Understanding Fibroids: Causes, Epidemiology, and Classifications
Fibroids can manifest with a wide range of clinical symptoms, including vaginal bleeding, pelvic pain, infertility, and adverse obstetric outcomes. Due to this variability, healthcare providers may find it challenging to navigate the overwhelming, confusing, or conflicting evidence guiding fibroid care. This chapter aims to provide a clear summary of the current evidence-based knowledge regarding fibroids, with a particular emphasis on Level I evidence.
Epidemiology
Prevalence
- Uterine leiomyomas, or fibroids, are benign monoclonal growths originating from the uterine myometrium.
- They are the most common benign neoplasms in women of reproductive age.
- Approximately 70-80% of women will have fibroids by the time they reach menopause.
- Fibroids are notably more prevalent and severe in Black women, affecting up to 80% of this demographic.
- Black women are often diagnosed at a younger age, have multiple fibroids, and are more likely to undergo fibroid-related surgeries compared to White women.
- Asians, Hispanics, and White women in the US generally have similar fibroid prevalence rates.
- In Europe, fibroid incidence tends to be lower overall, but around 50% of affected women remain asymptomatic.
Age and Hormonal Influence
- Fibroid prevalence increases with age.
- However, the symptomatology, especially in White women, decreases significantly after menopause due to hormonal changes.
Economic Impact
- Treating fibroids directly costs an estimated $4.1-9.4 billion annually in the US.
- When factoring in lost work and obstetric complications, the total cost could reach $5.9-34.4 billion annually
# Understanding the Etiology and Dynamics of Fibroids
Fibroids, also known as uterine leiomyomas, are complex growths that have a multifaceted etiology and exhibit diverse behavior. This section delves into the causes of fibroids, including genetic factors, hormonal influences, and inflammatory processes, and also explores the dynamic nature of fibroid growth and regression.
## Genetic and Hereditary Factors
### Two Types of Fibroids
- Fibroids are not a singular disease but appear to fall into at least two categories: genetic and common (sporadic) fibroids.
- Genetic fibroids, often linked to hereditary leiomyomatosis and renal cell carcinoma (HLRCC), result from fumarate hydratase gene mutations, leading to more severe disease.
- For fibroids not related to HLRCC, there seems to be a genetic predisposition, with a higher risk in individuals with a family history of fibroids.
- Genetic studies have revealed mutations that increase HOX gene expression, catechol-o-methyltransferase (COMT) levels, and decrease retinoic acid.
- Karyotype studies show that up to 40% of fibroids have at least one genetic anomaly.
- As monoclonal neoplasms, fibroids within the same uterus may possess different genotypes.
## Hormonal Responsiveness
- Fibroids are hormonally responsive, influenced by both estrogen and progesterone.
- Various physiological states affecting hormonal balance can impact fibroid growth.
- Factors associated with higher estrogen levels, such as early menarche, nulliparity, and elevated BMI, correlate with an increased risk of fibroid development.
- Fibroids contain significantly higher levels of aromatase, an enzyme involved in estrogen synthesis, resulting in a microenvironment with elevated estrogen levels.
- While estrogen has long been considered the primary driver of fibroid growth, it's now clear that progesterone plays a crucial role. Fibroids do not grow or maintain size with estrogen alone.
- Progesterone antagonists can cause fibroid tissue to shrink.
## Inflammatory and Hyperplastic Processes
- The initiation of fibroid development may be linked to inflammatory and hyperplastic processes.
- Seedling fibroids may arise in regions of myometrial hyperplasia (MMH) and disordered collagen.
- Myometrial smooth muscle cells (MSMCs) within fibroids display markers of inflammation and communicate through autocrine and paracrine pathways.
- Fibroids have fewer progenitor/stem cells and lower levels of anti-fibrotic factors like vitamin D3.
- Hypertension, particularly diastolic hypertension, increases the risk of symptomatic fibroids, possibly due to myometrial injury or cytokine release.
- Certain infections of smooth muscle, such as Chagas' disease, have also been linked to fibroids.
## Dynamic Nature of Fibroids
- Fibroids are highly dynamic, and each fibroid can exhibit unique behavior.
- A longitudinal study monitoring fibroid growth via serial MRIs found that, on average, fibroids grew by 9% over six months.
- Fibroid growth patterns varied: 34% exhibited rapid growth (>20% increase in size), while 7% spontaneously regressed (decreased in size).
- Even within the same patient, individual fibroids displayed independent behavior.
- In White women over age 45, growth slowed to 2%, but this wasn't the case for Black women of the same age, who experienced an average fibroid growth rate of 15% in six months.
- During pregnancy, 36% of fibroids were eliminated, and 72% regressed by more than 50%.
In summary, fibroids are a complex condition influenced by genetic, hormonal, and inflammatory factors. They exhibit considerable variability in growth and regression patterns, with each fibroid behaving differently within the same uterus. Understanding these diverse factors is crucial for effective management and treatment of fibroids.
# Diagnosing Fibroids: Understanding Symptoms and Imaging
Diagnosing fibroids involves a comprehensive assessment of clinical history and physical examination, but imaging studies are pivotal for accurate diagnosis and treatment planning. This section explores various diagnostic methods, their limitations, and the clinical presentations associated with uterine fibroids.
## Diagnostic Imaging Modalities
- **Ultrasound:** This widely used method offers accessibility but has limitations. It cannot fully assess the fibroid's relationship with the endometrium, distinguish adenomyosis from myometrial contractions, or identify ovarian or adnexal masses in the presence of pedunculated fibroids.
- **Saline Infusion Sonograms (SIS):** These, with or without 3D technology, articulate endometrial surfaces more clearly and define submucosal fibroids' nature.
- **Hysterosalpingograms:** While they indirectly characterize the endometrial cavity, they provide valuable information on tubal status or patency, which can be affected by fibroids.
- **MRI (Magnetic Resonance Imaging):** The preferred method, as it delineates a fibroid's proximity to surrounding tissues like endometrium, bowel, and bladder. It also distinguishes adenomyosis, atypical cellular fibroids, sarcomas, and degenerating fibroids.
- **CT Scans:** Historically used to assess fibroid relationships with surrounding organs or vessels, this modality is now rarely employed when MRI or ultrasound are available.
- **Surgical Pathology:** Remains the definitive method for diagnosing fibroids.
## Clinical Presentations of Uterine Fibroids
Uterine fibroids manifest in various clinical scenarios, largely determined by their size, location, and number. Management strategies are based on the signs and symptoms associated with fibroids.
### Vaginal Bleeding
- **Most Common Complaint:** Abnormal uterine bleeding is a prevalent issue linked to fibroids. However, specific fibroid characteristics that predict bleeding remain elusive.
- **Risk Factors:** Submucosal fibroids and large fibroids (>5 cm) increase the risk of abnormal bleeding.
- **Causes:** Abnormal bleeding often originates from the area surrounding the fibroid, potentially due to increased endometrial surface area, local endometrial atrophy, and global changes in endometrial expression of the HOX gene.
- **Endometrial Changes:** Large fibroids, even if not distorting the endometrial cavity, can lead to endometrial alterations.
### Pressure or Pain
- **Common Complaint:** Fibroids can exert pressure or cause pain, particularly when they grow significantly.
- **Size and Location:** Fibroids may grow to substantial dimensions, pressing against adjacent structures. Anterior fibroids can affect the bladder, leading to urinary frequency, incontinence, and renal issues. Posterior fibroids may cause constipation, obstruction, and diarrhea.
- **Calciļ¬ed and Twisting Fibroids:** As fibroids age, they may harden and exert greater pressure on surrounding tissues. Degenerating or twisting pedunculated fibroids can cause sudden, severe pain.
- **Pelvic Pain:** Studies indicate that women with fibroids, especially black women, are more likely to report severe non-cyclic pelvic pain. Cyclic pain or dysmenorrhea, however, is not associated with fibroids.
### Dyspareunia
- **Strong Association:** Fibroids are linked to dyspareunia, with patients having fibroids more likely to experience mild or severe dyspareunia.
- **Location Matters:** Anterior fibroids tend to cause deep dyspareunia more than fibroids in other locations.
### Impact on Pregnancy
- **Fertility Issues:** Fibroids can lead to infertility by obstructing fallopian tubes and interfering with gamete transport. They also create a hyper-estrogenic environment that can be inhospitable to embryo implantation.
- **Risk