Overview of treatment of uterine leiomyomas Author Elizabeth A Stewart, MD Section Editor Robert L Barbieri, MD Deputy Editor Sandy J Falk, MD

Last literature review version 17.1: January 2009|This topic last updated: November 25, 2008(More)

INTRODUCTIONUterine leiomyomas are benign tumors. Since histological confirmation of the clinical diagnosis is not necessary in most cases, asymptomatic uterine leiomyomas can usually be followed without intervention [1] . Women with leiomyomas whose physicians prescribed "watchful waiting" experienced no significant change in symptoms or decline in quality of life, thereby providing some reassurance to women who are asymptomatic or have mild symptoms and choose to avoid intervention [2] .

Prophylactic therapy to avoid potential future complications from myomas or their treatment is not recommended [3] . Possible exceptions include women with significant submucosal leiomyomas who are contemplating pregnancy and women with ureteral compression leading to moderate or severe hydronephrosis. In these women, prophylactic myomectomy may prevent miscarriage or urinary tract obstruction.

Relief of symptoms (eg, abnormal uterine bleeding, pain, pressure) is the major goal in management of women with significant symptoms [4] . The type and timing of any intervention should be individualized, based upon factors such as [5] : Size of the myoma(s) Location of the myoma(s) Severity of symptoms Patient age Reproductive plans and obstetrical history

An overview of the treatment of uterine leiomyomas will be presented here. The clinical manifestations, diagnosis, and natural history of these tumors are reviewed elsewhere. (See "Epidemiology, clinical manifestations, diagnosis, and natural history of uterine leiomyomas").

EXPECTANT MANAGEMENTThere is no high quality data regarding follow-up of fibroids in patients who are asymptomatic or who decline medical or surgical treatment. We order an initial imaging study (usually an ultrasound) to confirm that a pelvic mass is a fibroid and not an ovarian mass. After an initial evaluation, we perform annual pelvic exams and, in patients with anemia or menorrhagia, check a complete blood count. If symptoms or uterine size are increasing, we proceed with further evaluation and patient counseling regarding treatment options. We also screen women with menorrhagia for hypothyroidism, a disease that is common in reproductive age women.

MEDICAL THERAPYA comprehensive evidence-based report noted "a remarkable lack of randomized trial data demonstrating the effectiveness of medical therapies in the management of women with symptomatic fibroids" [6] . Given the high prevalence of both leiomyomas and the use of gonadal steroid preparations (eg, contraception, management of menstrual cycle abnormalities), it is difficult to isolate the effect of these drugs on mild leiomyoma-related symptoms.

Anecdotal data suggest medical therapy provides adequate symptom relief in some women, primarily in situations where bleeding is the dominant or only symptom. In general, 75 percent of women get some improvement over one year of therapy, but long-term failure rates are high [7] . A systematic review observed that in trials where women were randomly assigned to oral medical therapy, almost 60 percent had undergone surgery by two years [8] .

A trial of medical therapy in women with mild symptoms and/or mildly enlarged uteri can also be useful for helping to distinguish symptoms primarily related to leiomyomas from those primarily due to a concurrent problem. This is especially true in patients in whom concomitant issues, such as oligoovulation, may be contributing to abnormal uterine bleeding or infertility. However, caution should be exercised when raising the level of steroid hormones from the physiologic baseline, as there is indirect evidence from postmenopausal women taking hormone replacement therapy that leiomyomas grow in this setting [9-12] .

Hormonal therapiesCombined hormonal contraceptives and progestational agents are commonly prescribed to regulate abnormal uterine bleeding, but appear to have limited efficacy in the treatment of uterine leiomyomas [13,14] . These drugs can be useful in some women, particularly those with coexisting problems (eg, dysmenorrhea or oligoovulation); but they do not appear to be effective in decreasing bulk symptoms. There is also evidence that, in some women, contraceptive steroids may be associated with a decreased risk of uterine fibroids; however, it is not clear that these agents are useful for either primary or secondary prevention [15] .

Steroid hormones influence the pathogenesis of leiomyomas, but the relationship is complex. As an example, although there are high levels of both estrogen and progesterone during pregnancy and with oral contraceptive use, both decrease the risk of developing new leiomyomas but may lead to leiomyoma growth. The specific hormonal compound, the timing and duration of exposure, the delivery method (endogenous, oral, transdermal, depot, local) and other factors may all be important.

Oral contraceptive pills (OCP)Many texts continue to suggest that oral contraceptive pills are contraindicated in women with uterine leiomyomas. However, clinical experience suggests some women with heavy menstrual bleeding associated with leiomyomas respond to OCP therapy. This, plus data that OCPs decrease the risk of forming new leiomyomas and reduce symptoms from other concurrent gynecologic conditions, suggests that a therapeutic trial may be appropriate before proceeding to more invasive therapies. The purported mechanism of action is via endometrial atrophy.

This approach should be reassessed if a woman has exacerbation of bulk-related symptoms on OCPs. Since most pill formulations appear to work similarly, switching to other formulations does not appear to be effective in the woman who does not respond to a short trial of one formulation.

Data are not available regarding treatment using other methods of contraceptive steroid delivery (eg, ring, patch). However, with vaginal administration (Nuva Ring), the uterus is likely to receive a higher dose of medication than other systemic tissues, which could affect how leiomyomas respond to hormone therapy.

Levonorgestrel-releasing intrauterine systemThere are no randomized trials evaluating the use of levonorgestrel-releasing intrauterine system (IUS) for the treatment of menorrhagia related to uterine leiomyomas. Observational studies and a systematic review have shown a reduction in uterine volume and bleeding, and an increase in hematocrit after placement of this IUS [8,16-18] . The device is widely used for control of heavy menstrual bleeding and is endorsed for this indication by many experts. The presence of intracavitary leiomyomas amenable to hysteroscopic resection is a contraindication to use. A second advantage of this treatment is that it provides contraception for women who do not desire pregnancy. (See "Approach to intrauterine contraception").

Progestin implants, injections, and pillsAs with OCPs, it is difficult to discern the effectiveness of progestin-only contraceptive steroids specifically for treatment of leiomyomas. As with the breast, progesterone is a growth factor for myomas and may even be more critical than estrogen. That being said, progestin-only contraceptives cause endometrial atrophy and thus provide relief of menstrual bleeding-related symptoms. They can be considered for treatment of mild symptoms, especially for women who need contraception. There is also evidence from a large cohort study that these agents may decrease the risk of leiomyoma formation in black women [19] .

In contrast to gonadotropin-releasing agonists and antagonists, most of these "contraceptives" provide continuous exposure to low doses of hormones, which should minimize deleterious effects (see "Gonadotropin-releasing hormone agonists" below and see "Gonadotropin-releasing hormone antagonists" below).

Gonadotropin-releasing hormone agonistsGonadotropin-releasing hormone (GnRH) agonists are the most effective medical therapy for uterine myomas. These drugs work by initially increasing the release of gonadotropins, followed by desensitization and downregulation to a hypogonadotropic, hypogonadal state that clinically resembles menopause. Most women will develop amenorrhea, improvement in anemia (if present), and a significant reduction (35 to 60 percent) in uterine size within three months of initiating this therapy, thus achieving improvement in both categories of myoma symptomatology [13,14,20] .

However, there is rapid resumption of menses and pretreatment uterine volume after discontinuation of GnRH agonists. In addition, significant symptoms can result from the severe hypoestrogenism that accompanies such therapy, including hot flashes, sleep disturbance, vaginal dryness, myalgias and arthralgias, and possible impairment of mood and cognition [13] . Bone loss leading to osteoporosis after long-term (12+ months) use is the most serious complication and most often limits therapy. A rule of thumb for women with endometriosis is that approximately 6 percent of bone is lost over 12 months of therapy and 3 percent is regained following the cessation of therapy [21] . However, women with leiomyomas tend to be older and heavier than women with endometriosis, thus they may have less bone loss.

Because of the rapid rebound in symptoms and side effects, GnRH agonists are primarily used as preoperative therapy. GnRH agonists are approved for administration for three to six months prior to leiomyoma-related surgery to facilitate the procedure and enable correction of anemia [22] . Reduction in uterine size can facilitate subsequent surgery by reducing intraoperative blood loss and by increasing the number of women who are candidates for a vaginal procedure, a transverse (rather than vertical) abdominal incision, or a minimally-invasive procedure. Since oral iron supplementation alone will improve the preoperative hematocrit in a significant number of patients, the cost and adverse effects of GnRH agonists must be weighed against their efficacy [23] . (See "Myomectomy", section on Use of GnRH agonists).

GnRH agonists should not be used preoperatively for every myoma surgery, but with a particular endpoint in mind (volume reduction, resolution of anemia, or both). Although many physicians reflexively plan three or six months of treatment, interval assessment of goals is optimal because of the variability of response. Continuing GnRH agonist for six months prior to abdominal myomectomy to effect volume reduction is not optimal treatment if there is no volume reduction by two to three months. Likewise, treatment of a 2.8 cm leiomyoma prior to surgery is not helpful if the hysteroscopic surgeon can easily resect a 3-centimeter leiomyoma.

The side effects of long-term GnRH agonist administration can be minimized during therapy by giving add-back therapy with an estrogen-progestin after the initial phase of downregulation. A phase of downregulation is necessary to achieve shrinkage of leiomyomas even though simultaneous administration of a GnRH agonist and steroids can work for other diseases, such as endometriosis. Low dose estrogen-progestin therapy, such as used for menopausal replacement (equivalent to 0.625 mg of conjugated estrogen and 2.5 of medroxyprogesterone acetate or 5 mg norethindrone acetate) maintains amenorrhea and the reduction in uterine volume, while preventing significant hypoestrogenic side effects (eg, osteoporosis, vasomotor symptoms) [24] .

Rarely, GnRH-agonists are used to provide short-term relief to women close to menopause or with acute medical contraindications to surgery [25] . The United States Food and Drug Administration has approved use of leuprolide preoperatively in women with leiomyomas, but not for medical management of these tumors. Options include Lupron Depo (3.75 mg/month intramuscularly for up to three months) and Lupron Depot-3 (11.25 mg as a single intramuscular injection that is effective for three months).

Gonadotropin-releasing hormone antagonistsSimilar clinical results have been achieved with GnRH antagonists, which compete with endogenous GnRH for pituitary binding sites [26-29] . The advantage of antagonists over agonists is the rapid onset of clinical effects without the characteristic initial flare-up observed with GnRH agonist treatment. However, in the United States, these agents are marketed at doses used for ovulation induction and long-acting preparations are not available. Thus, treatment of leiomyomas is cumbersome due to the need for frequent injections (the doses used for leiomyomas are quite different from those employed in fertility protocols).

MifepristoneThe antiprogestin mifepristone (RU-486) reduces uterine volume by 26 to 74 percent in women with leiomyomas, comparable to the reduction observed with GnRH agonists [30-34] . While high dose regimens give comparable rates of amenorrhea to GnRH agonists, lower doses achieve an amenorrhea rate of 40 to 70 percent and, in other women, produce a reduction in menstrual flow while maintaining cyclicity. There is accumulating evidence that mifepristone provides symptomatic relief and improved quality of life [31,33] .

However, as with GnRH antagonists, the doses of mifepristone currently marketed in the United States make off-label clinical treatment of leiomyomas difficult (200 mg once for termination of pregnancy versus 5 to 50 mg/day for three to six months for myoma reduction). Use of a compounding pharmacy is required and many are reluctant to provide this compound due to political, rather than medical, concerns [35] . With high dose regimens, adverse effects, such as endometrial hyperplasia and transient elevations in serum aminotransferases, have been reported; this appears to be a rare occurrence with low dose regimens [30] . Regrowth occurs slowly following cessation of the drug [33] .

Selective progesterone receptor modulators have shown promising results for treatment of leiomyomas in pilot studies [36-38] . Use of these agents led to a reduction in duration and intensity of bleeding and a decrease in leiomyoma volume without deprivation of estrogen. (See "Therapeutic use and adverse effects of progesterone receptor antagonists and selective progesterone receptor modulators", section on Uterine myoma).

Danazol and gestrinoneAndrogenic steroids may be an effective treatment of leiomyoma symptoms in some women, but are associated with frequent side effects.

Danazol is a 19-nortestosterone derivative with androgenic and progestin-like effects. Its mechanisms of action include inhibition of pituitary gonadotropin secretion and direct inhibition of endometriotic implant growth, and direct inhibition of ovarian enzymes responsible for estrogen production. Since it induces amenorrhea and has been shown to have a direct effect on endometriosis implants, danazol likely inhibits autologous endometrium. Danazol may control anemia related to leiomyoma-related menorrhagia, but it does not appear to reduce uterine volume. Side effects are common (eg, weight gain, muscle cramps, decreased breast size, acne, hirsutism, oily skin, decreased high density lipoprotein levels, increased liver enzymes, hot flashes, mood changes, depression).

Another androgenic steroid, gestrinone, decreases myoma volume and induces amenorrhea in women with leiomyomas [39] . An advantage of this drug is that there is a carry-over effect after it is discontinued. In one study, as an example, uterine volume remained lower than pretreatment values 18 months after discontinuation of therapy in 89 percent of women treated for six months [39] . Gestrinone is not available in the United States.

RaloxifeneThe efficacy of selective estrogen receptor modulators for treatment of leiomyomas is unclear; while preclinical testing in animal models and treatment of postmenopausal women has been encouraging, clinical trials in reproductive age women have been less convincing [40] . A possible increased risk of venous thrombosis when high doses of raloxifene are used is an additional concern.

By comparison, studies in premenopausal women have been conflicting. In a trial in which 100 symptomatic premenopausal women were randomly assigned to receive a GnRH analog with either raloxifene or placebo, the raloxifene group achieved a greater reduction in leiomyoma size than the placebo group, but this did not result in a greater reduction in leiomyoma-related symptoms [41] . This trial did not address the efficacy of raloxifene alone. Another trial by the same authors in asymptomatic premenopausal women found no significant effect of raloxifene alone (60 to 180 mg/day for three to six months) on leiomyoma size or uterine bleeding compared to placebo [42] A smaller trial (25 patients) found raloxifene (180 mg/day for three months) inhibited leiomyoma growth in premenopausal women compared to untreated controls, in whom leiomyomas continued to enlarge [43] .

Larger controlled trials over extended treatment intervals should be performed to better ascertain the effect of raloxifene on leiomyomas in premenopausal women [44] .

Aromatase inhibitorsCase reports and small series have described shrinkage of symptomatic leiomyomas in perimenopausal women given aromatase inhibitors [45,46] . Although these agents have fewer side effects than many of the hormonal therapies discussed above, their potential role in management of uterine myomas requires further study to establish the duration of response, risks, and cost-effectiveness.

Antifibrinolytic agentsAntifibrinolytic agents, which are useful in the treatment of idiopathic menorrhagia, have not been well studied in leiomyoma related menorrhagia. These drugs are not available in the United States, but are widely used for the control of heavy menstrual flow elsewhere and have shown efficacy in treatment of heavy menstrual bleeding [47] . (See "Menorrhagia").

Nonsteroidal antiinflammatory drugsNonsteroidal antiinflammatory drugs (NSAIDs) have not been extensively studied in leiomyoma-related menorrhagia. NSAIDs do not appear to reduce blood loss in women with myomas [48,49] , but because they decrease painful menses, they can be useful in this population.

Future directionsThe biology of uterine leiomyomas has traditionally been explained in terms of steroid hormones; thus, virtually all current medical therapies are based upon manipulation of these hormones. However, an expanded view of the biology of this benign tumor (eg, the specific genes that are dysregulated) may open new avenues of pharmaceutical intervention and ultimately lead to new strategies for prevention [50,51] . (See "Pathogenesis of uterine leiomyomas").

Regulation of growth factor pathways is one area of innovative treatment. There is evidence that interferons can reverse the proliferative effects of basic fibroblast growth factor on leiomyoma cells in culture [52] . In a case report, a woman undergoing treatment with interferon-alfa for hepatitis C had dramatic and sustained shrinkage of a uterine leiomyoma after seven months of therapy [53] .

SURGERY

IndicationsSurgery is the mainstay of therapy for leiomyomas. Hysterectomy is the definitive procedure; myomectomy by various techniques, endometrial ablation, uterine artery embolization (UAE), magnetic resonance-guided focused-ultrasound surgery (MRgFUS) and myolysis are alternative procedures. (See "Myomectomy" and see "Endometrial ablation").

The following are indications for surgical therapy: Treatment of abnormal uterine bleeding, pain, or pressure symptoms (See "Epidemiology, clinical manifestations, diagnosis, and natural history of uterine leiomyomas", sections on Increased uterine bleeding and Pelvic pressure and pain) Treatment of infertility or recurrent pregnancy loss (See "Reproductive issues in women with uterine leiomyomas") Evaluation when there is suspicion of malignancy Both benign leiomyoma and malignant sarcomas can present as a uterine mass, and current diagnostic strategies are not able to definitely distinguish between the two. Most women with a uterine mass, even those with a rapidly enlarging uterus or mass, do NOT have a sarcoma [54] , and a rapidly enlarging mass alone in a premenospausal woman is not an indication for surgery [55] . It is important to confirm that a pelvic mass is uterine, and not adnexal, before deferring surgery.

Surgery should be considered in postmenopausal women with a new or enlarging pelvic mass, abnormal bleeding, and pelvic pain, where the incidence of sarcoma is higher (1 to 2 percent) [56] . Other risk factors for sarcoma formation include prior pelvic irradiation, tamoxifen use or the presence of cutaneous leiomyomas indicating possible HLRCC syndrome (Hereditary Leiomyomatosis and Renal Cell Carcinoma) [57-59] .

While not definitive, imaging with magnetic resonance can, in some cases, provide additional evidence for or against malignancy [60] . In one series, an endometrial biopsy was useful in diagnosis in approximately one third of sarcomas [61] . Failure to respond to conservative therapy, such as GnRH-agonist therapy and uterine artery embolization, also raises the suspicion for malignancy. (See "Uterine sarcoma: Classification, clinical manifestations, and diagnosis").

The American College of Obstetricians has concluded that there is insufficient evidence to support hysterectomy for asymptomatic leiomyomas solely to improve detection of adnexal masses, to prevent impairment of renal function, or to rule out malignancy [4] .

HysterectomyWe suggest hysterectomy for (1) women with acute hemorrhage who do not respond to other therapies; (2) women who have completed childbearing and have current or increased future risk of other diseases (cervical dysplasia, endometriosis, adenomyosis, endometrial hyperplasia, or increased risk of uterine or ovarian cancer) that would be eliminated or decreased by hysterectomy; (3) women who have failed prior minimally invasive therapy for leiomyomas; and (4) women who have completed childbearing and have significant symptoms, multiple leiomyomas, and a desire for a definitive end to symptomatology.

Leiomyomas are the most common indication for hysterectomy, accounting for 30 percent of hysterectomies in white and over 50 percent of hysterectomies in black women [62] . The cumulative risk of a hysterectomy for leiomyomas for all women between ages 25 and 45 is 7 percent, but is 20 percent in black women.

The main advantage of hysterectomy over other invasive interventions is that it eliminates both current symptoms and the chance of recurrent problems from leiomyomas. For many women who have completed childbearing, this freedom from future problems makes hysterectomy an attractive option.

The morbidity associated with hysterectomy may outweigh the benefits when there is a solitary subserous myoma, a pedunculated myoma, or a submucosal myoma readily excised via laparoscopy or hysteroscopy [63] . In these cases, an endoscopic myomectomy is a less morbid option. Avoiding the morbidity of hysterectomy should also be considered by women whose only symptom is bleeding, or who are perimenopausal; these women are often effectively treated with either a levonorgestrel-releasing IUS or endometrial ablation.

MyomectomyMyomectomy is an option for women who have not completed childbearing or otherwise wish to retain their uterus. The classic approach has been through a laparotomy incision, but laparoscopic procedures are becoming more common. Myomectomy complications appear to increase as the number of leiomyomas removed increases, but the exact relationship is unclear [62] .

Although myomectomy is an effective therapy for menorrhagia and pelvic pressure, the disadvantage of this procedure is the significant risk that more leiomyomas will develop from new clones of abnormal myocytes. Five years after myomectomy, 50 to 60 percent of patients will have new myomas detected by ultrasound [64,65] , and 10 to 25 percent will require a second major surgery after the first myomectomy [65-69] . This risk probably underestimates the true prevalence of myomata as assessed by systematic ultrasound investigation. If minimally invasive procedures are included, then approximately one-third of women undergoing abdominal myomectomy will have a second surgical procedure [70] . Risk factors for subsequent uterine surgery include uterine size less than 12 menstrual weeks at the time of initial surgery and weight gain in excess of 14 kg after age 18; the latter association may reflect greater estrogen exposure. In one study, the incidence of a second surgical procedure in women with either of these risk factors was 40 to 50 percent versus 17 to 20 percent in women with uterine size greater than 12 weeks or weight gain less than 4.5 kg [70] . Thus, performing myomectomy while the uterus is relatively small may result in a higher overall rate of surgery. However, others have reported different findings whereby the risk of recurrence was highest in women who preoperatively had larger uterine sizes and multiple leiomyomas [65] .

The risk of recurrence appears to be lower when only one leiomyoma is present and removed and in women who give birth after a myomectomy, but data are limited [66,71] .

Route Abdominal myomectomy A transabdominal myomectomy is the treatment of choice when there are multiple myomas, the uterus is significantly enlarged (myomas greater than 5 to 8 cm or volume greater than 16 weeks' size), or the myomas are deep and intramural [3] . The operative time, blood loss, and hospital stay are comparable to that with abdominal hysterectomy [72,73] . The risk of unplanned hysterectomy at the time of myomectomy is less than 1 percent for experienced surgeons [4] . (See "Myomectomy", section on Abdominal myomectomy).

After abdominal myomectomy, the risk of uterine rupture prior to labor is very low (about 0.002 percent) compared to after classical cesarean delivery (about 3.7 percent [74] ), although these data are based upon small series without complete pregnancy follow-up [75,76] . The common clinical practice of counseling women who have had a myomectomy with a transmural uterine incision to undergo an elective cesarean delivery clearly biases and under-reports the risk of rupture at term. (See "Myomectomy").

Women who undergo myomectomy with significant uterine disruption should wait several months before attempting to conceive; recommendations for delay range from three to six months. Also, if a woman is having difficulty conceiving following a myomectomy, early assessment of the uterine cavity and fallopian tubes with a hysterosalpingogram is advisable [63] . Myomectomy, particularly near the oviduct, can cause adhesions that may impair fertility. Laparoscopic myomectomy Laparoscopic myomectomy is an option in women with a uterus less than 17 weeks' size or with a small number of subserosal or intramural leiomyomas. The uterus must be small enough to allow visualization of the procedure through an endoscope. Factors reported to lead to an increased risk of conversion to an open procedure include size 5.0 cm, intramural or anterior location, and preoperative use of a GnRH-agonist [77] .

Whether reapproximation of the myometrium via laparoscopic suturing gives the uterine wall the same strength as multilayer closure at laparotomy is an area of controversy [76,78,79] . Ten cases of uterine rupture in women who underwent laparoscopic myomectomy have been reported, one was at 17 weeks of gestation and the remainder were at 27 to 35.5 weeks [80] . On the other hand, one of the largest series of pregnancies after laparoscopic myomectomy reported no uterine ruptures in 106 deliveries; 27 of the deliveries were vaginal. Only 10 uterine cavities in this series had been entered at myomectomy [80] .

Until further data are available, we suggest avoiding laparoscopic myomectomy in women whose primary goal is to achieve a pregnancy, especially when there is a deeply intramural leiomyoma. The experience of the surgeon with laparoscopic suturing and the availability of a robotic approach may also factor into this decision given that laparoscopic suturing is a highly complex skill. (See "Myomectomy", section on Laparoscopic myomectomy). Hysteroscopic myomectomy Hysteroscopic myomectomy is the procedure of choice for type 0 (entirely within the endometrial cavity) and I (at least 50 percent intracavitary) submucous myomas [3,81] . (See "Overview of hysteroscopy").

Although this technique requires highly skilled practitioners, it has several advantages compared to abdominal procedures:

(1)It is performed as same day surgery (2)Local anesthetic and sedation can be used (3)The recuperation period is very short (4) Good relief of symptoms is obtained. In one large series, fewer than 16 percent of women treated for menorrhagia underwent a second surgery in the nine-year follow-up period [82] .(5) Fertility rates are excellent and there have been no case reports of uterine rupture after hysteroscopic myomectomy [83] .

Type II (less than 50 percent of their mass in the endometrial cavity) submucous myomas may sometimes be approached hysteroscopically in the hands of expert surgeons, but often require multiple procedures [81] .

Endometrial ablationIn women who have completed childbearing, endometrial ablation, either alone or in combination with hysteroscopic myomectomy, is an option for management of bleeding abnormalities. Since intramural and subserosal leiomyomas are not affected by this procedure, bulk or pressure symptoms are unlikely to improve.

Some devices for endometrial ablation are designed only for use in a normal size cavity and cannot conform to an irregular cavity. When a submucous leiomyoma is present, microwave ablation is possible if the leiomyoma is less than 3 cm and leiomyoma resection with rollerball ablation is indicated if the leiomyoma is greater than 3 cm. (See "Endometrial ablation").

Although most case series of endometrial ablation have excluded women with significant myomas, one study that examined endometrial ablation with hysteroscopic myomectomy reported only an 8 percent risk for a second surgery after a mean of six years of follow-up [82] .

MyolysisMyolysis refers to laparoscopic thermal coagulation or cryoablation (cryomyolysis) of leiomyoma tissue [84-86] . This technique is easier to master than myomectomy, which requires suturing. However, localized tissue destruction without repair may increase the chance of subsequent adhesion formation or rupture during pregnancy [87] . (See "Myomectomy", section on Myolysis).

Candidates for myolysis are women with fewer than four leiomyomas with the largest leiomyoma less than 10 cm in diameter [3] . Fertility and pregnancy outcome after myolysis are not known; cases of both successful pregnancy and uterine rupture have been reported [3,88] . Therefore, this procedure should be reserved for women who have completed childbearing.

Myolysis combined with endometrial ablation is a more effective therapy than either procedure alone. In women with menorrhagia, a descriptive study that compared ablation alone versus with the combined procedure found that the risks of a second surgery were 38 and 13 percent, respectively [89] .

Uterine artery occlusionOcclusion of uterine vessels either via laparoscopy or a vaginally-placed clamp has been proposed as an alternative to uterine artery embolization (UAE), but experience is limited [90-94] . The advantages of this approach over UAE are that it avoids introduction of foreign bodies (eg, polyvinyl alcohol particles, coils, Gelfoam), and it may be associated with less postoperative pain. With laparoscopic approaches, assessment of the pelvis for other pathology is an advantage, the disadvantage is that it requires a surgical approach and general anesthesia. With the transvaginal approach, ureteral injury is a potential problem.

INTERVENTIONAL RADIOLOGY

Uterine artery embolizationUterine artery embolization (UAE), or uterine fibroid embolization (UFE), is a minimally invasive option for management of leiomyoma-related symptoms; excellent technical and clinical success has been reported. It is an effective option for women who are not surgical candidates or who wish to preserve their uterus, but the risks associated with subsequent pregnancy are unclear. There are a number of reports of successful pregnancies following UAE, but there have been reports of disorders of placentation and ovarian damage in case series of young women. However, for women in late perimenopause who view cessation of menses as an advantage, this effect on ovarian reserve may be a benefit rather than a side effect.

A systematic review concluded that women undergoing UAE have a shortened hospital stay and a quicker return to work than those undergoing hysterectomy or myomectomy [95] . However, they have more complications, unscheduled visits, and readmissions. Data also suggest that women with larger uteri and/or more leiomyomas at baseline are at greater risk of failure [96,97] . Like the situation with endometrial ablation, there appears to be a relatively high rate of reintervention for treatment failure [98] . Research is needed to see if better patient selection can minimize this risk. (See "Uterine fibroid embolization").

Magnetic resonance guided focused ultrasoundMagnetic resonance guided focused ultrasound surgery (eg, ExAblate 2000) is a more recent option for the treatment of uterine leiomyomas in premenopausal women who have completed childbearing. This noninvasive thermoablative technique converges multiple waves of ultrasound energy on a small volume of tissue, which leads to its thermal destruction, and can be performed as an outpatient procedure [99-102] . This system is not indicated for leiomyomas which are resectable with a hysteroscope, heavily calcified, in women contemplating future pregnancy or when intervening bowel of bladder could be damaged by treatment.

Magnetic resonance imaging gives good visualization of the anatomic structures and provides real-time thermal monitoring to optimize tissue destruction. Symptomatic improvement is observed within the first three months postprocedure, and this improvement has been maintained at least through 24 months follow-up, with more complete ablation leading to better outcomes [103-105] . Studies are needed to determine long-term outcome and optimal candidates for this procedure; comparative studies are also needed. Data on pregnancy outcome are limited to case reports [106] . Adverse event rates appear to be decreased with increased experience, despite more extensive treatment [104] . The procedure is time consuming and costly, but short-term morbidity is low and recovery is rapid.

INFORMATION FOR PATIENTSEducational materials on this topic are available for patients. (See "Patient information: Fibroids"). We encourage you to print or e-mail this topic review, or to refer patients to our public web site, www.uptodate.com/patients, which includes this and other topics.

SUMMARY AND RECOMMENDATIONSA research group found over 1000 articles in the literature on management of leiomyomas, but was unable to perform meta-analysis or determine clear evidenced-based answers to any of their nine predetermined clinical questions because the studies had multiple design and reporting flaws [107] . Therefore, treatment recommendations for management of uterine myomas are primarily based upon outcomes described in nonrandomized, and often uncontrolled, reports. Choice of treatment modality is also based upon the size and location of the leiomyomas (large versus small, submucosal/intramural/subserosal), type of leiomyoma-related symptoms (bleeding, pain, pressure, infertility), age of the patient (premenopausal, perimenopausal, postmenopausal), and patient preference (cost, convenience, desire for uterine conservation, side effects).

Asymptomatic women We suggest expectant management of asymptomatic women, except in the case of a woman with moderate or severe hydronephrosis or a woman with a hysteroscopically-resectable submucous leiomyoma who is pursuing pregnancy (Grade 2C). (See "Expectant management" above).

Postmenopausal women In the absence of hormonal therapy, leiomyomas generally become smaller and asymptomatic in postmenopausal women; therefore, intervention is not usually indicated. We suggest evaluation to exclude sarcoma in a postmenopausal woman with a new or enlarging pelvic mass (Grade 2C). The incidence of sarcoma is 1 to 2 percent in women with a new or enlarging pelvic mass, abnormal uterine bleeding, and pelvic pain. (See "Surgery" above).

Submucosal leiomyomas We recommend hysteroscopic myomectomy for women with appropriate submucosal leiomyomas that are symptomatic (eg, bleeding, miscarriage) (Grade 1C). This procedure allows future childbearing, usually without compromising the integrity of the myometrium, but is also an appropriate option in women who have completed childbearing since it is minimally invasive. Abdominal myomectomy is performed in women with significant symptoms and a submucous leiomyoma(s) not amenable to hysteroscopic resection. (See "Myomectomy" above).

Premenopausal women

Fertility optimization or preservation is desired Given the lack of information about the safety of pregnancy after other invasive procedures, we recommend abdominal myomectomy for treatment of symptomatic intramural and subserosal leiomyomas in women who wish to preserve their childbearing potential and who have no major contraindications to a surgical approach (Grade 1B). Hysteroscopic myomectomy is the preferred approach to submucosal leiomyomas. (See "Myomectomy" above).

However, for women for whom risk of intraoperative conversion to hysterectomy is high, or women who are considering a future pregnancy but will accept impaired fertility in exchange for an expedited recovery phase, other options such as uterine artery embolization and magnetic resonance guided focused ultrasound may be considered appropriate treatment options. (See "Uterine artery embolization" above and see "Magnetic resonance guided focused ultrasound" above).

Laparoscopic myomectomy is an option for women with a uterus less than 17 weeks' size or with a small number of subserosal or intramural leiomyomas. Future childbearing is possible; however, the integrity of the uterine incision during pregnancy has not been evaluated adequately and may be inferior to abdominal myomectomy. Due to reports of uterine rupture in pregnancy following some laparoscopic myomectomies, surgeons should discuss the risks and benefits of each option with patients, including possible risk of uterine rupture, as well as provide information regarding their experience with laparoscopic suturing.

Fertility preservation is not desired Hysterectomy is the definitive procedure for relief of symptoms and prevention of recurrent leiomyoma-related problems. (See "Hysterectomy" above).

We suggest use of GnRH agonists prior to a potentially complicated hysterectomy (or myomectomy) if the surgeon feels reduction in uterine/myoma volume will significantly facilitate the procedure or if there is significant anemia which has not responded to iron therapy (Grade 2B). (See "Gonadotropin-releasing hormone agonists" above). For women with abnormal uterine bleeding related to leiomyomas who wish to undergo the least invasive procedure, we suggest a trial of placement of a levonorgestrel-releasing intrauterine contraception over other drug therapies (Grade 2C). (See "Medical therapy" above and see "Levonorgestrel-releasing intrauterine system" above). Several more invasive options, both surgical and using interventional radiology, are available to symptomatic women (bleeding, pain, pressure) who have completed childbearing but wish to retain their uterus. There is no high quality evidence to recommend one procedure over another. (See "Surgery" above and see "Interventional radiology" above).

Since fertility and pregnancy outcome may be adversely affected after many of these procedures, we suggest not performing these procedures (other than myomectomy) for women considering future pregnancy (Grade 2C).

Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES Parker, WH. Uterine myomas: management. Fertil Steril 2007; 88:255. Carlson, KJ, Miller, BA, Fowler, FJ Jr. The Maine Women's Health Study: I. Outcomes of hysterectomy. Obstet Gynecol 1994; 83:556. Lefebvre, G, Vilos, G, Allaire, C, et al. The management of uterine leiomyomas. J Obstet Gynaecol Can 2003; 25:396. American College of Obstetricians and Gynecologists. Surgical alternatives to hysterectomy in the management of leiomyomas. ACOG practice bulletin 16. ACOG 2000; Washington, DC. Stewart, EA. Uterine fibroids. Lancet 2001; 357:293. Viswanathan, M, Hartmann, K, McKoy, N, et al. Management of uterine fibroids: an update of the evidence. Evid Rep Technol Assess (Full Rep) 2007; :1. Carlson, KJ, Miller, BA, Fowler, FJ Jr. The Maine Women's Health Study: II. Outcomes of nonsurgical management of leiomyomas, abnormal bleeding, and chronic pelvic pain. Obstet Gynecol 1994; 83:566. Marjoribanks, J, Lethaby, A, Farquhar, C. Surgery versus medical therapy for heavy menstrual bleeding. Cochrane Database Syst Rev 2006; :CD003855. Sener, AB, Seckin, NC, Ozmen, S, et al. The effects of hormone replacement therapy on uterine fibroids in postmenopausal women. Fertil Steril 1996; 65:354. Polatti, F, Viazzo, F, Colleoni, R, Nappi, RE. Uterine myoma in postmenopause: a comparison between two therapeutic schedules of HRT. Maturitas 2000; 37:27. Fedele, L, Bianchi, S, Raffaelli, R, Zanconato, G. A randomized study of the effects of tibolone and transdermal estrogen replacement therapy in postmenopausal women with uterine myomas. Eur J Obstet Gynecol Reprod Biol 2000; 88:91. Palomba, S, Sena, T, Morelli, M, et al. Effect of different doses of progestin on uterine leiomyomas in postmenopausal women. Eur J Obstet Gynecol Reprod Biol 2002; 102:199. Friedman, AJ, Barbieri, RL, Doubilet, PM, et al. A randomized, double-blind trial of a gonadotropin releasing-hormone agonist (leuprolide) with or without medroxyprogesterone acetate in the treatment of leiomyomata uteri. Fertil Steril 1988; 49:404. Carr, BR, Marshburn, PB, Weatherall, PT, et al. An evaluation of the effect of gonadotropin-releasing hormone analogs and medroxyprogesterone acetate on uterine leiomyomata volume by magnetic resonance imaging: a prospective, randomized, double blind, placebo-controlled, crossover trial. J Clin Endocrinol Metab 1993; 76:1217. Marshall, LM, Spiegelman, D, et al. A prospective study of reproductive. Fertil Steril 1998; 70:432. Grigorieva, V, Chen-Mok, M, Tarasova, M, Mikhailov, A. Use of a levonorgestrel-releasing intrauterine system to treat bleeding related to uterine leiomyomas. Fertil Steril 2003; 79:1194. Starczewski, A, Iwanicki, M. [Intrauterine therapy with levonorgestrel releasing IUD of women with hypermenorrhea secondary to uterine fibroids]. Ginekol Pol 2000; 71:1221. Magalhaes, J, Aldrighi, JM, de Lima, GR. Uterine volume and menstrual patterns in users of the levonorgestrel-releasing intrauterine system with idiopathic menorrhagia or menorrhagia due to leiomyomas. Contraception 2007; 75:193. Wise, LA, Palmer, JR, Harlow, BL, Spiegelman, D, et al. Reproductive factors, hormonal contraception, and risk of uterine leiomyomata in African-American women: a prospective study. Am J Epidemiol 2004; 159:113. Minaguchi, H, Wong, JM, Snabes, MC. Clinical use of nafarelin in the treatment of leiomyomas. A review of the literature. J Reprod Med 2000; 45:481. Surrey, ES, Hornstein, MD. Prolonged GnRH agonist and add-back therapy for symptomatic endometriosis: long-term follow-up. Obstet Gynecol 2002; 99:709. Lethaby, A, Vollenhoven, B, Sowter, M. Efficacy of pre-operative gonadotrophin hormone releasing analogues for women with uterine fibroids undergoing hysterectomy or myomectomy: a systematic review. BJOG 2002; 109:1097. Stovall, TG, Muneyyirci-Delale, O, Summitt, RL Jr, Scialli, AR. GnRH agonist and iron versus placebo and iron in the anemic patient before surgery for leiomyomas: a randomized controlled trial. Leuprolide Acetate Study Group. Obstet Gynecol 1995; 86:65. Thomas, EJ. Add-back therapy for long-term use in dysfunctional uterine bleeding and uterine fibroids. Br J Obstet Gynaecol 1996; 103 Suppl 14:18. de Aloysio, D, Altieri, P, Pretolani, G, et al. The combined effect of a GnRH analog in premenopause plus postmenopausal estrogen deficiency for the treatment of uterine leiomyomas in perimenopausal women. Gynecol Obstet Invest 1995; 39:115. Felberbaum, RE, Germer, U, Ludwig, M, et al. Treatment of uterine fibroids with a slow-release formulation of the gonadotrophin releasing hormone antagonist Cetrorelix. Hum Reprod 1998; 13:1660. Gonzalez-Barcena, D, Alvarez, RB, Ochoa, EP, et al. Treatment of uterine leiomyomas with luteinizing hormone-releasing hormone antagonist Cetrorelix. Hum Reprod 1997; 12:2028. Flierman, PA, Oberye, JJ, van der, Hulst VP, de Blok, S. Rapid reduction of leiomyoma volume during treatment with the GnRH antagonist ganirelix. BJOG 2005; 112:638. Felberbaum, RE, Kupker, W, Krapp, M, et al. Preoperative reduction of uterine fibroids in only 16 days by administration of a gonadotrophin-releasing hormone antagonist (Cetrotide). Reprod Biomed Online 2001; 3:14. Steinauer, J, Pritts, EA, Jackson, R, Jacoby, AF. Systematic review of mifepristone for the treatment of uterine leiomyomata. Obstet Gynecol 2004; 103:1331. Fiscella, K, Eisinger, SH, Meldrum, S, et al. Effect of mifepristone for symptomatic leiomyomata on quality of life and uterine size: a randomized controlled trial. Obstet Gynecol 2006; 108:1381. Murphy, AA, Kettel, LM, Morales, AJ, et al. Regression of uterine leiomyomata in response to the antiprogesterone RU 486. J Clin Endocrinol Metab 1993; 76:513. Eisinger, SH, Bonfiglio, T, Fiscella, K, et al. Twelve-month safety and efficacy of low-dose mifepristone for uterine myomas. J Minim Invasive Gynecol 2005; 12:227. Carbonell Esteve, JL, Acosta, R, Heredia, B, et al. Mifepristone for the treatment of uterine leiomyomas: a randomized controlled trial. Obstet Gynecol 2008; 112:1029. Hodgen, GD. Antiprogestins: the political chemistry of RU486. Fertil Steril 1991; 56:394. Chwalisz, K, Perez, MC, Demanno, D, et al. Selective progesterone receptor modulator development and use in the treatment of leiomyomata and endometriosis. Endocr Rev 2005; 26:423. Chwalisz, K, Larsen, L, Mattia-Goldberg, C, et al. A randomized, controlled trial of asoprisnil, a novel selective progesterone receptor modulator, in women with uterine leiomyomata. Fertil Steril 2007; 87:1399. Levens, ED, Potlog-Nahari, C, Armstrong, AY, et al. CDB-2914 for Uterine Leiomyomata Treatment: A Randomized Controlled Trial. Obstet Gynecol 2008; 111:1129. Coutinho, EM, Goncalves, MT. Long-term treatment of leiomyomas with gestrinone. Fertil Steril 1989; 51:939. Palomba, S, Sammartino, A, Di Carlo, C, et al. Effects of raloxifene treatment on uterine leiomyomas in postmenopausal women. Fertil Steril 2001; 76:38. Palomba, S, Russo, T, Orio, F Jr, et al. Effectiveness of combined GnRH analogue plus raloxifene administration in the treatment of uterine leiomyomas: a prospective, randomized, single-blind, placebo-controlled clinical trial. Hum Reprod 2002; 17:3213. Palomba, S, Orio, F Jr, Morelli, M, et al. Raloxifene administration in premenopausal women with uterine leiomyomas: a pilot study. J Clin Endocrinol Metab 2002; 87:3603. Jirecek, S, Lee, A, Pavo, I, et al. Raloxifene prevents the growth of uterine leiomyomas in premenopausal women. Fertil Steril 2004; 81:132. Lingxia, X, Taixiang, W, Xiaoyan, C. Selective estrogen receptor modulators (SERMs) for uterine leiomyomas. Cochrane Database Syst Rev 2007; :CD005287. Shozu, M, Murakami, K, Segawa, T, et al. Successful treatment of a symptomatic uterine leiomyoma in a perimenopausal woman with a nonsteroidal aromatase inhibitor. Fertil Steril 2003; 79:628. Varelas, FK, Papanicolaou, AN, Vavatsi-Christaki, N, et al. The effect of anastrazole on symptomatic uterine leiomyomata. Obstet Gynecol 2007; 110:643. Lethaby, A, Farquhar, C, Cooke, I. Antifibrinolytics for heavy menstrual bleeding. Cochrane Database Syst Rev 2000:CD000249. Makarainen, L, Ylikorkala, O. Primary and myoma-associated menorrhagia: role of prostaglandins and effects of ibuprofen. Br J Obstet Gynaecol 1986; 93:974. Ylikorkala, O, Pekonen, F. Naproxen reduces idiopathic but not fibromyoma-induced menorrhagia. Obstet Gynecol 1986; 68:10. Niu, H, Simari, RD, Zimmermann, EM, Christman, GM. Nonviral vector-mediated thymidine kinase gene transfer and ganciclovir treatment in leiomyoma cells. Obstet Gynecol 1998; 91:735. Al-Hendy, A, Lee, EJ, Wang, HQ, Copland, JA. Gene therapy of uterine leiomyomas: Adenovirus-mediated expression of dominant negative estrogen receptor inhibits tumor growth in nude mice. Am J Obstet Gynecol 2004; 191:1621. Lee, BS, Stewart, EA, Sahakian, M, Nowak, RA. Interferon-alpha is a potent inhibitor of basic fibroblast growth factor-stimulated cell proliferation in human uterine cells. Am J Reprod Immunol 1998; 40:19. Minakuchi, K, Kawamura, N, Tsujimura, A, Ogita, S. Remarkable and persistent shrinkage of uterine leiomyoma associated with interferon alfa treatment for hepatitis [letter]. Lancet 1999; 353:2127. Parker, WH, Fu, YS, Berek, JS. Uterine sarcoma in patients operated on for presumed leiomyoma and rapidly growing leiomyoma. Obstet Gynecol 1994; 83:414. ACOG practice bulletin. Alternatives to hysterectomy in the management of leiomyomas. Obstet Gynecol 2008; 112:387. Leibsohn, S, d'Ablaing, G, Mishell, DR Jr, Schlaerth, JB. Leiomyosarcoma in a series of hysterectomies performed for presumed uterine leiomyomas. Am J Obstet Gynecol 1990; 162:968. Wysowski, DK, Honig, SF, Beitz, J. Uterine sarcoma associated with tamoxifen use. N Engl J Med 2002; 346:1832. Tomlinson, IP, Alam, NA, Rowan, AJ, et al. Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat Genet 2002; 30:406. Stewart, EA, Morton, CC. The Genetics of Uterine Leiomyomas: What Clinicians Need to Know. Obstet Gynecol 2006; 107:917. Tanaka, YO, Nishida, M, Tsunoda, H, et al. Smooth muscle tumors of uncertain malignant potential and leiomyosarcomas of the uterus: MR findings. J Magn Reson Imaging 2004; 20:998. Schwartz, LB, Diamond, MP, Schwartz, PE. Leiomyosarcomas: clinical presentation. Am J Obstet Gynecol 1993; 168:180. Management of Uterine Fibroids. Summary, Evidence Report/Technology Assessment: Number 34. AHRQ Publication No. 01-E051, January 2001. Agency for Healthcare Research and Quality, Rockville, MD. www.ahrq.gov/clinic/epcsums/utersumm.htm (Accessed 3/7/05). Wallach, EE, Vlahos, NF. Uterine myomas: an overview of development, clinical features, and management. Obstet Gynecol 2004; 104:393. Fedele, L, Parazzini, F, Luchini, L, et al. Recurrence of fibroids after myomectomy: a transvaginal ultrasonographic study. Hum Reprod 1995; 10:1795. Hanafi, M. Obstet Gynecol 2005; 105:877. Malone, LJ. Myomectomy: Recurrence after removal of solitary and multiple myomas. Obstet Gynecol 1969; 34:200. Buttram, VC Jr. Uterine leiomyomata--aetiology, symptomatology and management. Prog Clin Biol Res 1986; 225:275. Acien, P, Quereda, F. Abdominal myomectomy: results of a simple operative technique. Fertil Steril 1996; 65:41. Fauconnier, A, Chapron, C, Babaki-Fard, K, Dubuisson, JB. Recurrence of leiomyomata after myomectomy. Hum Reprod Update 2000; 6:595. Stewart, EA, Faur, AV, Wise, LA, et al. Predictors of subsequent surgery for uterine leiomyomata after abdominal myomectomy(1). Obstet Gynecol 2002; 99:426. Candiani, GB, Fedele, L, Parazzini, F, Villa, L. Risk of recurrence after myomectomy. Br J Obstet Gynaecol 1991; 98:385. Hillis, SD, Marchbanks, PA, Peterson, HB. Uterine size and risk of complications among women undergoing abdominal hysterectomy for leiomyomas. Obstet Gynecol 1996; 87:539. Iverson, RE Jr, Chelmow, D, Strohbehn, K, et al. Relative morbidity of abdominal hysterectomy and myomectomy for management of uterine leiomyomas. Obstet Gynecol 1996; 88:415. Stotland, NE, Lipschitz, LS, Caughey, AB. Delivery strategies for women with a previous classic cesarean delivery: a decision analysis. Am J Obstet Gynecol 2002; 187:1203. Garnet, JD. Uterine rupture during pregnancy. An analysis of 133 patients. Obstet Gynecol 1964; 23:898. Dubuisson, JB, Fauconnier, A, Deffarges, JV, et al. Pregnancy outcome and deliveries following laparoscopic myomectomy. Hum Reprod 2000; 15:869. Dubuisson, JB, Fauconnier, A, Fourchotte, V, et al. Laparoscopic myomectomy: predicting the risk of conversion to an open procedure. Hum Reprod 2001; 16:1726. Nezhat, C. The "cons" of laparoscopic myomectomy in women who may reproduce in the future. Int J Fertil Menopausal Stud 1996; 41:280. Hockstein, S. Spontaneous uterine rupture in the early third trimester after laparoscopically assisted myomectomy. A case report. J Reprod Med 2000; 45:139. Seracchioli, R, Manuzzi, L, Vianello, F, et al. Obstetric and delivery outcome of pregnancies achieved after laparoscopic myomectomy. Fertil Steril 2006; 86:159. Wamsteker, K, Emanuel, MH, de Kruif, JH. Transcervical hysteroscopic resection of submucous fibroids for abnormal uterine bleeding: results regarding the degree of intramural extension. Obstet Gynecol 1993; 82:736. Derman, SG, Rehnstrom, J, Neuwirth, RS. The long-term effectiveness of hysteroscopic treatment of menorrhagia and leiomyomas. Obstet Gynecol 1991; 77:591. Ubaldi, F, Tournaye, H, Camus, M, et al. Fertility after hysteroscopic myomectomy. Hum Reprod Update 1995; 1:81. Goldfarb, HA. Laparoscopic coagulation of myoma (myolysis). Obstet Gynecol Clin North Am 1995; 22:807. Zupi, E, Piredda, A, Marconi, D, et al. Directed laparoscopic cryomyolysis: a possible alternative to myomectomy and/or hysterectomy for symptomatic leiomyomas. Am J Obstet Gynecol 2004; 190:639. Visvanathan, D, Connell, R, Hall-Craggs, MA, et al. Interstitial laser photocoagulation for uterine myomas. Am J Obstet Gynecol 2002; 187:382. Arcangeli, S, Pasquarette, MM. Gravid uterine rupture after myolysis. Obstet Gynecol 1997; 89:857. Vilos, GA, Daly, LJ, Tse, BM. Pregnancy outcome after laparoscopic electromyolysis. J Am Assoc Gynecol Laparosc 1998; 5:289. Goldfarb, HA. Combining myoma coagulation with endometrial ablation/resection reduces subsequent surgery rates. JSLS 1999; 3:253. Hald, K, Langebrekke, A, Klow, NE, et al. Laparoscopic occlusion of uterine vessels for the treatment of symptomatic fibroids: Initial experience and comparison to uterine artery embolization. Am J Obstet Gynecol 2004; 190:37. Yen, YK, Liu, WM, Yuan, CC, Ng, HT. Laparoscopic bipolar coagulation of uterine vessels to treat symptomatic myomas in women with elevated Ca 125. J Am Assoc Gynecol Laparosc 2001; 8:241. Lichtinger, M, Hallson, L, Calvo, P, Adeboyejo, G. Laparoscopic uterine artery occlusion for symptomatic leiomyomas. J Am Assoc Gynecol Laparosc 2002; 9:191. Lichtinger, M, Herbert, S, Memmolo, A. Temporary, transvaginal occlusion of the uterine arteries: a feasibility and safety study. J Minim Invasive Gynecol 2005; 12:40. Hald, K, Klow, NE, Qvigstad, E, Istre, O. Laparoscopic Occlusion Compared With Embolization of Uterine Vessels: A Randomized Controlled Trial. Obstet Gynecol 2007; 109:20. Gupta, J, Sinha, A, Lumsden, M, Hickey, M. Uterine artery embolization for symptomatic uterine fibroids. Cochrane Database Syst Rev 2006; :CD005073. Spies, JB, Bruno, J, Czeyda-Pommersheim, F, Magee, ST, et al. Long-term outcome of uterine artery embolization of leiomyomata. Obstet Gynecol 2005;106:933. Marret, H, Cottier, JP, Alonso, AM, et al. Predictive factors for fibroids recurrence after uterine artery embolisation. BJOG 2005; 112:461. Edwards, RD, Moss, JG, Lumsden, MA, Wu, O, et al. Uterine-artery embolization versus surgery for symptomatic uterine fibroids. N Engl J Med 2007; 356:360. Stewart, EA, Gedroyc, WM, Tempany, CM, et al. Focused ultrasound treatment of uterine fibroid tumors: Safety and feasibility of a noninvasive thermoablative technique. Am J Obstet Gynecol 2003; 189:48. Hindley, J, Gedroyc, WM, Regan, L, et al. MRI guidance of focused ultrasound therapy of uterine fibroids: early results. AJR Am J Roentgenol 2004; 183:1713. Smart, OC, Hindley, JT, Regan, L, Gedroyc, WG. Gonadotrophin-releasing hormone and magnetic-resonance-guided ultrasound surgery for uterine leiomyomata. Obstet Gynecol 2006; 108:49. Hesley, GK, Felmlee, JP, Gebhart, JB, et al. Noninvasive treatment of uterine fibroids: early Mayo Clinic experience with magnetic resonance imaging-guided focused ultrasound. Mayo Clin Proc 2006; 81:936. Stewart, EA, Rabinovici, J, Tempany, CM, et al. Clinical outcomes of focused ultrasound surgery for the treatment of uterine fibroids. Fertil Steril 2006; 85:22. Fennessy, FM, Tempany, CM, McDannold, NJ, et al. Uterine leiomyomas: MR imaging-guided focused ultrasound surgery--results of different treatment protocols. Radiology 2007; 243:885. Stewart, EA, Gostout, B, Rabinovici, J, et al. Sustained relief of leiomyoma symptoms by using focused ultrasound surgery. Obstet Gynecol 2007; 110:279. Gavrilova-Jordan, LP, Rose, CH, Traynor, KD, et al. Successful term pregnancy following MR-guided focused ultrasound treatment of uterine leiomyoma. J Perinatol 2007; 27:59. Myers, ER, Barber, MD, Gustilo-Ashby, T, et al. Management of uterine leiomyomata: What do we really know?. Obstet Gynecol 2002; 100:8.

Epidemiology, clinical manifestations, diagnosis, and natural history of uterine leiomyomas Author Elizabeth A Stewart, MD Section Editor Robert L Barbieri, MD Deputy Editor Sandy J Falk, MD

Last literature review version 17.1: January 2009|This topic last updated: December 10, 2008(More)

INTRODUCTIONUterine leiomyomas (ie, fibroids or myomas) are benign monoclonal tumors arising from the smooth muscle cells of the myometrium. They contain a large amount of extracellular matrix (collagen, proteoglycan, fibronectin) and are surrounded by a thin pseudocapsule of areolar tissue and compressed muscle fibers.

Fibroids are often described according to their location in the uterus, although many fibroids can have more than one location designation (show figure 1 and show picture 1A-B): Intramural fibroids develop from within the uterine wall. They may enlarge sufficiently to distort the uterine cavity or serosal surface. Some fibroids can be transmural and extend from the serosal to the mucosal surface. Submucosal myomas derive from myometrial cells just below the endometrium. These neoplasms often protrude into the uterine cavity. The extent of this protrusion is described by the European Society of Hysteroscopy classification system and is clinically relevant for predicting outcomes of hysteroscopic myomectomy [1] . A type 0 fibroid is completely intracavitary, type I has at least 50 percent of its volume in the cavity, whereas a type II has at least 50 percent of its volume in the uterine wall. Types 0 and I are hysteroscopically resectable, although significant hysteroscopic expertise may be needed to resect type I masses. Subserosal myomas originate from the serosal surface of the uterus. They can have a broad or pedunculated base (show ultrasound 1) and may be intraligamentary (ie, extending between the folds of the broad ligament). Cervical fibroids are located on the cervix, rather than the uterine corpus.

The diagnosis and natural history of uterine leiomyomas will be reviewed here. Treatment of uterine leiomyomas is discussed separately. (See "Overview of treatment of uterine leiomyomas").

PREVALENCE, EPIDEMIOLOGY, AND RISK FACTORSThe 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 "Pathogenesis of uterine leiomyomas" section on Steroid hormones).

Leiomyomas have not been described in prepubertal girls, but they are occasionally noted in adolescents. Most Caucasian women with symptomatic fibroids are in their 30s or 40s, however African American women develop disease on average four to six years younger and may present with disease in their 20s [2,3] . Myomas are clinically apparent in approximately 25 percent of reproductive aged women and noted on pathological examination in approximately 80 percent of surgically excised uteri [4,5] . In hysterectomy specimens sectioned at 2-mm intervals, premenopausal women had an average 7.6 fibroids [5] . Most, but not all, women have shrinkage of leiomyomas at menopause.

The relative risk and incidence of fibroids is two- to three-fold greater in black women than white women [6] . Clinically relevant fibroids (uterine enlargement greater than or equal to nine weeks size, fibroid greater than or equal to 4 cm, or submucosal fibroid) are detectable by transvaginal sonography in approximately 50 percent of perimenopausal black women and 35 percent of perimenopausal white women [7] . The cumulative incidence of fibroids of any size, including very small tumors, by age 50 was >80 percent for black women and almost 70 percent for Caucasians [7] . In a study of black women, those with self-reported polycystic ovary syndrome were at increased risk of developing fibroids [8] . Compared with white women, black women experience more severe disease based on their symptoms in a proposed severity algorithm. Also, among women undergoing hysterectomy, black women appear to have surgery at a younger age, have larger uteri, and more severe anemia [2,3] .

Other factors that may affect the risk of developing a leiomyoma include: Parity (having one or more pregnancies extending beyond 20 weeks) decreases the chance of fibroid formation [9-11] . In some cohorts, age and early age at first birth decreases risk and a longer interval since last birth increases risk [12] . Early menarche (