Uterine leiomyoma

Synonyms

4

Overview

Uterine leiomyoma,is a benign smooth muscle Tumor of the uterus. Most women have no symptoms while others may have painful or heavy periods. If they push on the bladder a frequent need to urinate may occur.It may also cause pain during sex or lower back pain. A woman can have one uterine leiomyoma or many of them. Occasionally leiomyoma may make it difficult to get pregnant although this is uncommon.

Symptoms

Leiomyoma, particularly when small, may be entirely asymptomatic. Symptoms depend on the location and size of the leiomyoma. Important symptoms include abnormal uterine bleeding, heavy or painful periods, abdominal discomfort or bloating, painful defecation, back ache, urinary frequency or retention, and in some cases, infertility. There may also be pain during intercourse, depending on the location of the fibroid. During pregnancy they may also be the cause of miscarriage, bleeding, premature labor, or interference with the position of the fetus.

While leiomyomas are common, they are not a typical cause for infertility, accounting for about 3% of reasons why a woman may not be able to have a child. The majority of women with uterine fibroids will have normal pregnancy outcomes. In cases of intercurrent uterine fibroids in infertility, a fibroid is typically located in a submucosal position and it is thought that this location may interfere with the function of the lining and the ability of the embryo to implant. Also larger leiomyoma may distort or block the fallopian tubes.

Causes

Leiomyomas are more common in obese women. Leiomyomas are dependent on estrogen and progesterone to grow and therefore relevant only during the reproductive years.

Genetics

Leimyomas are partly genetic as if a mother had fibroids, risk in the daughter is about three times higher than average.

Researchers have completed profiling of global gene expression for uterine leiomyoma. They found that only a few specific genes or cytogenetic deviations are associated with ULMs. An association with fatty acid synthase has been reported.

Familial leiomyomata

A syndrome (Reed's syndrome) that causes uterine leiomyomata along with cutaneous leiomyomata and renal cell cancer has been reported.This is associated with a mutation in the gene that produces the enzyme fumarate hydratase, located on the long arm of chromosome 1 (1q42.3-43). Inheritance is autosomal dominant.

Prevention

Although researchers continue to study the causes of leiomyomas, little scientific evidence is available on how to prevent them. Preventing uterine leiomyoma may not be possible, but only a small percentage of these tumors require treatment.

Diagnosis

While a bimanual examination typically can identify the presence of larger leiomyoma, gynecologic ultrasonography (ultrasound) has evolved as the standard tool to evaluate the uterus for leiomyoma. Sonography will depict the leiomyoma as focal masse with a heterogeneous texture, which usually cause shadowing of the ultrasound beam. The location can be determined and dimensions of the lesion measured. Also magnetic resonance imaging (MRI) can be used to define the depiction of the size and location of the fibroids within the uterus.

Imaging modalities cannot clearly distinguish between the benign uterine leiomyoma and the malignant uterine leiomyosarcoma, however, the latter is quite rare. Fast growth or unexpected growth, such as enlargement of a lesion after menopause, raise the level of suspicion that the lesion might be a sarcoma. Also, with advanced malignant lesions there may be evidence of local invasion. Biopsy is rarely performed and if performed, is rarely diagnostic. Should there be an uncertain diagnosis after ultrasounds and MRI imaging, surgery is generally indicated.

Other imaging techniques that may be helpful specifically in the evaluation of lesions that affect the uterine cavity are hysterosalpingography or sonohysterography.

Coexisting disorders

Leiomyoma that lead to heavy vaginal bleeding lead to anemia and iron deficiency. Due to pressure effects gastrointestinal problems such as constipation and bloatedness are possible. Compression of the ureter may lead to hydronephrosis. Leiomyoma may also present alongside endometriosis, which itself may cause infertility. Adenomyosis may be mistaken for or coexist with leiomyoma.

In very rare cases, malignant (cancerous) growths, leiomyosarcoma, of the myometrium can develop. In extremely rare cases uterine leiomyoma may present as part or early symptom of the hereditary leiomyomatosis and renal cell cancer Syndrome.

Prognosis

About 1 out of 1000 lesions are or become malignant, typically as a leiomyosarcoma on histology.A sign that a lesion may be malignant is growth after menopause. There is no consensus among pathologists regarding the transformation of leiomyoma into a sarcoma.

Metastasis

There are a number of rare conditions in which fibroids metastasize. They still grow in a benign fashion, but can be dangerous depending on their location.

Treatment

Most fibroids do not require treatment unless they are causing symptoms. After menopause fibroids shrink and it is unusual for them to cause problems. In those who have symptoms uterine artery embolization and surgical options have similar outcomes with respect to satisfaction.

Symptomatic uterine fibroids can be treated by:

• medication to control symptoms
• medication aimed at shrinking tumors
• ultrasound fibroid destruction
• myomectomy or radio frequency ablation
• hysterectomy
• uterine artery embolization

Medication

A number of medications may be used to control symptoms. NSAIDs can be used to reduce painful menses. Oral contraceptive pills are prescribed to reduce uterine bleeding and cramps. Anemia may have to be treated with iron supplementation. Vitamin D3 supplementation can be tried.

Levonorgestrel intrauterine devices are effective in limiting menstrual blood flow and improving other symptoms. Side effects are typically very moderate because the levonorgestrel (a progestin) is released in low concentration locally. There is now substantial evidence that Levongestrel-IUDs provide good symptomatic relief for women with fibroids. While most Levongestrel-IUD studies concentrated on treatment of women without leiomyoma a few reported very good results specifically for women with leiomyoma including a substantial regression of fibroids.

Cabergoline in a moderate and well tolerated doses has been shown in two studies to shrink leiomyoma effectively. Mechanism of action is unclear.

Ulipristal acetate is a synthetic selective progesterone receptor modulator which has been tested in several randomized trials with good results for the treatment of leiomyoma.

Danazol is an effective treatment to shrink fibroids and control symptoms. Its use is limited by unpleasant side effects. Mechanism of action is thought to be antiestrogenic effects. Recent experience indicates that safety and side effect profile can be improved by more cautious dosing.

Gonadotropin-releasing hormone analogs cause temporary regression of fibroids by decreasing estrogen levels. Because of the limitations and side effects of this medication it is rarely recommended other than for preoperative use to shrink the size of the fibroids and uterus before surgery. It is typically used for a maximum of 6 months or less because after longer use they could cause osteoporosis and other typically postmenopausal complications. The main side effects are transient postmenopausal symptoms. In many cases the fibroids will regrow after cessation of treatment, however significant benefits may persist for much longer in some cases. Several variations are possible, such as GnRH agonists with add-back regimens intended to decrease the adverse effects of estrogen deficiency. Several add-back regimes are possible, tibolone, raloxifene, progestogens alone, estrogen alone, and combined estrogens and progestogens.

Progesterone antagonists such as mifepristone have been tested, there is evidence that it relieves some symptoms and improves quality of life but because of adverse histological changes that have been observed in several trials it can not be currently recommended outside of research setting. Leiomyoma growth has recurred after antiprogestin treatment was stopped. Selective progesterone receptor modulators, such as Progenta, have been under investigation.

The selective progesterone receptor modulator asoprisnil is currently tested with very promising results as a possible use as a treatment for leiomyoma - the hope is that it will provide the advantages of progesterone antagonist without their adverse effects.

Aromatase inhibitors have been used experimentally to reduce leiomyoma. The effect is believed to be due partially by lowering systemic estrogen levels and partially by inhibiting locally overexpressed aromatase in fibroids. However, fibroid growth has recurred after treatment was stopped. Experience from experimental aromatase inhibitor treatment of endometriosis indicates that aromatase inhibitors might be particularly useful in combination with a progestogenic ovulation inhibitor.

Uterine artery embolization

Uterine artery embolization (UAE): is a noninvasive, endovascular procedure effectively treating symptomatic leiomyoma. Using interventional radiology techniques, the interventional radiologist occludes both uterine arteries, thus reducing blood supply to the fibroid. This intervention is not usually recommended when fertility should be preserved although subsequent pregnancies are usually possible. A small catheter (1 mm in diameter) is inserted into the femoral artery at the level of the groin under local anesthesia. Under imaging guidance, the interventional radiologist will enter selectively into both uterine arteries and inject small (500 µm) particles that will block the blood supply to the fibroids. A patient will usually recover from the procedure within a few days. The UAE procedure should result in limited blood supply to the fibroids which should prevent them from further growth, heavy bleeding and possibly shrink them.

Risk of miscarriage.

Studies indicate that women who undergo uterine artery embolization (UAE) as a treatment for uterine leiomyoma are at a higher risk for experiencing miscarriages in the future. Specifically, the risk of miscarrying was found to double when compared to women who had never undergone uterine artery embolization. When researchers compared miscarriage rates for pregnancies among different UAE studies in which submucosal leiomyoma were excluded, miscarriages rates were even apparent.

Uterine artery ligation

Uterine artery ligation, sometimes also laparoscopic occlusion of uterine arteries are minimally invasive methods to limit blood supply of the uterus by a small surgery that can be performed transvaginally or laparoscopically. The principal mechanism of action may be similar like in UAE but is easier to perform and fewer side effects are expected.

Radio frequency ablation

Radiofrequency ablation is a minimally invasive treatments for leiomyomas. In this technique the leiomyoma is shrunk by inserting a needle-like device into the fibroid through the abdomen and heating it with radio-frequency (RF) electrical energy to cause necrosis of cells. The treatment is a potential option for women who have leiomyoma, have completed child-bearing and want to avoid a hysterectomy.

Myomectomie

Myomectomy is a surgery to remove one or more leiomyomas. It is usually recommended when more conservative treatment options fail for women who want fertility preserving surgery or who want to retain the uterus.

There are three types of myomectomy:

• In a hysteroscopic myomectomy (also called transcervical resection), the leiomyoma can be removed by either the use of a resectoscope, an endoscopic instrument inserted through the vagina and cervix that can use high-frequency electrical energy to cut tissue, or a similar device.
• A laparoscopic myomectomy is done through a small incision near the navel. The physician uses a laparoscope and surgical instruments to remove the leiomyoma. Studies have suggested that laparoscopic myomectomy leads to lower morbidity rates and faster recovery than does laparotomic myomectomy.
• A laparotomic myomectomy (also known as an open or abdominal myomectomy) is the most invasive surgical procedure to remove fibroids. The physician makes an incision in the abdominal wall and removes the leiomyoma from the uterus.

Laparoscopic myomectomy has less pain and shorter time in hospital than open surgery.

Hysterectomie

Hysterectomy was the classical method of treating leiomyoma. Although it is now recommended only as last option, leiomyomas are still the leading cause of hysterectomies in the US.

Endometrial ablation

Endometrial ablation can be used if the leiomyomass are only within the uterus and not intramural and relatively small. High failure and recurrence rates are expected in the presence of larger or intramural leiomyomas.

Magnetic resonance guided focused utltrasound

Magnetic resonance guided focused ultrasound, is a non-invasive intervention (requiring no incision) that uses high intensity focused ultrasound waves to destroy tissue in combination with magnetic resonance imaging (MRI), which guides and monitors the treatment. During the procedure, delivery of focused ultrasound energy is guided and controlled using MR thermal imaging. Patients who have symptomatic leiomyoma, who desire a non-invasive treatment option and who do not have contraindictions for MRI are candidates for MRgFUS. About 60% of patients qualify. It is an outpatient procedure and takes one to three hours depending on the size of the fibroids. It is safe and about 75% effective. Symptomatic improvement is sustained for two plus years. Need for additional treatment varies from 16-20% and is largely dependent on the amount of leiomyoma that can be safely ablated; the higher the ablated volume, the lower the re-treatment rate.There are currently no randomized trial between MRgFUS and UAE. A multi-center trial is underway to investigate the efficacy of MRgFUS vs. UAE.