Uterine fibroids, also called leiomyomas or uterine myomas, are benign myometrial tumors of muscle and connective tissue. The incidence of malignancy is <1/770 to 10,000.¹ They are typically discrete nodular tumors that vary in size and number.

Fibroids are classified by location in the uterus relative to the myometrium.

• Subserosal: Located underneath the uterine serosa
• Intramural: Located in the myometrium proper
• Submucosal: Also known as intracavitary as they are located adjacent to the endometrium and protrude into the uterine cavity
• Pedunculated: Located on a pedicle or stalk, either from the serosa or in the cavity
• The above classifications are further detailed by the FIGO classification system (types 0 to 8)

Fibroids can occur singly but are often multiple. They can be located infrequently within the cervix, broad ligament, adnexa, vagina, vulva, or other unexpected structures. Parasitic fibroids attach to nearby pelvic structures and acquire a blood supply from a nonuterine source with potential detachment from the parent myometrium (Fig. 1). After uncontained morcellation, disseminated peritoneal leiomyomatosis can occur.¹

Uterine leiomyomas

Uterine myomas

Fibroids

• Estimated cumulative incidence of >70% in women by age 50
• 50% of fibroids are asymptomatic, but symptomatic uterine fibroids affect 25% to 50% of all women and 30% to 40% of perimenopausal women with possible effect on daily activities
• Most common benign solid pelvic tumor diagnosed in women and most common reason for benign hysterectomy
• Risk factors include age, family history, African American race, early menarche, exposure to diethylstilbestrol, obesity, hypertension, polycystic ovary syndrome, vitamin D deficiency, and nulliparity
• Black women typically develop fibroids and clinically significant symptoms at a younger age²
• Frequently diagnosed incidentally on pelvic examination
• Potential to enlarge during pregnancy as well as regress after menopause
• Approximately 200,000 hysterectomies, 30,000 myomectomies, thousands of selective uterine-artery embolizations and high-intensity focused MRI/ultrasound procedures, and a growing number of radiofrequency ablations are performed annually in the U.S. to remove or destroy uterine fibroids.

• Presenting symptoms:
  1. Abnormal uterine bleeding (most common, AUB-L) due to dilated endometrial vessels
  2. Chronic pelvic pain (dysmenorrhea, dyspareunia, pelvic pressure)
  3. Bulk symptoms (bloating, increase in abdominal girth)
  4. Anemia from menorrhagia
  5. Acute pain (torsion of pedunculated fibroid, infarction, degeneration)
  6. Urinary symptoms (frequency from bladder pressure, ureteral obstruction, urinary retention, incontinence in setting of prolapse)
  7. GI symptoms (rectosigmoid compression with constipation or intestinal obstruction, pain with defecation)
  8. Prolapse through cervix of pedunculated submucosal fibroid
  9. Infertility (sole etiology in 1%-3%, more likely subfertility with submucosal fibroid)³
  10. Pregnancy complications including preterm birth, small fetus for gestational age, malpresentation
  11. Enlarged, irregular uterus on pelvic examination

Fibroids arise from a single progenitor smooth muscle cell in the myometrium and are monoclonal. They are sensitive to endogenous but not exogenous estrogen and progesterone hormones, thus develop during the reproductive years. Malignant transformation of preexisting leiomyoma is extremely uncommon (<0.5%). There is a racial disparity in the prevalence, suggesting a genetic component, with most fibroids having a normal chromosomal makeup. A small group of individuals have an autosomal dominant disorder, hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC), in which there is a genetic mutation in the fumarate hydratase gene, causing diminished suppressor function in fibroid formation.³

• Ovarian mass (neoplastic, nonneoplastic, endometrioma)
• Adenomyosis/adenomyoma
• Endometriosis
• Endometrial polyp
• Endometrial carcinoma or hyperplasia
• Leiomyosarcoma/uterine carcinosarcoma
• Inflammatory mass (reproductive organ or GI origin)
• Pregnancy

• Complete pelvic examination, including speculum exam and bimanual exam
• Estimation of size of uterus/mass and location of fibroids via imaging
• Endometrial sampling may be indicated (biopsy or dilation and curettage) when abnormal bleeding and pelvic mass are present to evaluate for endometrial carcinoma; may identify but cannot rule out leiomyosarcoma, which has no reliable nonsurgical test available
• Fibroid biopsy not recommended¹
• If significant urinary symptoms are prominent, intravenous pyelogram to rule out impingement on urinary system

• Pregnancy test
• CBC
• Blood urea nitrogen/creatinine
• Thyroid-stimulating hormone

• Pelvic ultrasound (Fig. 2) is the primary diagnostic modality, with higher diagnostic accuracy via transvaginal ultrasound.
• MRI with contrast (Fig. E3) is helpful in planning treatment or if malignancy is strongly suspected. Also relevant to localize fibroid size, number, and location, especially if myomectomy or uterine artery embolism is contemplated.

• Saline infusion sonography can be helpful in determining location and protrusion into uterine cavity of submucosal fibroids.
• Diagnostic hysteroscopy can be performed in the office and may provide direct evidence of intrauterine pathology or submucosal fibroid that distorts uterine cavity.

• Patient observation and follow-up with periodic repeat pelvic exams to ensure that tumors are not growing rapidly, which could suggest malignancy.
• Hormonal therapies reduce bleeding symptoms and many have the added benefit of contraception. There is no evidence that exogenous estrogen or progestin increases risk of myomas.
  1. Combined hormonal methods with estrogen and progestin, including oral contraceptives, contraceptive patch, contraceptive vaginal ring
  2. Progestin-only agents including oral progestins, intramuscular progestin injection, levonorgestrel intrauterine device (IUD)
  3. Progesterone IUD significantly improves menorrhagia, but expulsion rate with myomas is 10% to 15%, and intracavitary fibroids are a contraindication. Enormous uteri may lead to migrated strings precluding simple retrieval

Gonadotropin-releasing hormone (GnRH) agonist, leuprolide, results in 25% to 50% reduction in uterine volume and cessation of menses within 3 mo of initiating treatment. Hypoestrogenism, reversible bone loss, and hot flushes are side effects. Consider low-dose progesterone replacement (add-back therapy) to minimize hypoestrogenic effects. GnRH agonist therapy is not recommended for longer than 6 mo without add-back or 12 mo with add-back due to these effects, so goal is to bridge to other treatment.

• Regrowth and return of bleeding symptoms occurs in 50% of treated patients within 3 mo after cessation.
• Indications for GnRH agonist:
  1. Anemia treatment to normalize hemoglobin before surgery
  2. Avoiding surgery in patients approaching menopause
  3. Preoperatively for large myomas to make hysterectomy, hysteroscopic resection/ablation more feasible
  4. Medical contraindication for surgery
• Use of GnRH agonists alters the consistency of the fibroid, making myomectomy more challenging.
• GnRH antagonists (FDA approved 2020 and 2021)-elagolix and relugolix. Both treatment options contain hormonal add-back (estradiol and norethindrone acetate) and can be prescribed for max of 2 yr. May still have light menses. Possible adverse effects include high blood pressure, worsening of lipids and liver enzymes, and loss of bone mineral density. Patients with history of venous thromboembolism or those who are over the age of 35 and smoke should not take these medications.
• Nonhormonal medical therapies:
• Nonsteroidal antiinflammatory drugs for pain; data do not support use as monotherapy for AUB-L menorrhagia.³
• Tranexamic acid, an oral antifibrinolytic, can decrease menorrhagia by 40% to 65%. Side effects include abdominal cramps, headaches, fatigue, and increased risk of venous thromboembolism.
• Other drugs used and under investigation:
• Danazol: Androgen and inhibitor of steroidogenesis, side effect of hirsutism.
• Mifepristone: Antiprogesterone reduces fibroid volume 40% to 50% with amenorrhea.
• Raloxifene: Selective estrogen receptor modulator, either alone or with GnRH agonist, reduces fibroid volume 70% up to 1 yr but only in postmenopausal patients.

• Indications:
• Abnormal uterine bleeding with anemia refractory to hormonal therapy
• Chronic pain with severe dysmenorrhea, dyspareunia, or lower abdominal pressure/pain
• Acute pain, torsion, or prolapsing submucosal fibroid
• Urinary symptoms or signs such as hydronephrosis
• Infertility or recurrent pregnancy loss with endometrial cavity-distorting fibroid as only finding⁴
• Enlarged uterus with compression symptoms or discomfort
• Rapid uterine enlargement premenopausal or any growth after menopause-this indication should involve gynecologic oncologist
• Procedures:
  1. Hysterectomy (definitive procedure): Vaginal, laparoscopic, robotic, or abdominal approach, dependent on surgical preference/expertise and uterine size.
  2. Myomectomy (preserves fertility): May be performed via abdominal, laparoscopic, or robotic approach; 60% recurrence at 5 yr postop⁵; significant hemorrhage risk, so control anemia preop
  3. Vaginal myomectomy for prolapsed pedunculated submucosal fibroid
  4. Hysteroscopic resection: Typically at least 50% of the fibroid must be intracavitary for a hysteroscopic approach to be successful. May need to be done in stages.
  5. Radiofrequency volumetric thermal ablation: FDA-approved uterine-sparing procedure in which laparoscopic or transcervical ultrasound-guided ablation of fibroids induces myolysis (necrosis) resulting in fibroid shrinking. Preliminary data on subsequent pregnancy are limited, but encouraging.³,⁶
  6. Magnetic resonance-guided focused ultrasound: ultrasound energy focused to cause fibroid coagulative necrosis. Enables fertility preservation, but due to numerous contraindications, many patients are ineligible.³
  7. Uterine artery embolization (UAE): Alternative to surgery performed by interventional radiologist, but its less invasive nature should be balanced against a higher rate for treatment failure or complications at 5 yr. Age 40 or less at time of embolization and history of previous myomectomy are predictors of UAE failure. If the patient wishes to preserve future fertility, UAE should not be performed. Contraindicated if history of GnRH agonist use or salpingectomy.³
  8. Endometrial ablation: Decreases menorrhagia, has limitations based on uterine cavity distortion.
  9. Patients who receive procedures other than definitive management are more likely to result in a second surgery if younger age/less proximity to menopause.

• Degeneration occurs when the fibroid outgrows its blood supply. During pregnancy, rare but typically seen in the second trimester. May see fever and leukocytosis, but symptoms improve within 48 h.³
• Leiomyosarcoma (<0.1%). The U.S. FDA voiced concern regarding the use of power morcellation in the peritoneal cavity during minimally invasive laparoscopy if a tissue containment system is not used due to the possibility of spreading occult malignancy. In 2020, FDA recommended against power morcellation if age >50 yr or postmenopausal.¹

Fibroids continue to grow during reproductive years, but symptoms improve after menopause.

Lack of evidence to support acupuncture or herbal therapy.² There is some research supporting use of vitamin D.⁷

Consultation with gynecologist for management and with gynecologic oncologist if suspicious of malignancy

Uterine Fibroids (Patient Information)

Dysfunctional Uterine Bleeding (Related Key Topic)