What is the pathophysiology of uterine leiomyoma (fibroids)?

From the Guidelines

Uterine fibroids are benign smooth muscle tumors that develop from the myometrium of the uterus, with a pathophysiology involving abnormal growth of monoclonal smooth muscle cells derived from a single progenitor cell that undergoes somatic mutations, particularly MED12 gene mutations, and are influenced by hormonal factors such as estrogen and progesterone 1.

Key Factors in Pathophysiology

• Hormonal factors, including estrogen and progesterone, play a crucial role in promoting fibroid growth through increased production of growth factors, extracellular matrix, and angiogenic factors 1
• Genetic and epigenetic factors, including cytogenetic abnormalities, influence fibroid development, with risk factors such as African ancestry, early menarche, nulliparity, and obesity increasing estrogen exposure 1
• Transforming growth factor-beta (TGF-β) and insulin-like growth factors contribute to excessive production of extracellular matrix proteins like collagen, fibronectin, and proteoglycans, creating the characteristic firm texture of fibroids 1

Clinical Implications

• Fibroids typically develop during reproductive years and often shrink after menopause due to decreased hormonal stimulation, confirming the hormone-dependent nature of these tumors 1
• The prevalence of fibroids varies with race, with Black women having an estimated incidence of fibroids by age 50 exceeding 80%, whereas White women have an incidence approaching 70% 1
• Fibroid-associated symptoms, such as menorrhagia, dysmenorrhea, pelvic pain and pressure, urinary urgency and frequency, and constipation, can be managed with various treatment options, including medical therapy, myomectomy, endometrial ablation, uterine fibroid embolization (UFE), MR-guided focused ultrasound (MRgFUS), and laparoscopic radiofrequency ablation 1

From the Research

Pathophysiology of Uterine Fibroids

• Uterine fibroids are common benign neoplasms, with a higher prevalence in older women and in those of African descent 2.
• They are characterized by the proliferation of uterine smooth muscle cells, embedded in an abundant extracellular matrix 3.
• Fibroids can cause abnormal uterine bleeding, pelvic pressure, bowel dysfunction, urinary frequency and urgency, urinary retention, low back pain, constipation, and dyspareunia 2, 4, 5.

Symptoms and Diagnosis

• Many fibroids are discovered incidentally on clinical examination or imaging in asymptomatic women 2.
• Ultrasonography is the preferred initial imaging modality for diagnosing uterine fibroids 2.
• Transvaginal ultrasound or magnetic resonance imaging scans can also be used to identify fibroids 4.

Treatment Options

• Medical therapy to reduce heavy menstrual bleeding includes hormonal contraceptives, tranexamic acid, and nonsteroidal anti-inflammatory drugs 2, 4.
• Gonadotropin-releasing hormone agonists or selective progesterone receptor modulators are an option for patients who need symptom relief preoperatively or who are approaching menopause 2, 4.
• Surgical treatment includes hysterectomy, myomectomy, uterine artery embolization, and magnetic resonance-guided focused ultrasound surgery 2, 4, 5.

Pathogenesis and Future Directions

• The pathogenesis of uterine fibroids is not fully understood, but it is thought to involve the proliferation of uterine smooth muscle cells and the accumulation of extracellular matrix 3.
• Future research should focus on identifying the underlying causes of uterine fibroids and developing targeted therapies to treat them 3, 6.
• New emerging options, such as gonadotropin-releasing hormone antagonists and selective progesterone receptor modulators, represent hopeful alternatives for the treatment of symptomatic uterine fibroids 6.