Uterine fibroids begin when a single smooth muscle cell in the uterine wall picks up a genetic mutation and starts multiplying on its own. That one altered cell divides again and again, building a firm, rounded growth made of muscle fibers and connective tissue. The process unfolds over months to years, driven by hormones, growth signals, and structural changes in the tissue itself.
It Starts With a Single Cell
Every fibroid is a monoclonal tumor, meaning the entire mass traces back to one mutated cell. During a normal menstrual cycle, the muscular wall of the uterus (the myometrium) responds to estrogen and progesterone by ramping up stem cell activity to prepare for a possible pregnancy. Occasionally, during one of these bursts of cell division, a stem cell acquires a mutation that gives it a growth advantage. That cell then multiplies independently, and its descendants form the fibroid.
Researchers have identified a distinct population of stem-like cells within fibroids that carry neoplastic mutations not found in the surrounding normal muscle. These stem cells appear to be the engine of the tumor: they sustain its long-term growth while the bulk of the fibroid is made up of their more mature daughter cells.
The Genetic Mutations Behind Fibroids
Four driver mutations account for the vast majority of fibroids. The most common, found in 50 to 80 percent of tumors, involves a gene called MED12, which helps regulate how cells read their DNA. A second type, seen in 10 to 20 percent of fibroids, involves overexpression of a gene called HMGA2, typically caused by a chromosomal rearrangement. Two rarer mutations, affecting metabolic and structural proteins, each account for roughly 1 to 2 percent of cases or less.
Different mutations appear to produce fibroids with different growth behaviors, which partly explains why two fibroids in the same uterus can grow at very different rates. Each one is its own independent clone with its own genetic profile.
How Hormones Fuel Growth
Estrogen and progesterone are the primary fuels for fibroid growth. Estrogen promotes the initial expansion of the cells, while progesterone plays a surprisingly central role in sustaining it. Progesterone activates receptors on mature fibroid cells, which then release growth signals that act on nearby stem cells. This indirect, relay-style signaling (called paracrine signaling) keeps the stem cells dividing without those stem cells needing to respond to progesterone directly.
One of the key pathways progesterone activates is the WNT/beta-catenin signaling system, which is critical in many types of tissue growth. The hormone also promotes the production of other growth substances, including insulin-like growth factor 2, that further stimulate stem cell proliferation. This explains why fibroids grow during the reproductive years, often enlarge during pregnancy when hormone levels surge, and typically shrink after menopause when estrogen and progesterone drop sharply.
The Role of Scar-Like Tissue
Fibroids are not just clumps of muscle cells. A large portion of their mass comes from extracellular matrix: a dense scaffold of collagen, fibronectin, and other structural proteins deposited between the cells. This is what gives fibroids their characteristic firmness. The process resembles fibrosis, the same kind of excessive scarring seen in conditions like liver cirrhosis, just happening in the uterine wall.
Fibroid cells produce far more of these matrix proteins than normal uterine muscle. A signaling molecule called TGF-beta is a major driver of this process. It stimulates collagen and fibronectin production while simultaneously blocking the enzymes that would normally break those proteins down. The result is a one-way accumulation: the fibroid builds its scaffold faster than the body can clear it. Other growth factors, including platelet-derived growth factor and insulin-like growth factors, reinforce the same cycle by promoting additional matrix production and smooth muscle cell proliferation.
The stiffness of the matrix itself creates a feedback loop. When fibroid cells sit in a mechanically stiff environment, they activate additional growth and fibrotic signaling pathways. In other words, the firmer the fibroid becomes, the more signals it generates to keep growing and depositing more tissue. Collagen cross-linking enzymes are more active in fibroids than in surrounding muscle, creating tightly woven, mature collagen fibers that resist breakdown even further.
Building a Blood Supply
Like any growing tissue, a fibroid needs oxygen and nutrients. As it expands, it stimulates the formation of new blood vessels through a process called angiogenesis. This new vasculature typically concentrates in a ring around the fibroid’s outer edge, forming what’s sometimes called a vascular pseudocapsule, visible on Doppler ultrasound. The blood vessels within fibroids tend to look normal and orderly, unlike the chaotic, irregular vessels seen in cancerous tumors.
When a fibroid outgrows its blood supply, the interior can become starved of oxygen. This leads to degeneration, where parts of the fibroid break down. It can cause sudden, sharp pain and is especially common during pregnancy, when fibroids may enlarge rapidly.
How Fast Fibroids Grow
A large study tracking fibroids in premenopausal women found a median growth rate of about 9 percent increase in volume every six months. But individual fibroids vary enormously. About a third of tracked fibroids were “rapid growers,” gaining more than 20 percent in volume over six months. Meanwhile, roughly 7 percent were spontaneously shrinking by 20 percent or more over the same period, with no treatment at all. Black and white women in the study shared the same median growth rate, though Black women tend to develop fibroids earlier and more frequently.
This variability means that some fibroids remain small and stable for years while others can grow from undetectable to grapefruit-sized in a relatively short time. The underlying genetic mutation, hormone levels, growth factor activity, and matrix stiffness all influence the pace.
Factors That Raise Formation Risk
Beyond the hormonal and genetic mechanisms, several external factors influence whether fibroids form and how aggressively they grow.
Vitamin D Deficiency
Fibroid cells have lower levels of vitamin D receptors than normal uterine muscle. Lab studies show that treating fibroid cells with vitamin D decreases their proliferation, reduces the production of extracellular matrix proteins, and dampens the WNT/beta-catenin signaling pathway that drives stem cell division. Epidemiological data consistently links low vitamin D levels with higher fibroid risk, which may partly explain the higher prevalence in Black women, who are more likely to have insufficient vitamin D due to differences in skin melanin and sun exposure.
Endocrine-Disrupting Chemicals
Certain synthetic chemicals that mimic or interfere with hormones appear to increase fibroid risk. The phthalate DEHP, commonly found in plastics and personal care products, has been associated with greater fibroid risk and severity in epidemiological studies. Bisphenol A (BPA), found in some food packaging and receipts, can affect biological pathways involved in fibroid development. These chemicals may act by amplifying the same estrogen and progesterone signaling that fibroids depend on.
Inflammatory Signals
Inflammatory molecules like TNF-alpha are found at higher levels in fibroid tissue than in normal uterine muscle. These cytokines stimulate excessive production of extracellular matrix and promote smooth muscle cell proliferation, creating a chronically inflamed microenvironment that favors continued fibroid growth.
What Happens After Menopause
When ovarian hormone production drops at menopause, fibroids lose their primary growth stimulus. Most fibroids gradually shrink as estrogen and progesterone levels fall, though they rarely disappear entirely. The dense collagen scaffold that makes up much of the fibroid’s bulk doesn’t dissolve quickly, and in some cases fibroids calcify over time, becoming hard, calcium-deposited masses that are generally harmless. Women who take hormone replacement therapy may maintain enough hormonal stimulation to keep existing fibroids from shrinking, or occasionally see them grow slightly.