Estrogens and uterine fibroids: an integrated view

Background: Uterine fibroids or uterine leiomyomata (UL) are common benign tu-mors of the uterine myometrium affecting a significant proportion of women at reproductive age. UL is a disease with complex etiology determined by many genetic and environmental factors. Estrogen is widely acknowledged as one of the main factors contributing to the risk and pathogenesis of UL. The aim of the study: To summarize available literature data about the estrogen-related environmental factors, genes and metabolic pathways, which may play a role in the disease. Materials and methods: The PubMed, Scopus, and Web of Science literature databases were searched for relevant articles using such keywords as ―uterine fibroids‖, ―uterine leiomyoma‖, ―estrogen‖, ―gene‖, ―association‖, ―expression‖, ―epigenetic‖ in various combinations. Results: Estrogen contributes to the risk and pathophysiology of UL in multiple ways. Apart from the well-known effect of estrogen on expression of many genes mediated by estrogen receptors, it increases sensitivity of myometrium to progesterone and thus influences expression of the progesterone-controlled genes. On the other hand, the data about association of various estrogen-related genes with UL are largely inconsistent and inconclusive. Conclusion: The observed heterogene-ity of UL apparently results from the diversity of mechanisms contributing to the disease. This makes identification of the causative genetic variants challenging and prompts for further studies of this problem.