INTRODUCTION — Uterine leiomyomas (also referred to as fibroids or myomas) are the most common pelvic neoplasm in females [1,2]. They are noncancerous monoclonal tumors arising from the smooth muscle cells and fibroblasts of the myometrium. They arise in reproductive-age females and, when symptomatic, typically present with symptoms of abnormal uterine bleeding and/or pelvic pain/pressure. Uterine fibroids may also have reproductive effects (eg, infertility, adverse pregnancy outcomes).
The epidemiology, diagnosis, and natural history of uterine leiomyomas are reviewed here. Leiomyoma histology and pathogenesis, management of uterine leiomyomas, differentiating leiomyomas from uterine sarcomas, and leiomyoma variants are discussed separately. (See "Uterine fibroids (leiomyomas): Treatment overview" and "Uterine fibroids (leiomyomas): Histology and pathogenesis" and "Uterine fibroids (leiomyomas): Differentiating fibroids from uterine sarcomas" and "Uterine fibroids (leiomyomas): Variants and smooth muscle tumors of uncertain malignant potential".)
TERMINOLOGY AND LOCATION — Uterine fibroids are described according to their location in the uterus although many fibroids have more than one location designation (figure 1 and picture 1A-B). The International Federation of Gynecology and Obstetrics (FIGO) classification system for fibroid location is as follows (figure 2) :
●Intramural myomas (FIGO type 3, 4, 5) – These leiomyomas are located within the uterine wall. They may enlarge sufficiently to distort the uterine cavity or serosal surface. Some fibroids may be transmural and extend from the serosal to the mucosal surface.
●Submucosal myomas (FIGO type 0, 1, 2) – These leiomyomas derive from myometrial cells just below the endometrium (lining of the uterine cavity). These neoplasms protrude into the uterine cavity. The extent of this protrusion is described by the FIGO/European Society of Hysteroscopy classification system and is clinically relevant for predicting outcomes of hysteroscopic myomectomy (figure 3)  (see "Uterine fibroids (leiomyomas): Hysteroscopic myomectomy", section on 'Leiomyoma characteristics'):
•Type 0 – Completely within the endometrial cavity
•Type 1 – Extend less than 50 percent into the myometrium
•Type 2 – Extend 50 percent or more within the myometrium
●Subserosal myomas (FIGO type 6, 7) – These leiomyomas originate from the myometrium at the serosal surface of the uterus. They may have a broad or pedunculated base (image 1) and may be intraligamentary (ie, extending between the folds of the broad ligament).
●Cervical myomas (FIGO type 8) – These leiomyomas are located in the cervix rather than the uterine corpus.
While conceptually straightforward, a study attempting to validate the FIGO classification system found significant disagreement on classification among experts .
PREVALENCE — Uterine leiomyomas are the most common pelvic tumor in females [1,2,6]. Incidence is difficult to determine since there are few longitudinal studies . In addition, the actual prevalence is unknown since studies have been conducted mainly in symptomatic patients or following hysterectomy. Representative studies include:
●In the Nurses' Health Study II, a large prospective study in the United States, over 95,000 females ages 25 to 44 were followed from 1989 to 1993 . The age-standardized incidence rates of fibroids confirmed by ultrasound or hysterectomy were 9.2 per 1000 woman-years overall, 30.6 for Black females, and 8.9 for White females. Overall incidences by age group were: 25 to 29 (3.3 per 1000 woman-years), 30 to 34 (6.8), 35 to 39 (10.3), and 40 to 44 (16.0).
●In a population-based study of an urban health plan in Washington, DC, 1364 females ages 35 to 49 years were randomly selected and assessed by survey and/or ultrasound . Newly detected fibroids were present in 59 percent of Black females and 43 percent of White females; for females in their late 40s, the estimated frequency of fibroids was >80 percent and near 70 percent for Black and White females, respectively.
●A cross-sectional study in Europe of 1756 patients with fibroid-related symptoms found myomas in 12 to 24 percent . Myomas are clinically apparent in approximately 12 to 25 percent of reproductive-age females and noted on pathologic examination in approximately 80 percent of surgically excised uteri [9,10].
●A detailed pathologic study of 100 hysterectomy specimens found myomas in 77 percent of uterine specimens . Most patients had multiple myomas, with an average of 7.6 fibroids.
●An ultrasound screening study of asymptomatic females aged 18 to 30 found a prevalence of 26 percent in Black females and 7 percent in White females .
The incidence and prevalence of leiomyomas increase with age during the reproductive years [1,8,12]. In an ultrasound screening study examining the incidence of fibroids in Black females, a high-risk group, age-specific incidence rates (cases/1000 person-years) for patients <30 years, 30 to 34 years, and 35 to 39 years were 49.7, 55.2, and 58.2, respectively; 23 percent of the study participants were excluded for having fibroids at the initial intake examination .
Leiomyomas have not been described in prepubertal girls, but they are occasionally noted in adolescents. Most, but not all, patients have shrinkage of leiomyomas after menopause.
Reproductive and endocrine factors — The epidemiology of leiomyomas parallels the ontogeny and life cycle changes of the reproductive hormones estrogen and progesterone. Although the growth of fibroids is responsive to gonadal steroids, these hormones are not necessarily responsible for the genesis of the tumors. (See "Uterine fibroids (leiomyomas): Histology and pathogenesis", section on 'Steroid hormones'.)
Parity — Parity (having one or more pregnancies extending beyond 20 weeks of gestation) decreases the chance of fibroid formation [13-15]. There is a suggestion that additional pregnancies further decrease the risk [7,15,16]. In some cohorts, older age at first birth was also associated with a decreased risk compared with younger age at first birth and a longer interval since last birth with an increased risk [7,16].
Early menarche — Early menarche (<10 years old) is associated with an increased risk of developing fibroids. This may account for the early onset of disease in Black patients, in whom menarche is generally earlier than in White patients [16-20]. In White patients, a specific polymorphism in the transcription factor HMGA2, one of the key driver mutations of leiomyomas, appears to be linked to both uterine leiomyomas and shorter adult height, suggesting that early menarche may be a key influence . Menarche is associated with increase of estradiol to postpubertal levels which can plausibly lead both to increased fibroid growth and early fusion of the long bone epiphyses leading to decreased height.
Hormonal contraception — Use of standard or lower dose oral contraceptives (OCs; ≤35 mcg ethinyl estradiol/day) does not appear to cause fibroids to grow; therefore, administration of these drugs is not contraindicated in patients with fibroids [13,16,21-23]. One possible exception was reported by the Nurses' Health Study, which suggested OC use was associated with an increased risk of leiomyomas in patients with early exposure to OCs (13 to 16 years old) .
Long-acting progestin-only contraceptives (eg, depot medroxyprogesterone) appear to protect against development of leiomyomas [16,23-25]. However, studies of postpartum fibroid regression suggest that these agents inhibit fibroid regression specifically when used in the postpartum period . Studies investigating the symptomatic control of bleeding by progestin intrauterine devices have shown small decreases in fibroid or uterine size [27,28].
Other endocrine factors — Prenatal exposure to diethylstilbestrol is associated with an increased risk of fibroids, supporting the role of early hormonal exposure in pathogenesis . (See "Outcome and follow-up of diethylstilbestrol (DES) exposed individuals".)
There are no credible cases of uterine enlargement with ovulation induction [30,31]. A nationwide cohort study of patients undergoing in vitro fertilization reported a decrease in risk of fibroids for patients with a higher response to ovarian stimulation than those with a normal response .
Environmental exposures such as phthalates, polychlorinated biphenyl, and bisphenol A appear to be linked to an increased risk of fibroids, possibly through endocrine disruption . (See "Overview of occupational and environmental risks to reproduction in females".)
Obesity — Most studies show a relationship between fibroids and increasing body mass index (BMI); however, a relationship with increased BMI, weight gain as an adult, or body fat varies across studies [21,34-38]. The relationship is complex and is likely modified by other factors, such as parity, and may be more related to change in body habitus as an adult.
Diet, alcohol, and smoking
●Diet – Studies regarding dietary effects on fibroids include:
•Significant consumption of beef and other reds meats (1.7-fold) or ham (1.3-fold) is associated with an increased relative risk of fibroids and consumption of green vegetables (0.5-fold) and fruit (especially citrus fruit) with a decreased risk [39,40].
•One report suggested that consumption of dairy products, but not soy products, is inversely related to fibroid risk in Black patients . There was no confounding effect of soy consumption, which is often a substitute for dairy products in lactose intolerant patients.
•Increases in dietary glycemic index or load are associated with a small increase in fibroid risk in some patients .
•While overall fat intake does not appear to be related, dietary consumption of marine omega-3 fatty acids (eg, docosahexaenoic acid or environmental pollutants associated with this type of fat) may be associated with an increase in fibroid risk in some patients [43,44].
•Dietary consumption of carotenoids is not associated with a change in risk for uterine leiomyoma .
•Dietary vitamin A from animal sources may also be associated with decreased fibroid risk .
•There is increasing evidence that vitamin D deficiency or insufficiency, which is more prevalent among Black patients, is linked to fibroid risk [46,47]. The major source of vitamin D is from synthesis from a prohormone when sunlight hits the skin, and this is inhibited by the higher levels of melanin in darker skin. This relationship is especially interesting because it is a biologically plausible explanation for the increased fibroid risk in Black patients that lends itself to prevention trials.
•Caffeine consumption is generally not a risk factor for fibroids, except for weak associations in patients under age 35 with high consumption of coffee or caffeine intake .
●Alcohol – Consumption of alcohol, especially beer, appears to be associated with an increased risk of developing fibroids .
●Smoking – Some studies have shown an association between smoking and a decreased risk of having fibroids, possibly through the inhibition of aromatase [13,49-51]. Other studies have not found this association [36,48].
Genetics — Studies imply a familial predisposition to leiomyomas in some patients. There is also evidence of specific susceptibility genes for fibroids [52-54].
The genetics of fibroids is discussed in detail separately. (See "Uterine fibroids (leiomyomas): Histology and pathogenesis", section on 'Genetics'.)
●Race/ethnicity – The incidence rates of fibroids are typically found to be two- to threefold greater in Black females than in White females [1,8,11,55,56]; differences in diet, lifestyle, psychosocial stress, perceived racism, and environmental exposures are thought to contribute to this disparity rather than race itself [57-63].
Black females compared with White females are also more likely to have clinically relevant fibroids (eg, larger uteri and fibroids, more severe anemia, faster growing fibroids) [17,64-66], develop symptoms earlier (on average four to six years younger [17,65]), and be managed surgically [55,67-69]. The etiology of these differences are unknown and cannot be explained by known factors that vary by race [8,70,71].
Data are mixed regarding whether Hispanic or Asian-Chinese females have an increased risk of uterine myomas compared with White females [8,56,67,72].
●Stress/major life events – Chronic stress and major life events may be associated with an increased leiomyoma risk [59,73]. In a meta-analysis including seven observational studies, there was a positive association with chronic psychological stress and fibroids, especially among non-Hispanic Black patients (odds ratio [OR] 1.24, 95% CI 1.14-1.34), and those with higher compared with lower categories of chronic stress (pooled OR 1.24, 95% CI 1.15-1.34) .
●Hypertension – Hypertension is associated with an increased leiomyoma risk. The risk is related to increased duration or severity of hypertension , and may be linked through the angiotensin-converting enzyme pathway [75,76]. There are some studies showing a decreased leiomyoma risk among patients with type 2 diabetes, which appears to have a stronger association among European Americans than African Americans [77-79].
●Uterine infection – Uterine infection was previously associated with an increased risk of leiomyomas, but a subsequent study of self-reported reproductive tract infection did not find an association [74,80], and one study found an inverse relationship with chlamydia exposure . Factors associated with cervical neoplasia are associated with a decreased risk [74,82]. Additional study is indicated regarding infectious agents and fibroid risk.
PREVENTION — Given the high prevalence, high recurrence risk following conservative treatment, and substantial impact on quality of life, preventive measures for uterine fibroids are needed. One study has suggested high physical activity, even after adjustment for body mass index and other confounders, was associated with a substantial decrease in risk of fibroid development . Etiologic investigations of vitamin D deficiency, inflammatory markers, hormonal receptors, and more are aimed at finding preventive targets.
CLINICAL FEATURES — Uterine leiomyomas are typically brought to medical attention due to symptoms or are found incidentally on pelvic imaging. Approximately 1 percent of females in a commercially insured population have fibroids that receive medical attention in a year .
The majority of myomas are small and asymptomatic, but many patients with fibroids have significant problems that interfere with some aspect of their lives and warrant therapy . These symptoms are related to the number, size, and location of the tumors. Myomas can occur as single or multiple tumors and range in size from microscopic to tens of centimeters. The size of the myomatous uterus is described in menstrual weeks as with the gravid uterus. As an example, a 20-week size myomatous uterus is not unusual and is often associated with heavy menses, increasing abdominal girth, and a sense of abdominal fullness similar to pregnancy.
Symptoms are classified into three categories :
●Heavy or prolonged menstrual bleeding
●Bulk-related symptoms, such as pelvic pressure and pain
●Reproductive dysfunction (ie, infertility, miscarriage, obstetric complications)
Among symptomatic patients with uterine fibroids, abnormal uterine bleeding (AUB) and menstrual cramps are the most common symptoms, occurring in approximately 26 to 29 percent of all patients. Black patients reported higher rates at 37 to 42 percent . Abdominal pain or tightness is reported in 19 percent of White patients and 34 percent of Black patients.
Heavy or prolonged menstrual bleeding — Heavy and/or prolonged menses is the typical bleeding pattern with leiomyomas and the most common fibroid symptom [88,89]. Intermenstrual bleeding and postmenopausal bleeding should prompt investigation to exclude endometrial pathology. For any AUB pattern, endometrial sampling should be performed if endometrial hyperplasia or carcinoma is suspected (table 1). It is important to keep in mind that a patient may have fibroids and concurrent endometrial neoplasia.
Heavy uterine bleeding may be responsible for associated problems, such as iron deficiency anemia, social embarrassment, and lost productivity in the work force.
●Submucosal myomas that protrude into the uterine cavity (eg, types 0 and 1) (figure 3) are most frequently related to significant heavy menstrual bleeding [4,6,90]. As an example, a retrospective study that included 912 patients with leiomyomas found that those with submucosal myomas were significantly more likely to be anemic than patients with myomas in other locations (34 versus 25 percent) .
●Intramural myomas are also commonly associated with heavy or prolonged menstrual bleeding, but subserosal fibroids are not considered a major risk for heavy menstrual bleeding.
The mechanism(s) of profuse menses in patients with leiomyomas are unclear but may include both microscopic and macroscopic abnormalities of the uterine vasculature, impaired endometrial hemostasis, or molecular dysregulation of angiogenic factors . A study of endometrial histology showed distinct endometrial changes even remote from the location of fibroids, indicating that fibroids located intramurally could also contribute to bleeding . In addition, a study of uterine peristalsis demonstrates altered uterine contractility near submucosal fibroids; one theory is that this inhibits the usual ability of the uterus to contract during menses .
The evaluation of patients with AUB is discussed in detail separately. (See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Terminology, evaluation, and approach to diagnosis".)
Bulk-related symptoms — The myomatous uterus is enlarged and irregularly shaped and can cause specific symptoms due to pressure from myomas at particular locations. These symptoms and findings include pelvic pain or pressure, urinary tract or bowel obstruction, or venous compression.
Pelvic pressure or pain — In general, pain is an underappreciated symptom of uterine fibroids. Pain may present as lower back pain, pelvic pain, and/or menstrual pain . Pelvic pressure, abdominal bloating, and abdominal protrusion may also be reported.
Urinary tract or bowel issues — The urinary tract or bowel may be compressed by fibroids, depending on their size and location. Symptoms and findings include:
●Urinary symptoms – A heterogeneous group of urinary symptoms including frequency, difficulty emptying the bladder, or, rarely, complete urinary obstruction may all occur in up to 60 percent of patients with fibroids . Bladder symptoms sometimes arise when an anterior fibroid presses directly on the bladder or a posterior fibroid pushes the entire uterus forward. In a small cohort study of patients with fibroids on ultrasound, 14 percent demonstrated hydronephrosis, more commonly on the right. Fibroids associated with hydronephrosis were larger with an average largest fibroid of 6 cm and a uterine size of 18 weeks .
●Bowel symptoms – Fibroids that place pressure on the rectum can result in constipation.
Venous compression — Very large uteri may compress the vena cava and lead to an increase in thromboembolic risk [97-99]. One small study has reported thromboembolism as the presenting complaint in approximately 4 percent patients with an enlarged fibroid uterus .
Other pain or discomfort issues
Painful menses — Painful menses is reported by many patients with fibroids. This pain in many patients appears to be correlated with heavy menstrual flow and/or passage of clots.
Painful intercourse — It is controversial whether patients with fibroids are more likely to experience painful intercourse than those without fibroids [100,101]. However, among patients with fibroids, anterior or fundal fibroids are the most likely to be associated with deep pain with intercourse. Number and size of fibroids do not appear to influence the incidence or intensity of painful intercourse.
Fibroid degeneration or torsion — Infrequently, fibroids cause acute pain from breaking down of the fibroid tissue (eg, carneous or red degeneration) (picture 2) or torsion of a pedunculated tumor.
Fibroid degeneration typically results in pelvic pain and may be associated with a low-grade fever, uterine tenderness on palpation, elevated white blood cell count, or peritoneal signs. The discomfort resulting from degenerating fibroids is self-limited, lasting from days to a few weeks, and usually responds to nonsteroidal anti-inflammatory drugs.
Diagnosis of fibroid degeneration is based on the presence of a fibroid with a typical symptom pattern. On ultrasound, a potential diagnosis of degeneration is suggested when pain is present when scanning directly over the fibroid (image 2). In cases where the etiology of pain is unclear, pelvic magnetic resonance imaging with gadolinium can be useful to make the diagnosis of degeneration since regions of degeneration within fibroids do not have enhancement following contrast administration . If acute pain is the sole indication for surgery for uterine fibroids, other disease processes, such as endometriosis, renal colic, or rare diagnoses such as pelvic tuberculosis, should be carefully excluded [103,104]. (See "Endometriosis: Pathogenesis, epidemiology, and clinical impact".)
Infertility or obstetric complications — Leiomyomas that distort the uterine cavity (submucosal or intramural with an intracavitary component) have been thought to result in difficulty conceiving a pregnancy and an increased risk of miscarriage . However, a large prospective cohort study that identified fibroids in the first trimester of pregnancy found that, while fibroids were associated with miscarriage in univariate analysis, in multivariate analysis, increasing age appeared to be the primary driver of this relationship . Similar findings were obtained in a systematic review that addressed confounders . (See "Uterine fibroids (leiomyomas): Treatment overview", section on 'Impact of fibroids on fertility'.)
In addition, leiomyomas have been associated with adverse pregnancy outcomes (eg, placental abruption, fetal growth restriction, malpresentation, and preterm labor and birth). (See "Uterine fibroids (leiomyomas): Issues in pregnancy".)
●Prolapsed fibroid – Infrequently, a submucosal leiomyoma will prolapse through the cervix and present with a mass, bleeding, and possible ulceration or infection. (See "Uterine fibroids (leiomyomas): Prolapsed fibroids".)
●Endocrine effects – Rare symptoms of fibroid tumors where fibroids can secrete ectopic hormones include:
•Polycythemia from autonomous production of erythropoietin .
•Hypercalcemia from autonomous production of parathyroid hormone-related protein .
DIAGNOSTIC EVALUATION — The clinical diagnosis of uterine leiomyomas is made based on a pelvic examination and pelvic ultrasound findings consistent with a uterine leiomyoma. Characteristic symptoms further support the clinical diagnosis, although many patients are asymptomatic. A definitive diagnosis by pathology evaluation is not obtained in all cases but should be pursued if there is reason to be suspicious that the uterine mass may not be a fibroid, but rather may be a uterine precancer or cancer. (See "Uterine fibroids (leiomyomas): Differentiating fibroids from uterine sarcomas".)
The pelvic examination findings are typically of an enlarged, mobile uterus with an irregular contour on bimanual pelvic examination; however, small submucosal or intramural fibroids will not produce a noticeably enlarged uterus or an irregular contour. The most common symptoms are heavy or prolonged menstrual bleeding, and fibroids may be associated with pelvic pain, infertility, or other symptoms. Typically, the clinical diagnosis is confirmed with a pelvic ultrasound.
History — A medical history is taken, including:
●Symptoms related to fibroids – The most common presenting symptoms of uterine fibroids are heavy or prolonged menstrual bleeding, pelvic pain or pressure, and infertility. For all symptoms, the duration, severity, and impact on quality of life should be assessed.
•It is important to assess the severity of heavy or prolonged menstrual bleeding. A menstrual history is taken and the volume and duration of bleeding elicited. Questions to assess uterine bleeding are shown in the table (table 2). For patients with heavy menstrual bleeding, questionnaires may help to assess the risk of a concomitant bleeding disorder . If there is any possibility the patient is pregnant, pregnancy testing should be performed. In addition, based on the bleeding pattern and risk factors, the clinician should consider the risk of endometrial hyperplasia or cancer and whether endometrial sampling should be performed (table 1). (See 'Clinical features' above.)
•For patients with pelvic pain or pressure, the location, severity, and characteristics of the pain should be assessed. Pain related to fibroids is not likely to have an acute onset, except in the infrequent cases of fibroid torsion and degeneration. In addition, while some patients with fibroids experience painful menses, the pain associated with fibroids can also be noncyclic. Pain associated with menses may also indicate adenomyosis, endometriosis, or primary painful menses.
Patients should be asked about other potential pain or bulk-related symptoms, including dyspareunia, urinary retention, or constipation.
•The patient should be asked about infertility, recurrent miscarriage, or obstetric complications that may be related to fibroids.
●Obstetric and gynecologic history, including prior history of uterine fibroids, history of pelvic pain, obstetric or gynecologic surgeries, and risk factors for uterine malignancies other than endometrial carcinoma (sarcoma, carcinosarcoma). Risk factors for sarcoma include postmenopausal status, Black race, tamoxifen, pelvic radiation, and hereditary leiomyomatosis and renal cell carcinoma. (See "Clinical features, diagnosis, staging, and treatment of uterine carcinosarcoma", section on 'Epidemiology and risk factors' and "Uterine sarcoma: Classification, epidemiology, clinical manifestations, and diagnosis", section on 'Risk factors'.)
●Relevant medical and surgical history, including those that are part of the differential diagnosis or may exacerbate the symptoms of a pelvic mass, pelvic pain, or abnormal uterine bleeding. This includes thyroid dysfunction, coagulation disorders, anticoagulant medications, nongynecologic conditions that cause pelvic or abdominal pain or mass, and prior pelvic or abdominal surgery.
Physical examination — The physical examination includes an abdominal and pelvic examination. Vital signs are taken, as appropriate. Fibroids are rarely associated with fever, except in some patients with degenerating fibroids. Patients with severe heavy menstrual bleeding may become anemic, but in otherwise healthy reproductive-age patients, a significant change in heart rate or blood pressure is rare as part of the clinical presentation.
The abdominal examination should include palpation for a pelvic-abdominal mass. Large fibroid uteri can be palpated abdominally. The level of the uterine fundus should be noted.
A thorough pelvic examination is performed. On bimanual pelvic examination, the size, contour, and mobility should be noted. An enlarged, mobile uterus with an irregular contour is consistent with a leiomyomatous uterus. These findings are helpful to follow changes in the uterus over time and to aid surgical planning (eg, transverse or vertical incision, vaginal surgery or abdominal approach).
The size is described in terms of the fundal height in the superior-inferior axis in comparison to a gravid uterus: Twelve weeks is palpable just above the pubic symphysis, 16 weeks is midway between the symphysis and umbilicus, and 20 weeks is at the umbilicus. An increase in size or an irregular contour may not be noted if the patient has small intramural or submucosal fibroids.
An enlarged uterus that is fixed raises suspicion of an inflammatory process (eg, endometriosis) or malignancy.
Infrequently, on speculum examination, a prolapsed submucosal fibroid is visible at the external cervical os. Prolapsed fibroids should be removed and are distinguished from a large endocervical or endometrial polyp by the firm consistency of the tissue and by pathology evaluation. (See "Uterine fibroids (leiomyomas): Prolapsed fibroids".)
Cervical fibroids can present as an enlargement of the cervix seen during speculum examination or felt on bimanual examination. A pedunculated cervical fibroid can also appear like a prolapsing fibroid. Cervical fibroids generally have to be confirmed by an imaging study.
Laboratory testing — Laboratory testing does not have a role in the diagnosis of uterine leiomyomas but is important in evaluating for other associated conditions, including:
●Pregnancy – A urine or serum human chorionic gonadotropin is ordered if the patient may be pregnant.
●Anemia – A hemoglobin/hematocrit should be ordered to diagnose anemia; a ferritin level may also be obtained. For those with anemia, clinicians must also consider concomitant etiologies, including bleeding disorders. This is discussed in detail elsewhere. (See "Diagnostic approach to anemia in adults" and "Approach to the adult with a suspected bleeding disorder".)
●Endometrial hyperplasia or carcinoma – Endometrial biopsy is performed for patients with abnormal uterine bleeding or risk factors for endometrial hyperplasia and/or carcinoma (eg, type 2 diabetes mellitus, obesity, chronic anovulation). (See "Overview of the evaluation of the endometrium for malignant or premalignant disease".)
There is also some evidence that uterine sarcomas can be diagnosed by endometrial biopsy. (See "Uterine fibroids (leiomyomas): Differentiating fibroids from uterine sarcomas", section on 'Endometrial sampling'.)
Imaging and endoscopy — Pelvic ultrasound is the imaging study of choice for uterine leiomyomas, based on the ability to visualize genital tract structures and cost-effectiveness. Ultrasound is typically performed in all patients, and then other studies, such as saline-infused sonogram, hysteroscopy, or magnetic resonance imaging (MRI), are ordered depending on the clinical indications.
Computed tomography has little clinical utility in delineating the position of fibroids relative to the endometrium or myometrium . Hysterosalpingograms can also sometimes show the distortion of the endometrial cavity but are best reserved for the patient needing assessment of fallopian tube patency for fertility.
Step one: Pelvic ultrasound — Pelvic ultrasound is the first-line study used to evaluate for uterine fibroids. Transvaginal ultrasound has high sensitivity (95 to 100 percent) for detecting myomas in uteri less than 10 gestational weeks' size . Precise localization of fibroids is limited in larger uteri or when there are many tumors. Fibroids are seen on ultrasound usually as hypoechoic, well-circumscribed round masses, frequently with shadowing; cellular fibroids may appear to be more isoechoic, making differentiation from the normal myometrium difficult, or hyperechoic. Adenomyomas can mimic the appearance of cellular fibroids or multiple small fibroids. Sarcoma is also difficult to differentiate on imaging.
On imaging, calcification in a fibroid generally implies that it has degenerated. These calcifications can be seen on plain film as "popcorn" calcifications in the pelvis. On ultrasound, the calcifications may appear as clumps or rim-like calcifications within a mass (image 3). At times, only the calcification is seen and not the soft tissue component. In general, if compared with a sonogram prenecrosis, the fibroid size will be smaller once it calcifies.
If fibroids are thought to be causing urinary tract obstruction, then a renal ultrasound can be obtained to assess for hydronephrosis. (See "Clinical manifestations and diagnosis of urinary tract obstruction (UTO) and hydronephrosis".)
Step two: Evaluate the uterine cavity in patients with suspected submucous fibroids or those desiring fertility
Saline infusion sonography — Saline infusion sonography (sonohysterography) is an imaging study in which pelvic ultrasound is performed while saline is infused into the uterine cavity. Use of this technique allows identification of submucosal lesions (some of which may not be seen on routine ultrasonography) and intramural myomas that protrude into the cavity and characterizes the extent of protrusion into the endometrial cavity (image 4). (See "Saline infusion sonohysterography".)
Saline infusion sonography is helpful when planning a hysteroscopic resection of a fibroid or evaluating the potential risks of fertility associated with a fibroid.
Hysteroscopy — Diagnostic hysteroscopy is useful for visualizing the endometrial cavity. Similar to saline infusion sonography, this allows evaluation for submucosal or protruding myometrial fibroids and can characterize the extent of protrusion. This can be performed in the office or operating room.
When the entire fibroid is visualized arising from a pedicle, or has a broad base, the lesion is hysteroscopically classified as intracavitary (type 0 fibroid). However, when the fibroid abuts the endometrium or protrudes into the myometrium, the depth of penetration cannot be ascertained hysteroscopically. Additionally, hysteroscopy less accurately predicts the size of the myoma compared with ultrasound and sonohysterography .
Hysteroscopy can help in the planning of a hysteroscopic resection of a submucosal fibroid if ultrasound has already confirmed size and proximity to the endometrium and rule out small polyps not seen on ultrasound.
Step three: Additional imaging as necessary when complex intervention is planned or malignant disease is suspected
Magnetic resonance imaging — MRI is the most effective modality for visualizing the size and location of all uterine myomas and can distinguish among leiomyomas, adenomyosis, and adenomyomas. Due to the expense of this modality, its use is best reserved for procedural planning for complicated procedures. For instance, for patients with type 3 through 6 uterine fibroids, an MRI can help the surgeon plan for laparoscopic myomectomy to know the expected depth into the myometrium (figure 2). It may also be useful before uterine artery embolization since imaging patterns predict uterine artery embolization outcome. MRI can also help identify features concerning for leiomyosarcoma [115,116]. This is discussed in more detail separately. (See "Uterine fibroids (leiomyomas): Differentiating fibroids from uterine sarcomas", section on 'Imaging' and "Uterine fibroids (leiomyomas): Treatment with uterine artery embolization".)
Role of contrast-enhanced ultrasound — Contrast-enhanced ultrasound (CEUS) has been studied as an alternative to MRI for evaluating fibroids characteristics; intravenously injected gas-filled microbubbles allow for visualization of the micro- and macrovasculature providing contrast-enhanced images of the uterus that is not otherwise visualized with ultrasound [117,118]. While CEUS is commonly used for imaging of other organs (eg, liver, heart), its diagnostic performance for evaluation of fibroids is limited and MRI is probably superior to CEUS for evaluation of fibroids and distinguishing fibroids and leiomyosarcoma. Thus, this approach remains investigational and further studies are needed.
DIAGNOSIS — Uterine leiomyomas are a clinical diagnosis based on pelvic imaging. The diagnosis is typically made based on a pelvic ultrasound finding of leiomyomas, although other imaging modalities may be used. The indication for pelvic imaging typically includes symptoms of abnormal uterine bleeding (AUB), pelvic pain or pressure, or infertility; some patients have an enlarged uterus on pelvic examination.
In general, pathology confirmation is not required to proceed with management, except in cases in which another lesion is suspected, such as a uterine sarcoma or leiomyoma variant. Unfortunately, it is difficult to differentiate benign leiomyomas from these conditions, and thus, some cases will be wrongly diagnosed as leiomyomas. (See "Uterine fibroids (leiomyomas): Differentiating fibroids from uterine sarcomas".)
Additional characteristics — Information on volume and location of tumors within the uterus, based on pelvic imaging, aids in determining the clinical impact and treatment planning. This includes:
●Are submucosal fibroids present? – These are the most likely to be associated with AUB or infertility, although these issues can occur with fibroids in other locations.
●Are fibroids in one or more than one location? – Treatment planning must take into consideration all fibroid locations. As an example, management of a single submucosal fibroid may be different than if there is a submucosal fibroids and several intramural fibroids.
●Is the volume or location of fibroids consistent with bulk-related symptoms? – Pelvic pain or pressure is likely to occur only if the uterus is sufficiently enlarged. In addition, urinary symptoms may occur if there is an anterior fibroid that abuts the bladder, or bowel symptoms may occur if there is a posterior or left fibroid that puts pressure on the rectum or sigmoid colon.
●Is there hydronephrosis? – Hydronephrosis due to ureteral obstruction by a fibroid uterus must be alleviated to avoid renal failure.
DIFFERENTIAL DIAGNOSIS — The differential diagnosis of uterine leiomyomas includes other conditions that cause uterine enlargement, abnormal uterine bleeding (AUB), pelvic pain, or infertility. It is important to note that leiomyomas are a common condition, and other coexisting conditions may be the etiology of the presenting symptoms.
The differential diagnosis of an enlarged uterus includes both benign and malignant conditions:
•Adenomyosis (diffuse infiltration of the myometrium) or adenomyoma.
•Metastatic disease – This is very rarely the cause of an enlarged uterus and typically from another reproductive tract primary; these lesions are likely to be myometrial but may invade the endometrium [119,120].
•Benign submucosal leiomyoma
•Endometrial polyp – These tend to be small and are unlikely to cause an enlarged uterus
•Endometrial carcinoma (may invade into the myometrium) or hyperplasia
•Carcinosarcoma – Considered an epithelial neoplasm
•Endometrial stromal sarcoma (mimics endometrium but invades the myometrium)
●Hematometra (blood within the uterine cavity, usually following an intrauterine procedure [eg, dilation and curettage])
Pregnancy should be excluded in any patient of reproductive age who presents with an enlarged uterus, AUB, and/or pelvic pain. (See "Clinical manifestations and diagnosis of early pregnancy", section on 'Diagnosis'.)
Most commonly, when faced with an enlarged uterus, uterine leiomyomas must be differentiated from uterine adenomyosis. Patients with adenomyosis more often present with a diffusely enlarged uterus, painful menses, and AUB. On examination in a patient with adenomyosis, the uterus is typically smooth, globular, and boggy. The two conditions are usually differentiated by imaging since each has a characteristic appearance on ultrasound. (See "Uterine adenomyosis".)
Patients may develop adenomyomas, which are benign glandular tumors within the myometrium. These can closely resemble leiomyomas on imaging. Adenomyosis and fibroids often occur in the same patient, making differentiation more difficult [121,122]. Intraoperatively, adenomyomas are generally more difficult to excise than leiomyomas. Leiomyomas are typically separated from the adjacent myometrium by a pseudocapsule. With adenomyomas, there is typically no tissue plane between the adenomyoma and the myometrium.
Benign or malignant uterine neoplasms must be differentiated from leiomyomas. The most common neoplastic condition that is part of the differential diagnosis is endometrial carcinoma. This is the most common site of gynecologic cancer in developed countries. Patients present with uterine bleeding and may have a uterine mass. However, the ultrasound findings in endometrial carcinoma are likely to be a thickened endometrium or, in the case of more advanced disease, a lesion invading from the endometrium to the myometrium. This is a distinctly different appearance than a fibroid, which may be seen to distort the endometrial cavity, but not actually invade from the endometrium to the myometrium. Endometrial sampling is the best method of diagnosis for endometrial carcinoma and should be performed if this is a potential diagnosis (table 1). (See "Clinical features, diagnosis, staging, and treatment of uterine carcinosarcoma".)
Leiomyomas are a common condition, and thus, it may be presumed that a patient has myomas rather than a rare smooth muscle neoplasm. This includes leiomyoma variants that manifest some facets of malignancy yet lack others. For example, they may metastasize but not be locally invasive and be histologically benign. Some of these variants show no facets of malignancy. These lesions appear to be exceedingly rare. (See "Uterine fibroids (leiomyomas): Variants and smooth muscle tumors of uncertain malignant potential".)
Clinicians should also consider the possibility of a uterine sarcoma. Uterine sarcoma is rare (3 to 7 per 100,000 in the United States population) and has a poor prognosis . Both leiomyomas and uterine sarcoma present as focal masses in the uterine myometrium. There are several histologic types of uterine sarcoma. The main type of sarcoma that may resemble a leiomyoma is leiomyosarcoma, which presents as a myometrial mass, often with AUB. In contrast, endometrial stromal sarcoma presents as an endometrial mass. However, this could potentially have a similar appearance to a submucosal leiomyoma. Differentiating benign leiomyomas from uterine sarcomas is a clinical challenge and most sarcomas are not detected preoperatively. If there is a suspicion of a uterine sarcoma, operative techniques that disrupt the specimen (eg, myomectomy, morcellation) should be avoided. (See "Uterine fibroids (leiomyomas): Differentiating fibroids from uterine sarcomas".)
Adenomatoid tumors are an uncommon type of mass of the female reproductive tract that can be seen in the myometrium or in the adnexa (the most common place is actually next to the fallopian tube) . They are mesothelial proliferations and are not histologically related to adenomyosis. They may grossly mimic leiomyomas.
The differential diagnosis of AUB is aided by pelvic imaging and a clinical description of the bleeding. Heavy or prolonged menstrual bleeding are typically the AUB patterns that are associated with leiomyomas, although these symptoms are also consistent with many other etiologies. Other AUB patterns, such as intermenstrual bleeding, irregular bleeding, or postmenopausal bleeding, are likely due to other causes. In the absence of a mass on pelvic ultrasound, leiomyomas can be excluded and other etiologies should be investigated (table 3 and figure 4). (See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Terminology, evaluation, and approach to diagnosis" and "Approach to the patient with postmenopausal uterine bleeding".)
Pelvic pain is a broad symptom category, and clarifying with the patient regarding the characteristics of the pain (ie, location, severity, timing of onset, duration, pattern, sensation, associated factors) is helpful in working through the differential diagnosis (table 4). Gastrointestinal, urinary tract, or other sources of pelvic pain should also be considered. In general, pain is not a major symptom in patients with fibroids. If discomfort is present, it is likely to be chronic, intermittent, dull pressure or pain. (See "Chronic pelvic pain in nonpregnant adult females: Causes".)
Female infertility has many etiologies. Fibroids are usually discovered, if present, on pelvic ultrasound that is part of the routine evaluation.
Premenopausal patients — With modern pelvic imaging, we have achieved an increased appreciation of the variability of growth and shrinkage of leiomyomas during the reproductive years [66,125,126]. Prospective studies have found that between 7 to 40 percent of fibroids regress over six months to three years [66,125]. There is also an increased appreciation of postpartum regression of fibroids [26,127].
Representative studies include:
●In one prospective study of 64 patients (mean age 44 years) with fibroids, the average growth rate was 1.2 cm in diameter over 2.5 years (range 0.9 to 6.8 cm) .
●A second study followed 72 patients with a total of 262 fibroids with magnetic resonance imaging (MRI) and reported a median growth rate of 9 percent at six-month follow-up. . There was wide variation in the growth of individual fibroids across all study participants (range decrease in size of 89 percent to increase in size of 138 percent) and for different fibroids within each patient. Within this prospective study, 36 patients with a total of 101 fibroids were evaluated with MRI at all time points for one year . Increase in volume of ≥30 percent in a three-month period was found in 37 myomas; rapid growth was more likely in tumors that were ≤5 cm in diameter.
Postpartum remodeling — It has been hypothesized that the postpartum remodeling of the uterus may have the effect of clearing smaller fibroids . One study supported this hypothesis with the finding that over one-third of participants with a single fibroid identified during pregnancy had none on postpartum ultrasound, and almost 80 percent of fibroids were smaller following pregnancy .
Postmenopausal patients — At menopause, menstrual cyclicity stops and steroid hormone levels wane, and there is a cessation of the abnormal uterine bleeding symptoms associated with fibroids. Most, but not all, patients have shrinkage of leiomyomas at menopause.
Patients on hormone therapy — Use of menopausal hormone therapy may cause some patients with leiomyomas to continue to have symptoms after menopause. The risk of symptoms may depend, in part, on the location of the fibroid (higher if submucosal ) and type of estrogen preparation (higher with transdermal estrogen in some studies [131,132] but not others ).
A systematic review including five randomized controlled trials found that postmenopausal hormone therapy was associated with some myoma growth, but this typically occurred without clinical symptoms . These findings were confirmed in a subsequent prospective study . Thus, the presence of leiomyomas is not a contraindication to use of postmenopausal hormone therapy and postmenopausal hormone therapy does not lead to development of new symptomatic fibroids in most patients. (See "Menopausal hormone therapy: Benefits and risks", section on 'Other possible risks'.)
IMPACT ON PATIENT AND SOCIETY
Quality of life — Patients with symptomatic fibroids report multiple symptoms as well as concerns about fibroids affecting relationships, employment, and overall health. In a systematic review of 18 randomized trials and 39 observational studies, patients with fibroids reported psychosocial stressors related to bodily pain, mental health, and social functioning, and had quality-of-life scores that were similar to, or lower (more severe) than, patients with other chronic diseases (eg, diabetes mellitus, breast cancer, cardiovascular disease) .
Compared with White patients, Black patients experience more severe disease based on their symptoms and have more extensive disease at the time of hysterectomy [17,65]. There is growing evidence of increases in symptomatology for Black patients with fibroids apart from those seeking surgical therapy, increased impairment of quality of life, different concerns regarding fibroids and the consequences of fibroid therapies, and less satisfaction with the information they receive about fibroids . Importantly, Black patients were almost three times as likely to be concerned about fertility and healthy pregnancy .
Economic impact — Uterine fibroids are costly to the health care system and the individual patient. Because they are the cause of 40 percent of hysterectomies, surgical costs and missed work days during recovery can add great expense to the treatment. Fibroids account for approximately USD $34 billion United States health care dollars annually . Annual excess cost per patient with fibroids was estimated at more than USD $4600, which included USD $771 in missed work days .
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Uterine fibroids (leiomyomas)".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Uterine fibroids (The Basics)")
●Beyond the Basics topics (see "Patient education: Uterine fibroids (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Terminology – Uterine leiomyomas (fibroids or myomas) are benign monoclonal tumors arising from the smooth muscle cells of the myometrium. Fibroids are typically described according to their location in the uterus (submucosal, intramural, subserosal, cervical) (figure 1 and figure 2). (See 'Terminology and location' above.)
●Prevalence – Uterine leiomyomas are the most common pelvic tumor in females. The incidence of leiomyomas parallels the life cycle changes of the reproductive hormones estrogen and progesterone. (See 'Prevalence' above and 'Reproductive and endocrine factors' above.)
●Clinical features – Symptoms attributable to uterine leiomyomas can generally be classified into three distinct categories: abnormal uterine bleeding (AUB), pelvic pressure and pain, and reproductive dysfunction. (See 'Clinical features' above.)
●Diagnosis – Uterine leiomyomas are a clinical diagnosis typically made based on a pelvic ultrasound finding of leiomyomas, although other imaging modalities may be used. The indication for pelvic imaging typically includes symptoms of AUB, pelvic pain or pressure, or infertility; some patients have an enlarged uterus on pelvic examination.
In general, pathology confirmation is not required to proceed with management, except in cases in which another more serious lesion is suspected, such as a uterine sarcoma or leiomyoma variant. Unfortunately, it is difficult to differentiate benign leiomyomas from these conditions, and thus, some cases will be wrongly diagnosed as leiomyomas. (See 'Diagnosis' above.)
●Imaging – Transvaginal ultrasound is the most widely used imaging modality for evaluating fibroids due to its availability and cost-effectiveness. Saline infusion sonography (sonohysterography) improves characterization of the extent of protrusion into the endometrial cavity by submucous myomas and allows identification of some intracavitary lesions not seen on routine ultrasonography. (See 'Imaging and endoscopy' above.)
●Postmenopausal patients – Relief of symptoms related to fibroids usually occurs at the time of menopause, when menstrual cyclicity stops and steroid hormone levels wane. Most, but not all, patients have shrinkage of leiomyomas at menopause. (See 'Postmenopausal patients' above.)
●Role of hormone therapy – Use of postmenopausal hormone therapy may cause some patients with leiomyomas to continue to have symptoms after menopause. Hormone therapy may be associated with an increase in size of existing myomas but not with the development of new myomas. (See 'Patients on hormone therapy' above.)
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