Fibroids

A fibroid is a slow-growing and non-cancerous tumour that is found in the wall of the uterus. A fibroid is composed of smooth muscle and connective tissue. There may be one or more fibroids, and they may range in size from as small as a pea to as large as a grape-fruit. Fibroids are common, appearing most often in women between the ages of 35 and 45. 

Causes

The cause of a uterine fibroid is thought to be related to an abnormal response to oestrogen hormones. Oral contraceptives that contain oestrogen can cause enlargement of fibroids, as can pregnancy. Decreased production of oestrogen after the menopause usually causes any fibroids to shrink.

Symptoms

In many cases, there are no symptoms. If a fibroid enlarges and projects into the cavity of the uterus, it may cause heavy or prolonged periods. A large fibroid may exert pressure on the bladder, causing frequent passing of urine, or on the bowel, causing backache or constipation. Fibroids that distort the uterine cavity may cause recurrent miscarriage or infertility. Rarely, a fibroid may become twisted, resulting in sudden pain in the lower abdomen.

Diagnosis and treatment

Fibroids that do not cause symptoms are often discovered during a routine pelvic examination. Ultrasound scanning can confirm the diagnosis. Small, symptomless fibroids generally require no treatment, but regular examination may be needed to assess growth. Surgery or microwave endometrial ablation (MEA) is required for fibroids causing serious symptoms. In some cases, they can be removed with a hysteroscope (a tubelike viewing instrument with surgical attachments) under general anaesthesia , leaving the uterus intact. Removal of fibroids usually results in regained fertility. Sometimes, however, a hysterectomy (removal of the uterus) is required.

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What Are Uterine Fibroids?

Uterine fibroids are benign tumours or growths that develop in the wall of the uterus. Benign means that they are not cancerous or precancerous. Fibroids are often symptomless but they can cause unpleasant and sometimes painful symptoms.In order to understand fibroids it is helpful to know more about the anatomy of a normal uterus. The majority of the uterus is formed of smooth muscle and this is known as the myometrium. The outer layer of the myometrium is called the serosa. The lining of the uterus is a layer known as the endometrium. It is the endometrium that is shed during a period at the time of menstruation. The endometrium is not made of muscle.

The cavity inside the uterus is usually known as the uterine cavity or sometimes as the endometrial cavity. Diagrams of the uterus usually show the uterine cavity as a triangular space but really it is a potential space because most of the time the uterus is collapsed and there is only a small amount of fluid lying between the endometrial layers of the uterus.

Sometimes the endometrium is referred to as the mucosal surface of the uterus. The uterus is made up of the body or fundus and the cervix. The cervix is the lower part of the uterus that protrudes into the vagina.

During pregnancy the uterus enlarges considerably and nourishes the growing fetus. The muscle cells of the uterus both increase in number and increase in size. This process of hyperplasia and hypertrophy may be important in helping to explain the reasons for growth of uterine fibroids. One theory of reasons for fibroid development hypothesises that fibroids are confused myometrial cells that behave as if the woman is pregnant all the time.

Fibroids are considered to be what is known as clonal tumours. A clone is a collection or group of cells which are genetically identical. Each fibroid is thought to arise from one single smooth muscle cell within the uterus. This process differs from the development of cancerous tumours. When malignant tumours develop one cell becomes abnormal and grows out of control with the potential to spread throughout the body. It is possible for many separate fibroids to grow and develop at the same time. Each fibroid develops from a different muscle cell.

Medical studies have found that more than 80% of women will have some evidence of fibroids when their uteruses are examined very closely. Most fibroids are small and cause no symptoms. It is usually only when fibroids become large that they tend to cause problems, but sometimes small fibroids can cause problems.

Fibroids vary greatly in size and location. When doctors or medical journals describe fibroids the size is usually described in centimetres or millimetres. it is unusual for fibroids to be spherical and their size is usually reported in three dimensions ( length, width and depth). If only one dimension is given it is usually the largest dimension.

The symptoms caused by fibroids depend on both the size and location of the fibroid.

There are 4 different locations and types of fibroid.

  1. Intramural fibroid
  2. Submucosal fibroid
  3. Subserosal fibroid
  4. Pedunculated fibroid

See diagram for illustration of the different locations of fibroids.

picture of types of fibroids in uterus

Fibroids that distort the endometrium or that protrude into the endometrial cavity are called sub mucosal fibroids because they are below the mucosal surface. Subserosal fibroids protrude from the outer layer of the uterus. They result in the uterus having an irregular shape and can often be felt during a pelvic examination. Intramural fibroids are those that are contained within the uterine wall. In general these fibroids cause enlargement of the uterus but do not usually make it feel irregular. The term pedunculated means that the fibroid has a stalk which connects it to the uterus.

The Diagnosis of Uterine Fibroids

The diagnosis of uterine fibroids is usually suspected when a woman has certain symptoms or when a doctor performing a pelvic examination finds an enlarged, irregular uterus. Then a pelvic ultrasound is usually carried out to confirm the diagnosis of fibroids and exclude other, more worrying diagnoses, such as ovarian cancer. If on examination the uterus is found to be enlarged but smooth then it is important to exclude pregnancy. Most, but not all, fibroids are seen on an ultrasound examination. An ultrasound examination is an excellent way of examining the uterus and the ovaries.

Ultrasound

Ultrasound has the following benefits: it is relatively comfortable and painless, it is relatively inexpensive, it is widely available and involves no exposure to potentially harmful x-rays. Generally a trans-vaginal ultrasound is preferred to an abdominal ultrasound, because this gives the best view of fibroids. This is because the uterus and fibroids are in the centre of the pelvis and lie right next to the top of the vagina. However, some fibroids are so large that they reach up above the pelvis, and in this situation ultrasound through the abdominal wall is used. This trans-abdominal approach usually requires that the woman has a full bladder. This is because the bladder acts as a window to see through. This type of scan can therefore take more time to prepare for, and may be slightly uncomfortable.

Ultrasound scans are not especially at good looking inside the cavity of the uterus and seeing small submucosal fibroids or endometrial polyps. Endometrial polyps are another benign abnormality that are often found within uterus. During ultrasound it is possible to determine the thickness of the endometrium. This is referred to as the endometrial stripe. The endometrial thickness is determined by measuring from the base of one side of the endometrial stripe to the base of the other. One problem is that submucosal fibroids may hide in this space.

Measuring the thickness of the endometrial stripe has been extremely useful when screening post menopausal women for endometrial cancer. This is because the normal lining of the endometrium in postmenopausal women is very thin. Measuring the thickness of the endometrium is less useful in premenopausal women, because the normal lining is thicker and the depth of the lining varies throughout the menstrual cycle.

Sonohysterogram or Saline-Infusion Hysterogram (SIS)

Thisis a way of opening up the endometrial cavity in order that the endometrium can be differentiated from structural lesions of the uterus. This technique is often required to show up small fibroids and polyps in premenopausal women. This is especially important if the main symptom that a woman is experiencing is heavy menstrual bleeding. This is because even small submucosal fibroids may be the cause of heavy menstrual bleeding. This technique is known as a saline-infusion sonogram (SIS) or sonohysterogram. It involves carrying out an ultrasound examination after sterile saline has been placed into the endometrial cavity to expand the uterine cavity. This allows the inside of the endometrial cavity to be seen better.

A transvaginal ultrasound is usually carried out first before a saline-infusion sonogram, because occasionally it is possible to see submucosal fibroids without the use of saline infusion. In order to carry out a sonohysterogram a speculum is placed within the vagina in order to expose the cervix. The cervix is then cleaned with an antiseptic solution and a small tube (catheter) is passed through the cervix and into the cavity of the uterus. Some catheters that are used have a small balloon at the tip which is filled with fluid to ensure the catheter does not slip out through the cervix. The speculum is removed, and with the catheter remaining in place, the vaginal probe ultrasound can then be inserted to assess the uterus.

Ultrasound pictures are taken as the saline flows into the endometrial cavity. At the end of the sonohysterogram, the balloon is deflated so that the area close to the cervix can be examined. Having a catheter passed through the cervix and uterus distended with saline can be painful. It is therefore recommended that most women take some form of analgesia, such as over-the-counter ibuprofen, about an hour before the test. This is usually sufficient to relieve the pain. If women have a relatively normal sized uterus the procedure is easily carried out. However, for those women who have large fibroids there are two problems that may arise. Firstly if the fibroids is within the cervix or close to the entrance of the uterus, then inserting the catheter may be difficult or even impossible (though this is unusual). Secondly, if the fibroids are large, the pressure of saline entering the endometrial cavity may not be sufficient to open up the cavity. Sometimes the cavity may appear to be normal, but really the view is limited, and a big fibroid may be hidden at the top of the cavity of the uterus.

Hysteroscopy

There are two other types of investigation that may be used to examine the inside of the uterus. Hysteroscopy performed as an outpatient, involves placing a fibre-optic endoscope into the cavity of the uterus to observe any lesions directly. This procedure typically uses saline to open up the cavity of the uterus. The hysteroscopy is usually carried out with a video monitor and camera so that both the gynaecologist and the woman being examined are able to view any lesions. This procedure is more expensive and more difficult to perform than saline-infusion sonogram, but some gynaecologists prefer this method because they feel that it shows up more clearly whether the lesions within uterus are submucosal fibroids or polyps.

When this form of hysteroscopy is carried out as an outpatient, the gynaecologist will usually use a flexible hysteroscope. These flexible hysteroscopes is are able to flex and bend in many directions and are therefore safer to use than a rigid histeroscope, which is basically a long metal tube. One of the major risks of hysteroscopy, or any procedure in which something is placed within the uterus, is uterine perforation. Uterine perforation is a medical term for making a whole through the uterine cavity. This is a potentially serious complication. A flexible tube that bends is much less likely to pass through the uterine wall than a straight solid tube.

Hysterosalpingogram

Another investigation that may be performed is known as a hysterosalpingogram (HSG). By using this investigation it is possible to gain information about the fallopian tubes as well as obtaining information about the cavity of the uterus . A hysterosalpingogram is usually used as part of investigations into causes of infertility. A hysterosalpingogram will show up the inside of the uterus and provide information about fallopian tube scarring or blockage, which is a major barrier to pregnancy. It is even possible for the occasional woman to fall pregnant following a hysterosalpingogram. The original theory to explain these pregnancies was that the dye cleaned out any sludge that may be blocking the tubes. However more recent studies have suggested that the dye affects a component of the immune system in a way which possibly then allows pregnancy.

A hysterosalpingogram is generally felt to be the most uncomfortable outpatient procedure that is carried out by gynaecologists. Therefore women need to take non-steroidal anti-inflammatory drugs before the procedure and many gynaecologists will also use local anaesthetic to numb the cervix in order to reduce the pain. Hysterosalpingograms also use x-ray guidance, with the risk of radiation, and therefore they are usually carried out in the interval between the end of a woman's period and ovulation to minimise the risk of exposing a a very early pregnancy to x-rays. A hysterosalpingogram results in exposure of the woman and her ovaries to low doses of radiation, and is therefore usually performed only in women who are actively trying to fall pregnant.

An HSG can be performed in several ways, some of which include placing a balloon within the cavity of the uterus. Whilst this is fine for women who do not have fibroids and when only looking at the tubes is important, it may be difficult to distinguish the balloon from a submucosal fibroid. Another way of performing a hysterosalpingogram involves attaching a device to the outside of the cervix and then releasing dye into the cervix, from where it can flow into the uterus and the fallopian tubes. When arranging a hysterosalpingogram it is important for the referring doctor to to be knowledgeable about whether the investigation will provide an adequate and useful examination of the uterine cavity.

MRI Scanning

Another investigation that is able to provide useful and precise information about the uterus is magnetic resonance imaging (MRI). An MRI scan is not usually performed as a first test; however it does provide useful additional information. An MRI scanner is a large type of scanner which is shaped like a giant doughnut, and the patient slides into the scanner on a movable bed. An MRI scan involves no x-ray exposure but there is a strong magnetic field. This means that metal objects cannot be taken into or worn inside the machine. It is therefore important that any metal objects such as jewellery (in particular body piercings which are often forgotten about) are removed before the procedure. Those people who have electronic implants such as pacemakers or defibrillators are unable to have an MRI scan safely. These devices however are rare in women with fibroids. One problem with an MRI scan is that some people experience claustrophobia when inside the machine. Therefore some patients are given when an eye mask, which is often helpful. Another problem is that the machine is noisy, so most departments will offer ear plugs. There are also size limitations and women who weighed more than 250 pounds often will not fit inside an MRI scanner. An MRI scan usually takes an hour to perform and is much more expensive than an ultrasound examination.

Sometimes an intravenous catheter is placed in a vein in the back of the hand or forearm, before an MRI scan is started. This is to enable a contrast agent, such as gadolinium, to be used at the end of the procedure. Gadolinium is a contrast agent that is injected into the blood circulation and shows up the regions of the uterus or fibroids which do not have a good blood flow.

Magnetic resonance imaging will clearly show up the number of fibroids and their positions within the uterus more precisely than an ultrasound scan. MRI will also show up other pathology and significant diseases more clearly. It is able to differentiate fibroids from another condition known as adenomyosis. MRI scanning can also give clues as to whether a uterine mass is a sarcoma or cancer, rather than being a typical fibroid. MRI carried out with gadolinium can also assess whether the blood flow to a fibroid has been cut off, and therefore make the diagnosis of a degenerated fibroid. All these conditions and situations are quite rare, and therefore the extra cost of an MRI is usually only justified when trying to identify a certain type of fibroid before carrying out a minimally invasive surgical technique, that will only be effective in treating that type of fibroid. However an MRI is clearly much less costly than the wrong surgical procedure.

One reason why MRI scan provides more information about the internal organs of the body is because it enables us to take many sets of pictures within the same study by changing the settings of the scanner. When using normal x-rays and ultrasound scanning, tissue density is used to differentiate between two neighbouring structures. Magnetic resonance imaging provides additional ways of showing up tissue which enables radiologists to differentiate between tissues of similar density as well as tissues of different density.

The two major types of MRI imaging sequences are known as T1 weighted images and T2 weighted images (T1 and T2 for short). MRI examines and determines how molecules within tissue react to the very high magnetic field produced by the scanning magnet. Fibroids and normal myometrium are best examined using T2 images. In these types of images most fibroids will appear darker than normal myometrium. They are, therefore, sometimes called black fibroids. On these T2 images fluid appears white, so the urine within the bladder and the small amount of fluid within the endometrial cavity appear white on T2 images.

Another advantage of MRI scanning is that it is able to predict the outcome of some treatments. In particular the outcome of uterine artery embolisation (UAE) and focused ultrasound surgery (FUS). This enables gynaecologists to identify those women who are good candidates for minimally invasive treatments, based on features other than the size and location of the fibroids. Some patterns may also be apparent from ultrasound and other investigations, but they have not yet been correlated and categorised with treatment outcome in the way that has been done with MRI scanning.

3D Ultrasound

A fairly new imaging investigation that is showing promise in investigation of uterine fibroids is three-dimensional ultrasound (3D-US). This investigation uses normal ultrasound technology but in addition takes a sweep of 360° to obtain a 360° view of the uterus. This enables the radiologist to reconstruct multiple images of the uterus to obtain a more complete picture of the relationship between structures within uterus. Three-dimensional ultrasound can also be used with SIS. Research is needed to determine how best to use this new technology in the diagnosis of fibroids.

CT Scanning

The other form of medical scan known as computed tomography (CT scan) is not usually of great use in the diagnosis of fibroids. However on the rare occasions where there is a mass in the pelvis and it is unclear whether the mass is present in the bowel or the uterus then CT scan with contrast agent placed in the bowel can be extremely helpful. A CT scan involves a significant amount of x-ray exposure, which is a major disadvantage of this investigation. CT scan also involves a doughnut like machine similar to an MRI scanner and therefore has some of the confinement limitations that an MRI has.

Other tests for fibroids

All current diagnostic tests involve imaging or viewing the fibroids in the uterus. Uterine fibroids cannot be detected using blood or saliva tests. The fact that treatments are aimed at intervening only once symptoms develop would not make these tests especially useful, even if they were available. However, if the point is reached where fibroids could be prevented, or there were medical treatments that would prevent tiny fibroids from growing to symptomatic fibroids, then other types of less invasive testing would be much more useful.

Early detection

Currently, the most important reason for detecting early fibroid disease is to prevent anaemia from prolonged heavy menstrual bleeding. Most women need to take iron tablets because of period related blood loss, and it is likely that iron supplementation is even more important for women with fibroids. For those women who have a type 0 or type 1 submucosal fibroid, early detection can be important. Because, the surgical risks are small, treatment is usually recommended as soon as symptoms begin. However, for most other types of fibroids, early intervention is not useful. Some gynaecologists have argued that early intervention is required to prevent fibroids from enlarging and leading to more problems. These gynaenocologists recommend prophylactic myomectomy. Most gynacologists do not agree with prophylactic myomectomy, because there is a high recurrence rate.

Pregnancy

If a women is planning to fall pregnant, then being aware that she has fibroids is useful. She should be aware that seeking medical assessment if she has difficulty falling pregnant or if she has multiple miscarriages is important. Some women who are concerned that they are having difficulty falling pregnant are in reality having multiple early miscarriages.

Exclude other conditions

Making the diagnosis of fibroids is important. However, just as important is excluding other medical or gynaecological problems that may be causing the symptoms that are being blamed on the fibroid. You do not want surgical treatment for a fibroid only to discover afterwards that the symptoms that resulted in the surgical procedure do not improve, and were due to another condition such as endometriosis or an ovarian cyst. The diagnosis is fairly easy in those women who have an enlarged uterus. After pregnancy has been excluded with a urine or blood test, an ultrasound scan is usually able to exclude the other major cause of fibroid type symptoms, which is an ovarian cyst. This is why it is important to carry out an ultrasound scan about a year after surgical treatment for a fibroid. Sometimes a repeat scan will show that the previously diagnosed fibroids were stable in size, but an ovarian cyst had developed. 

Treatments for Uterine Fibroids

Fibroids do not always require treatment. Many women have fibroids which cause no problems and can be quite safely left alone. Fibroids are benign and not cancerous.

Fibroids that do not cause symptoms are often discovered during a routine pelvic examination. The diagnosis is confirmed by abdominal and or pelvic ultrasound scanning, which is simple and painless. Small, symptomless fibroids generally do not require treatment but regular examination or ultrasound scanning may be needed to assess growth.

If fibroids are causing pain or other problems they may require treatment.

Treatment with medication:

Uterine fibroids can be treated with strong hormonal drugs which suppress production of the sex hormones oestrogen and testosterone. In women these block oestrogen and induce an early menopause. The drugs prevent oestrogen (the female hormone) from working. They are known as analogues of LNRH (leutinizing hormone releasing hormone). Examples include goserelin (Zoladex) and buserelin (Suprecur).

These drugs are given by injection in the case of goserelin and either by nasal spray or injection with buserelin. Goserelin can be given monthly or 3 monthly. It consists of a slow release pellet which is injected under the skin usually in the lower abdomen. The drug is then released slowly into the bloodstream.

These drugs are effective in shrinking uterine fibroids. The fibroids increase in size again when the drug is stopped. Goserelin is usually used to shrink fibroids before surgery. It is not often used as an alternative to surgery because of the problem of regrowth once the treatment is stopped.

The main problem with these medications is that they induce a menopausal state. The main side effects are therefore temporary infertility, loss of bone mass (osteoporosis), hot flushes, mood swings, depression, tiredness and vaginal dryness.

When the course of treatment is stopped the side effects will stop, but some women may have lost some bone mass. Loss of bone mass (demineralisation) can be reduced by additional treatment with a drug called raloxifene. This drug can also help shrink the fibroids further.

Fertility and fibroids return when the medications are discontinued.

Surgical Treatment:

Surgical treatment involves either removal of individual fibroids (myomectomy) or hysterectomy.

Fibroids can be removed surgically. This is known as myomectomy. It involves shelling out the fibroid from the uterus under a general anaesthetic, via a lower abdominal wall incision. Complications of myomectomy include severe bleeding requiring hysterectomy, infection and post-operative adhesions.

Hysterectomy is the ideal curative surgical treatment for women who no longer want children.

Fibroids can be removed by laparoscopic (keyhole) surgery. This results in a smaller scar but is technically more difficult and requires a patient and skilled surgeon.

Embolisation of fibroids:

This procedure is carried out by a radiologist (a doctor specialised in x-ray interpretation and treatment involving x-ray monitoring). It involves an injection of particles into the uterine artery supplying the uterus. This results in blockage of the uterine artery and shrinking of the fibroids. This is also known as uterine ablation. It is not widely available as a treatment and it can be very painful. The period of time spent in hospital is shorter for embolization than for surgery. 

The histology of fibroids (how they look under the microscope).

The main component of fibroids is the smooth muscle cell. The uterus, bladder and stomach are all organs within the body that are composed of smooth muscle cells. Muscles such as the biceps muscle in the upper arm are formed of skeletal muscle cells. The arrangement of smooth muscle cells within an organ such as the uterus is organised in a way that enables the uterus to stretch, and also contract during childbirth. Skeletal muscles are designed to pull and exert force to enable movement of limbs (for example).

Under the microscope smooth-muscle cells appear as long stretched out cells with a nucleus in the centre. They are grouped as interlacing bundles which are woven together. When examined microscopically fibroids appear differently from normal uterine muscle in that they have an increased amount of extracellular matrix (ECM). This extracellular matrix is composed of proteins and other substances which are found between cells that cause them to stick together. ECM typically has an increased quantity of collagen. It is this collagen that makes fibroids fibrous. It is also thought that ECM acts as a site of storage for a variety of substances that seemed to be important in causing the symptoms of fibroids. ECM is now known to be an extremely active and important component of any organ or tissue.

The way that fibroids appear under the microscope varies significantly. Some fibroids have many fibroid muscle cells with small bands of ECM between the muscle bundles. Other fibroids have lots of ECM with small areas of fibroid muscle cells. It does however appear that ECM is an important component of fibroids.

It is known that excess production of ECM results in in conditions other than fibroids. Surgical wounds and lacerations heal with scar tissue which includes ECM. If too much scar tissue forms after surgery then adhesions can develop or a keloid scar may form. Keloid scars are large raised hypertrophic scars. In keloid scars there is excessive production of scar tissue. It is possible that fibroids and keloid scars are related. Both fibroids and keloid scars are more frequent in black women and both seem to be related to an abnormality in control of ECM production.

The endometrium (lining of the uterus) is also an important factor in affecting the behaviour of fibroids. It is important to understand that it is the endometrial layer that is shared with each period. Therefore there could not be any abnormal menstrual bleeding in women with fibroids without the endometrium. When the endometrium is shed each month it is the upper two thirds of the endometrium which is lost. This is called the functional endometrium. The basal layer of the endometrium. which is about a third of the endometrium, remains and this then directs the buildup or regeneration of the endometrial lining for the next period of the menstrual cycle.

The endometrium under the microscope, typically appears normal in women with fibroids. In submucosal fibroids however sometimes there is an unusual type of endometrial lining which does not have the normal glandular structures. The medical term for this is aglandular functionalis (functional endometrium without glands). If a woman is having problems with heavy periods then this is sometimes due to a submucosal fibroid. Chronic endometritis is another pattern of endometrium that can suggest that a submucosal fibroid is present. But chronic endometritis is more often associated with infections of the uterus and other problems such as where pregnancy tissue not been cleared from the uterus (retained products of conception). Even if the endometrial lining looks normal under the microscope, an examination of the way that particular molecules are expressed, shows that the lining of the uterus in women with fibroids is different in important functional ways from that of normal uterine lining. These abnormalities may be the explanation for the infertility,pregnancy related problems and abnormal bleeding experienced by women with fibroids.

Fibroids vary considerably in position appearance and size. When examined under the microscope there are even more differences apparent. These differences probably result in the differences in the behaviour of different fibroids. More research needs to be done into understanding the biology of fibroids so that they can be categorised better. A greater understanding of the differences between different types of fibroids is important in understanding why some women are asymptomatic and some women have problems with fibroids such as pain bleeding and in fertility. 

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