Hormones and pathogenesis of uterine fibroids

The role of ovarian steroid hormones in the pathogenesis of uterine fibroids is supported by epidemiological, clinical, and experimental evidence. Estradiol and progesterone induce mature leiomyoma cells to release mitogenic stimuli to adjacent immature cells, thereby providing uterine leiomyoma with undifferentiated cells that are likely to support tumor growth. Progesterone action is required for the complete development and proliferation of leiomyoma cells, while estradiol predominantly increases tissue sensitivity to progesterone by increasing the availability of progesterone receptors (PRs). The selective estrogen receptor modulator (SERM) raloxifene and the selective PR modulators (SPRMs) mifepristone, asoprisnil, and ulipristal acetate have been shown in clinical trials to inhibit fibroid growth. The role of sex steroids is critical for leiomyoma development and maintenance, but a number of autocrine and paracrine messengers are involved in this process; hence, numerous pathways remain to be explored in therapeutic innovations for treating this common disease. (C) 2015 Elsevier Ltd. All rights reserved.