Description

• Uterine leiomyomas are well-circumscribed, pseudoencapsulated, benign monoclonal tumors composed mainly of smooth muscle with varying amounts of fibrous connective tissue (1).
• Three major subtypes
  • Subserous: common; external; may become pedunculated
  • Intramural: common; within myometrium; may cause marked uterine enlargement
  • Submucous: ~5% of all cases; internal, evoking abnormal uterine bleeding and infection; occasionally protruding from cervix
• Rare locations: broad, round, and uterosacral ligaments
• System affected: reproductive
• Synonym(s): fibroids; myoma; fibromyoma; myofibroma; fibroleiomyoma

Epidemiology

Incidence

• Cumulative incidence up to 80%
  • 60% in African American women by age 35 years; 80% by age 50 years
  • 40% in Caucasian women by age 35 years; 70% by age 50 years (1),(2)
• Incidence increases with each decade during reproductive years.
• Rarely seen in premenarchal females
• Predominant sex: females only

Etiology and Pathophysiology

• Enlargement of benign smooth muscle tumors that may lead to symptoms affecting the reproductive, GI, or genitourinary system
• Complex multifactorial process involving transition from normal myocyte to abnormal cells and then to visibly evident tumor (monoclonal expansion)
  • Hormones (1): Increases in estrogen and progesterone are correlated with myoma formation (i.e., rarely seen before menarche). Estrogen receptors in myomas bind more estradiol than normal myometrium.
  • Growth factors (1)
    • Increased smooth muscle proliferation (transforming growth factor β [TGF-β], basic fibroblast growth factor [bFGF])
    • Increase DNA synthesis (epidermal growth factor [EGF], platelet-derived growth factor [PDGF], activin, myostatin)
    • Stimulate synthesis of extracellular matrix (TGF-β)
    • Promote mitogenesis (TGF-β, EGF, insulin-like growth factor [IGF], prolactin)
    • Promote angiogenesis (bFGF, vascular endothelial growth factor [VEGF])
  • Vasoconstrictive hypoxia (1): proposed, but not confirmed, mechanism of myometrial injury during menstruation

Genetics

• A variety of somatic chromosomal rearrangements have been described in 40% of uterine myomas. Mutations in the gene encoding mediator complex subunit 12 (MED12) on the X chromosome were found in 70% of myomas in one study (3).
• Higher levels of aromatase and therefore estrogen have been found in myomas in African American women (3).

Risk Factors

• African American heritage: 2.9 times greater risk than Caucasian women; occur at a younger age, are more numerous, larger, and more symptomatic (1),(2)
• Early menarche (<10 years)
• Oral contraceptive use before 16 years old (2)
• Nulliparous
• Hypertension
• Familial predisposition: 2.5 times more likely in women with a first-degree relative with myomas (1)
• Obesity: Risk increases by 21% with each 10 kg of weight gain (1).
• Alcohol
• Risk decreased by parity, progesterone-only contraceptives, diet (fruits, veggies, low fat dairy) (2).

Commonly Associated Conditions

Endometrial and breast cancer also associated with high, unopposed estrogen stimulation