Basics
Description
- Uterine myomas are benign smooth muscle cell tumors, also called fibroids and leiomyomas.
- Described by location, although most myomas involve more than one layer of the uterus
- Subserosal: Projects into the pelvis, may be pedunculated
- Intramural: Within uterine wall
- Submucosal: Projects into the uterine cavity
- May arise from cervix or broad ligament
- Range from microscopic to easily palpable, size described in gestational weeks
- May be single or multiple
- Most common solid pelvic tumor in women, most common indication for hysterectomy
Epidemiology
- True incidence and prevalence are unknown because myomas are usually asymptomatic
- Typically become symptomatic in women between the ages of 30 and 40
- Black women are 2 " 3 times more likely to develop myomas, are younger at time of diagnosis and hysterectomy, have higher uterine weights, and are more likely to be anemic.
Incidence
Estimated at 12.8/1,000 women aged 25 " 44
Prevalence
- Clinically apparent in approximately 25% of reproductive-age women
- May exceed 75% in surgical pathology series
Risk Factors
- Early menarche
- Nulliparity
- Oral contraceptive use before age 16
- Black race
- Hypertension
- Increased alcohol or red meat consumption
Genetics
- Family and twin studies suggest a genetic predisposition.
- Associated with 3 hereditary syndromes:
- Reed 's syndrome: Uterine and subcutaneous myomas
- Bannayan-Zonana syndrome: Uterine myomas, lipomas, and hemangiomas
- Hereditary leiomyomatosis and renal cell carcinoma syndrome
General Prevention
- Depot medroxyprogesterone acetate may prevent by suppressing cyclic variation of hormones
- No evidence that diet prevents myomas
Pathophysiology
- Heavy/prolonged menses
- Increased vascularity and venous congestion
- Increased surface area of uterine cavity
- Compression of pelvic structures
- Acute pelvic pain
- Torsion of pedunculated myoma
- Protrusion of myoma through cervix
- Infarction as myoma outgrows blood supply
- Impaired fertility
- Distortion of uterine cavity may interfere with sperm transport or implantation.
Etiology
- Transformation of normal smooth muscle cell to cell responsive to cyclic hormone variation, followed by clonal proliferation
- Likely involves multiple growth factors
- Perimenopausal growth related to high estrogen levels during anovulatory cycles
Associated Conditions
- Iron-deficiency anemia
- Endometritis
- Adenomyosis
- Impaired fertility (with significant distortion of uterine cavity or postoperative adhesions)
Diagnosis
- May be found incidentally on bimanual examination or pelvic imaging
- Pelvic/reproductive
- Heavy, prolonged menses, may be associated with fatigue, dyspnea, palpitations
- Pelvic pressure or fullness
- Acute pelvic pain
- Gastrointestinal
- Increased abdominal girth
- Constipation, tenesmus (posterior myomas)
- Urinary
- Frequency, urgency (anterior myomas)
History
- Menstrual, sexual, obstetrical histories
- Quantify blood loss during menses
Physical Exam
- Enlarged, firm, irregular uterus
- Peritoneal signs (infarcted myoma)
- Conjunctival pallor, tachycardia
Tests
Lab
- ²- hCG
- Thyroid-stimulating hormone
- CBC
- Iron, total iron-binding capacity, ferritin
- Type and crossmatch before surgery
Imaging
- Transvaginal ultrasound to confirm diagnosis, evaluate for ovarian neoplasm
- Renal ultrasound to evaluate for obstruction
- MRI to visualize individual myomas, identify malignant sarcomas, detect adenomyosis, plan complex surgeries and uterine artery embolization
- Hysterosalpingography to define submucosal myomas or to evaluate uterus and fallopian tubes
Surgery
Endometrial biopsy to evaluate abnormal bleeding
Pathological Findings
- Multinodular uterine tumor
- Smooth muscle fibers organized in bundles, surrounded by fibrous tissue
Differential Diagnosis
- Abnormal uterine bleeding
- Anovulation
- Thyroid dysfunction
- Endometrial hyperplasia or malignancy
- Pelvic pain
- Endometriosis
- Adenomyosis
- Ectopic pregnancy
- Torsion or rupture of ovarian cyst
- Pelvic inflammatory disease
- Pelvic mass
- Pregnancy
- Adenomyosis, uterine polyp
- Ovarian malignancy
- Leiomyosarcoma
Treatment
- Insufficient data to compare treatments or recommend treatment to asymptomatic women
- Drug therapy may be sufficient for women nearing menopause; none improve fertility.
Medication
- Iron supplementation to correct anemia
- Trial of oral contraceptives reasonable to attempt control of bleeding; use of levonorgestrel intrauterine device has also been reported
- Tranexamic acid (1,300 mg t.i.d. for up to 5 days during menses) exerts antifibrinolytic effects to reduce bleeding by approximately 30% (1)[A].
- Studied only in smaller fibroids
- Contraindicated if risk for thrombosis
- Fibroid infarction reported
- Gonadotropin-releasing hormone (GnRH) agonists (2)[B]
- Cause hypoestrogenic state and decrease uterine artery blood flow
- Leuprolide: 3.75 mg IM monthly or 11.25 mg IM depot every 3 months, only FDA-approved agent
- Nafarelin: 400 ¼g intranasally b.i.d. (alternate nostrils)
- Goserelin: 3.6 mg implant SC every 28 days
- Reduce uterine size by up to 65% and induce amenorrhea within 3 months in most women
- Preoperative use can correct anemia and allow less invasive approach, but may complicate dissection or embolization.
- Side effects and expense limit long-term use.
- Associated with hot flushes, vaginal dryness, mood swings, and accelerated bone loss, although addition of hormone replacement therapy may reduce side effects
- Myomas regain pretreatment size within months after drug is stopped.
- Not well studied beyond 6 months of use
- Ulipristal acetate (5 or 10 mg daily), a selective progesterone-receptor modulator, controls bleeding in approximately 90% of women (NNT 1.4) and decreases fibroid volume by approximately 20% (3,4)[B]
- Studied in 13-week trial of symptomatic women planning hysterectomy
- Induced amenorrhea in majority of subjects
- Headache and breast discomfort most common side effects, but comparable to placebo
- Benign endometrial changes more common with ulipristal
- Both doses found to be noninferior to leuprolide for control of bleeding, with a lower incidence of hot flashes, in a separate study
- Danazol or progestins can induce amenorrhea, but true benefit unknown
- Mifepristone, selective estrogen receptor modifiers, and aromatase inhibitors may have benefit, but their use is largely investigational.
Additional Treatment
Issues for Referral
- Refer to fertility specialist to evaluate for other causes of infertility
- Refer to urology for ureteral obstruction
Surgery
- Indications for surgery
- Contraindication to, intolerance of, or failure of drug therapy
- Concern for malignancy
- Mass effect causing pain, pressure, or urinary or GI tract symptoms
- Distortion of uterine cavity causing infertility or repeated pregnancy loss
- Carries risk of infection, bleeding, damage to adjacent organs, adhesion formation
- Consider autologous blood donation
Rapid growth (increase in uterine size by 6 weeks in 1 year) in a nonpregnant woman or growth in a menopausal woman suggests malignancy and should prompt surgical removal.
- Hysterectomy
- Definitive treatment as it eliminates symptoms and the development of new myomas
- Indicated for extensive disease, uncontrolled acute hemorrhage, suspected malignancy, and myomas in association with other pelvic abnormalities
- Associated with significant improvement in symptoms and quality of life
- Precludes future pregnancy
- Abdominal myomectomy
- Removal of myomas via laparotomy while preserving uterus
- Indicated for multiple or deep intramural myomas, >3 larger than 5 cm, or uterus >18 weeks in size
- Preferred in women desiring future pregnancy as risk of uterine rupture is extremely low
- May involve more time and greater blood loss than hysterectomy
- Laparoscopic myomectomy (5)[B]
- Removal of myomas via laparoscope while preserving uterus
- Indicated for ≤3 intramural or subserosal myomas ≤5 cm in diameter or uterine size <18 weeks
- Longer surgery but reduced bleeding and recovery compared with abdominal approach
- Risk of uterine rupture is controversial.
- Hysteroscopic myomectomy
- Removal of intracavitary submucosal myomas via endoscope introduced through the cervix
- More effective combined with endometrial ablation, but precludes pregnancy
- May be performed as outpatient procedure
- Myolysis
- Thermo- or cryoablation of myoma via laparoscopy with decrease in size over 3 " 6 months; may carry increased risk of adhesions and uterine rupture
- Indicated for ≤3 myomas, largest <10 cm
- More effective combined with endometrial ablation, but precludes pregnancy
- Magnetic resonance guided focused ultrasound thermoablation available, but few long-term outcome data
- Uterine artery embolization (6)[B]
- Procedure under fluoroscopy in which gel, beads, or coils are introduced through a catheter to the uterine artery
- Disrupts blood supply, causing degeneration
- Rapid recovery compared with surgery
- Usually requires brief hospitalization for pain control
- Resolution of bleeding symptoms in up to 75% reported at 5 years, up to 20% require second procedure to treat symptoms
- May be less effective for large, pedunculated, or submucosal tumors
- Associated with significant pain, fever, nausea, vomiting, and myalgias in first 48 hours; sepsis and death have been reported
- Early menopause reported in up to 3% of women under 45
- Long-term effect on fertility and pregnancy outcomes not known
In-Patient Considerations
Initial-Stabilization
- Control severe bleeding and pain
- Treat iron-deficiency anemia
Ongoing Care
Follow-Up Recommendations
- No high-quality trials support preconception myomectomy in asymptomatic women
- Large myomas may be associated with pain, bleeding, breech presentation, premature labor, or increased risk of cesarean section.
- Rapid growth may occur in first trimester in response to estrogen, increased blood flow, or edema, but most enlarge by <10%.
- Risk of abruption increases if the placenta overlies a myoma.
- Considerations after myomectomy
- Adhesions may impair fertility.
- Postpone pregnancy at least 6 months
- Cesarean delivery may be preferable after laparoscopic myomectomy.
Patient Monitoring
- Asymptomatic myomas may be followed by exam or ultrasound every 3 months to determine growth pattern, then every 6 months if stable
- Examine at same time in cycle to limit effects of hormonal stimulation on tumor size
- Watchful waiting may be appropriate for large, asymptomatic myomas in women approaching menopause if malignancy has been excluded.
- Annual bone mineral density studies if GnRH agonist is continued >6 months; consider calcium and bisphosphonate therapy
Prognosis
- Most symptomatic women require surgery
- May recur after myomectomy
- Risk increases with number of myomas
- Up to 60% recurrence at 5 years
- Up to 25% require second surgery
- Regress during menopause
Complications
- Secondary infection of degenerating myoma
- Osteoporosis secondary to GnRH agonist
- Malignant transformation (rare)
References
1Lukes A, Moore K, Muse K. Tranexamic acid treatment for heavy menstrual bleeding. Obstet Gynecol. 2010;116:865 " 875. [View Abstract]2Lethaby A, Vollenhove B, Sowter MC. Pre-operative GnRH analogue therapy before hysterectomy or myomectomy for uterine fiboids. Cochrane Database Syst Rev. 2011;1:CD000547. [View Abstract]3Donnez J, Tatarchuk T, Bouchard P Ulipristal acetate versus placebo for fibroid treatment before surgery. N Engl J Med. 2012;366:409 " 420. [View Abstract]4Donnez J, Tomaszewski J, Vazquez F Ulipristal acetate versus leuprolide acetate for uterine fibroids. N Engl J Med. 2012;366:421 " 432. [View Abstract]5Jin C, Hu Y, Chen X. Laparoscopic versus open myomectomy " a meta-analysis of randomized controlled trials. Eur J Obstet Gynecol Reprod Biol. 2009;145(1):14 " 21. [View Abstract]6Gupta JK, Sinha A, Lumsden MA. Uterine artery embolization for symptomatic uterine fibroids. Cochrane Database Syst Rev. 2009;1:CD005073.
Additional Reading
1 Alternatives to hysterectomy in the management of leiomyomas. Obstet Gynecol. 2008;112:387 " 400.
Codes
ICD9
- 218.0 Submucous leiomyoma of uterus
- 218.1 Intramural leiomyoma of uterus
- 218.9 Leiomyoma of uterus, unspecified
- 218.2 Subserous leiomyoma of uterus
ICD10
- D25.0 Submucous leiomyoma of uterus
- D25.1 Intramural leiomyoma of uterus
- D25.9 Leiomyoma of uterus, unspecified
- D25.2 Subserosal leiomyoma of uterus
SNOMED
- 95315005 uterine leiomyoma (disorder)
- 95279007 submucous leiomyoma of uterus (disorder)
- 93616000 intramural leiomyoma of uterus (disorder)
- 95280005 subserous leiomyoma of uterus (disorder)
Clinical Pearls
- Common in reproductive-age women
- Most are asymptomatic, but can cause significant morbidity
- Base treatment on woman 's age, proximity to menopause, symptoms, myoma burden, other conditions, preferences, and desire for pregnancy, as well as availability of physicians experienced with the selected treatment