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- 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
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
- 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 (2).
- Higher levels of aromatase and therefore estrogen have been found in myomas in African American women (2).
- African American heritage
- Early menarche (<10 years)
- Oral contraceptive use before 16 years old (3)
- Familial predisposition
- 2.5 times more likely in women with a first-degree relative with myomas (1)
- Risk increases by 21% with each 10 kg of weight gain (1).
- Risk decreased by parity, progesterone-only contraceptives, diet (fruits, veggies, low fat dairy) (3)
Commonly Associated Conditions
Endometrial and breast cancer also associated with high, unopposed estrogen stimulation