Uterine fibroid: from pathogenesis to clinical management

Uterine fibroid or leiomyoma is the most common benign gynecological tumor in premenopausal women (15e25%). Even though it is a well-known clinical problem and has been studied extensively, the last decade was characterized by an incredible amount of novel information on the pathogenesis and a concomitant increase of therapeutic proposals. Hence, the present issue aims to update the various biological and medical aspects related to uterine fibroid. The hypothesis of generation of leiomyoma stem cells, the role of epigenetic/cytogenetic anomalies/ mutations, and the overexpression of micro-RNA are of great interest in exploring increased cell proliferation and excessive formation of extracellular matrix. The role of sex steroid hormones (estrogens, progesterone) still remains a key point in the pathogenesis of uterine leiomyoma, and, particularly, estrogen receptors (ERs) and progesterone receptors (PRs) play a role in the development and maintenance of tumor growth, and new receptor modulators are attractive for the medical treatment of uterine fibroid. Estrogens and progesterone act via a large group of growth factors (in particular, the family of transforming growth factor beta (TGFB)), which in turn by activation of multiple signaling pathways regulate major cellular processes, including proliferation, angiogenesis and fibrosis; these have stimulated an interest toward the development of new drugs. An incredible progress in diagnostic procedures for uterine fibroids has been obtained by ultrasound and magnetic resonance imaging (MRI), thus allowing differential diagnosis of adenomyosis or malignant myometrial pathology. Abnormal uterine bleeding (AUB), pelvic pain, dysmennorhea, and infertility remain the most common symptoms of uterine fibroids. The recent FIGO PALM-COEIN classification includes leiomyoma as a major cause of AUB, even though some patients depending on the fibroid localization do not present with such symptomatology. The presence of a large number of uterine fibroids causes infertility, even though some patients with fibroid may become pregnant without any complications. But, in particular, the presence of submucosal or intramural fibroids affects the local anatomy of functional endometrioma/myometrium, thus reducing the ability for embryo implantation. Pregnant patients with fibroids are at a high risk, especially of abortion, placenta previa, preterm birth, or postpartum hemorrhage and should be closely followed up obstetricians. In order to improve AUB, dysmennorhea, pelvic pain, or infertility, a wide range of therapeutic options for uterine fibroids are available and must remain individualized: surgery, hormonal drugs, uterine artery embolization, and high-intensity focused ultrasound are the current options (HIFU). Selection of the appropriate treatment is based on the patient’s age, symptoms, desire of pregnancy, number, size and localization of the fibroids, and concomitance of medical or surgical complications. The development of endoscopic surgery with minimally invasive surgery is the modern trend; thus, the use of hysteroscopy is very effective and less invasive with regard to AUB and/or infertility.