From obesity to uterine fibroids: an intricate network

Uterine fibroids (UFs) are benign monoclonal tumors consisting of smooth muscle cells and connective tissue that develop within the uterine wall. Also known as uterine leiomyomas, UFs represent one of the most common pelvic tumors, affecting over 70% of women by the onset of menopause, and are one of the leading causes for hysterectomy in the US. Leiomyomas could be completely asymptomatic, but at the same time are a major cause of hospitalization. Annually, among women aged 15–54, UFs-related treatments account for 42 per 10,000 hospitalizations, and in most of the cases the hospital stay is accompanied by some type of surgical procedure (hysterectomy, myomectomy). Indeed, UFs may be responsible for a wide range of severe and chronic symptoms (heavy menstrual bleeding, anemia, pelvic pressure, bladder/bowel dysfunction, pelvic non-cyclic pain, dyspareunia, infertility, pregnancy complications) with a deep impact on patients quality-of-life. Many risk factors have been identified, including black race, positive family history for UFs, genetic predisposition, use of oral contraceptives or intrauterine devices, nulliparity, early menarche, lifestyle factors, and, recently, obesity. The exact proportion of obese patients undergoing surgical procedures for UFs varies among studies. In a study mainly focused on feasibility and outcome of laparoscopy, the percentage of overweight/ obese patients who underwent surgery for UFs (myomectomy/hysterectomy) was 24%. Although the etiology is largely unknown, leiomyomas are estrogenand progesterone-dependent tumors characterized by an increased and disorganized proliferation of smooth muscle cells with an over-production of extracellular matrix (ECM). UFs seem to have an increased sensitivity to sex steroid hormones which is associated with a higher expression of estrogen receptor-a (ER-a) and progesterone receptor (PR) when compared to the normal myometrium. Furthermore, in the luteal phase while normal myometrial cells become quiescent, UFs tissue shows an increase in estrogen-regulated genes, which promotes cell proliferation and grows in response to progesterone (which typically has a suppressive effect on the myometrium). Recently, a possible correlation with obesity has been taken into consideration, but definitive conclusions have not been drawn. Obesity is chronic disease that nowadays represents a significant global burden of disability and a major public health concern. Several mechanisms may promote the development of UFs in pre-menopausal women with excessive body fat: