DIFFERENTIATED APPROACH TO TREATMENT OF ENDOMETRIAL HYPERPLASIA WITHOUT ATYPIA IN WOMEN OF REPRODUCTIVE AGE

Abstract

The aim of the study – to develop differential diagnostic criteria for the use of hormonal therapy with the use of progestogens for the treatment of endometrial hyperplasia (EH) without atypia in women of reproductive age, taking into account clinical and morphological and immunohistochemical data. To investigate the effect of estrogen receptor expression, progesterone and the proliferation marker KI-67 in hyperplated endometrium without atypia in women of reproductive age on the effectiveness of therapy.

Materials and Methods. A prospective cohort study was conducted in 85 patients of reproductive age (25–46 years) with abnormal uterine bleeding (AUB). The control group consisted of 15 patients with changes in endometrial secretory type. Material for morphological and immunohistochemical studies was obtained by scraping the uterine cavity. The study of progesterone receptors was carried out by immunohistochemical method in the laboratory of Dnipropetrovsk Medical Academy immunohistochemistry. All patients received treatment with micronized progesterone at a dose of 100 mg per day continuously for 6 months. To determine the effect of the use of progesterone was investigated the expression of estrogen receptors, progesterone and a marker of proliferation of KI-67 in histological samples of the endometrium immunohistochemical method. The criterion for cure was: no complaints in patients and no EH on the results of endometrial tube biopsy after 6 months treatment.

Results and Discussion. According to the results of the study of women with no effect of therapy, in contrast to women with effective therapy, there was a decrease in the expression of receptors to progesterone by 65 %, while the expression of estrogen receptors was higher than normal by 50–56 % in both subjects groups. The proliferative potential of the glandular tissue in EH in the reproductive period, estimated at Ki-67 level, with PNH was 3.2 times, with AMH – 4.5 times higher than normal, while in the stroma in both types of EH it did not differ from normal performance.

Conclusions. Studies have shown that in addressing the question of the appointment of pathogenetic therapy using micronized progesterone for the treatment of endometrial hyperplasia without atypia, it is recommended to use a differential approach, which is that the treatment should take into account the level of expression of progesterone receptors in the tissue. A high level of expression will determine the satisfactory effect of progestin therapy. Low expression of progesterone receptors will make the endometrial tissue insensitive to progestin therapy. Another criterion for the appointment of progestin therapy is the determination of the proliferative activity of hyperplasia epithelium using the Ki-67 marker. He concludes that, with different types of EH, there are populations of cells that have different potentials for proliferation and the ability to spontaneously regress. This is more true of glandular epithelial cells. Since proliferation depends on the amount of PE, it can be assumed that different types of EH, differing in the level of proliferative activity, will respond differently to the same hormonal influences and, therefore, approaches to the treatment of these conditions should be different. Thus, when prescribing pathogenetic therapy using progestins, it is necessary to distinguish two groups of women: with a hormone-sensitive form of EH and a hormone-insensitive or hormone-resistant form of EH without atypia. Other treatments must be used to treat such women.