Large fibroids may outgrow their blood supply and degenerate - described as hyaline, myxomatous, calcific, cystic, fatty, necrotic or red (usually only during pregnancy).
Effects of Estrogen and Progesterone in Uterine FIbroids
UFs have excessive production of a disorganized but stable extracellular matrix (ECM) and altered collagen fibrils in the ECM - fibroid collagen fibers (bunches of fibrils) are short, widely dispersed and lying non-parallel, compared to well-packed and lying parallel in the myometrium (smooth muscle tissue of the uterus).
It is the abnormal and overproduced ECM that causes UF expansion , and not the slowly proliferating fibroid cells - UF tumors contain decreased/disrupted matrix metalloproteinases (MMPs) and more proteins in their ECM, such as collagen subtypes, proteoglycans, fibronectin, matrix glycoproteins and matricellular proteins (in particular thrombospondin-1 (TSP-1), which activates TGF- β and has a role in angiogenesis). The ECM binds cytokines and growth factors ready for action in the vicinity of the UF. Integrins are changed in UFs
- The stability of this allbeit disorganized ECM requires therapeutic interventions that address ECM dissolution in addition to inhibiting cell proliferation
- Transforming Growth Factors-β1 and β3 (TGF- β1,TGF- β3) - have a central role in UF enlargement, in that they stimulate production/deposition of ECM and are acknowledged as important growth factors in fibrotic disease. E.g. Fibroids have more concentrated TGF-β receptors. Conversely, reduced TGF-β expression yields reduced ECM production and fibroid shrinkage
- Other growth factors acting on myometrial (uterine smooth muscle) cells - epidermal growth factor (EGF), Insulin-Like Growth Factor (IGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF)
Increased profibrotic cytokines (E.g. IL-1, IL-6, interferon, TNF- α) in UFs - involved with inflammatory response, cytokines are produced when growth factors act on target tissue.
UFs grow at different rates (even in the same woman) - and with different growth-rate patterns in white and African-American women
>50% of UFs are asymptomatic (i.e. have no symptoms) - ~70% of women by age 45 will be diagnosed with UFs, but only a fraction of those will cause problems or require treatment. (Merck Manual)
Organochlorine pesticides stimulate leiomyomata cell proliferation in animals - organochlorines are xenoestrogens (i.e. mimic estrogen in the body). (Hodges et al, 2000)
References
Hodges LC, Bergerson JS, Hunter DS, Walker CL. (2000 Apr) Estrogenic effects of organochlorine pesticides on uterine leiomyoma cells in vitro. Toxicol Sci. ;54(2):355-364. PubMed
Walker CL, Stewart EA (June 10, 2005) Uterine fibroids: the elephant in the room. Science. ; 308.
