Fibroids: basic science and etiology

Abstract

Uterine leiomyomas, commonly called fibroids, are the most common smooth muscle tumor in women. However, the etiology of leiomyomas remains largely unknown. Leiomyomas have been considered to grow under the influence of ovarian steroids, such as estrogen and progesterone. However, leiomyomas show more increased cell proliferation than the myometrium with abnormalities of factors such as cytokines, growth factors, and cell cycle regulatory factors. As the intermediate elements, cytokines and growth factors regulated by the ovarian steroids are now considered to exert their growth-stimulatory effects on leiomyomas. Leiomyomas are also characterized by increased cell proliferation and tissue fibrosis. Recently, it has been proposed that smooth muscle cells respond to injury or ischemia with increased cell proliferation and production of extracellular matrix that are critical for the pathogenesis of uterine leiomyomas. We speculate that myometrial contraction for cessation of menstrual bleeding could induce ischemic injury or ischemic–reperfusion injury to the myometrial smooth muscle cells that are proliferating during the luteal phase of the menstrual cycle. These cells could be candidates for progenitor cells of leiomyomas. If this is the case, repetition of the menstrual cycle itself is important for the pathogenesis of uterine leiomyomas.