Haponova O. New approaches to diagnosis, selection and prognosis of the effectiveness of therapy for endometrial hyperplasia in women of reproductive age

The paper represents analysis of clinical data of 892 women with the pathology of endometrium in accordance with the results of the histological examination of biopsy samples, including 403 cases of endometrial hyperplasia without atypia (HE) in women of the reproductive age (RA) as well as generalized results of the immunohistochemical examination (ІHC) of endometrium samples (Ki-67, Cyclin D1, р21, ER, PGR, E-cadherin) before and after treating HE of 101 women of reproductive age with the administration of gestagens. It has been determined that in RA women in the interval from 36 to 45 years old GE occurred most frequently – 29.6% (2.6% in the period up to 25 years old and 13% in the period from 26 to 35 years old). 403 women suffered instrumental ablation of endometrium, 134 of them were treated with gestagens, 269 of them were not prescribed gestagens. In 78 (58.2%) females, after treatment with gestagens, a persistent regression of HE was observed according to the results of a 3-year follow-up catamnesis, and in 56 (41.8%) women a relapse of HE was diagnosed. In females who did not receive medical treatment, the relapse was observed in 167 (60.2%); without a relapse – 107 (39.8%) for the same period of time. The results of the immunohistochemical study of the cell cycle markers in the endometry of women with positive and negative results of gestagen therapy (micronized progesterone, dydrogesterone) showed that in the endometriosis of women with HE resistance to gestagen therapy, the expression of PGR in gland cells (50.8 ± 0.7) and stroma (47.3 ± 0.8) was significantly lower than in the corresponding structures of endometrium of women with HE with a positive result of the gestagen therapy (183.7 ± 3.1 and 166.4 ± 2.3; p <0.05 respectively), moreover, in comparison with unchanged proliferative (193.2 ± 8.5 and 178.7 ± 6.3; p <0.05 respectively) and secretory (140.2 ± 4.4 and 116.6 ± 3.1; p <0.05 respectively) endometrium. It has been proven that in 86.4% endometrial samples of females with resistance to gestagens, E-cadherin expression was not determined, and only 13.6% cases of the samples manifested its weak expression which testifies to the presence of a small number of cells with differentiation under the influence of gestagens. The conclusion was made that the resistance of HE to the infusion of gestagens could be explained by the low expression of PGR in the cells of endometrium even before the treatment and in such cases the administration of gestagens in women with HE is not reasonable. It has been determined that the positive effect of gestagens in the treatment of women with HE is connected with the activation of the suppressor gene p21 and inhibition of the expression of the Cyclin D1 gene, which is responsible for the initiation of mitosis in endometrial cells, as well as stimulation of the differentiation of cells and the loss of the proliferation ability which was supported by the increase in the expression of the glycoprotein of the intercellular adhesion E-cadherin and the decrease in the number of cells with a positive IHC reaction to the Ki-67 in response to treatment. The carried out examination has also proven that the type of gestagen is not of significant importance in the reduction of the proliferation of endometrium from with PGR (+) in patients with HE, a positive result was achieved due to the administration of the micronized progesterone as well as its synthetic analog dydrogesterone