Uterine Fibroid

Aka: Uterine Fibroid, Uterine Leiomyoma, Uterine Leiomyomata, Uterine Myoma

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II. Epidemiology

  1. Most common solid pelvic tumor in women
  2. More common in non-white women
  3. Lifetime Prevalence: 80%

III. Risk factors: Positive (increased risk of fibroids)

  1. Overweight women (increased Body Mass Index)
  2. Advancing age (until Menopause)
    1. Rare before Puberty
    2. Age 20-30 years: 4% fibroid Incidence
    3. Age 30-40 years: Up to 18% fibroid Incidence
    4. Age 40-60 years: 33% fibroid Incidence
    5. Regress after Menopause
  3. Hyperestrogenic states or EstrogenAgonist use
    1. Enlarge in pregnancy (and regress after Menopause)
  4. Black women with higher Incidence
    1. Larger fibroids
    2. More symptomatic fibroids
  5. Comorbid Hypertension
  6. Family History of Uterine Fibroids
  7. Nulliparity

IV. Risk Factors: Negative (lower risk of fibroids)

  1. Five pregnancies or more
  2. Menopause (fibroids typically regress)
  3. Oral Contraceptive or Depo Provera use
  4. Tobacco Abuse

V. Pathophysiology

  1. Benign tumors arising from uterine, myometrial Smooth Muscle
    1. Malignant Leiomyosarcoma is uncommon (0.23%)
  2. Hormonally mediated
    1. Enlarge with Estrogen and Growth Hormone
    2. Regress with Progesterone
  3. Types of leiomyoma
    1. Subserosal leiomyoma
      1. Project outside Uterus
    2. Intramural leiomyoma
      1. Limited to within the myometrium
    3. Submucous leiomyoma
      1. Project into uterine cavity

VI. Symptoms

  1. Symptomatic in 20-50% of fibroid disease
  2. Menorrhagia (prolonged or heavy menstrual flow, most common)
    1. Fibroids are most common cause of Menorrhagia
  3. Pelvic pressure or Pain Sensation (large fibroids)
    1. Pelvic discomfort or Low Back Pain
    2. Dyspareunia
    3. Urine symptoms (urine frequency, urine urgency, urine retention)
    4. Constipation
    5. Exacerbated by pregnancy (see below)
  4. Pregnancy complications
    1. Mixed study results, but at least one large study demonstrates increased complication risk
    2. Recurrent Miscarriage
    3. Premature labor
    4. Fetal Malpresentation
    5. Labor complications including cesarean delivery
    6. Placental Abruption
    7. Stout (2010) Obstet Gynecol 116(5): 1056-63 [PubMed]
  5. Controversial - relationship to fibroids not supported by evidence
    1. Infertility

VII. Signs

  1. Abdominal exam
    1. Uterus palpable above Symphysis Pubis
  2. Bimanual examination
    1. Enlarged, mobile and irregular uterine contour

VIII. Differential Diagnosis

  1. Adenomyoma or Adenomyosis
  2. Ectopic Pregnancy
  3. Intrauterine Pregnancy
  4. Endometrial Cancer
  5. Endometrial Polyp
  6. Endometriosis
  7. Malignant Leiomyosarcoma (0.23% of fibroids)
    1. Age over 45 years old (OR 20)
    2. Post-Menopause (OR 9.7)
    3. History of pelvic radiation
    4. Tamoxifen use
    5. MRI Findings
      1. Intramural Hemorrhage (OR 21)
      2. Endometrial thickening (OR 11)
      3. T2-Weighted signal heterogeneity (OR 10)
      4. Non-myometrial origin (OR 4.9)
    6. References
      1. Tomassin-Naggara (2013) Eur Radiol 23(8):2306-14 [PubMed]

IX. Diagnostics

  1. Transvaginal Ultrasound
    1. Best initial test due to cost efficacy
    2. Least Test Sensitivity and Specificity (misses small fibroids)
  2. Pelvic MRI
    1. Best for fibroid mapping preoperatively
    2. Expensive
  3. Sonohysterography or hysteroscopy
    1. Good Test Sensitivity and Specificity, but invasive

X. Management: Surgery

  1. Hysterectomy
    1. Fibroids account for up to 33-39% of hysterectomies
    2. Indications
      1. Postmenopausal women with enlarging fibroids
      2. Peristent Abnormal Uterine Bleeding
      3. Symptomatic fibroids refractory to other measures
  2. Myomectomy
    1. Performed with hysteroscopy, laparoscopy, robotic-assisted or laparotomy
    2. Excision of fibroids with preservation of Uterus
    3. High risk of recurrence (15-30% in 5 years)
      1. Up to 10% of women will subsequently undergo Hysterectomy within 5-10 years
    4. Indications (typically in women who want to preserve fertility)
      1. Submucosal Fibroids <3 cm (and >50% tumor is intracavitary)
  3. Uterine Fibroid Embolization
    1. Uterine arteries occluded with polyvinyl Alcohol foam (or other embolic agents)
      1. Incomplete embolization used now to reduce pain
      2. Intervention Radiology procedure under IV sedation
      3. Well tolerated (less painful than surgery)
      4. Post-embolization syndrome (low grade fever, pain and passing of fibroid tissue vaginally) is common
    2. Second procedure required in 20-33% of cases within 5 years
    3. References
      1. McLucas (2001) J Am Coll Surg 192:100 [PubMed]
      2. Edwards (2007) N Engl J Med 356: 360-70 [PubMed]
      3. Van der Kooij (2010) ACOG 203(105): e1-13 [PubMed]
  4. Myolysis
    1. Fibroid destruction by coagulation necrosis (Nd-YAG laser, bipolar needle or MR-guided focused Ultrasound)
    2. Often combined with endometrial ablation
    3. Recurrence rate not yet established
    4. Indications
      1. Fibroids in women who want to preserve fertility

XI. Management: Medical

  1. Observation (preferred for asymptomatic cases)
    1. Most fibroids decrease in size with Menopause
  2. Agents effective in Menorrhagia but are not typically effective at reducing fibroid size
    1. Often used as first-line measures due to lower adverse effects
    2. Levonorgestrel IUD (Mirena IUD)
      1. Sayed (2011) Int J Gynaecol Obstet 112(2): 126-30 [PubMed]
    3. Progestins (e.g. Depo Provera)
    4. Oral Contraceptive cycling
      1. Minimally effective (much less effective than Mirena IUD)
    5. NSAIDs
      1. Reduce blood loss and pain
    6. Tranexamic Acid (Lysteda, Cyklokapron)
      1. Take two 650 mg tabs (1.3 g) orally three times daily for up to the first 5 days of the Menstrual Cycle
      2. Avoid combining with Estrogen containing products (increased thrombosis risk)
      3. Peitsidis (2014) World J Clin Cases 2(12): 893-8 [PubMed]
    7. Other agents
      1. Androgenic agents (e.g. Danazol)
  3. GnRH Antagonists
    1. Indicated in Fibroid related Menorrhagia, refractory to other measures above
    2. Limit to no more than 2 years of use
    3. GnRH Antagonists lower Estradiol and Progesterone levels (menopausal levels)
      1. Reduce Menstrual Bleeding
      2. Increases bone loss, Hot Flashes (hence add back therapy as below)
      3. Does not provide Contraception and should not be used with Hormonal Contraception
    4. Combination Agents with add-back Hormones ($1000/month in 2022)
      1. Relugolix/Estradiol/Norethindrone (Myfembree) once daily
      2. Elagolix/Estradiol/Norethindrone (Oriahnn) twice daily
    5. References
      1. (2022) Presc Lett 29(2): 10-1
  4. GnRH Agonists (induce hypoestrogenism)
    1. Indicated in perimenopausal women, or preoperatively to reduce size
    2. Limit to short term use (e.g. bridging to Hysterectomy)
    3. Decreases Estrogen and Progesterone via negaive feedback
      1. Results in Amenorrhea and fibroid mass reduction
      2. Fibroids recur when medication stopped
      3. Hypoestrogenic side effects (Hot Flushes, BMD risk)
    4. Injectable GnRH Agonists include Leuprolide, Goserelin, Triptorelin
    5. Used in combination with Progesterone
      1. Reduces Hot Flushes (vasomotor symptoms)
    6. Lethaby (2002) BJOG 109(10): 1097-108 [PubMed]
  5. Selective Progesterone receptor modulators (SPRM)
    1. Mifepristone (Mifepex) 5 mg daily
      1. Eisinger (2003) Obstet Gynecol 101:243-50 [PubMed]
      2. Fiscella (2006) Obstet Gynecol 108:1381-7 [PubMed]
    2. Ulipristal (Ella)
      1. Carbonell Esteve (2008) Obstet Gynecol 112(5): 1029-36 +PMID:18978102 [PubMed]
  6. Other measures not found consistently effective
    1. Raloxifene (Evista)

XII. References

  1. Stewart (2012) Mayo POIM Conference, Rochester
  2. De La Cruz (2017) Am Fam Physician 95(2): 100-7 [PubMed]
  3. Evans (2007) Am Fam Physician 75:1503-8 [PubMed]
  4. Myers (2002) Obstet Gynecol 100:8-17 [PubMed]
  5. Rackow (2006) Gynecol Clin North Am 33:97-113 [PubMed]
  6. Vilos (2015) J Obstet Gynaecol Can 37(2): 157-81 [PubMed]

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