Uterine fibroids (leiomyomas) are non-cancerous tumors that develop in the muscular wall of the uterus. These growths are common, affecting up to 80% of women by age 50, though many never experience symptoms. While the exact cause of fibroid formation is not fully understood, their growth is driven by a complex interplay of internal and external factors that act as fuel. Understanding what feeds these tumors involves chemical signals, genetic predispositions, and lifestyle influences that contribute to their proliferation and maintenance.
Primary Hormonal Drivers of Growth
Fibroids are highly dependent on the reproductive hormones Estrogen and Progesterone, which is why they develop during the reproductive years and typically shrink after menopause. Fibroid cells possess a significantly higher density of receptors for both hormones compared to normal uterine tissue. This increased receptor expression makes the tumor acutely sensitive to circulating hormone levels.
Estrogen acts as a growth promoter, stimulating the proliferation and division of the smooth muscle cells. It also upregulates the expression of progesterone receptors within the fibroid tissue. This primes the fibroid cells to become more responsive to Progesterone.
Progesterone is equally influential in maintaining fibroid growth. Instead of stimulating cell division, progesterone exerts an anti-apoptotic effect, preventing fibroid cells from undergoing programmed cell death. This promotion of cell survival allows the tumor mass to persist and accumulate. The combined action of estrogen promoting cell creation and progesterone preventing cell destruction is a major mechanism behind fibroid development.
Non-Hormonal Cellular Growth Factors
Beyond sex hormones, fibroid growth is driven by localized, non-hormonal signals produced within the tumor microenvironment. These signals act as downstream messengers, including peptide growth factors that command cellular actions like division and survival.
Transforming Growth Factor-beta (TGF-β) is highly expressed in fibroid tissue. TGF-β is a profibrotic agent that drives the development of fibrous tissue. Its presence stimulates the excessive production of the Extracellular Matrix (ECM), the dense scaffolding that gives fibroids their firm, rubbery texture.
The ECM, a network of proteins like collagen, is abnormally large and disorganized in fibroids. This excessive matrix deposition accounts for the majority of the tumor’s physical growth. Fibroid cells expand by creating a massive amount of this structural material, rather than multiplying rapidly. Insulin-like Growth Factor (IGF) also promotes cell proliferation and survival, often working with TGF-β and sex hormones.
Genetic and Demographic Predisposing Factors
While hormones and growth factors provide the immediate fuel, inherent, non-modifiable factors determine susceptibility. Genetic predisposition plays a significant part, with a family history increasing the risk by approximately three times. Fibroids are genetically distinct from normal uterine cells, often featuring a mutation in the Mediator complex subunit 12 (MED12) gene.
This genetic change is found in over half of all fibroid tumors, suggesting it initiates susceptibility to hormonal and growth factor stimulation. Demographic factors highlight a pronounced disparity in risk and severity. Black women have a significantly higher incidence, with over 80% developing fibroids by age 50, compared to about 70% of white women.
Fibroids in Black women also tend to develop at younger ages, are more numerous, and present with more severe symptoms. Age is a factor, as fibroids are most prevalent during the reproductive years when hormone levels are high. After menopause, when ovarian hormone production declines, the tumors typically regress and shrink.
Lifestyle and Environmental Modulators
External factors related to diet and lifestyle can modulate the internal environment, indirectly fueling fibroid growth by altering hormone balance and inflammatory states. Obesity is a risk factor because adipose (fat) tissue produces and stores estrogen, leading to higher circulating levels of the hormone. This increased estrogen exposure provides more growth fuel for the fibroid cells.
Several lifestyle factors are associated with fibroid risk:
- Vitamin D deficiency has been linked to a higher risk, suggesting adequate levels may inhibit fibroid cell proliferation.
- High consumption of red meat has been associated with an increased risk.
- Alcohol consumption, particularly heavy drinking, is positively associated with fibroid risk, possibly by affecting hormone metabolism or increasing inflammation.
Maintaining a healthy weight and ensuring sufficient intake of fruits and vegetables, which contain anti-inflammatory and hormone-regulating compounds, can help mitigate these environmental influences.