Non-hormonal therapy of patients with fibrocystic mastopathy in combination with endometrial hyperplasia

Introduction. The article presents a comparative analysis of the treatment of patients with combined estrogen-dependent pathology of female reproductive system: fibrocystic mastopathy and endometrial hyperplasia without atypia. The experience of treatment with an indole-carbinol-containing drug as monotherapy while using a levonorgestrel-releasing intrauterine system is presented.Aim. To evaluate the clinical efficacy of indolecarbinol in the treatment of patients with combined estrogen-dependent pathology of the female reproductive system.Materials and methods. The authors studied the responses to the treatment of patients with fibrocystic mastopathy and simple endometrial hyperplasia (n = 65) with the indole-carbinol-containing drug at a dose of 400 mg once daily for 12 months. All patients were divided into two groups: Group I (n = 32) – women who refused hormone therapy (indole-carbinol monotherapy); Group II (n = 33) – the use of indole-carbinol while using the levonorgestrel-releasing intrauterine system. Diagnostic methods: clinical and laboratory examination, ultrasound examination of mammary glands and pelvic organs, mammography, nipple discharge cytology at baseline and 6 and 12 months after the start of therapy. Before study group assignment to treatment, all patients underwent hysteroscopy with endometrial biopsy and histological examination. Descriptive statistics were used to evaluate the data: p-values below 0.05 were considered statistically significant.Results and discussion. The presented experience in treating women with combined pathology of the female reproductive system (fibrocystic mastopathy and endometrial hyperplasia without atypia) with the indole-carbinol-containing drug showed high clinical efficacy in mastopathy (relief of mastodynia (83.0 ± 1.6%), improvement of the ultrasound view of BI-RADS (66.1 ± 1.4%), reductions in mammographic density (66.1 ± 2.1%, p < 0.05)), high tolerability and satisfactory compliance. This drug combined with hormone therapy is recommended for the treatment of endometrial hyperplasia.Сonclusion. The use of indole-carbinol in the treatment of benign hyperplastic processes in mammary glands and endometrial hyperplasia is pathogenetically substantiated and shows high clinical efficacy

Study of danazol active agent effect on Mcf10a breast cells redox phosphorylation

Fibrocystic mastopathy is one of the most complex breast pathologies, occurring in about 60% of women. The causes and molecular mechanisms of cyst formation in fibrocystic mastopathy are not fully understood, and effective treatment methods are not widely implemented. However, there is evidence of the fibrocystic mastopathy malignization risk. We studied the molecular effect of the active agent danazol on the respiratory complex in mitochondria, which occur in various concentrations and are considered the cell energy center. A method of permeation with special agents was developed to improve the cell membrane permeability in the intracellular proteins and nucleic acids analysis. The scientists aimed to study the Mcf10a cell line mitochondrial respiratory complex using the permeabilization method. Purpose: To study the effect of different danazol concentrations on Mcf10a breast cells redox phosphorylation in women with fibrocystic mastopathy. Results: Monitoring the redox phosphorylation process using complex respiratory substrates affecting the Msf10A breast cells respiratory chain showed the danazol 30 μM effect on the respiratory complex I. Conclusions: According to oxygraphic records, 10 minutes’ exposure to danazol 30 μM after permeabilization with digitonin increased the Msf10A cells’ oxidative phosphorylation compared with the control. The respiratory rate decreased by 45% ten minutes after treatment with digitonin.

Study of danazol active agent effect on Mcf10a breast cells redox phosphorylation

Relevance: Fibrocystic mastopathy is one of the most complex breast pathologies, occurring in about 60% of women. The causes and molecular mechanisms of cyst formation in fibrocystic mastopathy are not fully understood, and effective treatment methods are not widely implemented. However, there is evidence of the fibrocystic mastopathy malignization risk. We studied the molecular effect of the active agent danazol on the respiratory complex in mitochondria, which occur in various concentrations and are considered the cell energy center. A method of permeation with special substances was developed to improve the cell membrane permeability in the intracellular proteins and nucleic acids analysis. The scientists aimed to study the Mcf10a cell line mitochondrial respiratory complex using the permeabilization method. Purpose: To study the effect of different danazol concentrations on Mcf10a breast cells redox phosphorylation in women with fibrocystic mastopathy. Results: Monitoring the redox phosphorylation process using the respiratory complex substrates affecting the Msf10A breast cells respiratory chain showed the danazol 30 μM effect on the respiratory complex I. Conclusions: According to oxygraphic records, 10 minutes’ exposure to danazol 30 μM after permeabilization with digitonin increased the Msf10A cells’ oxidative phosphorylation compared with the control. The respiratory rate decreased by 45% ten minutes after treatment with digitonin.

Modeling of fibrocystic mastopathy in experiment on animals

Nowadays, hormonal imbalance is proven to be a factor that influences initiation of malignant and benign breast tumors. To study the aspects of participation of sex hormones in damage to organs and tissues, it may be necessary to model a common womens pathology fibrocystic disease of mammary glands characterized by the most pronounced effects of this pathogenetic factor, on experimental animals. Aim. To create a model of fibrocystic disease of mammary gland with the subsequent possibility of studying morphological manifestations of the disease in natural and drug-induced pathomorphism. Materials and Methods. The pathology was induced by intramuscular injection of 0.5 ml of 2% synestrol and 0.5 ml of 2.5% progesterone to virgin female rats on the 1st, 7th, 14th, 21st, 28th and 35th days of the experiment. For examination, histological preparations of inguinal mammary glands were made. The preparations were described and studied using morphometric analysis. Results. In the result of the experiment, pronounced macro- and microscopic alterations of mammary glands were found. Microscopic picture was similar to that observed in fibrocystic mastopathy in women. Almost all the morphometric parameters underwent reliable alterations in correspondence with the given pathology. Conclusion. A model of fibrocystic disease of mammary gland was obtained that may be used for further study of morphogenesis and methods of correction.

FIBROCYSTIC MASTOPATHY

The lecture provides information for specialist doctors: oncologists, surgeons, mammologists, general practitioners on the diagnosis and treatment of fibrocystic mastopathy. The current data on the etiology and pathogenesis, classification and clinic of the disease are presented, well-known and new diagnostic methods, advantages and disadvantages of each method are described in detail. Issues of differential diagnostics are highlighted, optimal tactics, methods of conservative and surgical treatment are proposed

Application possibilities of biguanides for fibrocystic breast disease in women of reproductive age

Hypothesis/aims of study. The ongoing global problem of health care and medical science is an associated increase in the frequency of endocrine and metabolic diseases and cancer, including in women of childbearing age. Thus, the frequency of diabetes in the population has been growing rapidly for many years. Similar trends were observed in the dynamics of the frequency of cancer pathology, especially of breast cancer, which is one of the leading places in the structure of the cancer incidence in the female population. It is known that diabetes and related insulin resistance have a very negative effect on the female reproductive function, leading to hyperplastic processes of the mammary glands. The least studied problem so far is understanding the mechanisms of development, timely diagnosis, prevention, and treatment of fibrocystic mastopathy, the proliferative forms of which underlie malignant tumors, while its atypical variations are regarded as a precancerous condition. It is likely that the pathogenesis of hyperplastic processes in the mammary gland and the risk of neoplastic transformation in disorders of carbohydrate metabolism may have special factors. The actual problem is the development of a method for pathogenetically substantiated correction of fibrocystic breast disease. This is essential for the development of pharmacological strategies for secondary prevention of breast cancer and, in this regard, it is of great interest to study application possibilities of biguanides. The purpose of the present study was to conduct a comparative assessment of the effectiveness of metformin therapy in fibrocystic mastopathy patients with and without insulin resistance. Study design, materials, and methods. The study involved 120 women, aged 18 to 40 years inclusive, with clinical and / or ultrasound signs of fibrocystic breast disease. According to the results of calculating HOMA index, patients were divided into two groups: the first group comprised 66 patients with insulin resistance (HOMA > 2.5) and the second group consisted of 54 patients with no insulin resistance (HOMA < 2.5). Assessment of mastalgia was performed using the Visual Analogue Scale. Breast ultrasound examination was performed on days 5 to 7 of the menstrual cycle. For the purpose of quantitative image analysis of the breast parenchyma, the following parameters were evaluated: a) thickness of the parenchyma (fibroglandular zone); b) diameter of the milk ducts; c) echogenicity. All patients received metformin at a dose of 1500 mg per day. Dynamic control of the clinical picture of the disease, as well as of mammographic breast parenchymal pattern, was performed after 3 and 6 months from the start of therapy. Results and conclusion. After 6 months of therapy, there was a decrease in the frequency of mastalgia, and significant changes in breast ultrasound picture were observed. The data obtained on the positive effect of metformin on clinical mastitis and structural changes in the mammary parenchyma in patients with mastopathy allow considering such an approach as a promising therapeutic strategy in this pathological association.