Uterine fibroids
Classification and external resources
Uterine Fibroids
ICD-10	D25.
ICD-9	218.9
OMIM	150699
DiseasesDB	4806
eMedicine	radio/777
MeSH	D007889

A uterine fibroid (also uterine leiomyoma, myoma, fibromyoma, leiofibromyoma, fibroleiomyoma, and fibroma) (plural of ... myoma is ...myomas or ...myomata) is a non-cancerous (benign) tumor that originates from the smooth muscle layer (myometrium) and the accompanying connective tissue of the uterus. Fibroids are the most common benign tumors in females and typically found during the middle and later reproductive years. While most fibroids are asymptomatic, they can grow and cause heavy and painful menstruation, painful sexual intercourse, and urinary frequency and urgency. Uterine fibroids is the major indication for hysterectomy in the US.^[1] Fibroids are often multiple and if the uterus contains too many leiomyomatas to count, it is referred to as uterine leiomyomatosis. The malignant version of a fibroid is uncommon and termed a leiomyosarcoma.

[edit] Prevalence

A relatively large submucosal leiomyoma; it fills out the major part of the endometrial cavity

About 20-40% of women will be diagnosed with leiomyoma.^[1] The condition is about twice as common in black women as white women.^[2] Estrogen receptors on fibroids cause them to respond to estrogen stimulation during the reproductive years. During hypoestrogenic states, such as after menopause, leiomyoma are expected to shrink. Leiomyoma are more common in overweight women (because of increased estrogen from adipose aromatase activity).^[3]

[edit] Pathology and histology

Leiomyomas grossly appear as round, well circumscribed (but not encapsulated), solid nodules that are white or tan, and show whorled appearance on histological section. The size varies, from microscopic to lesions of considerable size. Typically lesions the size of a grapefruit or bigger are felt by the patient herself through the abdominal wall.

Micrograph of a lipoleiomyoma, a type of leiomyoma. H&E stain.

Microscopically, tumor cells resemble normal cells (elongated, spindle-shaped, with a cigar-shaped nucleus) and form bundles with different directions (whorled). These cells are uniform in size and shape, with scarce mitoses. There are three benign variants: bizarre (atypical); cellular; and mitotically active.

Estrogen, for decades, has been known to stimulate fibroids, but more recent studies have also revealed a possible role of progesterone and progestins to fibroid growth as well,^[4][5] and applicability of progestin agonists as part of treatment are currently being considered.^[6]

In very rare cases, malignant (cancerous) growths, leiomyosarcoma, of the myometrium can develop.^[7]

[edit] Location

An enucleated uterine leiomyoma – external surface on left, cut surface on right.

large subserosal fibroid

Growth and location are the main factors that determine if a fibroid leads to symptoms and problems.^[1] A small lesion can be symptomatic if located within the uterine cavity while a large lesion on the outside of the uterus may go unnoticed. Different locations are classified as follows:

• Intramural fibroids are located within the wall of the uterus and are the most common type; unless large, they may be asymptomatic.
• Subserosal fibroids are located underneath the mucosal (peritoneal) surface of the uterus and can become very large. They can also grow out in a papillary manner to become pedunculated fibroids. These pedunculated growths can actually detach from the uterus to become a parasitic leiomyoma.
• Submucosal fibroids are located in the muscle beneath the endometrium of the uterus and distort the uterine cavity; even small lesion in this location may lead to bleeding and infertility. A pedunculated lesion within the cavity is termed an intracavitary fibroid and can be passed through the cervix.
• Cervical fibroids are located in the wall of the cervix (neck of the uterus). Rarely fibroids are found in the supporting structures (round ligament, broad ligament, or uterosacral ligament) of the uterus that also contain smooth muscle tissue.

Fibroids may be single or multiple. Most fibroids start in an intramural location, that is the layer of the muscle of the uterus. With further growth, some lesions may develop towards the outside of the uterus or towards the internal cavity. Secondary changes that may develop within fibroids are hemorrhage, necrosis, calcification, and cystic changes.

[edit] Symptoms

Generally, symptoms relate to the location of the lesion and its size (mass effect). Important symptoms include abnormal gynecologic hemorrhage, heavy or painful periods, abdominal discomfort or bloating, painful defecation, back ache, urinary frequency or retention, and in some cases, infertility.^[8] There may also be pain during intercourse, depending on the location of the fibroid. During pregnancy they may be the cause of miscarriage, bleeding, premature labor, or interference with the position of the fetus.

Fibroids, particularly when small, may be entirely asymptomatic. The U.S. Department of Health & Human Services states that "Fibroids are almost always benign (not cancerous). Rarely (less than one in 1,000) a cancerous fibroid will occur. This is called leiomyosarcoma. Doctors think that these cancers do not arise from an already-existing fibroid. Having fibroids does not increase the risk of developing a cancerous fibroid. Having fibroids also does not increase a woman's chances of getting other forms of cancer in the uterus."^[9]

While fibroids are common, they are not a typical cause for infertility accounting for about 3% of reasons why a woman may not have a child.^[10] Typically in such cases a fibroid is 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.^[10] Also larger fibroids may distort or block the fallopian tubes.

[edit] Diagnosis

While a bimanual examination typically can identify the presence of larger fibroids, gynecologic ultrasonography (ultrasound) has evolved as the standard tool to evaluate the uterus for fibroids. Sonography will depict the fibroids as focal masses 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. However fast growth or unexpected growth such as enlargement of a lesion after the 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. A more recent study has suggested that diagnostic capabilities using MRI have improved the ability to detect sarcomatous lesions.^[11] 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.

[edit] Coexisting disorders

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

[edit] Treatment

submucosal fibroid in hysteroscopy

Treatment of an intramural fibroid by laparoscopic surgery

After treatment of an intramural fibroid by laparoscopic surgery

[edit] Expectant management

The presence of fibroids does not mean that they need to be treated; lesions can be managed expectantly depending on the symptomatology and presence of related conditions. Thus most cases of fibroids are managed by "watchful waiting" which includes periodic sonographic assessment. After menopause fibroids shrink and it is unusual for fibroids to cause problems.

The presence of symptomatic uterine fibroids can be solved by:

[edit] Surgery

Surgery: Surgical removal of a uterine fibroid usually takes place via hysterectomy, in which the entire uterus is removed, or myomectomy, in which only the fibroid is removed. It is possible to remove multiple fibroids during a myomectomy. Although a myomectomy cannot prevent the recurrence of fibroids at a later date, such surgery is increasingly recommended, especially in the case of women who have not completed bearing children or who express an explicit desire to retain the uterus. There are three different types of myomectomy:

• In a hysteroscopic myomectomy, the fibroid is removed by the use of a resectoscope, an endoscopic instrument that can use high-frequency electrical energy to cut tissue. Hysteroscopic myomectomies can be done as an outpatient procedure, with either local or general anesthesia used. Hysteroscopic myomectomy is most often recommended for submucosal fibroids. A French study collected results from 235 patients suffering from submucous myomas who were treated with hysteroscopic myomectomies; in none of these cases was the fibroid greater than 5 cm.^[12]
• A laparoscopic myomectomy requires a small incision near the navel. The physician then inserts a laparoscope into the uterus and uses surgical instruments to remove the fibroids. Studies have suggested that laparoscopic myomectomy leads to lower morbidity rates and faster recovery than does laparotomic myomectomy.^[13] As with hysteroscopic myomectomy, laparoscopic myomectomy is not generally used on very large fibroids. A study of laparoscopic myomectomies conducted between January 1990 and October 1998 examined 106 cases of laparoscopic myomectomy, in which the fibroids were intramural or subserous and ranged in size from 3 to 10 cm.^[14]
• 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 fibroid from the uterus. A particularly extensive laparotomic procedure may necessitate that any future births be conducted by Caesarean section.^[10] Recovery time from a laparatomic procedure is generally expected to be four to six weeks.

[edit] Uterine artery embolization

Uterine artery embolization (UAE): Using interventional radiology techniques, the interventional radiologist occludes both uterine arteries, thus reducing blood supply to the fibroid^[15] . 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 results in the supposed shrinking of the fibroids and of the uterus, thus alleviating the symptoms. However, it is important to note that significant adverse effects resulting from uterine artery embolization have been reported and documented in the medical literature including death, infection, misembolization, loss of ovarian function, unsuccessful fibroid expulsion, pain, foul vaginal odor, hysterectomy, and failure of embolization surgery [1] [2].

[edit] Medication

[edit] Primary

Medical therapy: Currently, the only medication approved to reduce fibroids are the Gonadotropin-releasing hormone analogs. GNRH analogs, however, are short term treatments only because they lead to estrogen-deficiency and may cause osteoporosis. Aromatase inhibitors have been used experimentally to reduce fibroids. Progesterone antagonists have been shown in small studies to decrease the size of uterine fibroids. Thus mifepristone was effective in a placebo-controlled pilot study.^[16] Selective progesterone receptor modulators, such as Progenta, have been under investigation.

[edit] Secondary

A number of secondary medications are in use to alleviate symptoms caused by fibroids. This allows an otherwise expectant approach to bring the patient hopefully to menopause when symptoms naturally regress. Thus oral contraceptive pills, either combination pills with low-dose estrogens or progestin-only, are prescribed in an effort to reduce uterine bleeding and cramps. Such medications seem to have little or no effect on the size of the lesions.^[10] Anemia may have to be treated with iron supplementation. NSAIDs can be used to reduce painful menses.

[edit] Other

HIFU (High intensity focused ultrasound), also called Magnetic Resonance guided Focused Ultrasound, is a non-invasive intervention (requiring no incision) that uses high intensity focused ultrasound waves to ablate (destroy) tissue in combination with Magnetic Resonance Imaging (MRI), which guides and monitors the treatment. This technique is relatively new; it was approved by the FDA in 2004.^[17]

The use of vitex herbal medicine lacks supporting evidence.

[edit] Malignancy

About 1 out of 1000 lesions^[10] are or become malignant, typically as a leiomyosarcoma on histology. A signs that a lesion may be malignant is growth after menopause.^[10] There is no consensus among pathologists regarding the transformation of Leiomyoma into a sarcoma. Most pathologists believe that a Leiomyosarcoma is a de novo disease^{[citation needed]}.

[edit] See also

• Hysterectomy Educational Resources and Services (HERS) Foundation
• Fibroma
• Leiomyoma

[edit] References

1. ^ ^{a b c} Wallach EE, Vlahos NF. "Uterine myomas: an overview of development, clinical features, and management". Obstet Gynecol 104 (2004), pp. 393–406. 
2. ^ Uterine Fibroids - The Merck Manuals Online Medical Library
3. ^ Uterine Fibroids - The Merck Manuals Online Medical Library
4. ^ Nisolle M, Gillerot S, Casanas-Roux F, Squifflet J, Berliere M, Donnez J (1999). "Immunohistochemical study of the proliferation index, oestrogen receptors and progesterone receptors A and B in leiomyomata and normal myometrium during the menstrual cycle and under gonadotrophin-releasing hormone agonist therapy". Hum. Reprod. 14 (11): 2844–50. doi:10.1093/humrep/14.11.2844. PMID 10548634. http://humrep.oxfordjournals.org/cgi/content/full/14/11/2844. 
5. ^ "Advances in Uterine Leiomyoma Research: The Progesterone Hypothesis". http://ehp.niehs.nih.gov/members/2000/suppl-5/791-793rein/rein-full.html. Retrieved 2007-08-25. 
6. ^ Celik H, Sapmaz E (2003). "Use of a single preoperative dose of misoprostol is efficacious for patients who undergo abdominal myomectomy". Fertil. Steril. 79 (5): 1207–10. doi:10.1016/S0015-0282(03)00076-1. PMID 12738519. 
7. ^ Fibroids - What is it? - Introduction
8. ^ Fibroid Tumors
9. ^ http://www.4woman.gov/faq/uterine-fibroids.cfm#1
10. ^ ^{a b c d e f} American Society of Reproductive Medicine Patient Booklet: Uterine Fibroids, 2003
11. ^ Goto A, Takeuchi S, Sugimura K, Maruo T (2002). "Usefulness of Gd-DTPA contrast-enhanced dynamic MRI and serum determination of LDH and its isozymes in the differential diagnosis of leiomyosarcoma from degenerated leiomyoma of the uterus". Int. J. Gynecol. Cancer 12 (4): 354–61. doi:10.1046/j.1525-1438.2002.01086.x. PMID 12144683. 
12. ^ Polena, V., et al. "Long-term results of hysteroscopic myomectomy in 235 patients." European Journal of Obstetrics & Gynecology and Reproductive Biology 130 (2007): 232-237.
13. ^ Agdi, M. and Tulandi, T. “Endoscopic management of uterine fibroids.” Best Practice & Research Clinical Obstetrics & Gynecology, online publication 4 Mar 2008.
14. ^ Soriano, D. et al. "Pregnancy outcome after laparoscopic and laparoconverted myomectomy." European Journal of Obstetrics & Gynecology and Reproductive Biology 108 (2003): 194-198.
15. ^ The Embolisation Process: What's Involved
16. ^ Engman M, Granberg S, Williams ARW, Meng CX, Lalitkumar PGL, Gemzell-Danielsson K (August 2009). "Mifepristone for Treatment of Uterine Leiomyoma. A Prospective Randomized Placebo Controlled Trial". Human Reproduction 24 (8): 1870-9. PMID 19389793. 
17. ^ FDA (2004-10-22). "FDA Approves New Device to Treat Uterine Fibroids". Press release. http://www.fda.gov/bbs/topics/answers/2004/ans01319.html. Retrieved 2008-05-26.