Uterine fibroids develop from a combination of hormonal signals, genetic mutations, and environmental influences, not a single cause. Up to 70% to 80% of people with a uterus in the U.S. develop fibroids by age 50, with roughly a third experiencing symptoms significant enough to need treatment. Understanding what drives their growth can help you make sense of your own risk and the options available to you.
Hormones Fuel Fibroid Growth
Estrogen and progesterone are the two primary hormones behind fibroid development, which is why fibroids almost always appear during the reproductive years and tend to shrink after menopause. For a long time, estrogen got most of the blame. But the relationship is more nuanced: estrogen’s main role is priming fibroid cells to respond to progesterone by increasing the number of progesterone receptors on their surface. Fibroid tissue contains significantly more of these receptors than the normal surrounding uterine muscle.
Progesterone then does the heavy lifting. It switches on genes that promote cell multiplication while switching off genes that would normally slow growth down. It also blocks the natural self-destruct process that damaged or excess cells normally undergo, allowing fibroid cells to accumulate instead of dying off on schedule. On top of that, progesterone stimulates the production of growth-signaling proteins that push fibroid cells to keep dividing and to build up the dense, fibrous tissue that gives fibroids their characteristic firmness.
A Single Gene Mutation Starts Most Fibroids
Between 50% and 80% of fibroids carry a mutation in a gene called MED12. These are gain-of-function mutations, meaning they don’t disable the gene but instead cause it to behave in an abnormal, growth-promoting way. The MED12 protein normally helps regulate how other genes are turned on and off. When it’s mutated, it disrupts several signaling pathways and ramps up the production of collagen and other structural proteins that form the bulk of fibroid tissue.
Each fibroid typically grows from a single mutated cell, which is why a person can have multiple fibroids that are genetically distinct from one another. You don’t inherit fibroids directly, but a family history of fibroids does increase your risk, suggesting that inherited traits in how your body handles hormone signaling or DNA repair play a role in whether that initial mutation takes hold.
How Fibroids Build Their Own Structure
A fibroid isn’t just a ball of dividing cells. Much of its mass comes from an excessive buildup of structural proteins outside the cells, particularly collagen types I, III, and V, along with fibronectin and sugar-protein complexes called proteoglycans. This buildup is what makes fibroids feel firm or rubbery during an exam.
The stiffness of this structural framework depends on how heavily the collagen fibers are cross-linked to each other. Fibroids produce higher levels of the enzyme responsible for this cross-linking compared to normal uterine tissue, creating an increasingly rigid scaffold. That stiffness isn’t just a passive feature. The surrounding cells sense the mechanical pressure and respond by producing even more structural protein, creating a self-reinforcing cycle of growth.
Several growth-signaling proteins drive this process. One family in particular promotes collagen and fibronectin production while simultaneously blocking the enzymes that would normally break those proteins down. Another growth signal manages cell proliferation and further stimulates collagen and proteoglycan production. Together, these signals create an environment where fibroid tissue continuously remodels and expands.
Epigenetic Changes Keep Fibroid Stem Cells Active
Fibroids contain a small population of stem-like cells that are responsible for sustaining the tumor’s growth. These cells have a distinctive pattern of chemical tags on their DNA, with thousands of regions more heavily “methylated” (chemically marked to silence genes) compared to the more mature cells in the same fibroid. This heavy methylation suppresses genes involved in muscle contraction, hormone response, and cell maturation, essentially locking these stem cells in an immature, actively dividing state.
When researchers used a drug that strips away these chemical tags in lab studies, the stem cell population dropped by about 40%, and genes important for cell maturation switched back on. This suggests the epigenetic silencing isn’t just a byproduct of fibroid biology but an active mechanism keeping fibroids alive and growing.
Race and Ethnicity Affect Risk Significantly
Black women face a disproportionately higher risk of developing fibroids. A large study from an integrated health care system found that Black patients had more than three times the rate of fibroid diagnosis compared to white patients after adjusting for age. Black women also tend to develop fibroids at younger ages, have larger or more numerous tumors, and experience more severe symptoms. The reasons are not fully understood but likely involve a combination of genetic susceptibility, differences in vitamin D levels, and social determinants of health including chronic stress and unequal access to care.
Early Puberty and Reproductive History
The earlier your body begins producing reproductive hormones, the longer your uterine tissue is exposed to their growth-promoting effects. Starting your period before age 11 is associated with roughly a 40% higher risk of developing fibroids compared to starting at the average age of 12 to 13. Conversely, starting menstruation at 15 or later is associated with a 37% lower risk. Pregnancy appears to have a protective effect, and people who have never been pregnant tend to have a higher fibroid burden.
Vitamin D Deficiency and Fibroid Size
Vitamin D acts as a natural counterbalance to estrogen and progesterone in uterine tissue. It reduces the number of hormone receptors on fibroid cells and promotes cell death pathways that fibroids normally suppress. In a clinical trial of 69 women with fibroids and vitamin D deficiency, those who received vitamin D supplements for 10 weeks saw their fibroids shrink to an average of about 53 millimeters, compared to 61 millimeters in the placebo group. The fibroids in the placebo group didn’t change significantly.
This connection may partly explain the racial disparity in fibroid prevalence, since Black women in the U.S. have substantially higher rates of vitamin D deficiency due to differences in skin melanin content and its effect on vitamin D synthesis from sunlight.
Body Weight and Estrogen Production
Carrying excess body fat increases fibroid risk through a straightforward hormonal mechanism. Fat tissue contains an enzyme that converts other hormones into estrogen, so the more adipose tissue you have, the higher your circulating estrogen levels tend to be. That additional estrogen promotes fibroid growth by the same pathways described above: increasing progesterone receptor availability and fueling the hormonal cycle that drives cell proliferation and structural protein buildup. Higher BMI is consistently identified as an independent risk factor for fibroids across large population studies.
Environmental Chemicals That Mimic Hormones
Endocrine-disrupting chemicals, synthetic compounds that interfere with your body’s hormone signaling, are an emerging piece of the puzzle. Phthalates, found in plastics, personal care products, and food packaging, have received the most attention. A group of phthalate breakdown products related to the common plasticizer DEHP has been linked to increased fibroid risk and larger uterine volume across multiple studies. In lab experiments, DEHP exposure caused human fibroid cells to proliferate faster and resist cell death, mimicking the effects of progesterone.
Bisphenol A (BPA), found in hard plastics and can linings, tells a similar story. At low concentrations, BPA pushed fibroid cells into their growth phase and increased proliferation in lab studies. The exposure levels used in these experiments are relevant to what people encounter in daily life, though translating lab findings to real-world risk is always imperfect. Reducing your exposure to plasticized food containers, especially when heated, is a reasonable precaution based on the current evidence.