Despite the longstanding history of the study of hyperproliferative processes and benign tumours of the uterus, the increase in the frequency of uterine fibroids, and adenomyosis and endometrial hyperplasia associated with it has been noticed in the recent decades all over the world. Analysis of uterine leiomyoma incidence indicates not only its growth but also the increase in the number of women of early reproductive age [1, 3, 5, 6].
The tumour development from “lump anlage” to the macroscopic state takes 5 years on an average. The onset of the disease happens at the age of 30 when endocrine, somatic and gynaecological disorders accumulate. Accumulation of pathological factors at this age causes somatic mutation in the cells of the reproductive system that is likely to play a leading role at the stage of proliferative component formation in the regeneration process of damaged endometrial cells [1, 3, 4].
Leiomyoma is often combined with dyshormonal breast and thyroid disorders, obesity and hepatobiliary diseases [2, 4]. In case of its combination with breast pathology uterine leiomyoma primarily develops on the background of chronic stress, in women with hereditary predisposition to proliferative diseases and aggravated allergic history, and accompanied by thyroid dysfunction, increased body mass index, liver and cardiovascular system diseases, while isolated leiomyoma is often detected on the background of chronic inflammatory diseases of the genitals and vaginal dysbiosis, abortions, prolonged use of intrauterine contraceptive drugs, post-abortion and postpartum complications [1, 3, 5, 6]. It should also be noted that the isolated uterine leiomyoma may have asymptomatic slow growth, sometimes to a large size, and symptoms of adjacent organs compression, while the development of combined leiomyoma is often accompanied by rapid growth and severe clinical manifestation even in its small size: meno-, and metrorrhagia and pain syndrome that significantly impair quality of women’s life [1, 3, 5].
Thus, basic sciences progress achieved over the past decades has given an opportunity to make a significant step forward in the study of etiology and pathogenesis of uterine leiomyoma, but the problem of trigger mechanisms for its development is topical nowadays.
The objective of the research was to evaluate the features of hyperplastic processes in uterus on the background of dishormonal and metabolic disorders.
60 women of reproductive age with uterine leiomyoma participated in the clinical trial. They gave their informed written consent. The control group consisted of 20 healthy women of reproductive age without any pathology of the pelvic organs and severe concomitant somatic and gynaecological diseases. The criteria for inclusion in the study group included reproductive age (18-45 years); excessive body weight with concomitant uterine leiomyoma that had to be treated. The exclusion criteria were patients with chronic inflammatory pelvic diseases, exacerbation of concomitant somatic diseases, cancer, and diabetes. The first group consisted of 30 patients with hyperplastic uterine processes without concomitant extragenital pathology, the second group (main group) consisted of 30 patients with a high body mass index. Statistical analysis of the material was performed with the help of a personal computer and an application to work with Microsoft Excel spreadsheets via package “STATISTICA for Windows®-6.0’. In order to identify risk factors and predict complications we used the methods of calculating odds ratio (OR) and its 95% confidence interval (CI).
The major age differences in the development of uterine fibroids on the background of obesity are worth mentioning: the uterine fibroids occurred very rarely before 25 years of age; at the age of 25 to 35 this pathology was noted in 16.66% of patients; in socially active women of reproductive age (age 35 -40 years) this nosology occurred 1.6 times more frequently in women with excess body weight.
Cardiovascular diseases and diseases of gastrointestinal tract prevailed in women of the main group. We revealed concomitant disorders of genitals and breasts in 85.0% of cases represented mainly by chronic inflammation of the pelvic organs (63.3%), fibro-cystic form of mastitis (40.0%). Chronic diseases of the hepatobiliary system were detected in 30 (50.0%) patients, among them chronic hepatitis of cholestatic aetiology was diagnosed in 7 (23.3%) and chronic cholecystopancreatitis in 2 (6.6%) women with fibroids. Five patients (16.6%) of the main group had calculous cholecystitis, and in 9 cases (30.0%) non-alcoholic fatty liver disease was observed indicating a statistically significant increase in not only biliary dyskinesia but also in liver pulp lesions.
The analysis of reproductive function detected twofold increase in the performed instrumental interventions in history, the increase in the percentage of late miscarriage and premature birth.
Body-weight ratio was within normal limits (18.5-24.9) only in 12 (20.0%) of women with fibroids, while in the control group the normal rate was 85.0% (p<0.05). Overweight was observed in 38 (63.33%) of examined women against 10.00% in controls (p<0.05). In addition, obesity of the second degree (30.0-34.9) was found in 21 women (35.0%).
It should be noted that adenomyosis occurs in 70.0% of cases in patients of the main group (in women 35-40 years old more often), the proportion of endometrial hyperplasia increases up to 63.33% of cases after 40 years of age as evidenced by the activation of proliferative processes in the endometrium with initiation of polyposis formation, significant growth of M-echo indexes and increasing ovary volume due to polycystic changes. Women with obesity were diagnosed with endometrial polyps in nearly 36.66% of cases and with the endometrium of transition type only in 26.66%.
The results of the research found the main factors contributing to the development of uterine fibroids in women with obesity. They included the age of 30-45 years, instrumental intervention in the womb (abortion, diagnostic curettage, etc. (OR = 8.2; 95% CI: 5.1-13.5)); chronic inflammatory diseases of genitalia (OR = 7.9; 2.9-21.9); hormonal imbalances (fibro-cystic breast disease, thyroid disorders (OR = 8.61; 3.1-23.8), liver and gastrointestinal tract disorders (OR = 5.8; 2.1-15.9) sexual disorders and stress inductive factors (OR = 2.6; 1.4-7.1) (usually fibroids occur in 1-2 years after severe stress). Significant percentage of adenomyosis and endometrial hyperplastic processes was observed. Growth of tumors in women with obesity increases to 35-40 years of age, and is associated not only with a progressive decrease in the functional activity of the ovaries, their sensitivity to gonadotrophic stimulation, but also with chronic functional exertion of regulation systems on the background of metabolic disorders of hemostasis and homeostasis in this category of women.
One of the most significant risk factors for hyperplastic processes of the reproductive organs is obesity and metabolic disorders associated with it. The number of combined forms of hyperplastic processes in the uterus increases by 1.9 times in case of activity of metabolic disorders and dysfunction of hepatocytes on the background of obesity. The main risk factor for fibroids in obese women is hepatocytes dysfunction on the background of a high percentage of hepatobiliary pathology, endocrine pathology – 68.3% (thyroid dysfunction, fibro-cystic breast changes). Morphological and histological structure of endometrium in obese women leads to the growth of endometrial polyps (36.66%).
Our studies indicate the need for classification of women with the mentioned factors on the background of metabolic disorders. Such patients should belong to the risk group due to development and progression of hyperplastic processes of the reproductive organs determining the search for important diagnostic and prognostic criteria and the development of preventive measures.