Mechanisms and Pathogenesis of Adenomyosis

Purpose of the Review The purpose of this review is to provide a synopsis of all the mechanisms involved in the pathogenesis of adenomyosis. It will summarize recent advances in the field, discussing current controversies, and considering potential future directions. Recent Findings Adenomyosis pathogenesis is still a topic under investigation, however advancements in the understanding of disease development and mechanisms have been made. New data coming from new next generation sequencing-based studies and more-in-depth acquisitions on sex hormones imbalance, neuroangiogenesis, inflammation, fibrosis and cell proliferation have been obtained. Adenomyosis is a uterine disorder that affects women of reproductive age, characterized by a benign invasion of the endometrium basalis (glands and stroma) within the myometrium. So far, three theories for the pathophysiology of adenomyosis have been proposed: An invagination of the endometrial basalis into the myometrium by tissue injury and repair. The development from adult stem cells or displaced embryonic mullerian remnants. An "invasion from outside to inside". In order to invade and develop, endometrial cells require a series of pathogenetic mechanisms which drive to adenomyosis. Altered sex steroids hormones receptors may be the primary event which causes increased endometrial cell proliferations and differentiation from epithelial to mesenchymal cells. Once invaded the myometrium, an inflammatory reaction is displayed, probably driven by local immune changes. The processes of neuroangiogenesis and fibrosis are also involved in the adenomyosis development and may explain some of the associated clinical symptoms (dysmenorrhea, abnormal uterine bleeding, and infertility).