to the study vitamin D in the development of different pathologies. It is known that vitamin D 3 is produced under the influence of ultraviolet radiation or enters the human body with food. Vitamin D deficiency often contributes to diseases in childhood [7], stress and mental disorders [8], autoimmune diseases, cancer, bone pathology [9] and others. Disorders of the reproductive system can also occur due to the deficiency of this vitamin, in particular, complications of pregnancy [10], menstrual disorders in adolescence [11], infertility and polycystic ovary syndrome [12], uterine leiomyoma [13,14].
The objective: to study the level of vitamin D (25-hydroxycalciferol (25(OH)D)) in blood serum of women with AUB and chronic psychogenic stress.

MATERIALS AND METHODS
100 women of reproductive age with AUB and chronic psychogenic stress formed the basic group. The comparison group consisted of 50 patients with AUB without chronic psychogenic stress. 30 healthy women with normal parameters of the menstrual cycle and without AUB and chronic psychogenic stress were included in the control group. Inclusion criteria: AUB, age 18-45 years, satisfactory condition of the sample of the material from the uterine cavity for histological examination, chronic psychogenic stress, patient consent. Exclusion criteria: pregnancy, premenstrual dysphoric disorder, acute pelvic inflammatory disease, mental disorders, blood diseases associated with coagulation disorders, hypothyroidism, hyperthyroidism, hormonal adrenal tumors, chronic intestinal diseases, severe somatic pathology.
AUB was diagnosed according to the recommendations of Order N 353 of the Ministry of Health of Ukraine «On approval and implementation of medical and technological documents for standardization of medical care for abnormal uterine bleeding» dating 13.04.2016 and the Unified Clinical Protocol of primary, secondary (specialized) and tertiary (highly specialized) medical care for abnormal uterine bleeding [2]. The presence of chronic psychogenic stress was exposed on the basis of a clinical interview with a psychologist. The level of stress was assessed by the Perceived Stress Scale-10, PPS-10 [15]. The higher the indicators demonstrate the higher the stress level. The research was performed in «Kreminna Multidisciplinary Hospital of Kreminna District Council» and approved by the Ethics Commission of the Shupyk National Medical Academy of Postgraduate Education (protocol N1 dating 15.01.2018).
The concentration of vitamin D (25-hydroxycalciferol (25(OH)D)) was determined in the blood serum by ELISA method using a set of reagents DBS-Diagnostics Biochem Canada Inc. Optimal level of vitamin D was in the ranges of 30-50 ng/ml, suboptimal level -21-29 ng/ ml, vitamin D deficiency -less than 20 ng/ml [16]. The program Statistica10 was used to process the results. The criterion χ 2 and Mann-Whitney test were used to compare the data of the the groups.

RESULTS AND THEIR DISCUSSION
The average age of women with AUB was similar in both groups, 31.09±0.60 years in the basic group and33.06±0.91 -in the comparison one. However, in the control group this indicator was significantly lower (26.33±0.87 years; p < 0.001) than in women with AUB. The average mean of body mass index was 22.37±0.35 kg/m 2 in the basic group, 23.89±0.43 kg/m 2 -in the comparison group and 23.69±0.47 kg/m 2 -in control one. The level of perceived stress in patients with AUB and chronic stress (32.24±0.44) was increased in 1.97 times relative to healthy women (16.33±0.64; p<0.001), and in patients with AUB without chronic stress -1.12 times (18.24±0.66).
The concentration of vitamin D in the blood serum was significantly lower in patients with AUB than in healthy women. Thus, in women in the basic group its level was on 28.01 % lower compared to controls (21.49±0.76 ng/ml and 29.85±1.68 ng/ml; respectively; p<0.001), in patients in the comparison group -on 13.94 % (25.69±1.04 ng/ ml; p=0.045). Optimal concentration of vitamin D was in 11 (36.67 %) control persons, that was in 2.29 times higher than in the basic group (16 (16.00 %) patients, χ 2 =4.80, p=0.03) and in 1.41 times more compared to the comparison group (13 (26.00 %) individuals). Suboptimal level of vitamin D had 16 (53.33 %) women in the control group, 43 (43.00 %) -basic and 29 (58.00 %) -comparison one. The rate of deficiency of vitamin D in patients with AUB and chronic stress was increased in 4.56 times compared to the healthy women (41 (41.00 %) and 3 (9.00 %) individuals, respectively; χ 2 = 8.57; p = 0.003), and in patients with AUB without chronic stress -1.78 time (8 (16.00 %) women).
Vitamin D deficiency was found in the patients with different reproductive pathologies. In patients with chronic AUB and posthemorrhagic anemia caused by adenomyosis and polyps the concentration of vitamin D was decreases till 49.6-49.7±26.2 nmol/l [17]. It's known that hypovitaminosis of vitamin D is a risk factor for the development of uterine fibroids [18]. That is why additional use of vitamin D during the treatment of uterine fibroids is an effective approach of the management to correct the uterine sizes, severity of the symptoms and improve the quality of life of the patients. The results of our study correspond with these researches.

CONCLUSIONS
There is the insufficient vitamin D concentration in women with abnormal uterine bleeding which is more severe in the persons with chronic psychogenic stress.