Uterine Myomas

Basics

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

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