Growth of uterine leiomyomata among premenopausal black and white women

Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 01/2009; 105(50):19887-92. DOI: 10.1073/pnas.0808188105
Source: PubMed


Uterine leiomyomata (fibroids) are the leading cause of hysterectomy in the United States. Black women have a greater fibroid burden than whites, yet no study has systematically evaluated the growth of fibroids in blacks and whites. We prospectively tracked growth for 262 fibroids (size range: 1-13 cm in diameter) from 72 premenopausal participants (38 blacks and 34 whites). Fibroid volume was measured by computerized analysis of up to four MRI scans over 12 months. We used mixed effects models to identify factors that are associated with growth, and results were converted to percent change per 6 months for clinical relevance. The median growth rate was 9% (range: -89% to +138%). Seven percent of fibroids regressed (>20% shrinkage). Tumors from the same woman grew at different rates (within-woman component of variation was twice the component among women; both were significant, P < 0.001). Black and white women less than 35 years of age had similar fibroid growth rates. However, growth rates declined with age for whites but not for blacks (P = 0.05). The odds of a tumor growing more than 20% in 6 months also decreased with age for whites but not for blacks (P < 0.01). Growth rates were not influenced by tumor size, location, body mass index, or parity. We conclude that (i) spontaneous regression of fibroids occurs; (ii) fibroids from the same woman grow at different rates, despite a uniform hormonal milieu; (iii) fibroid size does not predict growth rate; and (iv) age-related differences in fibroid growth between blacks and whites may contribute to the higher symptom burden for black women.

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Available from: Shyamal Peddada
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    • "However, the present study had some limitations, including the brief time between exposure measurement and outcome ascertainment . The natural history of fibroids is complex and fibroids can have notable growth in the six months prior to their detection (Peddada et al., 2008). Thus, chemical levels measured at the time of diagnosis may reflect a relevant period at least for their shortterm growth. "
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    ABSTRACT: Bisphenol A, benzophenone-type UV filters, and phthalates are chemicals in high production and use including in a range of personal care products. Exposure of humans to these chemicals has been shown to affect endocrine function. Although short-lived, widespread exposure may lead to continual opportunity for these chemicals to elicit health effects in humans. The association of these chemicals with incident uterine leiomyoma, an estrogen sensitive disease, is not known. Urinary concentrations of bisphenol A (BPA), five benzophenone-type UV filters (2-hydroxy-4-methoxybenzophenone (2OH-4MeO-BP), 2,4-dihydroxybenzophenone (2,4OH-BP), 2,2׳-dihydroxybenzophenone (2,2׳OH-4MeO-BP), 2,2׳4,4׳-tetrahydroxybenzophenone (2,2׳4,4׳OH-BP), and 4-hydroxybenzophenone (4OH-BP), and 14 phthalate monoesters were quantified in 495 women who later underwent laparoscopy/laparotomy at 14 clinical sites for the diagnosis of fibroids. Significantly higher geometric mean creatinine-corrected concentrations of BPA, 2,4OH-BP, and 2OH-4MeO-BP were observed in women with than without fibroids [BPA: 2.09 µg/g vs. 1.46 µg/g p=0.004; 2,4OH-BP:11.10 µg/g vs. 6.71 µg/g p=0.01; 2OH-4MeO-BP: 11.31 µg/g vs. 6.10 µg/g p=0.01]. Mono-methyl phthalate levels were significantly lower in women with than without fibroids (1.78 µg/g vs. 2.40 µg/g). However, none of the exposures were associated with a significant odds ratio even when adjusting for relevant covariates. There was a lack of an association between select nonpersistent chemicals and the odds of a fibroid diagnosis.
    Full-text · Article · Feb 2015 · Environmental Research
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    • "Moreover, tumors in African-American women are more aggressive , as they present with larger leiomyomas and more significant symptoms than their Caucasian counterparts (Day Baird et al., 2003; Walker and Stewart, 2005). In addition to racial differences, leiomyomas show a high degree of heterogeneity in growth even within the same woman, and especially in women with multiple tumors (Peddada et al., 2008). Despite the high prevalence of these tumors, relatively little is known about their specific etiology. "
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    ABSTRACT: BACKGROUND Uterine leiomyoma is the most common benign tumor in women and is thought to arise from the clonal expansion of a single myometrial smooth muscle cell transformed by a cellular insult. Leiomyomas cause a variety of symptoms, including abnormal uterine bleeding, pelvic pain, bladder or bowel dysfunction, and recurrent pregnancy loss, and are the most common indication for hysterectomy in the USA. A slow rate of cell proliferation, combined with the production of copious amounts of extracellular matrix, accounts for tumor expansion. A common salient feature of leiomyomas is their responsiveness to steroid hormones, thus providing an opportunity for intervention.
    Full-text · Article · Sep 2014 · Human Reproduction Update
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    • "This same clinical investigation reported that women of African American ancestry continued to increase the size of their fibroids after age 35 until menopause. However, women who were identified as white tended to have nongrowing tumors during those ages (as discussed by [107]). When the fibroid tissues of women in this study who underwent surgery were studied for gene expression, dermatopontin was consistently downregulated as reported by others (discussed by [72]). "
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    ABSTRACT: The role of the extracellular matrix (ECM) and mechanotransduction as an important signaling factor in the human uterus is just beginning to be appreciated. The ECM is not only the substance that surrounds cells, but ECM stiffness will either compress cells or stretch them resulting in signals converted into chemical changes within the cell, depending on the amount of collagen, cross-linking, and hydration, as well as other ECM components. In this review we present evidence that the stiffness of fibroid tissue has a direct effect on the growth of the tumor through the induction of fibrosis. Fibrosis has two characteristics: (1) resistance to apoptosis leading to the persistence of cells and (2) secretion of collagen and other components of the ECM such a proteoglycans by those cells leading to abundant disposition of highly cross-linked, disoriented, and often widely dispersed collagen fibrils. Fibrosis affects cell growth by mechanotransduction, the dynamic signaling system whereby mechanical forces initiate chemical signaling in cells. Data indicate that the structurally disordered and abnormally formed ECM of uterine fibroids contributes to fibroid formation and growth. An appreciation of the critical role of ECM stiffness to fibroid growth may lead to new strategies for treatment of this common disease.
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