Background. Justification. The article discusses the issues of diagnosis and treatment of progestogen-resistant forms of endometrial hyperplasia without atypia, which are relevant today due to numerous negative consequences for women, namely abnormal uterine bleeding, infertility, and the risk of malignancy. Objective of the study: Аssessment of the degree of pathological molecular changes in endometrial cells, which may act as predictors for determining an individual treatment strategy for endometrial hyperplasia without atypia in women Materials and methods. 311 women with a histological diagnosis of endometrial hyperplasia without atypia were treated with various forms of progestogens for 6 months in a continuous mode. Results. The absence of regression of endometrial hyperplasia without atypia or its recurrence over the next 3 years was diagnosed in 23 (23.9%) of 96 women after therapy with micronized progesterone at a dose of 200 mg/day, in 30 (18.6%) of 161 women who received 20 mg of dydrogesterone daily and in 9 (16.7%) of 54 women who received an intrauterine system with levonorgestrel as therapy. To clarify the reason for this circumstance, the expression of estrogen receptors and progesterone receptors (PGR), kinase-dependent cyclin Cdk-D1, Ki-67 protein, and glycoprotein E-cadherin was studied by immunohistochemical methods in primary and control morphological samples of the endometrium after treatment. 63 endometrial samples with negative and 48 samples with positive results of progestogen therapy were studied. It was found that in 73.02% of women with negative results of progestogen therapy, the expression of PGR was absent in the studied endometrial samples (H-index PGR < 50), in the remaining 26.98% of samples their low expression was found, both in the glands and in the stroma (H-index 53.6 ± 0.8 and 42.5 ± 0.6, respectively). On the contrary, in endometrial samples of women with regression of endometrial hyperplasia without atypia against the background of treatment with progestogens, the expression of PGR was positive in 97.92% of cases, and the average values of the PGR H-index, which were 194.1 ± 4.1 and 168.2 ± 2.1 in glandular and stroma cells, respectively, were significantly higher than in the previous sample (p < 0.05). Therefore, adequate receptivity is a necessary condition for the implementation of the genomic-mediated mechanism of the influence of progestogens on the activity of genes that control proliferation and contribute to its inhibition. The authors believe that the lack of regression of endometrial hyperplasia under the influence of progestogens is probably associated with the features of the expression of PGR in progestogen-resistant patients. After the appointment of the gonadotropin-releasing hormone analogue goserelin acetate (Zoladex®, AstraZeneca) to such women for the next six months, regression of endometrial hyperplasia occurred in 93.8% of cases. At the molecular level, a 7.3-fold decrease in the number of glandular cells expressing cyclin Cdk-D1 and a 64.2% decrease in the expression of the Ki-67 protein was noted. Conclusions. The study showed that there are objective grounds for the use of gonadotropin-releasing hormone analogues in women with endometrial hyperplasia without atypia, in whom progestogen therapy was insufficiently effective, as well as as a first-line therapy in women with low expression of PGR in glandular cells at the stage of primary histological screening.
Потапов et al. (Fri,) studied this question.