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Uterine Fibroids

(Leiomyomas; Myomas)

by David G. Mutch, MD, Scott W. Biest, MD

Uterine fibroids are benign uterine tumors of smooth muscle origin. Fibroids frequently cause abnormal uterine bleeding, pelvic pain and pressure, urinary and intestinal symptoms, and pregnancy complications. Diagnosis is by pelvic examination, ultrasonography, or other imaging. Treatment of symptomatic patients depends on the patient’s desire for fertility and her desire to keep her uterus. Treatment may include oral contraceptives, brief presurgical gonadotropin-releasing hormone therapy to shrink fibroids, progestin therapy, and more definitive surgical procedures (eg, hysterectomy, myomectomy).

Uterine fibroids are the most common pelvic tumor, occurring in about 70% of women by age 45. However, many fibroids are small and asymptomatic. About 25% of white and 50% of black women eventually develop symptomatic fibroids. Fibroids are more common among women who have a high body mass index. Potentially protective factors include parturition and cigarette smoking.

Most fibroids in the uterus are subserous, followed by intramural, then submucosal. Occasionally, fibroids occur in the broad ligaments (intraligamentous), fallopian tubes, or cervix. Some fibroids are pedunculated. Most fibroids are multiple, and each develops from a single smooth muscle cell, making them monoclonal in origin. Because they respond to estrogen , fibroids tend to enlarge during the reproductive years and decrease in size after menopause.

Fibroids may outgrow their blood supply and degenerate. Degeneration is described as hyaline, myxomatous, calcific, cystic, fatty, red (usually only during pregnancy), or necrotic. Although patients are often concerned about cancer in fibroids, sarcomatous change occurs in < 1% of patients.

Symptoms and Signs

Fibroids can cause abnormal uterine bleeding (eg, menorrhagia, menometrorrhagia). If fibroids grow and degenerate or if pedunculated fibroids twist, severe acute or chronic pressure or pain can result. Urinary symptoms (eg, urinary frequency or urgency) can result from bladder compression, and intestinal symptoms (eg, constipation) can result from intestinal compression.

Fibroids may increase risk of infertility. During pregnancy, they may cause recurrent spontaneous abortion, premature contractions, or abnormal fetal presentation or make cesarean delivery necessary.

Diagnosis

  • Imaging (ultrasonography, saline infusion sonography, or MRI)

The diagnosis is likely if bimanual pelvic examination detects an enlarged, mobile, irregular uterus that is palpable. Confirmation requires imaging, which is usually indicated if

  • Fibroids are a new finding.

  • They have increased in size.

  • They are causing symptoms.

  • They need to be differentiated from other abnormalities (eg, ovarian masses).

When imaging is indicated, ultrasonography (usually transvaginal) or saline infusion sonography (sonohysterography) is typically done. In saline infusion sonography, saline is instilled into the uterus, enabling the sonographer to more specifically locate the fibroid in the uterus. If ultrasonography, including saline infusion sonography (if done), is inconclusive, MRI, the most accurate imaging test, is usually done.

Treatment

  • Sometimes gonadotropin-releasing hormone (GnRH) analogs or other drugs for temporary relief of minor symptoms

  • Myomectomy (to preserve fertility) or hysterectomy for symptomatic fibroids

Asymptomatic fibroids do not require treatment. Patients should be reevaluated periodically (eg, every 6 to 12 mo).

For symptomatic fibroids , medical options, including suppression of ovarian hormones to stop the bleeding, are suboptimal and limited. However, clinicians should consider first trying medical treatment before doing surgery. GnRH analogs can be given before surgery to shrink fibroid tissues; these drugs often stop menses and allow blood counts to increase. In perimenopausal women, expectant management can usually be tried because symptoms may resolve as fibroids decrease in size after menopause.

Drugs

Several drugs are used to relieve symptoms, reduce fibroid growth, or both.

GnRH analogs are often the drugs of choice. They can reduce fibroid size and bleeding. They are given IM or sc (eg, leuprolide 3.75 mg IM q mo, goserelin 3.6 mg sc q 28 days), as a subdermal pellet, or as nasal spray. These drugs can decrease estrogen production. GnRH analogs are most helpful when given preoperatively to reduce fibroid and uterine volume, making surgery technically more feasible and reducing blood loss during surgery. In general, these drugs should not be used in the long term because rebound growth to pretreatment size within 6 mo is common and bone demineralization may occur. To prevent bone demineralization when these drugs are used long term, clinicians should give patients supplemental estrogen (add-back therapy), such as a low-dose estrogen-progestin combination.

Exogenous progestins can partially suppress estrogen stimulation of uterine fibroid growth. Progestins can decrease uterine bleeding but may not shrink fibroids as much as GnRH analogs. Medroxyprogesterone acetate 5 to 10 mg po once/day or megestrol acetate 40 mg po once/day taken 10 to 14 days each menstrual cycle can limit heavy bleeding, beginning after 1 or 2 treatment cycles. Alternatively, these drugs may be taken every day of the month (continuous therapy); this therapy often reduces bleeding and provides contraception. Depot medroxyprogesterone acetate 150 mg IM q 3 mo has effects similar to those of continuous oral therapy. Before IM therapy, oral progestins should be tried to determine whether patients can tolerate the adverse effects (eg, weight gain, depression, irregular bleeding). Progestin therapy causes fibroids to grow in some women. Alternatively, a levonorgestrel-releasing intrauterine device (IUD) may be used to reduce uterine bleeding.

Other drugs that can be used to help reduce fibroid growth include

  • Antiprogestins

  • Selective estrogen receptor modulators (SERMS)

  • Danazol

For antiprogestins (eg, mifepristone), the dosage is 5 to 50 mg once/day for 3 to 6 mo. This dose is lower than the 200-mg dose used for termination of pregnancy; thus, this dose must be mixed specially by a pharmacist and may not always be available.

SERMS (eg, raloxifene) may help reduce fibroid growth, but whether they can relieve symptoms as well as other drugs is unclear.

Danazol , an androgenic agonist, can suppress fibroid growth but has a high rate of adverse effects (eg, weight gain, acne, hirsutism, edema, hair loss, deepening of the voice, flushing, sweating, vaginal dryness) and is thus often less acceptable to patients.

NSAIDs can be used to treat pain but probably do not decrease bleeding.

Tranexamic acid (an antifibrinolytic drug) can reduce uterine bleeding by up to 40%. The dosage is 1300 mg q 8 h for up to 5 yr. Its role is evolving.


Surgery

Surgery is usually reserved for women with any of the following:

  • A rapidly enlarging pelvic mass

  • Recurrent uterine bleeding refractory to drug therapy

  • Severe or persistent pain or pressure (eg, that requires opioids for control or that is intolerable to the patient)

  • A large uterus that has a mass effect in the abdomen, causing urinary or intestinal symptoms or compressing other organs and causing dysfunction (eg, hydronephrosis, urinary frequency, dyspareunia)

  • Infertility (if pregnancy is desired)

  • Recurrent spontaneous abortions (if pregnancy is desired)

Other factors favoring surgery are completion of childbearing and the patient's desire for definitive treatment.

Myomectomy is usually done laparoscopically or hysteroscopically (using an instrument with a wide-angle telescope and electrical wire loop for excision), with or without robotic techniques. Hysterectomy can also be done laparoscopically or vaginally. Most indications for these procedures are similar. Patient choice is important, but patients must be fully informed about anticipated difficulties and sequelae of myomectomy vs hysterectomy.

If women desire pregnancy or want to keep their uterus, myomectomy is used. In about 55% of women with infertility due to fibroids alone, myomectomy can restore fertility, resulting in pregnancy after about 15 mo. However, hysterectomy is often necessary or preferred by the patient. Factors that favor hysterectomy include

  • It is more definitive treatment. After myomectomy, new fibroids may begin to grow again, and about 25% of women who have a myomectomy have a hysterectomy about 4 to 8 yr later.

  • Multiple myomectomy can be much more difficult to do than hysterectomy.

  • Other, less invasive treatments have been ineffective.

  • Patients have other abnormalities that make surgery more complicated (eg, extensive adhesions, endometriosis).

  • Hysterectomy would decrease the risk of another disorder (eg, cervical intraepithelial neoplasia, endometrial hyperplasia, endometriosis, ovarian cancer in women with a BRCA mutation).

Newer procedures may relieve symptoms, but duration of symptom relief and efficacy of the procedures in restoring fertility have not been evaluated. Such procedures include

  • High-intensity focused sonography

  • Cryotherapy

  • Radiofrequency ablation

  • Magnetic resonance-guided focused ultrasound surgery

  • Uterine artery embolization

Uterine artery embolization aims to cause infarction of fibroids throughout the uterus while preserving normal uterine tissue. After this procedure, women recover more quickly than after hysterectomy or myomectomy, but rates of complications and return visits tend to be higher.


Choice of treatment

Treatment should be individualized, but some factors can help with the decision:

  • Asymptomatic fibroids: No treatment

  • Postmenopausal women: Trial of expectant management (because symptoms tend to remit as fibroids decrease in size after menopause)

  • Symptomatic fibroids, particularly if pregnancy is desired: Uterine artery embolization, another new technique (eg, high-intensity focused sonography), or myomectomy

  • Severe symptoms when other treatments were ineffective, particularly if pregnancy is not desired: Hysterectomy, possibly preceded by drug therapy (eg, with GnRH analogs)


Key Points

  • Fibroids occur in about 70% of women by age 45 but do not always cause symptoms.

  • If necessary, confirm the diagnosis with imaging, usually ultrasonography (sometimes with saline infusion sonography) or MRI.

  • For temporary relief of minor symptoms, consider drugs (eg, GnRH analogs, progestins, SERMs, mifepristone, tranexamic acid, danazol).

  • For more lasting relief, consider surgery (eg, newer procedures or myomectomy, particularly if fertility may be desired; hysterectomy for definitive therapy).

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • MEGACE
  • MIRENA, PLAN B
  • PROVERA
  • ZOLADEX
  • MIFEPREX
  • LUPRON
  • No US brand name
  • EVISTA

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