Introduction. The chronic, progressive, recurrent nature of the endometriosis results new avenues of targeted therapy for genital endometriosis with high therapeutic efficacy and minimal side effects must be explored. Nowadays, the standard of prolonged specific therapy for endometriosis is the dienogest 2 mg daily, which has already been proven to be effective in vitro, in vivo and in clinical practice. Purpose: to evaluate the effectiveness of new types of targeted pathogenetic therapy for endometriosis on the model of endometriosis in rats compared to dienogest and without treatment. Materials and methods. Endometriosis was induced on 69 Wistar rats by autotransplantation of uterine fragments onto the inner surface of the abdominal wall. After 14 days, the heterotopies had been measured by laparoscopy and then rats were randomized of into one of 6 experimental groups (dienogest, letrozole, cabergoline, metformin, vitamin D, melatonin) or a control group. All drugs were administered daily orally for three weeks, after which an autopsy and re-measuring of the size of endometrial implants were performed. Results. The most pronounced decrease in the size of endometrial implants was observed in the group of animals treated with dienogest (complete resorption - 48%, regression - 48%, without dynamics - 4%) and letrozole (complete resorption - 44%, regression - 56%) without the statistically significant difference between groups. In other groups, a significant decrease in the size of endometrial implants was demonstrated compared with the control, without a statistically significant difference between the groups. Findings. The presented study confirms the absence at the present time of oral drugs for the treatment of endometriosis, comparable in efficacy and safety with dienogest. Further research are needed to evaluate the different combinations of dopamine agonists, biguanides, vitamin D, melatonin as the supplement to the classic hormone-modulating therapy for endometriosis or as monotherapy in patients with contraindications to standard hormone therapy.

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Hypothesis/aims of study. Melatonin is found in almost all living organisms, the range of its effects being quite diverse. Effects of this hormone in the human body are realized via two ways, through specific receptors and non-receptor pathways. Melatonin may act through both membrane and nuclear receptors. In the present work, the expression of MTR1 and MTR2 melatonin receptors was studied in the eutopic endometrium and endometrioid heterotopies, and the level of melatonin metabolite, 6-sulfatoxymelatonin, in daily urine in patients with genital endometriosis (GE) was analyzed. Study design, materials and methods. The experimental group included 67 patients of reproductive age with a verified diagnosis of GE, and the control group consisted of 18 individuals with an ovulatory menstrual cycle without gynecological pathology. The 6-sulfatoxymelatonin level in daily urine was determined by enzyme immunoassay. The study of MTR1 and MTR2 melatonin receptor expression in the endometrium and endometrioid heterotopies was performed in 24 patients with GE and in 10 women of reproductive age who were examined for infertility who did not have gynecological pathology based on diagnostic laparoscopy. To study the expression of melatonin receptors, the endometrium and endometrial heterotopy sampling was carried out from day 18 to day 22 of the menstrual cycle. Morphological assessment included histological and immunofluorescence studies using confocal laser scanning microscopy. Results. In patients with GE, there was found a tendency to a decrease in 6-sulfatoxymelatonin excretion in daily urine compared to the control group. It was also found that the total relative expression area of melatonin receptors in the endometrium of women with GE was significantly lower compared to the endometrium of patients from the control group. Significant differences between the average brightness and optical density were not found. In addition, it was revealed that the relative expression areas of MTR1 and MTR2 melatonin receptors in the eutopic endometrium and in endometrioid heterotopies did not differ significantly. A negative correlation was stated between the relative expression area of melatonin receptors and GE prevalence. Particular attention is paid to the role of melatonin in the development of GE and to the possibilities of working out new treatment regimens with its use. Conclusion. The data obtained confirm the undoubted role of melatonin in the pathogenesis of GE, however, the development of new treatment regimens with its use requires further study.

BACKGROUND: Genital endometriosis is one of the most pressing problems of modern gynecology. Melatonin is a promising drug with a potentially curative effect on endometriosis. AIM: The aim of this study was to conduct a comparative analysis of the genetic polymorphism of some genes encoding enzymes involved in melatonin metabolism. MATERIALS AND METHODS: The genetic polymorphism in the NAT2 and CYP1B1 genes encoding enzymes involved in melatonin metabolism in patients with different tolerance to this drug was analyzed by PCR-RFLP analysis. RESULTS: In patients with genital endometriosis, the presence of a wild-type allele (N) of the NAT2 gene was associated with poor tolerance of melatonin. The NAT2 (N / N) rapid acetylator phenotype combined with the low catalytic activity of CYP1B1 (C / C) occurred more frequently in endometriosis patients having poor melatonin tolerability compared to the group of patients who tolerated the therapy well. CONCLUSIONS: For patients with genital endometriosis with the wild-type (N) allele of the NAT2 gene, melatonin administration is inappropriate due to numerous side effects during the drug use.