Uterine fibroid
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Uterine fibroids, also known as uterine leiomyomas, fibromyoma or fibroids, are benign smooth muscle tumors of the
uterus The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the hollow organ, organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic development, embryonic and prenatal development, f ...
, part of the
female reproductive system The human female reproductive system is made up of the internal and external sex organs that function in the reproduction of new offspring. The reproductive system is immature at birth and develops at puberty to be able to release matured ov ...
. Most people with fibroids have no symptoms while others may have painful or heavy periods. If large enough, they may push on the
bladder The bladder () is a hollow organ in humans and other vertebrates that stores urine from the kidneys. In placental mammals, urine enters the bladder via the ureters and exits via the urethra during urination. In humans, the bladder is a distens ...
, causing a frequent need to urinate. They may also cause pain during penetrative sex or
lower back pain Low back pain or wiktionary:lumbago#Etymology, lumbago is a common musculoskeletal disorders, disorder involving the muscles, nerves, and bones of the back, in between the lower edge of the ribs and the lower fold of the buttocks. Pain can var ...
. Someone can have one uterine fibroid or many. It is uncommon but possible that fibroids may make it difficult to become
pregnant Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...
. The exact cause of uterine fibroids is unclear. However, fibroids run in families and appear to be partly determined by
hormone A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...
levels. Risk factors include
obesity Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...
and eating
red meat In gastronomy, red meat is commonly red when raw (and a dark color after it is cooked), in contrast to white meat, which is pale in color before (and after) cooking. In culinary terms, only flesh from mammals or fowl (not fish) is classified ...
. Diagnosis can be performed by
pelvic examination A pelvic examination is the physical examination of the external and internal female pelvic organs. It is frequently used in gynecology for the evaluation of symptoms affecting the female reproductive and urinary tract, such as pain, bleeding, ...
or
medical imaging Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to revea ...
. Treatment is typically not needed if there are no symptoms. NSAIDs, such as
ibuprofen Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to relieve pain, fever, and inflammation. This includes dysmenorrhea, painful menstrual periods, migraines, and rheumatoid arthritis. It can be taken oral administration, ...
, and
paracetamol Paracetamol, or acetaminophen, is a non-opioid analgesic and antipyretic agent used to treat fever and mild to moderate pain. It is a widely available over-the-counter drug sold under various brand names, including Tylenol and Panadol. Parac ...
(acetaminophen) may help with pain. According to
The Mayo Clinic Mayo Clinic () is a private American academic medical center focused on integrated healthcare, education, and research. It maintains three major campuses in Rochester, Minnesota; Jacksonville, Florida; and Phoenix/Scottsdale, Arizona. Mayo C ...
, NSAIDs may help relieve pain tied to fibroids, but they do not reduce bleeding caused by fibroids as they are not hormonal medicines.
Iron Iron is a chemical element; it has symbol Fe () and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, forming much of Earth's o ...
supplements may be needed in those with heavy periods. Medications of the gonadotropin-releasing hormone agonist class may decrease the size of the fibroids but are expensive and associated with side effects. If greater symptoms are present, surgery to remove the fibroid or uterus may help. Uterine artery embolization may also help.
Cancerous Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
versions of fibroids are very rare and are known as leiomyosarcomas. They do not appear to develop from benign fibroids. About 20% to 80% of women develop fibroids by the age of 50. In 2013, it was estimated that 171 million women were affected worldwide. They are typically found during the middle and later reproductive years. After
menopause Menopause, also known as the climacteric, is the time when Menstruation, menstrual periods permanently stop, marking the end of the Human reproduction, reproductive stage for the female human. It typically occurs between the ages of 45 and 5 ...
, they usually decrease in size. In the
United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...
, uterine fibroids are a common reason for surgical removal of the uterus.


Signs and symptoms

Some people with uterine fibroids do not have symptoms. Abdominal pain, anemia and increased bleeding can indicate the presence of fibroids. There may also be pain during intercourse (penetration), depending on the location of the fibroid. During
pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...
, they may also be the cause of
miscarriage Miscarriage, also known in medical terms as a spontaneous abortion, is an end to pregnancy resulting in the loss and expulsion of an embryo or fetus from the womb before it can fetal viability, survive independently. Miscarriage before 6 weeks ...
, bleeding,
premature labor Preterm birth, also known as premature birth, is the Childbirth, birth of a baby at fewer than 37 weeks Gestational age (obstetrics), gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 ...
, or interference with the position of the fetus. A uterine fibroid can cause rectal pressure. The abdomen can grow larger mimicking the appearance of pregnancy. Some large fibroids can extend out through the cervix and vagina. While fibroids 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.American Society of Reproductive Medicine Patient Booklet: ''Uterine Fibroids'', 2003
The majority of people 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.


Risk factors

Some risk factors associated with the development of uterine fibroids are modifiable. Fibroids are more common in obese women. Fibroids are dependent on estrogen and progesterone to grow and therefore relevant only during the reproductive years.


Diet

Diets high in fruits and vegetables tend to lower the risk of developing fibroids. Fibers, vitamin A, C and E, phytoestrogens, carotenoids, meat, fish, and dairy products are of unclear effect. Normal dietary levels of vitamin D may reduce the risk of developing fibroids.


Genetics

Fifty percent of uterine fibroids demonstrate a genetic abnormality. Often a translocation is found on some chromosomes. Fibroids are partly genetic. If a mother had fibroids, risk in the daughter is about three times higher than average. Black women have a 3–9 times increased chance of developing uterine fibroids than white women. Only a few specific genes or cytogenetic deviations are associated with fibroids. 80–85% of fibroids have a mutation in the mediator complex subunit 12 (
MED12 Mediator of RNA polymerase II transcription, subunit 12 homolog (S. cerevisiae), also known as MED12, is a human gene found on the X chromosome. Clinical significance Mutations in ''MED12'' are responsible for at least two different forms of X ...
) gene.


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 In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...
.


Pathophysiology

Fibroids are a type of uterine leiomyoma. Fibroids 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 themself through the abdominal wall. 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. The appearance of prominent nucleoli with peri-nucleolar halos should alert the pathologist to investigate the possibility of the extremely rare hereditary leiomyomatosis and renal cell cancer (Reed) syndrome.


Location and classification

Growth and location are the main factors that determine if a fibroid leads to symptoms and problems. 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 muscular wall of the uterus and are the most common type. Unless they are large, they may be asymptomatic. Intramural fibroids begin as small nodules in the muscular wall of the uterus. With time, intramural fibroids may expand inwards, causing distortion and elongation of the uterine cavity. * Subserosal fibroids are located on the surface of the uterus. They can also grow outward from the surface and remain attached by a small piece of tissue and then are called pedunculated fibroids. * Submucosal fibroids are located in the muscle beneath the endometrium of the uterus and distort the uterine cavity; even small lesions in this location may lead to bleeding and
infertility In biology, infertility is the inability of a male and female organism to Sexual reproduction, reproduce. It is usually not the natural state of a healthy organism that has reached sexual maturity, so children who have not undergone puberty, whi ...
. 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. Since 2011 the FIGO published their consensus paper on the classification of fibroids, namely from 0 to 8. This is part of the PALM COEIN classification and is the most frequently used in clinical practise and research. * Type 0: pedunculated submucosal, intracavitary (i.e. inside of the uterus) * Type 1: submucosal, <50% intramural * Type 2: submucosal, ≥50% intramural * Type 3: contacts the endometrium, 100% intramural * Type 4: intramural (i.e. completely inside the wall of the uterus) * Type 5: subserosal, ≥50% intramural * Type 6: subserosal, <50% intramural * Type 7: pedunculated subserosal * Type 8: other (e.g. cervical, parasitic) There are also hybrid leimyomas, like the type 2-5 which are both subserosal as submucosal. Fibroids may be single or multiple. Most fibroids start in the muscular wall 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. They tend to calcify after menopause. If the uterus contains too many to count, it is referred to as ''diffuse uterine leiomyomatosis''.


Extrauterine fibroids of uterine origin, metastatic fibroids

Fibroids of uterine origin located in other parts of the body, sometimes also called parasitic myomas have been historically extremely rare, but are now diagnosed with increasing frequency. They may be related or identical to metastasizing leiomyoma. They are in most cases still hormone dependent but may cause life-threatening complications when they appear in distant organs. Some sources suggest that a substantial share of the cases may be late complications of surgeries such as myomectomy or hysterectomy. Particularly laparoscopic myomectomy using a morcellator has been associated with an increased risk of this complication. 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. *In leiomyoma with vascular invasion, an ordinary-appearing fibroid invades into a vessel but there is no risk of recurrence. *In intravenous leiomyomatosis, leiomyomata grow in veins with uterine fibroids as their source. Involvement of the heart can be fatal. *In benign metastasizing leiomyoma, leiomyomata grow in more distant sites such as the lungs and lymph nodes. The source is not entirely clear. Pulmonary involvement can be fatal. *In disseminated intraperitoneal leiomyomatosis, leiomyomata grow diffusely on the peritoneal and omental surfaces, with uterine fibroids as their source. This can simulate a malignant tumor but behaves benignly.


Pathogenesis

Fibroids are monoclonal tumors and approximately 40–50% show karyotypically detectable chromosomal abnormalities. When multiple fibroids are present they frequently have unrelated genetic defects. Specific mutations of the
MED12 Mediator of RNA polymerase II transcription, subunit 12 homolog (S. cerevisiae), also known as MED12, is a human gene found on the X chromosome. Clinical significance Mutations in ''MED12'' are responsible for at least two different forms of X ...
protein have been noted in 70 percent of fibroids. The exact cause of fibroids is not clearly understood, but the current working hypothesis is that genetic predispositions, prenatal hormone exposure and the effects of hormones, growth factors and
xenoestrogens Xenoestrogens are a type of xenohormone that imitates estrogen. They can be either synthetic or natural chemical compounds. Synthetic xenoestrogens include some widely used industrial compounds, such as PCBs, BPA, and phthalates, which have ...
cause fibroid growth. Known risk factors are African descent,
obesity Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...
,
polycystic ovary syndrome Polycystic ovary syndrome, or polycystic ovarian syndrome, (PCOS) is the most common endocrine disorder in women of reproductive age. The name is a misnomer, as not all women with this condition develop cysts on their ovaries. The name origin ...
,
diabetes Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...
,
hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...
, and never having given birth. It is believed that estrogen and progesterone have a mitogenic effect on leiomyoma cells and also act by influencing (directly and indirectly) a large number of
growth factor A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for ...
s,
cytokine Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
s and apoptotic factors as well as other hormones. Furthermore, the actions of estrogen and progesterone are modulated by the cross-talk between estrogen, progesterone and
prolactin Prolactin (PRL), also known as lactotropin and mammotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secr ...
signaling which controls the expression of the respective nuclear receptors. It is believed that estrogen promotes growth by up-regulating
IGF-1 Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a hormone similar in molecular structure to insulin which plays an important role in childhood growth, and has anabolic effects in adults. In the 1950s IGF-1 was called " sulfa ...
, EGFR, TGF-beta1, TGF-beta3 and PDGF, and promotes aberrant survival of leiomyoma cells by down-regulating p53, increasing expression of the anti-apoptotic factor PCP4 and antagonizing PPAR-gamma signaling. Progesterone is thought to promote the growth of leiomyoma through up-regulating EGF, TGF-beta1 and TGF-beta3, and promotes survival through up-regulating
Bcl-2 Bcl-2, encoded in humans by the ''BCL2'' gene, is the founding member of the Bcl-2 family of regulator proteins. BCL2 blocks programmed cell death (apoptosis) while other BCL2 family members can either inhibit or induce it. It was the first a ...
expression and down-regulating
TNF-alpha Tumor necrosis factor (TNF), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation. TNF is produced primarily by activated macrophages, and induces inflammation by binding to its receptors o ...
. Progesterone is believed to counteract growth by downregulating IGF-1. Expression of transforming growth interacting factor (TGIF) is increased in leiomyoma compared with myometrium. TGIF is a potential repressor of TGF-β pathways in myometrial cells. Aromatase and 17beta-hydroxysteroid dehydrogenase are aberrantly expressed in fibroids, indicating that fibroids can convert circulating androstenedione into estradiol. Similar mechanism of action has been elucidated in
endometriosis Endometriosis is a disease in which Tissue (biology), tissue similar to the endometrium, the lining of the uterus, grows in other places in the body, outside the uterus. It occurs in women and a limited number of other female mammals. Endomet ...
and other endometrial diseases. Aromatase inhibitors are currently considered for treatment, at certain doses they would completely inhibit estrogen production in the fibroid while not largely affecting ovarian production of estrogen (and thus systemic levels of it). Aromatase overexpression is particularly pronounced in African-American women. Genetic and hereditary causes are being considered and several epidemiologic findings indicate considerable genetic influence especially for early onset cases. First degree relatives have a 2.5-fold risk, and nearly 6-fold risk when considering early onset cases.
Monozygotic twins Twins are two offspring produced by the same pregnancy.MedicineNet > Definition of Twin Last Editorial Review: 19 June 2000 Twins can be either ''monozygotic'' ('identical'), meaning that they develop from one zygote, which splits and forms two e ...
have double concordance rate for hysterectomy compared to dizygotic twins. Expansion of uterine fibroids occurs by a slow rate of cell proliferation combined with the production of copious amounts of
extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and bio ...
. A small population of the cells in a uterine fibroid have properties of
stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell ...
s or
progenitor cell A progenitor cell is a biological cell that can differentiate into a specific cell type. Stem cells and progenitor cells have this ability in common. However, stem cells are less specified than progenitor cells. Progenitor cells can only diffe ...
s, and contribute significantly to ovarian steroid-dependent growth of fibroids. These stem-progenitor cells are deficient in estrogen receptor α and progesterone receptor and instead rely on substantially higher levels of these receptors in surrounding differentiated cells to mediate estrogen and progesterone actions via
paracrine signaling In cellular biology, paracrine signaling is a form of cell signaling, a type of cellular communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as parac ...
.


Diagnosis

Physical examination and ultrasound are sufficient for diagnosing uterine fibroids in the majority of people. When ultrasound findings are inconclusive,
magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and ...
(MRI) may be able to confirm the diagnosis of uterine fibroids in most cases. In addition, MRI can identify benign uterine fibroids with atypical imaging features and fibroids with variant growth patterns. MRI can also identify other uterine (e.g. adenomyosis, endometrial polyps, endometrial cancer) and extrauterine (e.g. benign and malignant ovarian tumors, endometriosis) disorders that may mimic the appearance of uterine fibroids and/or contribute to the patient's symptoms. However, a small proportion of uterine fibroids can mimic other malignant uterine tumors (e.g. leiomyosarcoma) on all available imaging modalities (e.g. ultrasound, CT, MRI and PET-CT). Malignant tumors of the uterine wall (e.g. leiomyosarcoma) are very rare. Findings suggestive of a malignant uterine tumor rather than a benign fibroid include, fast or unexpected growth (particularly after menopause), interruption/effacement of the endometrial stripe, lymph node enlargement, invasion of adjacent organs and metastases to distant organs (e.g. lung). MRI findings suggestive of a malignancy include nodular/ill-circumscribed tumor margins, intermediate/high T2-weighted signal intensity of the solid tumor components, regions with high signal T1-weighted sequences in keeping with subacute hemorrhage, fine/wispy enhancement of the solid parts of the tumor, and restricted diffusion on diffusion-weighted imaging (DWI). A 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. File:9cmFibroidPelvicCongestionS.png, A very large (9 cm) fibroid of the uterus which is causing pelvic congestion syndrome as seen on CT File:9cmFibroidUS.png, A very large (9 cm) fibroid of the uterus which is causing pelvic congestion syndrome as seen on
ultrasound Ultrasound is sound with frequency, frequencies greater than 20 Hertz, kilohertz. This frequency is the approximate upper audible hearing range, limit of human hearing in healthy young adults. The physical principles of acoustic waves apply ...
File:Leiomyoma of the Uterus.jpg, A relatively large submucosal leiomyoma; it fills out the major part of the endometrial cavity. File:UterineFirboid.png, A small uterine fibroid seen within the wall of the myometrium on a cross-sectional ultrasound view File:Calcifiedfibroids.PNG, Two calcified fibroids (in the uterus) File:Subserosal uterine fibroid.png, A subserosal uterine fibroid with a diameter of 5 centimeters File:Pelvic MRI 05 fibroids.jpg, MRI image with multiple uterine leiomyomas File:Giant Myoma.jpg, Giant leiomyomas almost filling the abdomen File:Histopathology of uterine leiomyoma.jpg,
Histopathology Histopathology (compound of three Greek words: 'tissue', 'suffering', and '' -logia'' 'study of') is the microscopic examination of tissue in order to study the manifestations of disease. Specifically, in clinical medicine, histopatholog ...
of uterine fibroids typically show smooth muscle in a whorled (fascicular) pattern. File:Histopathology of uterine leiomyoma (Van Gieson's stain).jpg, This variant of Van Gieson's stain distinguishes muscle (yellow) from connective tissue (red). File:Beta-catenin immunohistochemistry in leiomyoma.jpg,
Immunohistochemistry Immunohistochemistry is a form of immunostaining. It involves the process of selectively identifying antigens in cells and tissue, by exploiting the principle of Antibody, antibodies binding specifically to antigens in biological tissues. Alber ...
for
β-catenin Catenin beta-1, also known as β-catenin (''beta''-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene. β-Catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcr ...
in uterine leiomyoma, which is negative as there is only staining of cytoplasm but not of cell nuclei.
Negative
immunohistochemistry Immunohistochemistry is a form of immunostaining. It involves the process of selectively identifying antigens in cells and tissue, by exploiting the principle of Antibody, antibodies binding specifically to antigens in biological tissues. Alber ...
staining for
β-catenin Catenin beta-1, also known as β-catenin (''beta''-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene. β-Catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcr ...
in cell nuclei is a consistent finding in uterine leiomyomas, and helps in distinguishing such tumors from β-catenin positive spindle cell tumors.


Coexisting disorders

Fibroids that lead to heavy vaginal bleeding lead to
anemia Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...
and
iron deficiency Iron deficiency, or sideropenia, is the state in which a body lacks enough iron to supply its needs. Iron is present in all cells in the human body and has several vital functions, such as carrying oxygen to the tissues from the lungs as a key ...
. Due to pressure effects gastrointestinal problems such as
constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The Human feces, stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the ...
and bloatedness are possible. Compression of the ureter may lead to
hydronephrosis Hydronephrosis is the hydrostatic dilation of the renal pelvis and Renal calyx, calyces as a result of obstruction to urine flow downstream. Alternatively, hydroureter describes the dilation of the ureter, and hydronephroureter describes the dila ...
. Fibroids may also present alongside
endometriosis Endometriosis is a disease in which Tissue (biology), tissue similar to the endometrium, the lining of the uterus, grows in other places in the body, outside the uterus. It occurs in women and a limited number of other female mammals. Endomet ...
, which itself may cause infertility.
Adenomyosis Adenomyosis is a medical condition characterized by the growth of cells that proliferate on the inside of the uterus (endometrium) atypically located among the cells of the uterine wall (myometrium), as a result, thickening of the uterus occurs. ...
may be mistaken for or coexist with fibroids. In very rare cases, malignant (cancerous) growths, leiomyosarcoma, of the myometrium can develop. In extremely rare cases uterine fibroids may present as part or early symptom of the hereditary leiomyomatosis and renal cell cancer syndrome.


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. Uterine fibroids that cause symptoms can be treated by: * medication to control symptoms (i.e., symptomatic management) * medication aimed at shrinking tumors * ultrasound fibroid destruction * surgical removal of fibroids ( myomectomy) or using heat to reduce size (
radiofrequency ablation Radiofrequency ablation (RFA), also called fulguration, is a medical procedure in which part of the electrical conduction system of the heart, tumor, sensory nerves or a dysfunctional tissue is ablated using the heat generated from medium fre ...
) * surgical removal of the womb (
hysterectomy Hysterectomy is the surgical removal of the uterus and cervix. Supracervical hysterectomy refers to removal of the uterus while the cervix is spared. These procedures may also involve removal of the ovaries (oophorectomy), fallopian tubes ( salpi ...
) * blocking the blood supply of fibroids ( uterine artery embolization) In those who have symptoms, uterine artery embolization and surgical options have similar outcomes with respect to satisfaction. For decades, a common approach to treating symptomatic fibroids was "either get a hysterectomy or wait until menopause diminishes the symptoms," but minimally invasive (small incision) and noninvasive (no incision) options were often not offered. Especially since the 2010s, minimally invasive and noninvasive options are increasingly being offered as they have advanced on their technological journey from being new and unusual to being common clinical practice.


Medication

A number of medications may be used to control symptoms. Painkillers (
NSAID Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...
s) can be used to reduce painful menstrual periods. Oral contraceptive pills may be prescribed to reduce uterine bleeding and cramps.
Anemia Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...
may be treated with iron supplementation. Levonorgestrel intrauterine devices are effective in limiting menstrual blood flow and improving other symptoms. Side effects are typically few as the
levonorgestrel Levonorgestrel is a hormonal medication used in a number of birth control methods. It is combined with an estrogen to make combination birth control pills. As an emergency birth control, sold under the brand names Plan B One-Step and Julie, ...
(a
progestin A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural female sex hormone progesterone in the body. A progestin is a '' synthetic'' progestogen. ...
) is released in low concentration locally. While most levongestrel-IUD studies concentrated on treatment of women without fibroids a few reported good results specifically for women with fibroids including a substantial regression of fibroids. Cabergoline in a moderate and well-tolerated dose has been shown in two studies to shrink fibroids effectively. The mechanism of action responsible for how cabergoline shrinks fibroids is unclear.
Ulipristal acetate Ulipristal acetate, sold under the brand name Ella among others, is a medication used for emergency contraception (birth control) and uterine fibroids. As emergency contraception it should be used within 120 hours of vaginally penetrating inte ...
is a synthetic
selective progesterone receptor modulator A selective progesterone receptor modulator (SPRM) is an agent that acts on the progesterone receptor (PR), the biological target of progestogens like progesterone. A characteristic that distinguishes such substances from full receptor agonists ...
(SPRM) that has tentative evidence to support its use for presurgical treatment of fibroids with low side-effects. Long-term UPA-treated fibroids have shown volume reduction of about 70%. In some cases UPA alone is used to relieve symptoms without surgery, and to allow successful pregnancies without fibroid regrowth. Indeed, in the tumor cells, the molecule blocks the cell proliferation, induces their
apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
and stimulates the remodeling of the extensive fibrosis by matrix metalloproteinases, hence explaining the long-term benefit. Yet, due to some rare but severe hepatic injuries after UPA treatment, the licence was suspended in 2020 in the EU and voluntary removed in Canada.
Danazol Danazol, sold as Danocrine and other brand names, is a medication used in the treatment of endometriosis, fibrocystic breast disease, hereditary angioedema and other conditions. It is taken oral administration, by mouth. The use of danazol is ...
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 six months or less because after longer use they could cause
osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in Bone fracture, fracture risk. It is the most common reason f ...
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. Fibroid growth has recurred after antiprogestin treatment was stopped. Aromatase inhibitors have been used experimentally to reduce fibroids. 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 Endometriosis is a disease in which Tissue (biology), tissue similar to the endometrium, the lining of the uterus, grows in other places in the body, outside the uterus. It occurs in women and a limited number of other female mammals. Endomet ...
indicates that aromatase inhibitors might be particularly useful in combination with a progestogenic ovulation inhibitor.


Uterine artery

Uterine artery embolization (UAE) is a noninvasive procedure that blocks blood flow to fibroids, causing them to shrink. Long-term outcomes with respect to how happy people are with the procedure are similar to that of surgery. There is tentative evidence that traditional surgery may result in better fertility. One review found that UAE doubles the future risk of
miscarriage Miscarriage, also known in medical terms as a spontaneous abortion, is an end to pregnancy resulting in the loss and expulsion of an embryo or fetus from the womb before it can fetal viability, survive independently. Miscarriage before 6 weeks ...
. UAE also appears to require more repeat procedures than if surgery was done initially. A person will usually recover from the procedure within a few days. 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. The 2016 NICE (National Institute of Clinical Excellence – the non governmental public body that publishes guidelines in the use of health technologies and good clinical practice in the United Kingdom) guidelines state UAE/UFE can be offered to people with symptomatic fibroids (fibroids being usually >30mm in size). Patients should be informed that UAE and myomectomy (the surgical removal of fibroids) may potentially allow them to retain their fertility.


Myomectomy

Uterine myomectomy, Myomectomy is a surgery to remove one or more fibroids. It is usually recommended when more conservative treatment options fail for patients who want fertility preserving surgery or who want to retain the uterus. There are three types of myomectomy: * In a ''hysteroscopy, hysteroscopic'' myomectomy (also called ''transCervix, cervical resection''), the fibroid can be removed by either the use of a resectoscope, an endoscopy, endoscopic instrument inserted through the vagina and cervix that can use high-frequency electrical energy to cut tissue, or a similar device. * A ''laparoscopy, laparoscopic'' myomectomy is done through a small incision near the navel. The physician uses a laparoscope and surgical instruments to remove the fibroids. Studies have suggested that laparoscopic myomectomy leads to lower morbidity rates and faster recovery than does laparotomic myomectomy. * A ''laparotomy, 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 fibroids from the uterus. Laparoscopic myomectomy has less pain and shorter time in hospital than open surgery. An analysis of 15,000 patients found that those who had myomectomy required fewer additional procedures to manage fibroids (including hysterectomies) over the next 5 years than those who had UAE.


Hysterectomy

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


Endometrial ablation

Endometrial ablation can be used if the fibroids 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 fibroids.


Other procedures

Radiofrequency ablation is a minimally invasive treatments for fibroids. In this technique the fibroid 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 people who have fibroids, have completed child-bearing and want to avoid a hysterectomy. Magnetic resonance guided focused ultrasound, is a non-invasive intervention (requiring no incision) that uses high intensity focused
ultrasound Ultrasound is sound with frequency, frequencies greater than 20 Hertz, kilohertz. This frequency is the approximate upper audible hearing range, limit of human hearing in healthy young adults. The physical principles of acoustic waves apply ...
waves to destroy tissue in combination with
magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and ...
(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 fibroids, who desire a non-invasive treatment option and who do not have contraindications 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 to 20% and is largely dependent on the amount of fibroid 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.


Prognosis

About 1 out of 1,000 lesions are or become malignant, typically as a leiomyosarcoma on histology. A sign that a lesion may be malignant is growth after
menopause Menopause, also known as the climacteric, is the time when Menstruation, menstrual periods permanently stop, marking the end of the Human reproduction, reproductive stage for the female human. It typically occurs between the ages of 45 and 5 ...
. 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, for example Uterine fibroid#Extrauterine fibroids of uterine origin, metastatic fibroids, extrauterine fibroids. They still grow in a benign fashion, but can be dangerous depending on their location.


Epidemiology

About 20% to 80% of women develop fibroids by the age of 50. Globally in 2013 it was estimated that 171 million women were affected. They are typically found during the middle and later reproductive years. After
menopause Menopause, also known as the climacteric, is the time when Menstruation, menstrual periods permanently stop, marking the end of the Human reproduction, reproductive stage for the female human. It typically occurs between the ages of 45 and 5 ...
they usually decrease in size. Surgery to remove uterine fibroids occurs more frequently in women in "higher social classes". Adolescents develop uterine fibroids much less frequently than older women. Up to 50% of people with uterine fibroids have no symptoms. The prevalence of uterine fibroids among teenagers is 0.4%.


Europe

The incidence of uterine fibroids in Europe is thought to be lower than the incidence in the US.


United States

Eighty percent of African American women will develop benign uterine fibroid tumors by their late 40s, according to the National Institute of Environmental Health Sciences. African American women are two to three times more likely to get fibroids than Caucasian women. In African American women fibroids seem to occur at a younger age, grow more quickly, and are more likely to cause symptoms. This leads to higher rates of surgery for African Americans, both myomectomy, and hysterectomy. Increased risk of fibroids in African Americans causes them to fare worse in in-vitro fertility treatments and raises their risk of premature births and delivery by Caesarean section. It is unclear why fibroids are more common in African American women. Some studies suggest that black women who are obese and who have high blood pressure are more likely to have fibroids. Other suggested causes include the tendency of African American women to consume food with less than the daily requirements for vitamin D.


Related legislation


United States

The 2005 S.1289 bill was read twice and referred to the committee on Health, Labor, and Pensions but never passed for a United States Senate, Senate or United States House of Representatives, House vote; the proposed Uterine Fibroid Research and Education Act of 2005 mentioned that $5 billion is spent annually on
hysterectomy Hysterectomy is the surgical removal of the uterus and cervix. Supracervical hysterectomy refers to removal of the uterus while the cervix is spared. These procedures may also involve removal of the ovaries (oophorectomy), fallopian tubes ( salpi ...
surgeries each year, which affect 22% of African Americans and 7% of Caucasian women. The bill also called for more funding for research and educational purposes. It also states that of the $28 billion issued to NIH, $5 million was allocated for uterine fibroids in 2004.


Other animals

Uterine fibroids are rare in other mammals, although they have been observed in certain dogs and Baltic grey seals.


Research

Selective progesterone receptor modulators, such as progenta, have been under investigation. Another selective progesterone receptor modulator asoprisnil is being tested with promising results as a possible use as a treatment for fibroids, intended to provide the advantages of progesterone antagonists without their adverse effects. Low dietary intake of vitamin D is associated with the development of uterine fibroids. Myomectomy and uterine artery embolisation seem to be equally effective in improving Quality of life (healthcare), quality of life, as measured 4 years after surgery.


Notes


References


External links


NIH Fibroid Treatment Study: Information and NIH research
{{DEFAULTSORT:Uterine Fibroids Gynaecological neoplasia Benign neoplasms Wikipedia medicine articles ready to translate Uterine tumour