Finkova O. Features of hormonal contraception in women with uterine leiomyoma

The dissertation is devoted to a complex study of 230 women with uterine leiomyoma, which obtained new data on the effect of various hormonal contraceptives on the proliferative activity of tumor cells, evaluated the effects of their estrogenic and progestogenic components on the molecular mechanisms of cell proliferation (cyclin Cdk-1, Kі-67, p21, ER, PgR) and expression of growth factors (VEGF, eNOS), which allowed to identify the group of hormonal contraceptives with the most pronounced cytoprotective effect and to optimize approaches to personalized choice of effective contraception in women with uterine leiomyoma. It has been shown that hormonal contraceptives, which contained dienogest (2 mg), gestodene (0.075 mg) and levonorgestrel (0.15 mg), are able to inhibit proliferative processes in uterine leiomyoma cells through mechanisms of suppression of expression of Ki-67 antigen, kinase-dependent cyclin CDK-1, angiogenic eNOS factors VEGF and to affect the expression of the p21 suppressor gene. At the same time, hormonal contraceptives did not significantly affect the expression of estrogen (ER) and progesterone receptors (PgR) in uterine leiomyoma tissues, which was increased almost threefold in uterine leiomyoma cells, and therefore did not increase its proliferative potential. It was found that increasing the dose of ethinyl estradiol in combined hormonal contraceptives from 20 mcg to 30 mcg did not lead to a significant increase in the expression of Ki-67 antigen, and dose of 20 mcg of ethinyl estradiol did not reduce mitosis, indicating no potentiating effect of estrogens on the growth of a new uterine leiomyoma. It was also found that levonorgestrel intrauterine system did not significantly affect the proliferative potential of uterine leiomyoma, as well as the mechanisms of initiation (kinase-dependent cyclin Cdk-1) and inhibition of mitosis in the tumor (p21 suppressor gene), and therefore did not inhibit its growth, but compared with combined oral contraceptive, significantly reduced the amount of menstrual blood loss in women with symptomatic uterine leiomyoma. Justified new criteria for selecting hormonal contraceptives in women with uterine leiomyoma with focus on combined oral contraceptives, containing progestogens with the most pronounced antiproliferative properties (dienogest, desogestrel and levonorgestrel), especially after myomectomy to prevent tumor recurrence.