Fibromyomas?

Uterine fibroids are benign tumors that develop from the smooth muscle of the uterus. It is also known as leiomyomas, myomas, or fibromyomas. Uterine fibroids are extremely common in women of childbearing age and usually regress after menopause. Although there may be symptoms such as heavy menstrual bleeding, sometimes there may be no symptom at all and a woman may be unaware that she has a fibroid. Uterine fibroids are usually round in shape and can grow to a massive size. It can occur as a single large growth or multiple smaller growths. Depending upon the size and location of the fibroid, it may lead to infertility or produce complications during pregnancy. Very rarely do uterine fibroids become cancerous.

How does a uterine fibroid develop?

Pathophysiology of Uterine Fibroids
The uterus is a pear-shaped organ composed of the body of the uterus on top and the cervix below, which connects at its lower end to the vagina. Extending from the upper part of the uterus on either side are the fallopian tubes. Near the end of each tube is an ovary. The uterine wall is composed of smooth muscular tissue or myometrium, covered on the surface by a serous or peritoneal layer and on the inside by the mucosal layer known as endometrium. Hormones regulate the reproductive system in women and include : Gonadotropin-releasing hormone (GnRH) secreted by the hypothalamus. GnRH stimulates the pituitary gland to produce follicle stimulating hormone (FSH) and luteinizing hormone (LH). FSH and LH stimulate the ovaries to secrete estrogen and progesterone. The effects of these hormones are discussed further under female hormones.

The growth of uterine fibroids are hormone mediated. Estrogen, progesterone and growth factors play a role in tumor growth. Fibroids may grow rapidly during pregnancy due to the effect of hormones and are seen to regress after menopause. Drugs containing estrogen, such as oral contraceptives, may also cause fibroids to grow.

The term fibroid is often misleading since it does not contain any fibrous tissue but is made up entirely of smooth muscular tissue of the uterus. For this reason, the term leiomyoma is more accurate in describing the growth. Fibroids start in the muscle layer of the uterus where a single muscle cell may reproduce repeatedly to form a pale, firm, rubbery mass which is clearly demarcated from the surrounding muscle tissue. The cut surface of a fibroid shows a characteristic whorled, spiral pattern of fibers. The fibroid may be confined within the muscular layer of the uterus (intramural), or may grow on the surface of the uterus beneath the peritoneum (subserosal), or it may grow into the uterine cavity beneath the endometrium (submucosal). When the muscular action of the uterus attempts to expel the submucosal tumor, it can give rise to a fibroid polyp or a pedunculated fibroid. These tumors are hormone mediated. Estrogen, progesterone and growth factors play a role in tumor growth. Fibroids may grow rapidly during pregnancy due to the effect of hormones and are seen to regress after menopause. Drugs containing estrogen, such as oral contraceptives, may cause fibroids to grow.
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Diagnosing Fibroids in the Uterus

Most cases of uterine fibroids are asymptomatic there is no signs or symptoms indicating a fibroid. Often uterine fibroids are detected incidentally in the course of a routine pelvic examination, when investigating the cause of infertility or during a prenatal ultrasound. In certain cases, such as in obese women, the diagnosis may become difficult at times. A fibroid may be confused with pregnancy, ovarian tumor or uterine adenomyosis and should be differentiated from uterine fibroid.

History
Taking a careful case history is the first step in diagnosis. A woman may visit a gynecologist with complaints of :

menstrual irregularities heavy bleeding pelvic discomfort lower abdominal pain difficulty falling pregnant

These symptoms are not unique to uterine fibroids. Read more on Uterine Fibroids Symptoms.

Pelvic Examination
The next step is doing a physical examination, including a pelvic examination. Sometimes, a fibroid may be large enough to be felt through the abdomen and may be mistaken for a pregnant uterus. In most cases, however, a pelvic examination is necessary and a fibroid may be detected as an enlarged, mobile, irregular uterus or a mass on the uterus. The pelvic examination is followed by one or more of the various imaging techniques below to accurately identify the shape, size, location, number and type of uterine fibroid. Read more on Types of Uterine Fibroids.

Ultrasound
Ultrasound uses sound waves to create an image of the uterus and the surrounding structures can provide further information about the fibroid in addition to detecting its presence. The shape, size, position and number of fibroids can be detected with an ultrasound examination (ultrasonography). A variation of ultrasound is the hysterosonography. This method uses sterile saline to expand the uterine cavity and thus give a better image of the uterine lining. The case history, along with a pelvic examination and ultrasonography are usually all that will be needed to confirm the diagnosis of fibroids. Further tests may be done as required in case to exclude other conditions and to rule out cancer.

Hysteroscopy
The hysteroscope is a thin, flexible tube with a tiny camera and a light source at its end. This is inserted into the uterus through the vagina and cervix. The uterine cavity can be visualized by this device and any fibroid present can then be detected.

Hysterosalpingography (HSG)
This is a special type of x-ray of the uterus and fallopian tubes done after delivering a radio-opaque dye into the uterus through the vagina. Fibroids within the uterine cavity and changes in the size and shape of the uterus and fallopian tubes can be detected by this method. HSG is usually advised when infertility is a concern.

CT Scan and MRI

Computed tomography (CT) scans and magnetic resonance imaging (MRI) are more accurate imaging tests but are rarely needed for diagnosis of fibroids unless ultrasonography reports are inconclusive. They may be helpful in recording growth of fibroids over time.

Endometrial Biopsy

Biopsy of the uterine lining involves taking a tissue sample from the uterus by passing a small instrument through the vagina into the cervix and uterus. It may need to be done if cancer is suspected.

Laparoscopy
This is a minimally invasive surgical procedure where a small fiberoptic camera is inserted into the abdomen through a tiny incision on the abdomen, just below or through the umbilicus (belly button). Fibroids on the surface of the uterus can be seen by this method.
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A very large (9cm) fibroid of the uterus which is causing pelvic congestion syndrome as seen on CT

A very large (9cm) fibroid of the uterus which is causing pelvic congestion syndrome as seen on US]] changes.

[edit] Pathogenesis
Fibroids are monoclonal tumors, approximately 40 to 50% show karyotypically detectable chromosomal abnormalities. When multiple fibroids are present they will usually have mostly unrelated genetic defects. Exact aetiology is not nearly 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.[7] 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.[2] This protective effect might be partially mediated by an interaction estrogen and the oxytocin receptor.[8]

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 factors, cytokines 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 upregulating 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, TGFbeta1 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.[9][10][11] Expression of transforming growth interacting factor (TGIF) is increased in leiomyoma compared with myometrium.[12] TGIF is a potential repressor of TGF- pathways in myometrial cells.[12] Whereas in premenopausal fibroids the ER-beta, ER-alpha and progesterone receptors are found overexpressed, in the rare postmenopausal fibroids only ER-beta was found significantly overexpressed.[13] Most studies found that polymorphisms in ER and PR gene encodings are not correlated with incidence of fibroids in Caucasian populations [14][15] 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.[16] 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.[17] PPAR-gamma agonists may also counteract leiomyoma growth by several other mechanisms of action such as TGF-beta3 expression inhibition.[18] 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.[19][20] Aromatase and 17beta-hydroxysteroid dehydrogenase are aberrantly expressed in fibroids, indicating that fibroids can convert circulating androstenedione into estradiol.[21] Similar mechanism of action has been elucidated in endometriosis and other endometrial diseases.[22] 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 [23] 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.[24] Like keloids, fibroids have disregulated production of extracellular matrix. Recent studies suggest that this production may represent an abnormal response to ischemic and mechanical tissue stress.[25] Several factors indicate significant involvement of extracellular signaling pathways such as ERK1 and ERK2, which in fibroids are prominently influenced by hormones.[26] Paradoxically and unlike most other conditions involving significant fibrosis the Cyr61 gene has been found downregulated in fibroids.[27] 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.[27]