Etiology and Pathogenesis of Uterine Leiomyomas: A Review

Comparative Pathobiology Group, Laboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
Environmental Health Perspectives (Impact Factor: 7.98). 07/2003; 111(8):1037-54. DOI: 10.1289/ehp.5787
Source: PubMed


Uterine leiomyomas, or fibroids, represent a major public health problem. It is believed that these tumors develop in the majority of American women and become symptomatic in one-third of these women. They are the most frequent indication for hysterectomy in the United States. Although the initiator or initiators of fibroids are unknown, several predisposing factors have been identified, including age (late reproductive years), African-American ethnicity, nulliparity, and obesity. Nonrandom cytogenetic abnormalities have been found in about 40% of tumors examined. Estrogen and progesterone are recognized as promoters of tumor growth, and the potential role of environmental estrogens has only recently been explored. Growth factors with mitogenic activity, such as transforming growth factor- (subscript)3(/subscript), basic fibroblast growth factor, epidermal growth factor, and insulin-like growth factor-I, are elevated in fibroids and may be the effectors of estrogen and progesterone promotion. These data offer clues to the etiology and pathogenesis of this common condition, which we have analyzed and summarized in this review.

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    • "Since self-reporting in a clinical setting was used in this study, there may be some experimental bias of the results based on the self-reporting of patients. Additionally, since at least 20% of the controls and cases were in the reproductive age group, ages 31–40, most frequently associated with the diagnosis of UL (Baird et al., 2003; Flake et al., 2003), it was not seen as a limit to this present study, but is presented here as an epidemiological descriptor of UL in Barbados. The associations with waist circumference and obesity indicators in this study clearly need replication in a larger sample size with clinical confirmation by ultrasound. "
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    ABSTRACT: Uterine leiomyoma is a major reproductive health disease among women and in particular Black women. The present study sought to determine whether a single nucleotide polymorphism (SNP) of CYP17 (rs743572) was associated with the risk of developing uterine leiomyoma (UL) in affected women in Barbados; a majority Black population. It also sought to determine if BMI, waist circumference and oestradiol levels were associated with UL in this group. A total of 96 random persons were assessed in a case–control study using a PCR-RFLP assay, and measurements of body mass index, waist circumference, and oestradiol levels were also assessed. Our results showed no genetic association with the risk of UL and this gene. The genetic distribution of CYP 17α- alleles resembled a normal Hardy–Weinberg distribution, and a relatively low risk of 0.25 at a confidence interval at 95%, of UL disease development. However, a significant association was found between oestradiol levels and fibroids, as well as oestradiol levels and BMI, at P < 0.05 among cases. Therefore our study indicates that significant associations between physiochemical factors comprising BMI, waist circumference, and oestrogen levels are disease indicators in this population. In conclusion, our findings suggest that obesity and its associated risk factors are important in a majority Black Caribbean population, although the sample size needs to be increased.
    Meta Gene 12/2014; 2(1):358–365. DOI:10.1016/j.mgene.2014.03.006
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    • "Uterine leiomyoma, the most common gynecologic neoplasm, occurs in .70% of reproductive-age women (Lumsden and Wallace, 1998; Rein, 2000; Flake et al., 2003). Steroid hormones are believed to play critical roles in the pathogenesis of the tumor (Burroughs et al., 2000; Di et al., 2008); however, despite much investigation, including genetic and molecular approaches, the underlying mechanism of uterine leiomyoma remains unclear. "
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    ABSTRACT: STUDY QUESTION Does tumor necrosis factor-α (TNF-α) differentially regulate matrix metalloproteinase-2 (MMP-2) expression in leiomyomas compared with normal myometrium?
    Human Reproduction 11/2014; 30(1). DOI:10.1093/humrep/deu300 · 4.57 Impact Factor
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    • "Myomas have been found to mimic the fibrotic process, and have been shown to specifically upregulate collagen types I and III (9–11). In addition, it has been proposed that the pathogenesis of myomas is comparable to an injury response (analogous to keloid development) following surgery (12). Mladenović-Mihailović et al (13) investigated the immunocytochemical characteristics of smooth muscle cells (SMCs) and connective tissue components of uterine submucosal myomas. "
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    ABSTRACT: Uterine fibroids are the most common type of benign, gynecologic neoplasm and are the primary indication for performance of a hysterectomy, accounting for >200,000 hysterectomies annually in the USA. At present, females are younger and exhibit larger leiomyomas at the time of diagnosis. Cancer-associated fibroblasts in tumor microenvironments have emerged as an important target for cancer therapy. Repeated stimulation by infectious or non-infectious agents in the uterine tissues, including inflammation, mechanical forces or hypoxia, stimulate the resident fibroblasts to undergo specific activation and, thus, are significant in tumorigenesis. Furthermore, complex signaling pathways regulate the mechanisms of fibroblastic activation. The current review focuses on the molecular mechanisms of fibroblastic activation and the potential association with uterine leiomyoma pathogenesis, enabling an integrated pathogenic analysis for review of the therapeutic options.
    Oncology letters 08/2014; 8(2):479-486. DOI:10.3892/ol.2014.2225 · 1.55 Impact Factor
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