Uterine fibroids (leiomyomas) are benign smooth muscle tumors of the uterus. Fibroids frequently cause abnormal uterine bleeding and pelvic pressure and sometimes urinary or intestinal symptoms, infertility, or pregnancy complications. Diagnosis is by pelvic examination, ultrasonography, or other imaging studies. Treatment of patients depends on symptoms and desire for fertility and preferences regarding surgical treatments. Treatment may include estrogen-progestin contraceptives, progestin therapy, tranexamic acid, and surgical procedures (eg, hysterectomy, myomectomy).
Uterine fibroids (leiomyomas) are the most common pelvic tumor, occurring in approximately 70% of White women and 80% of Black women in the United States by age 50 (1). Many fibroids are small or asymptomatic. There is an increased risk of uterine fibroids in Black women and those with early menarche, obesity, and hypertension; high parity (3 or more births) is associated with a decreased risk (2).
Fibroids are smooth muscle tumors that usually arise from the myometrium. Locations of fibroids in the uterus are
Subserosal
Intramural
Submucosal
Occasionally, fibroids occur in the broad ligaments (intraligamentous), cervix, or, rarely, fallopian tubes. Some fibroids are pedunculated, and others are sessile. Submucosal fibroids may extend into the uterine cavity (intracavitary submucosal fibroids).
The International Federation of Gynecology and Obstetrics (FIGO) classification system for causes of abnormal uterine bleeding (PALM-COEIN system) has a subclassification for location of fibroids and the degree to which they protrude into the endometrial cavity (3).
PALM-COEIN* Uterine Leiomyoma (Fibroid) Subclassification System
Leiomyoma Location Categories | Type | Specific Location in the Uterus |
Submucosal (in contact with the endometrium and/or protruding into the uterine cavity) | 0 | Pedunculated intracavitary |
1 | < 50% intramural | |
2 | ≥ 50% intramural | |
3 | Contacts endometrium, 100% intramural | |
Other: Intramural (within the myometrium); subserosal (in contact with the serosa and/or protruding into the peritoneal cavity); or other locations (eg, cervical, parasitic) | 4 | Intramural |
5 | Subserosal ≥ 50% intramural | |
6 | Subserosal < 50% intramural | |
7 | Subserosal pedunculated | |
8 | Other (specify, eg, cervical, parasitic) | |
Hybrid (in contact with both the endometrium and the serosa) | 2–5† | Image shows one example: Submucosal and subserosal, each with less than half the diameter in the endometrial and peritoneal cavities |
* PALM-COEIN is a mnemonic for the structural causes (PALM) and nonstructural (COEIN) causes of abnormal bleeding (see figure PALM-COEIN Classification System). | ||
† Hybrid leiomyomas are documented as 2 numbers separated by a hyphen. By convention, the first number refers to the relationship with the endometrium and the second number refers to the relationship to the serosa. | ||
Definitions: Endometrium = glandular lining of the uterine cavity (also referred to as the endometrial cavity); myometrium = smooth muscle layer of the uterus, located between the endometrium and serosa; serosa = thin outer lining of the uterus that faces the peritoneal (abdominal) cavity, composed of mesothelium and loose connective tissue. | ||
Adapted from Munro MG, Critchley HOD, Fraser IS; FIGO Menstrual Disorders Committee. The two FIGO systems for normal and abnormal uterine bleeding symptoms and classification of causes of abnormal uterine bleeding in the reproductive years: 2018 revisions [published correction appears in Int J Gynaecol Obstet. 2019 Feb;144(2):237]. Int J Gynaecol Obstet. 2018;143(3):393-408. doi:10.1002/ijgo.12666. | ||
Most patients have multiple fibroids. Each fibroid 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.
(U.S. Navy photograph)
References
1. Baird DD, Dunson DB, Hill MC, et al: High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am J Obstet Gynecol 188(1):100-107, 2003. doi:10.1067/mob.2003.99
2. Pavone D, Clemenza S, Sorbi F, et al: Epidemiology and Risk Factors of Uterine Fibroids. Best Pract Res Clin Obstet Gynaecol 46:3-11, 2018. doi:10.1016/j.bpobgyn.2017.09.004
3. Munro MG, Critchley HOD, Fraser IS; FIGO Menstrual Disorders Committee: The two FIGO systems for normal and abnormal uterine bleeding symptoms and classification of causes of abnormal uterine bleeding in the reproductive years: 2018 revisions [published correction appears in Int J Gynaecol Obstet. 2019 Feb;144(2):237]. Int J Gynaecol Obstet 143(3):393-408, 2018. doi:10.1002/ijgo.12666
Symptoms and Signs of Uterine Fibroids
Many fibroids are asymptomatic; approximately 15 to 30% of patients with fibroids develop severe symptoms (1). Fibroids can cause abnormal uterine bleeding (eg, heavy menstrual bleeding, intermenstrual bleeding). Bleeding can be severe enough to cause anemia.
Bulk symptoms, including pelvic pain or pressure, result from the size or position of fibroids or uterine enlargement due to fibroids. Urinary symptoms (eg, urinary frequency or urgency) can result from bladder compression, and intestinal symptoms (eg, constipation) can result from intestinal compression.
Less commonly, fibroids grow and degenerate or pedunculated fibroids twist, and severe acute or chronic pressure or pain can result.
Fibroids may be associated with infertility, especially if the fibroids are submucosal. During pregnancy, they may cause pain, recurrent spontaneous abortion, premature contractions, or abnormal fetal presentation or make cesarean delivery necessary. Fibroids may also cause postpartum hemorrhage, especially if located in the lower uterine segment.
Symptoms and signs reference
1. Havryliuk Y, Setton R, Carlow JJ, et al: Symptomatic Fibroid Management: Systematic Review of the Literature. JSLS 21(3):e2017.00041, 2017. doi:10.4293/JSLS.2017.00041
Diagnosis of Uterine Fibroids
Imaging (ultrasonography, saline infusion sonography, or MRI)
The diagnosis of uterine fibroids is likely if bimanual pelvic examination detects an enlarged, irregular, mobile uterus.
If an enlarged, irregular, mobile uterus is a new finding or if pelvic examination findings have changed (eg, increased uterine size, possible adnexal mass, fixed mass, new finding of tenderness), imaging studies should be done to evaluate for fibroids or other gynecologic pathology (eg, ovarian masses). Imaging may also be done if the patient has new symptoms (eg, bleeding, pain).
When imaging is indicated, ultrasonography (usually transvaginal) is typically the preferred first-line test. If submucosal fibroids with an intracavitary component are suspected due to abnormal uterine bleeding, saline infusion sonography may be done. In saline infusion sonography, saline is instilled into the uterus, enabling the sonographer to more specifically visualize the uterine cavity.
If ultrasonography, including saline infusion sonography (if done), is inconclusive, MRI is usually done. If available, MRI should be performed in a patient prior to myomectomy to localize the fibroids. Hysteroscopy can be used to directly visualize suspected submucosal uterine fibroids and, if needed, to biopsy or resect small fibroids.
Patients with postmenopausal bleeding should be evaluated for uterine cancer.
Treatment of Uterine Fibroids
Hormonal or nonhormonal medications to decrease bleeding (eg, nonsteroidal anti-inflammatory drugs [NSAIDs], tranexamic acid, estrogen-progestin contraceptives, or progestins)
Myomectomy (to preserve fertility) or hysterectomy
Sometimes other procedures (eg, uterine fibroid embolization)
Treatment options can be classified as medical, procedural, or surgical.
Asymptomatic fibroids do not require treatment. Patients should be reevaluated periodically (eg, every 6 to 12 months).
For symptomatic fibroids, medical options are typically used first, prior to considering procedural or surgical treatments. Treatment with medications is effective in some patients, but is often suboptimal. However, clinicians should consider first trying medical treatment before doing surgery. In perimenopausal women with mild symptoms, expectant management may be tried because symptoms may resolve as fibroids decrease in size after menopause.
Medications to treat fibroids
Medications used to treat fibroids may be hormonal or nonhormonal. First-line medical therapy is usually with medications that decrease bleeding, are easy to use, and are well-tolerated, including
Estrogen-progestin contraceptives
Progestins (eg, levonorgestrel intrauterine device [IUD])
Tranexamic acid
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Estrogen-progestin contraceptives or a levonorgestrel IUD are good options for patients who also want contraception.
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 agonists. Medroxyprogesterone acetate 5 to 10 mg orally once a day or megestrol acetate 40 mg orally once a day taken for 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 every 3 months 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.
Tranexamic acid (an antifibrinolytic drug) can reduce uterine bleeding by up to 40%. The dosage is 1300 mg every 8 hours for up to 5 days. Its role is evolving
NSAIDs can be used to treat pain but probably do not decrease bleeding.
Other medications that are sometimes used to treat symptomatic fibroids include
GnRH analogs
Antiprogestins
Selective estrogen receptor modulators (SERMs)
Danazol
GnRH analogs are either agonists (eg, leuprolide) or antagonists (elagolix and relugolix) that inhibit the hypothalamic-pituitary-ovarian axis and induce hypogonadism, resulting in a decrease in estrogen production. In general, these drugs should not be used in the long term because rebound growth to pretreatment size within 6 months is common. GnRH analog use is often limited by hypoestrogenic adverse effects such as menopausal symptoms, unfavorable changes in lipid profile, and/or decreased bone density. 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.
GnRH analogs are used if other medications have not been effective and bleeding is persistent, and the patient is anemic. Alternatively, they are given preoperatively to reduce fibroid and uterine volume, making surgery technically more feasible and reducing blood loss during surgery. GnRH agonists may be given as follows:
IM or subcutaneously (eg, leuprolide 3.75 mg IM every month, goserelin 3.6 mg subcutaneously every 28 days)
As a subdermal pellet
As nasal spray (eg, nafarelin)
GnRH antagonists are available in oral preparations formulated for low-dose add-back therapy to limit hypoestrogenic adverse effects.
For antiprogestins (eg, mifepristone), the dosage is 5 to 50 mg once a day for 3 to 6 months. 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.
Procedures to treat fibroids
Uterine artery embolization is an image-guided treatment option that aims to cause infarction of fibroids throughout the uterus while preserving normal uterine tissue. For this procedure, the uterus is visualized using fluoroscopy, catheters are placed in the femoral artery and advanced into the uterine artery, and then embolic particles are used to occlude blood supply to the fibroids. After this procedure, women recover more quickly than after hysterectomy or myomectomy, but rates of complications (eg, bleeding, uterine ischemia) and return visits tend to be higher. Treatment failure rates are 20 to 23%; in such cases, definitive treatment with hysterectomy is required. Patients who are considering further childbearing should be counseled that the procedure may increase certain obstetric outcomes, including spontaneous abortion, cesarean delivery, and postpartum hemorrhage (1).
Magnetic resonance-guided focused ultrasound surgery is a uterine-sparing, percutaneous procedure that uses high-intensity ultrasound waves to ablate fibroids.
Surgery for fibroids
Surgery is usually reserved for women with any of the following:
A rapidly enlarging pelvic mass
Recurrent uterine bleeding refractory to medications
Severe or persistent pain or pressure (eg, that requires pain medications 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 submucosal fibroids may be interfering with conception)
Recurrent spontaneous abortion (if pregnancy is desired)
Other factors favoring surgery are completion of childbearing and a patient's desire for definitive treatment.
For patients with severe bleeding, gonadotropin-releasing hormone (GnRH) agonists can be given before surgery to shrink fibroid tissues; these drugs often stop menses and allow blood counts to increase.
Radiofrequency fibroid ablation uses real-time ultrasound to identify the fibroids and apply radiofrequency energy from a handpiece using a laparoscopic or transcervical approach.
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, vaginally, or by laparotomy.
Most indications for myomectomy and hysterectomy are similar, and patients should be counseled about risks and benefits of each procedure.
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 months. Multiple myomectomy can be more technically difficult than hysterectomy. Multiple myomectomy often involves increased bleeding, postoperative pain, and adhesions, and may increase risk of uterine rupture during subsequent pregnancies.
Pearls & Pitfalls
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Factors that favor hysterectomy include
The patient does not desire future childbearing.
Hysterectomy is a 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 years later.
The patient has other abnormalities that make a more complex surgery like myomectomy more complicated (eg, extensive adhesions, endometriosis).
Hysterectomy would treat or decrease the risk of another disorder (eg, cervical intraepithelial neoplasia, endometrial hyperplasia, endometriosis, ovarian cancer in women with a BRCA mutation, Lynch syndrome).
If hysterectomy or myomectomy is done laparoscopically, techniques must be used to remove the fibroid tissue through the small laparoscopic incisions. Morcellation is a term that describes cutting fibroids or uterine tissue into small pieces; this may be done with a scalpel or an electromechanical device. Women who have surgery for presumed uterine fibroids may have an unsuspected, undiagnosed sarcoma or other uterine cancer, although this is rare, and estimated incidence varies from 1 in 770 to < 1 in 10,000 surgeries (2). If intraperitoneal morcellation is done, malignant cells may be disseminated throughout the peritoneum. Surgeons may use methods to prevent dissemination of tissue during morcellation, including extraperitoneal morcellation (tissue is grasped and pulled through the incision) or use of an intraabdominal bag to contain tissue. Morcellation should not be used in patients with suspected uterine cancer or significant risk factors, particularly for uterine sarcoma. Prior to surgery for presumed fibroids, patients should be evaluated for uterine cancer, if indicated, and informed that if morcellation is used, there is a very small risk of disseminating cancerous cells (3).
Choice of treatment
Treatment of uterine fibroids should be individualized, but some factors can help with the decision:
Asymptomatic fibroids: No treatment, continue to follow patient
Postmenopausal women: Patients with postmenopausal bleeding should be evaluated for uterine cancer. If results are benign or pressure symptoms are the main issues, a trial of expectant management is reasonable (because symptoms tend to remit as fibroids decrease in size after menopause)
Symptomatic fibroids, particularly if pregnancy is desired: Uterine artery embolization, other techniques (eg, high-intensity focused sonography), or myomectomy
Severe symptoms when other treatments were ineffective, particularly if pregnancy is not desired: Hysterectomy, possibly preceded by medical therapy
Treatment references
1. Homer H, Saridogan E: Uterine artery embolization for fibroids is associated with an increased risk of miscarriage. Fertil Steril. 2010;94(1):324-330. doi:10.1016/j.fertnstert.2009.02.069
2. Hartmann KE, Fonnesbeck C, Surawicz T, et al. Management of Uterine Fibroids [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2017 Dec. (Comparative Effectiveness Review, No. 195.)
3. American College of Obstetricians and Gynecologists’ Committee on Gynecologic Practice: Uterine Morcellation for Presumed Leiomyomas: ACOG Committee Opinion, Number 822 [published correction appears in Obstet Gynecol. 2021 Aug 1;138(2):313]. Obstet Gynecol 137(3):e63-e74, 2021. doi:10.1097/AOG.0000000000004291
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 medications (eg, estrogen-progestin contraceptives, tranexamic acid, progestins, or GnRH analogs).
For more lasting relief, consider surgery (eg, myomectomy or other uterus-conserving procedures, particularly if fertility may be desired; hysterectomy for definitive therapy).
