Updated: Feb 1
How do fibroids form? Fibroid specialist Dr. Michael Lalezarian explains what causes uterine fibroids to grow.
On our website we have a fantastic review of the risk factors for developing uterine fibroids. Risk factors are patient attributes that increase the risk of developing a certain condition - in this case uterine fibroids. They have been determined by decades of observational research. However, many patients still wonder “what are the biological mechanisms causing my uterus to grow these uncomfortable benign masses”? The (best available) explanation is rooted in advanced genetics, anatomy, and biochemistry. Here we will try to address this question without getting uncomfortably deep into these subjects.
The healthy uterus is composed of three primary layers of tissue: the endometrium, the myometrium, and the perimetrium. Let’s refresh. The endometrium (inside layer) is the mucous membrane that lines the inside of the uterus. The endometrium thickens during the menstrual cycle and sheds to cause normal bleeding during menstruation. The myometrium (middle layer) is composed primarily of smooth muscle cells (hence the prefix myo) whose primary function is uterine contraction - a normal physiological phenomenon occuring during the menstrual cycle, often termed “menstrual cramps”. Uterine contractions also occur during childbirth, with greater frequency and intensity. The perimetrium (outer layer) lines the outside of the uterus.
Transformation of Myometrial Stem Cells into Fibroid Progenitor Cells
Contained within the myometrium are a type of cell called “myometrial stem cells”. These cells are present in every healthy female and are capable of transforming into the healthy functioning smooth muscle cells of the myometrium, but under certain conditions they may transform into “fibroid progenitor cells”. The fibroid progenitor cell is the type of cell that can eventually turn into the harmful cell types that make up the clinical fibroid.¹⁻²
Generally speaking, things begin with some genetic changes to the myometrial stem cells. That is, permanent alterations occur in the DNA of the cell capable of becoming many other uterine cell types. Scientists are capable of determining exactly which genes are normal and which are changed (“mutated”) using laboratory techniques, and to-date a number have been studied. As an example of said changes, the MED12 gene has been found mutated (changed) in 50-84% of fibroids in racially diverse cohorts.¹
Think of the DNA (genes) as the “brain” of the cell, and the chemicals and molecules in the cell’s vicinity as the cell’s “environment”. When the “brain” changes, so does the “behavior” of the cell. We also know that a new environment can cause people to behave differently. The same is true for cells. In combination with other biochemical imbalances and alterations to chromosomes, these genetic changes can lead to transformation of the “myometrial stem cell” into a “fibroid progenitor cell”.
As far as exactly why these genetic and chromosomal changes occur in the myometrial stem cells, the science is unclear. Typically, it is much easier to identify “what happened” than “why it happened”, often because the “why it happened” is a combination of many factors.
Growth of the Preclinical Fibroid into a Clinical Fibroid Mass
Under the influence of mutations in specific genes, external stimulating factors (such as the hormones estrogen and progesterone), and other disrupted cell-signaling pathways, the fibroid progenitor cell can differentiate (turn into) a “preclinical fibroid”. The preclinical fibroid is an early-stage (often microscopic) fibroid that has not caused symptoms. Subsequently, the cells within the preclinical fibroid may go on to grow in an accelerated manner and progress into clinical disease. Factors that influence the progression from “preclinical” to “clinical” disease include environmental factors such as diet, vitamin D, sex hormones, and exposure to toxins, as well as a number of biological factors¹ that we won’t get into for the sake of complexity, but you are welcome to read about them further in Nature.
About the Author
Dr. Michael Lalezarian is a practicing interventional radiologist with the Fibroid Specialists of University Vascular in Los Angeles, CA. In addition to patient care, Dr. Lalezarian teaches and supervises medical students, residents, and fellows as a full time teaching Professor in the Department of Radiology at UCLA. He is regarded as an expert in uterine fibroid embolization. You can view Dr. Lalezarian's full bio here.
This blog post was written with research and editorial assistance from OnChart™.
 Elizabeth A Stewart et al (2016). Nature Reviews Disease Primers: Uterine fibroids. Nature Reviews Disease Primers 2016;2:1-18.
 Elizabeth A Stewart (2015). Uterine Fibroids. New England Journal of Medicine. 2015;372:1646-55.
The Materials available on the FibroidSpecialists.org blog are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients.