Gromova O. L.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

Abstract. Non-atypical endometrial hyperplasia (HE) is a common pathology in premenopausal women. General practice requires the use of progestins with sufficiently high indirect efficacy. However, the frequency and the most predictable time of relapse has not been resolved yet, nor have the factors that lead to prognosis for lack of efficacy and relapse. The aim of the work was to study the long-term results of using an oral form of a progestins, dydrogesteron, in the therapy of premenopausal women. Materials and methods of the study. We examined both direct and distant results of 6-month HE treatment with dydrogesteron 20 mg/day in 161 women. Histological examination of endometrial samples after 6 months (immediately after completion of treatment), 12 and 24 months were followed up. Progesterone receptor expression (PGR) was also tested in 36 women responding positively to dydrogesteron therapy (HE+) and 30 women without any effect (HE-), and cell proliferation antigen Ki-67 and cell adhesion protein E-kadherinin the samples of women before and after treatment. Results. At the 6-month follow-up, immediately after the end of treatment with dydrogesteron, a normal endometrial structure (NE) was obtained in 131 (81.4%) women (i.e., HE+, sensitive to dydrogesteron), 30 (18.6%) women (HE-) were insensitive to dydrogesteron and received the LH-RH agonist. There was no progression of HE to atypia in any of the women at this phase. At the 12-month follow-up, 125 in 131 HE+ women (95.4%) remained positive, but 4 (3.0%) experienced a relapse of HE, and 2 (1.5%) progressed to atypical hyperplasia (AHE). The samples of all 30 female HEs after treatment with the LH-RH agonist also demonstrated NE. The cumulative efficacy of hormone therapy at 12 months was 77.6%. At 24 months of therapy, out of 131 HE+ women, 94 (71.7%) were still negative, and 26 (19.8%) experienced a relapse of HE. There was also relapse in 2 (6.6%) women with HE-, who used LH-RH agonist. Progression to AHE was detected in 3 (2.2%) HE+ women, to adenocarcinoma in 2 (1.5%). When PGR and Ki-67 antigen and cell adhesion protein E-cadherin were compared, there were significant differences in the HE+ and HE- samples of the endometrium. At HE+, 97.2% of women had positive PGR expression, at HE- it was negative 73.3% and low in the other 22.7%. The HE+ resulted in a decrease of the Ki-67 proliferation index after treatment versus before therapy (respectively 22.6±1.2% and 8.2±0.5%; p < 0.05). The number of E-cadherinnegative cells decreased from 16.4% to 3.7% in HE+, and from 49.2% to 13.1% in weak IHC-reaction. The number of cells with moderate IHC-responsiveness increased from 34,4% to 55,7%, and up to 27,5% of cells with significant IHC-responsiveness to E-cadherin appeared. In HE-, the majority of tested endometrial samples (86.4%) were completely devoid of E-cadherin expression, and the remaining samples (13.6%) had a weak reaction. Conclusions. Dydrogesteron at a dose of 20 mg/day in 6 months without interruption provides positive results in the treatment of HE in premenopausal women with PGR-positive endometrium. At the same time, the use of dydrogesteron in the treatment of HE in women with low PGR presence in endometrial cells is inappropriate. A significant risk of relapse of HE by the end of the second year after treatment completion requires mandatory follow-up with endometrial pypel-biopsy and prevention of relapse with prolonged duration of dydrogesteron or prolonged forms of progestin withdrawal. LH-RH agonists should be the first choice for women with negative or poor progesterone receptor availability in the endometrium at the beginning of treatment, and surgical treatment should be used for relapse of HE or progression to atypia.

non-atypical endometrial hyperplasia, dydrogesteron, long-term results of treatment, nuclear receptors to progesterone, Кі-67, Е-cadherin

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    Publication of the article:

    «Bulletin of problems biology and medicine» Issue 1 (159), 2021 year, 38-43 pages, index UDK 618.14-006.55

    DOI:

    10.29254/2077-4214-2021-1-159-38-43