Uterine fibroids
Encyclopedia
A uterine fibroid (the plural of myoma is myomas or myomata) is a benign
(non-cancerous) 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. Some fibroids may interfere with pregnancy although this appears to be very rare.
In the US, symptoms caused by uterine fibroids are a very frequent indication for hysterectomy
. Fibroids are often multiple and if the uterus contains too many leiomyomata to count, it is referred to as diffuse uterine leiomyomatosis. The malignant version of a fibroid is extremely uncommon and termed a leiomyosarcoma
.
, 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 be the cause of miscarriage
, bleeding, premature labor, or interference with the position of the fetus.
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."
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. 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. Also larger fibroids may distort or block the fallopian tubes.
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.
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:
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.
tumors, approximately 40 to 50% show karyotypically
detectable chromosomal abnormalities
. When multiple fibroids are present they frequently have unrelated genetic defects. Specific mutations of the MED12
protein, have been noted in 70 percent of fibroids.
Exact aetiology is not clearly understood, current working hypothesis is that genetic predispositions, prenatal hormone exposure and the effects of hormones, growth factors and xenoestrogens cause fibroid growth. Known risk factors are African-American descent, nulliparity, obesity
, polycystic ovary syndrome
, diabetes and hypertension
.
Fibroid growth is strongly dependent on estrogen
and progesterone
. Although both estrogen and progesterone are usually regarded as growth promoting they will also cause growth restriction in some circumstances. Paradoxically fibroids will rarely grow during pregnancy despite very high steroid hormone levels and pregnancy appears to exert a certain protective effect. This protective effect might be partially mediated by an interaction estrogen and the oxytocin receptor
.
It is believed that estrogen and progesterone have both mitogenic effect on leiomyoma cells and also act by influencing (directly and indirectly) a large number of growth factor
s, cytokine
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
signalling which controls the expression of the respective nuclear receptors. It is believed that estrogen is growth promoting by up-regulating IGF-1, EGFR
, TGF-beta1, TGF-beta3 and PDGF, promotes aberrant survival of leiomyoma cells by down-regulating p53
, increasing expression of the anti-apoptotic factor PCP4
and antagonizing PPAR-gamma signalling. Progesterone is thought to promote the growth of leiomyoma through up-regulating EGF
, TGF-beta1 and TGF-beta3, and the survival through up-regulating Bcl-2
expression and down-regulating TNF-alpha. 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.
Whereas in premenopausal fibroids the ER-beta, ER-alpha and progesterone receptor
s are found overexpressed, in the rare postmenopausal fibroids only ER-beta was found significantly overexpressed. Most studies found that polymorphisms in ER and PR gene encodings are not correlated with incidence of fibroids in Caucasian populations however a special ER-alpha genotype was found correlated with incidence and size of fibroids. The higher prevalence of this genotype in black women may also explain the high incidence of fibroids in this group.
Uterine leiomyoma was more sensitive than normal myometrium to PPAR-gamma receptor activation resulting in reduced survival and apoptosis of leiomyoma cells. The mechanism is thought to involve negative cross-talk between ER and PPAR signaling pathways. Several PPAR-gamma ligands were considered as potential treatment. PPAR-gamma agonists may also counteract leiomyoma growth by several other mechanisms of action such as TGF-beta3 expression inhibition.
Hypertension
is significantly correlated with fibroids. Although a causal relationships is not at all clear the hypothesis has been formulated that atherosclerotic injury to uterine blood vessels and the resulting inflammatory state may play a role. Furthermore endocrine factors related to blood pressure such as angiotensin II are suspected to cause fibroid proliferation via angiotensin II type 1 receptor.
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
and other endometrial diseases. Aromatase inhibotors 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 Afro-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 have double concordance rate for hysterectomy compared to dizygotic twins.
Like keloid
s, fibroids have disregulated production of extracellular matrix
. Recent studies suggest that this production may represent an abnormal response to ischemic and mechanical tissue stress. Several factors indicate significant involvement of extracellular signaling pathways
such as ERK1 and ERK2, which in fibroids are prominently influenced by hormones. Paradoxically and unlike most other conditions involving significant fibrosis the Cyr61
gene has been found downregulated in fibroids.
Cyr61 is also known for its role as tumor suppressing factor and in angiogenesis
. Hence fibroids are one of the very few tumors with reduced vascular density.
(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. 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. A more recent study has suggested that diagnostic capabilities using MRI have improved the ability to detect sarcomatous lesions. 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.
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.
In very rare cases, malignant (cancerous) growths, leiomyosarcoma
, of the myometrium can develop.
Symptomatic uterine fibroids can be treated by:
s 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.
Levonorgestrel intrauterine devices are highly effective in limiting menstrual blood flow. 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 fibroids a few reported very good results specifically for women with fibroids including a substantial regression of fibroids. One reported problem is that women with large fibroids had more frequently spontaneous expulsion of the IUD, however many of those asked for reinsertion of the device indicating a high rate of satisfaction despite the expulsion.
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.
Dostinex in a moderate and well tolerated dosis has been shown in 2 studies to shrink fibroids effectively. Mechanism of action is completely unclear.
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. Its is typically used for a maximum of 6 months or shorter 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 persists for much longer time 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.
Aromatase inhibitor
s 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. Experience from experimental aromatase inhibitor treatment of endometriosis
indicates that aromatase inhibitors might be particularly useful in combination with a progestogenic ovulation inhibitor.
Progesterone
antagonists have been shown in small studies to decrease the size of uterine fibroids. Mifepristone
was effective in a placebo-controlled pilot study.Selective progesterone receptor modulator
s, 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 fibroids - the hope is that it will provide the advantages of progesterone antangonitst without their adverse effects.
The long term safety of progesterone antagonists as well as selective progesterone receptor modulators has yet to be established.
(UAE): 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.
A retrospective cohort study showed that UAE has much fewer serious adverse effects than hysterectomy (odds ratio
0.25) and similar rates of satisfaction. In this study, 86% of women treated with UAE would recommend the treatment to a friend compared to 70% of those treated by hysterectomy.
is one of the newest 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 women who have fibroids, have completed child-bearing and want to avoid a hysterectomy.
There are three techniques types of myomectomy:
is 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.
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.
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 fibroids, 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 fibroid that can be safely ablated; the higher the ablated volume, the lower the re-treatment rate. In comparison to available treatment options, the cost effectiveness of MRgFUS in the U.S. and U.K. has been found to be reasonable and comparable to alternative treatments (hysterectomy, pharmacotherapy, uterine artery embolization). There are currently no randomized trial between MRgFUS and UAE. A multi-center trial is underway to investigate the efficacy of MRgFUS vs. UAE.
The condition is about twice as common in black women as white women.
Leiomyoma are more common in obese women.
Fibroids are dependent on estrogen and progesterone to grow and therefore relevant only during the reproductive years, they are expected to shrink after menopause.
Research has not proven why fibroids are more common in African American women but there are some speculations. Some studies suggest that black women who are obese and who have high blood pressure are more likely to have fibroids. Additionally, national surveys show that black women consume fewer servings of dairy than white women and have lower intake of calcium, magnesium and phosphorus. Boston University School of Medicine researchers found that increased dairy intake in African American woman decreases their risk of fibroids. Additionally, research evidence has demonstrated that women with a family history of fibroids are twice more likely to develop fibroids than women with no family history- thus perpetuating the cycle of fibroid prevalence in African Americans. However, although there is much speculation much more research must be done to determine why fibroid prevalence is higher in African American women.
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. Most pathologists believe that a Leiomyosarcoma is a de novo
disease.
This institution also has a lot of clinical trials focused on African American women. The focus of one study is the search for a specific gene associated with the development of fibroids. Since one risk factor for uterine fibroids is having a family history of fibroids, the results of this study will provide some answers on the heredity of the illness. Some women may interact with the healthcare system by getting an ultrasound to diagnosis symptoms if they’ve had a mother, sister or grandmother who has previously suffered with these benign tumors.
Benign
A benign tumor is a tumor that lacks the ability to metastasize. Common examples of benign tumors include moles and uterine fibroids.The term "benign" implies a mild and nonprogressive disease. Indeed, many kinds of benign tumors are harmless to human health...
(non-cancerous) tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
that originates from the smooth muscle layer (myometrium
Myometrium
The myometrium is the middle layer of the uterine wall, consisting mainly of uterine smooth muscle cells , but also of supporting stromal and vascular tissue...
) and the accompanying connective tissue of the uterus
Uterus
The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...
.
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. Some fibroids may interfere with pregnancy although this appears to be very rare.
In the US, symptoms caused by uterine fibroids are a very frequent indication for hysterectomy
Hysterectomy
A hysterectomy is the surgical removal of the uterus, usually performed by a gynecologist. Hysterectomy may be total or partial...
. Fibroids are often multiple and if the uterus contains too many leiomyomata to count, it is referred to as diffuse uterine leiomyomatosis. The malignant version of a fibroid is extremely uncommon and termed a leiomyosarcoma
Leiomyosarcoma
Leiomyosarcoma , aka LMS, is a malignant cancer of smooth muscle....
.
Signs and symptoms
Fibroids, particularly when small, may be entirely asymptomatic. Symptoms depend on the location of the lesion and its size. Important symptoms include abnormal gynecologic hemorrhageGynecologic hemorrhage
Gynecologic hemorrhage represents excessive bleeding of the female reproductive system. Such bleeding could be visible or external, namely bleeding from the vagina, or it could be internal into the pelvic cavity or form a hematoma. Normal menstruation is not considered a gynecologic hemorrhage, as...
, heavy or painful periods, abdominal discomfort or bloating, painful defecation, back ache, urinary frequency or retention, and in some cases, infertility
Infertility
Infertility primarily refers to the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term...
. There may also be pain during intercourse, depending on the location of the fibroid. During pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
they may be the cause of miscarriage
Miscarriage
Miscarriage or spontaneous abortion is the spontaneous end of a pregnancy at a stage where the embryo or fetus is incapable of surviving independently, generally defined in humans at prior to 20 weeks of gestation...
, bleeding, premature labor, or interference with the position of the fetus.
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
Leiomyosarcoma
Leiomyosarcoma , aka LMS, is a malignant cancer of smooth muscle....
. 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."
While fibroids are common, they are not a typical cause for infertility
Infertility
Infertility primarily refers to the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term...
accounting for about 3% of reasons why a woman may not have a child. 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. Also larger fibroids may distort or block the fallopian tubes.
Pathophysiology
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.Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...
active.
Location
- Intramural fibroids are located within the wall of the uterus and are the most common type; unless 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 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 infertilityInfertilityInfertility primarily refers to the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term...
. 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 ligamentRound ligament of uterusThe round ligament of the uterus originates at the uterine horns, in the parametrium. The round ligament leaves the pelvis via the deep inguinal ring, passes through the inguinal canal and continues on to the labia majora where its fibers spread and mix with the tissue of the mons...
, 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.
Pathogenesis
Fibroids are monoclonalMonoclonal
Monoclonal cells are defined as a group of cells produced from a single ancestral cell by repeated cellular replication. Thus they can be said to form a single "clone". The process of replication can occur in vivo, or may be stimulated in vitro for laboratory manipulations...
tumors, approximately 40 to 50% show karyotypically
Karyotype
A karyotype is the number and appearance of chromosomes in the nucleus of an eukaryotic cell. The term is also used for the complete set of chromosomes in a species, or an individual organism.p28...
detectable chromosomal abnormalities
Chromosome abnormalities
A chromosome anomaly, abnormality or aberration reflects an atypical number of chromosomes or a structural abnormality in one or more chromosomes. A Karyotype refers to a full set of chromosomes from an individual which can be compared to a "normal" Karyotype for the species via genetic testing. A...
. When multiple fibroids are present they frequently have unrelated genetic defects. Specific mutations of the MED12
MED12
Mediator of RNA polymerase II transcription, subunit 12 homolog , also known as MED12, is a human gene found on the X chromosome...
protein, have been noted in 70 percent of fibroids.
Exact aetiology is not clearly understood, current working hypothesis is that genetic predispositions, prenatal hormone exposure and the effects of hormones, growth factors and xenoestrogens cause fibroid growth. Known risk factors are African-American descent, nulliparity, obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
, polycystic ovary syndrome
Polycystic ovary syndrome
Polycystic ovary syndrome is one of the most common female endocrine disorders. PCOS is a complex, heterogeneous disorder of uncertain aetiology, but there is strong evidence that it can to a large degree be classified as a genetic disease....
, diabetes and hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
.
Fibroid growth is strongly dependent on estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
and progesterone
Progesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
. Although both estrogen and progesterone are usually regarded as growth promoting they will also cause growth restriction in some circumstances. Paradoxically fibroids will rarely grow during pregnancy despite very high steroid hormone levels and pregnancy appears to exert a certain protective effect. This protective effect might be partially mediated by an interaction estrogen and the oxytocin receptor
Oxytocin receptor
The oxytocin receptor, also known as OXTR, is a protein which functions as receptor for the hormone and neurotransmitter oxytocin. In humans, the oxytocin receptor is encoded by the OXTR gene., which has been localized to human chromosome 3p25....
.
It is believed that estrogen and progesterone have both mitogenic effect on leiomyoma cells and also act by influencing (directly and indirectly) a large number of growth factor
Growth factor
A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation and cellular differentiation. Usually it is a protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes....
s, cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
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
Prolactin also known as luteotropic hormone is a protein that in humans is encoded by the PRL gene.Prolactin is a peptide hormone discovered by Henry Friesen...
signalling which controls the expression of the respective nuclear receptors. It is believed that estrogen is growth promoting by up-regulating IGF-1, EGFR
Epidermal growth factor receptor
The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...
, TGF-beta1, TGF-beta3 and PDGF, promotes aberrant survival of leiomyoma cells by down-regulating p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
, increasing expression of the anti-apoptotic factor PCP4
PCP4
Purkinje cell protein 4 is a protein that in humans is encoded by the PCP4 gene.-Further reading:...
and antagonizing PPAR-gamma signalling. Progesterone is thought to promote the growth of leiomyoma through up-regulating EGF
Epidermal growth factor
Epidermal growth factor or EGF is a growth factor that plays an important role in the regulation of cell growth, proliferation, and differentiation by binding to its receptor EGFR...
, TGF-beta1 and TGF-beta3, and the survival through up-regulating Bcl-2
Bcl-2
Bcl-2 is the founding member of the Bcl-2 family of apoptosis regulator proteins encoded by the BCL2 gene. Bcl-2 derives its name from B-cell lymphoma 2, as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in...
expression and down-regulating TNF-alpha. Progesterone is believed to counteract growth by downregulating IGF-1. Expression of transforming growth interacting factor
Transforming growth interacting factor
Transforming growth interacting factor is a potential repressor of TGF-β pathways in myometrial cells. Expression of TGIF is increased in uterine leiomyoma compared with myometrium....
(TGIF) is increased in leiomyoma compared with myometrium. TGIF is a potential repressor of TGF-β pathways in myometrial cells.
Whereas in premenopausal fibroids the ER-beta, ER-alpha and progesterone receptor
Progesterone receptor
The progesterone receptor also known as NR3C3 , is an intracellular steroid receptor that specifically binds progesterone...
s are found overexpressed, in the rare postmenopausal fibroids only ER-beta was found significantly overexpressed. Most studies found that polymorphisms in ER and PR gene encodings are not correlated with incidence of fibroids in Caucasian populations however a special ER-alpha genotype was found correlated with incidence and size of fibroids. The higher prevalence of this genotype in black women may also explain the high incidence of fibroids in this group.
Uterine leiomyoma was more sensitive than normal myometrium to PPAR-gamma receptor activation resulting in reduced survival and apoptosis of leiomyoma cells. The mechanism is thought to involve negative cross-talk between ER and PPAR signaling pathways. Several PPAR-gamma ligands were considered as potential treatment. PPAR-gamma agonists may also counteract leiomyoma growth by several other mechanisms of action such as TGF-beta3 expression inhibition.
Hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
is significantly correlated with fibroids. Although a causal relationships is not at all clear the hypothesis has been formulated that atherosclerotic injury to uterine blood vessels and the resulting inflammatory state may play a role. Furthermore endocrine factors related to blood pressure such as angiotensin II are suspected to cause fibroid proliferation via angiotensin II type 1 receptor.
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
Endometriosis is a gynecological medical condition in which cells from the lining of the uterus appear and flourish outside the uterine cavity, most commonly on the ovaries. The uterine cavity is lined by endometrial cells, which are under the influence of female hormones...
and other endometrial diseases. Aromatase inhibotors 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 Afro-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 have double concordance rate for hysterectomy compared to dizygotic twins.
Like keloid
Keloid
A keloid is a type of scar, which depending on its maturity, is composed mainly of either type III or type I collagen. It is a result of an overgrowth of granulation tissue at the site of a healed skin injury which is then slowly replaced by collagen type 1...
s, fibroids have disregulated production of extracellular matrix
Extracellular matrix
In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.Extracellular...
. Recent studies suggest that this production may represent an abnormal response to ischemic and mechanical tissue stress. Several factors indicate significant involvement of extracellular signaling pathways
Extracellular signal-regulated kinases
In molecular biology, extracellular-signal-regulated kinases or classical MAP kinases are widely expressed protein kinase intracellular signalling molecules that are involved in functions including the regulation of meiosis, mitosis, and postmitotic functions in differentiated cells...
such as ERK1 and ERK2, which in fibroids are prominently influenced by hormones. Paradoxically and unlike most other conditions involving significant fibrosis the Cyr61
CYR61
Protein CYR61 is a protein that in humans is encoded by the CYR61 gene.-Further reading:...
gene has been found downregulated in fibroids.
Cyr61 is also known for its role as tumor suppressing factor and in angiogenesis
Angiogenesis
Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over terminology, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for the formation of new blood...
. Hence fibroids are one of the very few tumors with reduced vascular density.
Diagnosis
While a bimanual examination typically can identify the presence of larger fibroids, gynecologic ultrasonographyGynecologic ultrasonography
Gynecologic ultrasonography or Gynecologic sonography refers to the application of medical ultrasonography to the female pelvic organs, specifically the uterus, the ovaries, the Fallopian tubes, as well as the bladder, the adnexa, the Pouch of Douglas, and any findings in the pelvis of relevance...
(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. 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. A more recent study has suggested that diagnostic capabilities using MRI have improved the ability to detect sarcomatous lesions. 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
Hysterosalpingography
Hysterosalpingography is a radiologic procedure to investigate the shape of the uterine cavity and the shape and patency of the fallopian tubes. It entails the injection of a radio-opaque material into the cervical canal and usually fluoroscopy with image intensification...
or sonohysterography.
Coexisting disorders
Fibroids that lead to heavy vaginal bleeding lead to anemiaAnemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
and iron deficiency
Iron deficiency (medicine)
Iron deficiency is one of the most common of the nutritional deficiencies. Iron is present in all cells in the human body, and has several vital functions...
. Due to pressure effects gastrointestinal problems are possible such as constipation
Constipation
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...
and bloatedness. Compression of the ureter may lead to hydronephrosis
Hydronephrosis
Hydronephrosis is distension and dilation of the renal pelvis calyces, usually caused by obstruction of the free flow of urine from the kidney, leading to progressive atrophy of the kidney...
. Fibroids may also present alongside endometriosis
Endometriosis
Endometriosis is a gynecological medical condition in which cells from the lining of the uterus appear and flourish outside the uterine cavity, most commonly on the ovaries. The uterine cavity is lined by endometrial cells, which are under the influence of female hormones...
, which itself may cause infertility. Adenomyosis
Adenomyosis
Adenomyosis is a medical condition characterized by the presence of ectopic glandular tissue found in muscle. The term adenomyosis is derived from the terms adeno- , myo- , and -osis...
may be mistaken for or coexist with fibroids.
In very rare cases, malignant (cancerous) growths, leiomyosarcoma
Leiomyosarcoma
Leiomyosarcoma , aka LMS, is a malignant cancer of smooth muscle....
, of the myometrium can develop.
Treatment
Most fibroids do not require treatment unless they are causing symptoms. After menopause fibroids shrink and it is unusual for fibroids to cause problems.Symptomatic uterine fibroids can be treated by:
- medication to control symptoms
- medication aimed at shrinking tumours
- ultrasound fibroid destruction
- various surgically aided methods to reduce blood supply of fibroids
- myomectomy or radio frequency ablation
- hysterectomy
- treatment for infection and anemia
- embolizationEmbolizationEmbolization is a non-surgical, minimally-invasive procedure performed by an interventional radiologist and interventional neuroradiologists. It involves the selective occlusion of blood vessels by purposely introducing emboli.-Therapeutic applications:...
Medication
A number of medications are in use to control symptoms caused by fibroids. NSAIDNon-steroidal anti-inflammatory drug
Nonsteroidal anti-inflammatory drugs, usually abbreviated to NSAIDs or NAIDs, but also referred to as nonsteroidal anti-inflammatory agents/analgesics or nonsteroidal Anti-inflammatory medicines , are drugs with analgesic and antipyretic effects and which have, in higher doses, anti-inflammatory...
s 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.
Levonorgestrel intrauterine devices are highly effective in limiting menstrual blood flow. Side effects are typically very moderate because the levonorgestrel
Levonorgestrel
Levonorgestrel is a second generation synthetic progestogen used as an active ingredient in some hormonal contraceptives.-Chemistry:...
(a progestin
Progestin
A progestin is a synthetic progestogen that has progestinic effects similar to progesterone. The two most common uses of progestins are for hormonal contraception , and to prevent endometrial hyperplasia from unopposed estrogen in hormone replacement therapy...
) 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 fibroids a few reported very good results specifically for women with fibroids including a substantial regression of fibroids. One reported problem is that women with large fibroids had more frequently spontaneous expulsion of the IUD, however many of those asked for reinsertion of the device indicating a high rate of satisfaction despite the expulsion.
Danazol
Danazol
Danazol is a derivative of the synthetic steroid ethisterone, a modified testosterone. Also known as 17alpha-ethinyl testosterone. Before becoming available as a generic drug, Danazol was marketed as Danocrine in the United States. It was approved by the U.S. Food and Drug Administration as the...
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.
Dostinex in a moderate and well tolerated dosis has been shown in 2 studies to shrink fibroids effectively. Mechanism of action is completely unclear.
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. Its is typically used for a maximum of 6 months or shorter because after longer use they could cause osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
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 persists for much longer time 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
Tibolone
Tibolone is a synthetic steroid hormone drug, which is fairly non-selective in its binding profile, acting as an agonist at all five of the Type I steroid hormone receptors. It is used mainly for treatment of endometriosis, as well as hormone replacement therapy in post-menopausal women...
, raloxifene
Raloxifene
Raloxifene is an oral selective estrogen receptor modulator that has estrogenic actions on bone and anti-estrogenic actions on the uterus and breast...
, progestogens alone, estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
alone, and combined estrogens and progestogens.
Aromatase inhibitor
Aromatase inhibitor
Aromatase inhibitors are a class of drugs used in the treatment of breast cancer and ovarian cancer in postmenopausal women. AIs may also be used off-label to treat or prevent gynaecomastia in men....
s 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. Experience from experimental aromatase inhibitor treatment of endometriosis
Endometriosis
Endometriosis is a gynecological medical condition in which cells from the lining of the uterus appear and flourish outside the uterine cavity, most commonly on the ovaries. The uterine cavity is lined by endometrial cells, which are under the influence of female hormones...
indicates that aromatase inhibitors might be particularly useful in combination with a progestogenic ovulation inhibitor.
Progesterone
Progesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
antagonists have been shown in small studies to decrease the size of uterine fibroids. Mifepristone
Mifepristone
Mifepristone is a synthetic steroid compound used as a pharmaceutical. It is a progesterone receptor antagonist used as an abortifacient in the first months of pregnancy, and in smaller doses as an emergency contraceptive. During early trials, it was known as RU-38486 or simply RU-486, its...
was effective in a placebo-controlled pilot study.Selective progesterone receptor modulator
Selective progesterone receptor modulator
A selective progesterone receptor modulator is an agent that acts on the progesterone receptor. A characteristic that distinguishes such substances from receptor full agonists and full antagonists is that their action differs in different tissues...
s, such as Progenta, have been under investigation.
The selective progesterone receptor modulator
Selective progesterone receptor modulator
A selective progesterone receptor modulator is an agent that acts on the progesterone receptor. A characteristic that distinguishes such substances from receptor full agonists and full antagonists is that their action differs in different tissues...
Asoprisnil
Asoprisnil
Asoprisnil is an investigational selective progesterone receptor modulator developed by Schering and TAP Pharmaceutical Products, tested for treatment of progesterone sensitive myomata....
is currently tested with very promising results as a possible use as a treatment for fibroids - the hope is that it will provide the advantages of progesterone antangonitst without their adverse effects.
The long term safety of progesterone antagonists as well as selective progesterone receptor modulators has yet to be established.
Uterine artery embolization
Uterine artery embolizationUterine artery embolization
Uterine artery embolization is a procedure where an interventional radiologist uses a catheter to deliver small particles that block the blood supply to the uterine body...
(UAE): Using interventional radiology
Interventional radiology
Interventional radiology is a specialty of radiology, in which image-guided procedures are used to diagnose and treat a multitude of diseases across all body systems...
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
Local anesthesia
Local anesthesia is any technique to induce the absence of sensation in part of the body, generally for the aim of inducing local analgesia, that is, local insensitivity to pain, although other local senses may be affected as well. It allows patients to undergo surgical and dental procedures with...
. 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.
A retrospective cohort study showed that UAE has much fewer serious adverse effects than hysterectomy (odds ratio
Odds ratio
The odds ratio is a measure of effect size, describing the strength of association or non-independence between two binary data values. It is used as a descriptive statistic, and plays an important role in logistic regression...
0.25) and similar rates of satisfaction. In this study, 86% of women treated with UAE would recommend the treatment to a friend compared to 70% of those treated by hysterectomy.
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. This is a relatively new method which demonstrated similar efficacy similar like UAE but is easier to perform and for this reason fewer side effects are expected. UAE currently appears much more effective than this method in direct comparison.Radio frequency ablation
Radiofrequency ablationRadiofrequency ablation
Radio frequency ablation is a medical procedure where part of the electrical conduction system of the heart, tumor or other dysfunctional tissue is ablated using the heat generated from the high frequency alternating current to treat a medical disorder...
is one of the newest 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
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
of cells. The treatment is a potential option for women who have fibroids, have completed child-bearing and want to avoid a hysterectomy.
Myomectomy
Myomectomy is a surgery to remove one or more fibroids. It is usually recommended when more conservative treatment options fail for women who want fertility preserving surgery or who express desire to retain the uterus. This surgery is fertility preserving although in some circumstances subsequent pregnancies can be difficult or impossible.There are three techniques types of myomectomy:
- In a hysteroscopicHysteroscopyHysteroscopy is the inspection of the uterine cavity by endoscopy with access through the cervix. It allows for the diagnosis of intrauterine pathology and serves as a method for surgical intervention .-Method:...
myomectomy, the fibroid is removed by the use of a resectoscope, an endoscopicEndoscopyEndoscopy means looking inside and typically refers to looking inside the body for medical reasons using an endoscope , an instrument used to examine the interior of a hollow organ or cavity of the body. Unlike most other medical imaging devices, endoscopes are inserted directly into the organ...
instrument inserted through the vagina and cervix 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. - A laparoscopicLaparoscopyLaparoscopy is an operation performed in the abdomen or pelvis through small incisions with the aid of a camera...
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. 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. - A laparotomicLaparotomyA laparotomy is a surgical procedure involving a large incision through the abdominal wall to gain access into the abdominal cavity. It is also known as coeliotomy.- Terminology :...
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 sectionCaesarean sectionA Caesarean section, is a surgical procedure in which one or more incisions are made through a mother's abdomen and uterus to deliver one or more babies, or, rarely, to remove a dead fetus...
. Recovery time from a laparatomic procedure is generally expected to be four to six weeks.
Hysterectomy
HysterectomyHysterectomy
A hysterectomy is the surgical removal of the uterus, usually performed by a gynecologist. Hysterectomy may be total or partial...
is 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 ablationEndometrial ablation
Endometrial ablation is a medical procedure that is used to remove or destroy the endometrial lining of a uterus. This technique is most often employed for people who suffer from excessive or prolonged bleeding during their menstrual cycle but cannot or do not wish to undergo a hysterectomy. ...
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.
Magnetic resonance guided focused ultrasound
Magnetic Resonance guided Focused Ultrasound, is a non-invasive intervention (requiring no incision) that uses high intensity focused ultrasoundUltrasound
Ultrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Ultrasound is thus not separated from "normal" sound based on differences in physical properties, only the fact that humans cannot hear it. Although this limit varies from person to person, it is...
waves to destroy tissue in combination with magnetic resonance imaging
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
(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 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 fibroid that can be safely ablated; the higher the ablated volume, the lower the re-treatment rate. In comparison to available treatment options, the cost effectiveness of MRgFUS in the U.S. and U.K. has been found to be reasonable and comparable to alternative treatments (hysterectomy, pharmacotherapy, uterine artery embolization). There are currently no randomized trial between MRgFUS and UAE. A multi-center trial is underway to investigate the efficacy of MRgFUS vs. UAE.
Epidemiology
About 20–40% of women will be diagnosed with leiomyoma but only a fraction of those will cause problems or require treatment.The condition is about twice as common in black women as white women.
Leiomyoma are more common in obese women.
Fibroids are dependent on estrogen and progesterone to grow and therefore relevant only during the reproductive years, they are expected to shrink after menopause.
In African-Americans
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 three times more likely to get fibroids than Caucasian women. Also, in African-American women, fibroids also 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. Furthermore, 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 Cesarean section.Research has not proven why fibroids are more common in African American women but there are some speculations. Some studies suggest that black women who are obese and who have high blood pressure are more likely to have fibroids. Additionally, national surveys show that black women consume fewer servings of dairy than white women and have lower intake of calcium, magnesium and phosphorus. Boston University School of Medicine researchers found that increased dairy intake in African American woman decreases their risk of fibroids. Additionally, research evidence has demonstrated that women with a family history of fibroids are twice more likely to develop fibroids than women with no family history- thus perpetuating the cycle of fibroid prevalence in African Americans. However, although there is much speculation much more research must be done to determine why fibroid prevalence is higher in African American women.
Prognosis
About 1 out of 1000 lesions are or become malignant, typically as a leiomyosarcomaLeiomyosarcoma
Leiomyosarcoma , aka LMS, is a malignant cancer of smooth muscle....
on histology. A sign that a lesion may be malignant is growth after menopause
Menopause
Menopause is a term used to describe the permanent cessation of the primary functions of the human ovaries: the ripening and release of ova and the release of hormones that cause both the creation of the uterine lining and the subsequent shedding of the uterine lining...
. There is no consensus among pathologists regarding the transformation of leiomyoma
Leiomyoma
A leiomyoma is a benign smooth muscle neoplasm that is not premalignant. They can occur in any organ, but the most common forms occur in the uterus, small bowel and the esophagus.- Etymology:* Greek:** λεῖος leios "smooth"...
into a sarcoma. Most pathologists believe that a Leiomyosarcoma is a de novo
De novo
In general usage, de novo is a Latin expression meaning "from the beginning," "afresh," "anew," "beginning again." It is used in:* De novo transcriptome assembly, the method of creating a transcriptome without a reference genome...
disease.
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.- In leiomyoma with vascular invasion, an ordinary-appearing fibroid invades into a vessel but there is no risk of recurrence.
- In Intravenous leiomyomatosisIntravenous leiomyomatosisIntravenous leiomyomatosis is a rare condition seen exclusively in women in which leiomyomata, benign smooth muscle tumors, are found in veins. The masses are benign-appearing but can spread throughout the venous system leaving the uterus and even cause death when growing into the heart from the IVC...
, leiomyomata grow in veins with uterine fibroids as their source. Cardiac involvement 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.
Society and culture
The Center for Uterine Fibroids which is associated with Brigham and Women’s Hospital in Boston MA (http://www.fibroids.net/index.html) is currently recruiting volunteers for an investigation of all aspects of the aetiology, pathology of fibroids and development of treatment options.This institution also has a lot of clinical trials focused on African American women. The focus of one study is the search for a specific gene associated with the development of fibroids. Since one risk factor for uterine fibroids is having a family history of fibroids, the results of this study will provide some answers on the heredity of the illness. Some women may interact with the healthcare system by getting an ultrasound to diagnosis symptoms if they’ve had a mother, sister or grandmother who has previously suffered with these benign tumors.