Uterine fibroids.

Copyright © 2013 Massachusetts Medical Society Uterine fibroids (leiomyomas) represent the most common tumor in women. These lesions disrupt the functions of the uterus and cause excessive uterine bleeding, anemia, defective implantation of an embryo, recurrent pregnancy loss, preterm labor, obstruction of labor, pelvic discomfort, and urinary incontinence and may mimic or mask malignant tumors. By the time they reach 50 years of age, nearly 70% of white women and more than 80% of black women will have had at least one fibroid; severe symptoms develop in 15 to 30% of these women.1,2 Uterine fibroids in black women are significantly larger at diagnosis than those in white women, are diagnosed at an earlier age, and are characterized by more severe symptoms and a longer period of sustained growth.3-5 Approximately 200,000 hysterectomies, 30,000 myomectomies, and thousands of selective uterineartery embolizations and high-intensity focused ultrasound procedures are performed annually in the United States to remove or destroy uterine fibroids. The annual economic burden of these tumors is estimated to be between $5.9 billion and $34.4 billion.6 There may be one predominant uterine fibroid or a cluster of many fibroids (Fig. 1). Very large fibroids can cause the uterus to expand to the size reached at 6 or 7 months of pregnancy. The location and size of the fibroid in the uterus are critical determinants of its clinical manifestations. As compared with other fibroids, submucous fibroids that extend into the uterine cavity are the most disruptive to endometrial integrity, implantation, and the capacity of the myometrium to contract and stop menstrual bleeding from the endometrial blood vessels; thus, even small submucous fibroids are associated with excessive or irregular bleeding, infertility, and recurrent pregnancy loss. In contrast, subserous fibroids that grow out into the peritoneal cavity can exert pressure that is sensed by the patient as pelvic discomfort only if they reach a certain size. Intramural fibroids that reside in the myometrial wall represent an intermediary group. Regardless of their size or location, fibroids may have paracrine molecular effects on the adjacent endometrium that are extensive enough to cause excessive uterine bleeding or defective implantation.7 Uterine fibroids are monoclonal tumors that arise from the uterine smoothmuscle tissue (i.e., the myometrium).8 Histologically, fibroids are benign neoplasms composed of disordered smooth-muscle cells buried in abundant quantities of extracellular matrix (Fig. 1). The cells proliferate in vivo at a modest rate. Formation of the extracellular matrix also accounts for a substantial portion of tumor expansion. Uterine fibroids are almost always benign.9 A striking feature of uterine fibroids is their dependency on the ovarian steroids estrogen and progesterone.10 Ovarian activity is essential for fibroid growth, and most fibroids shrink after menopause. The sharp elevations and declines in the production of estrogen and progesterone that are associated with very early pregnancy and the postpartum period have a dramatic effect on fibroid growth.11-13 Gonadotropin-releasing-hormone (GnRH) analogues, which suppress ovarian activity and reduce circulating levels of estrogen and progesterone, shrink fibroids and reduce associated uterine bleeding.14