The dissertation summarizes the results of complex retrospective and prospective studies in 1460 premenopausal women with hyperproliferative endometrial conditions. A new concept of endometrial hyperplasia development and progression has been proposed. Analysis of the effectiveness of therapeutic measures and prophylaxis of disease recurrence has been made. The examination of the patients included morphological, immunohistochemical, genetic, molecular studies measuring the expression of: Cyclin D1, p21, Ki-67, ER, PGR, β-catenin, E-cadherin, MMP-9, VAC, Bcl-2, caspase - 3; p53, p16, VEGF, CD34, polymorphism of the p53 genes and the L-myc gene. It has been proven that endometrial hyperplasia without atypia and with atypia, as well as endometrial cancer, have different phenotypes, which indicates their different origins, therefore, different approaches to therapy. The necessity of determining the receptor state of the endometrium before onset of treatment of endometrial hyperplasia without atypia with gestagens has been substantiated. It has been proven that the low expression of progesterone receptors in the endometrium in women with hyperplasia without atypia indicates a probable hormone resistance and the prescription of progestins in such women is not advisable due to the lack of conditions for their molecular interaction with progesterone-deposited genes of endometrial cells.It was found that the positive effect of progestins in the treatment of women with non-atypical hyperplasia is associated with the activation of the p21 suppressor gene and inhibition of the expression of the Cyclin D1 gene, which is responsible for the initiation of mitosis in endometrial cells, as well as the stimulation of cell differentiation and loss of their ability to proliferate, as evidenced by an increase in the level of the expression of intercellular adhesion glycoprotein E-cadherin and β-catenin as a result of treatment.In women with hyperplasia without atypia, three different phenotypes of the endometrium were first identified: regressive, stationary, and progressive, which provide an opportunity for an individual approach to therapy: controlled observation without treatment for regressive, conservative treatment for stationary and surgical treatment for a progressive phenotype. It has been proven that in women with atypical endometrial hyperplasia in endometrial cells, there is a significant decrease or loss of estrogen and progesterone receptors, which makes it insensitive to any hormonal therapy and indicates the need for hysterectomy in such women. Based on the results of the study, targeted diagnostics, an individual strategy for the treatment and prevention of hyperplasia without atypia relapses were developed, taking into account the peculiarities of the endometrial genophenotype, and its effectiveness in premenopausal women was also proved.
