Proceedings from the Third National Institutes of Health International Congress on Advances in Uterine Leiomyoma Research: comprehensive review, conference summary and future recommendations

Abstract

BACKGROUND Uterine fibroids are the most common gynecologic tumors in women of reproductive age yet the etiology and pathogenesis of these lesions remain poorly understood. Age, African ancestry, nulliparity and obesity have been identified as predisposing factors for uterine fibroids. Symptomatic tumors can cause excessive uterine bleeding, bladder dysfunction and pelvic pain, as well as associated reproductive disorders such as infertility, miscarriage and other adverse pregnancy outcomes. Currently, there are limited noninvasive therapies for fibroids and no early intervention or prevention strategies are readily available. This review summarizes the advances in basic, applied and translational uterine fibroid research, in addition to current and proposed approaches to clinical management as presented at the 'Advances in Uterine Leiomyoma Research: 3rd NIH International Congress'. Congress recommendations and a review of the fibroid literature are also reported. METHODS This review is a report of meeting proceedings, the resulting recommendations and a literature review of the subject. RESULTS The research data presented highlights the complexity of uterine fibroids and the convergence of ethnicity, race, genetics, epigenetics and environmental factors, including lifestyle and possible socioeconomic parameters on disease manifestation. The data presented suggest it is likely that the majority of women with uterine fibroids will have normal pregnancy outcomes; however, additional research is warranted. As an alternative to surgery, an effective long-term medical treatment for uterine fibroids should reduce heavy uterine bleeding and fibroid/uterine volume without excessive side effects. This goal has not been achieved and current treatments reduce symptoms only temporarily; however, a multi-disciplined approach to understanding the molecular origins and pathogenesis of uterine fibroids, as presented in this report, makes our quest for identifying novel targets for noninvasive, possibly nonsystemic and effective long-term treatment very promising. CONCLUSIONS The Congress facilitated the exchange of scientific information among members of the uterine leiomyoma research and health-care communities. While advances in research have deepened our knowledge of the pathobiology of fibroids, their etiology still remains incompletely understood. Further needs exist for determination of risk factors and initiation of preventive measures for fibroids, in addition to continued development of new medical and minimally invasive options for treatment.

Fucoidan Inhibits the Proliferation of Leiomyoma Cells and Decreases Extracellular Matrix-Associated Protein Expression

“…Most women with ULs are asymptomatic; however, 20% of ULs patients usually suffer from a reduced quality of life with symptoms such as abnormal uterine bleeding, pelvic pain, frequent urination, and infertility [3,4]. Although the etiology remains unclear, genetic factors, cytokines, growth factors, steroid hormones (estrogens and progestogens) and/or their receptors, and excessive production of extracellular matrix (ECM) plays pivotal roles in the development of ULs [3,5]. In addition, hypoxia can trigger stem cell proliferation during the initiation of fibrosis, leading to fibroids [6].…”

Medical Management of leipmyomas-emphasis for different geographical regions

“…Mammalian Target of rapamycin (MTOR) which is known to be a master regulator of proliferation is activated in many tumours and possibly by mechanisms which are similar to some human fibrosis syndromes and/or mutations of upstream tumor suppressor genes. These suggests several key pathways involved as shown by animal models, suggests complexities of fibroid development and individualized therapies [56] .…”

Fibroid growth and medical options for treatment

“…Risk factors for developing fibroids, apart from ethnic origin and heredity, include situations causing prolonged high exposure to estrogens and/or progesterone, such as early age of menarche (5,6), polycystic ovary syndrome (7), obesity (8), and late pregnancy (9). Consistent with these epidemiologic data, the best known stimulator of tumor growth is the combined action of estrogens and progesterone.…”

“…Growth factors, cytokines, and chemokines (1) have also been described as playing a role. Several animal and in vitro models (5) developed over the past decade have contributed to a better understanding of the disease.…”

“…1) (11). Heavy menstrual bleeding is the most frequent fibroid-related symptom, resulting in reduced quality of life and anemia (5), and it can be related either to the location of the fibroid (submucosal) or to fibroid-related endometrial dysfunction (11). In addition, associated endometrial lesions may be present in up to 20% women with abnormal uterine bleeding, particularly adenomyosis (12)(13)(14)(15).…”