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Abnormal Uterine Bleeding

Causes | Evaluation | Treatment Options

The average menstrual cycle is 28 days (normal range 24-35 days) in length and menstruation normally spans 3-5 days (normal range 2-7 days). The average amount of blood loss during a period is 30ml, equivalent to 2 tablespoons. It is considered abnormal if a woman looses more than 80ml during her period (equal to 5 ½ tablespoons). The medical term for abnormally heavy menstrual cycle is menorrhagia. Listed below are some of the indication that a woman is having abnormal uterine bleeding;

• Menstrual flow soaks through one or more sanitary pads or tampons every hour
• Need to use double sanitary protection to control menstrual flow
• Need to change sanitary protection at night
• Menstrual period that lasts longer than seven days
• Menstrual flow includes large blood clots Heavy menstrual flow interferes with regular lifestyle
• Constant pain or cramping in the lower abdomen during a menstrual period Periods less than 24 days apart or more than 35 days apart
• Periods that come in between regular menstrual periods (irregular periods)
• Tiredness, fatigue or shortness of breath (symptoms of anemia)
• Bleeding that occurs after the menopause (post-menopausal bleeding) is usually abnormal and should always be evaluated by a physician.

Common causes of post-menopausal bleeding include the intake of hormones, thin and fragile lining of the uterus and vagina (vaginal atrophy), infection, cellular changes in the vagina, cervix or uterus that could lead to cancer with time and cancer in the vagina, cervix or uterus.

Some of the Causes of Abnormal Uterine Bleeding

1. No ovulation or irregular ovulation. This can be caused by:              
• No identifiable cause (most common)
• Stress, exercise, obesity, rapid weight changes
• Abnormal hormone production (most common are thyroid problems, too much prolactin and abnormally high levels of male hormones
• Medications that can increase prolactin production (mostly medications used for depression and
  schizophrenia
2. Problems with the uterus, cervix or vagina
• Lining of the uterus (endometrium)
    Thickening of the endometrium (polyp)
     Infection
     Abnormal cellular changes (hyperplasia)
     Cancer
• Uterine muscle
     Uterine fibroids
     Endometrial glands inside the uterine muscle (adenomyosis)
• Cervix
      Polyp (almost always benign)
      Infection (can be sexually transmitted such as Chlamydia)
      Benign cellular changes (ectropion)
      Abnormal cellular changes
      Cancer
• Vagina
      Infection
      Thinning of the vaginal lining in post-menopausal women
  
3. Abnormal blood coagulation
   • Inherited disorders, the most common is called von Willebrand's disease. Special blood testing is needed  to diagnose this condition.
   • Other rare disorders of coagulation or disease that affect the coagulation process (such as leukemia). These disorders will usually be picked up by a standard blood test.

Evaluation of Abnormal Uterine Bleeding

1. History
   First your doctor will obtain a detailed history about your bleeding patterns. Here are some of the key pieces of information your doctor will need to know:
   • Are your periods regular? Having regular periods is a relatively good sign of ovulation
   • Are you using any medication? Some medication can influence bleeding patterns.
   • Is there history of abnormal bleeding in you or your family? Abnormal bleeding patterns include excessive bleeding associated with dental work or surgery, very easy bruising and heavy bleeding for start of menses.
     
2. Blood tests
   • Pregnancy test
   • Complete blood count (CBC). This gives your physician information about the number of red blood cells, white blood cells and platelets. A hemoglobin level is a measure of the number of red blood cells, with a normal range in women of 12-16 g/dl. Therefore women with a hemoglobin level of less than 12 g/dl are considered to have anemia. The number of white blood cells can indicate infection (increased) or problems with the immune system (decreased). The platelets promote the coagulation of blood, so a low number of platelets could indicate that a patient is at a higher risk for bleeding during surgery.
   • Ferritin. This is an indication of the bodies' iron stores. If there is increased blood loss during menstruation, the bone marrow will produce more red blood cells to compensate. Iron is one of the building blocks of red blood cells and with heavy demand over time the iron stores of the body can become depleted.
   • Thyroid-function tests. The thyroid gland controls the body metabolism. If the thyroid gland is too active or not active enough this can cause an imbalance in other hormones, which in turn can cause abnormal uterine bleeding.
   • Prolactin. Produced by the pituitary gland in the brain, prolactin normally controls milk production during and after pregnancy. Prolactin levels also rise during stress, intercourse and following meals. Some women have an elevated level of prolactin, which is sometimes caused by a small benign tumor of the pituitary gland. This can cause abnormal bleeding patterns.
   • Testosterone. Even though this is usually referred to as a male hormone, women normally have testosterone in their blood stream as well. If these levels become abnormally high however this can lead to abnormal bleeding patterns. The most common cause is polycystic ovarian syndrome (PCOS) and rarely a testosterone-producing tumor on the ovary or the adrenal gland.
     
3. Office evaluation
   There are some additional tests your doctor might decide to do depending on your history and symptoms. Some of the more common ones include:
   • Pap smear. To screen for abnormal cells in the cervix or cervical cancer
   • Endometrial biopsy. This involves inserting a narrow plastic tube through the vagina and cervix into the uterus to get a sample from the lining of the uterus (endometrium). First a speculum is placed in the vagina. Sometimes, the cervix needs to be grasped with a special clamp for counter-traction (this is not always necessary). Then the plastic tube is passed through the cervix. At it's end there is a small opening and inside the hollow tube is a small plunger that can be withdrawn for gentle suction. The tube is twisted inside the uterine cavity, thereby gently scraping cells from the lining of the uterus that are in turn suctioned into the plastic tube by withdrawing the plunger. This portion usually takes less than a minute. Most women experience pain during an endometrial biopsy, the average pain level is 3-5 (on a scale from 0 to 10). A pathologist examines the tissue retrieved during the endometrial biopsy through a microscope.
   • Pelvic ultrasound. The ultrasound machine emits high frequency sound waves that travel differently through tissue depending on tissue density and makeup. The ultrasound machine then picks up the echo of the sound wave, calculates the signal and converts it to an image on the screen. The ultrasound examination provides excellent visualization of the uterus and ovaries and it is more likely to pick up abnormalities than a regular manual examination, especially in the ovaries. The ultrasound is usually performed with a special vaginal probe that is inserted into the vagina. This allows the ultrasound probe to be close to the uterus and ovaries, resulting in a more accurate examination. Sometimes the ultrasound is also performed through the abdominal wall, especially if a woman has a large uterus because of uterine fibroids or a very large ovarian cyst. In these cases the ultrasonic energy cannot reach far enough to see the whole uterus or ovary. The ultrasound examination usually takes 5 to 10 minutes and is not very uncomfortable.
   • Saline infusion sonohysterography. This is an extension of the pelvic ultrasound exam. A small plastic catheter is placed into the uterus and during the ultrasound exam, 10 to 15 ml of water are injected into the uterine cavity. The water gently opens up the uterine cavity and acts as a contrast medium during ultrasound. This allows for a more precise visualization of the endometrium, especially if there is suspicion of uterine polyps or fibroids that are being pushed into the uterine cavity.
   • Office hysteroscopy. The hysteroscope is inserted through the vagina and then the cervix, allowing the physician to view the uterus from the inside. This is especially useful in cases where there is abnormal uterine bleeding, uterine fibroids or polyps or during an infertility work-up. Because the hysteroscope is very thin (only 3-4mm), it can pass almost painlessly through the cervix, allowing the physician to do the procedure in the office with no required anesthesia. The average pain level that women feel during office hysteroscopy is only 2 to 3 on a ten point scale where zero is no pain and ten is worst pain ever. This allows accurate diagnosis and treatment for smaller issues.

These diagnostic options replace a procedure called dilatation and curettage (D&C) which at one time was considered the standard of care. This procedure is performed in the operating room, often under general anesthesia. The cervix is dilated and a sharp scraping device (curette) is advanced into the uterus through the cervix. The curette is then used to scrape the endometrium and the tissue that is released is removed and sent to pathology for examination. Unfortunately, the D&C is a blind procedure, i.e. the phycisian is not able to see inside the uterine cavity and can therefore miss a significant number of abnormal structures. One study found that a D&C missed significant abnormalities in over 60% of cases. In addition, this causes significant inconvenience to the patient when compared with the office evaluation procedures. Therefore, this is no longer a recommended option for the diagnosis of abnormal uterine bleeding.

Treatment Options for Abnormal Uterine Bleeding

There are several treatment options for abnormal uterine bleeding that need be to tailored to the individual clinical situation.

Hormonal manipulation

If your work-up indicates that you have an abnormally working thyroid gland, this will obviously need to be addressed. Your gynecologist might enlist the help of an endocrinologist to best tailor your therapy. Most patients can be treated with medications, however some require surgery, where a portion or all of the thyroid gland is removed. Prolactin is normally found in the blood stream (normal range 5-20 ng/ml). Mildy elevated prolactin levels (20-40 ng/ml) should be confirmed by a repeated blood test, since this can be affected by physical or emotional stress, exercise, meals and intercourse. Once hyperprolactinemia is confirmed your doctor will start to look for a cause. The more common causes include a benign tumor of the pituitary gland (lactotroph adenoma) and side effects of certain medications (mostly medications used for depression or scizophrenia). Less frequent causes include other brain tumors and poorly functioning thyroid gland. Your doctor will order an MRI exam of your brain to rule out any tumors. Very high levels of testosterone will prompt the physician to look for tumors of the adrenal glands and the ovaries, using ultrasound and a CT scan. Abnormal coagulation tests obviously merit further work-up and treatment, usually in cooperation with a hematologist.

If your pap smear is abnormal your doctor might want to do a test for human papilloma virus (HPV), since certain types of HPV increase your risk of having severe cellular changes that can lead to cancer. If your cellular changes are mild it is best to wait and repeat the pap test in a few months, since these changes often go away on their own. If you have more advanced disease you might have to have a microscopic examination of your cervix (colposcopy) and a biopsy of your cervix. This gives more detailed information about the amount of cellular changes you have. Sometimes women need to have a cone biopsy, where a portion of the cervix is removed in order to clear the abnormal areas. In the case of cervical cancer, some women will have to undergo a radical hysterectomy (see chapter on gynecologic oncology) or even radiation treatment.

The endometrial biopsy was performed to check for abnormal cells inside the uterus, i.e. in the endometrium. The endometrial cells can start to grow out of control (endometrial hyperplasia) and sometimes they become abnormally shaped in the process (atypia). If nothing is done this can lead to endometrial cancer. The most common cause for this is an imbalance in the amount of the two main female hormones, estrogen and progesterone. Estrogen stimulates the growth of the endometrial cells and is more prominent in the first half of the menstrual cycle, while progesterone stabilises the endometrial cells. If there proportionately more estrogen than progesterone in the blood stream for some time, the endometrial cells can start to grow too much. This can happen in women with polycystic ovary syndrome, in women who are overweight (the fat tissue produces estrogen) and in women who take estrogen containing hormones. This is also much more common in women over the age of 40. If your endometrial biopsy shows simple hyperplasia, this can be treated with progesterone for three months and a repeated biopsy at that time. If you have complex hyperplasia with atypia your risk of developing cancer is very high (35-43%) and most doctors would recommend a hysterectomy to prevent the development of cancer of the uterus. Unfortunately, about 25% of patients with complex endometrial hyperplasia with atypia already have small areas of cancer and so if women absolutely do not want to have a hysterectomy, at the very least they will need to undergo a hysteroscopy with resection of the endometrium and targeted biopsies.

If your hormonal work-up is normal, one reasonable option is to start taking birth control pills in an attempt to normalize your bleeding patterns. A three month trial is resonable and works well in a large number of women. Please remember that the birth control pill is not a good option in certain women, such as women who are older than 35 and smoke or have high blood pressure. In addition, women who might have a high risk of forming blood clots because of family history or women who have had blood clots in the past probably should not take birth control pills.

Intrauterine contraceptive device (IUD)

The Mirena progesterone IUD is a small t shaped plastic device that is inserted into the uterus in the office. The device contains progesterone that is slowly released into the uterus over a period of five years. A very small portion of the progesterone enters the bloodstream, but most of it stays in the uterus. This minimizes potential systematic (general) hormonal side effects. It acts as a contraceptive by thickening the cervical mucus making it impossible for sperm to enter the uterus. The progesterone IUD is also a very effective treatment option for abnormal uterine bleeding. One study evaluated 50 women with abnormal uterine bleeding who were on a waiting list for a hysterectomy and had the Mirena IUD placed in the meantime. Only three months following insertion 37 women had acceptable bleeding patterns and overall 41 of the women ended up not needing to have surgery (90%). The advantages of the hormonal IUD include ease of use, effective to control bleeding, excellent contraception, reversible treatment and low incidence of side effects. Disadvantages include the need for replacement every five years, occasional hormonal side effects (increased hair growth, acne, breast tenderness, headache, mood changes) and vaginal spotting. The vaginal spotting is most common in the first 3-6 months of use. With continued use, 70% of women will have very little periods and 30% of women will stop having periods completely while the IUD is in place. Although it is harmless, some women are uncomfortable with not having periods, so it is important to be aware of this possibility before use.

Hysteroscopy

Hysteroscopy can be a valuable tool for the treatment of abnormal bleeding. Submucosal fibroids, i.e. fibroids that are protruding into the uterine cavity can be removed using a hysteroscopic techniques. Uterine polyps can also be removed in a similar manner. Smaller fibroids and polyps can be removed in the office without the need for general anesthesia, but larger lesions will need to be removed in the operating room, either under general anesthesia or local anesthesia with sedation. These procedures are often long and require significant dilatation of the cervix which can be very uncomfortable. In addition, there is the potential for fluid overload as was discussed in an earlier chapter. A special type of hysteroscope, called a resectoscope, is wider than a standard hysteroscope and carries within it a channel that allows several specialized instruments to pass through. One of these instruments has a small wire loop at the end of it that is made out of metal that is a relatively poor conductor of electricity. The loop is connected to a device that sends electrical current through it. Because the electrical current has a hard time going through the poor conducting metal, the metal heats up significantly. This hot metal loop is then used to cut through a fibroid or a polyp inside the uterus. This is almost similar to cutting through hard butter with a hot knife. The fibroid or polyp are gradually cut into several little chips of tissue that are able to pass through the cervix. Another recent invention uses a small morcellator, which is similar to an old fashioned apple corer that gradually chops up the fibroid or polyp and suctions the chips out of the uterus. A disadvantage of using the metal loop is that since there is electricity running through the loop, it is not possible to use liquid such as saline that conducts electricity. The physician will therefore need to use a hypotonic water solution, which as discussed in the section on hysteroscopy, has a greater potential to cause problems with thinning of the blood and electrolyte imbalance. The advantage of the morcellator is that it can be used in saline since there is no electricity there, however it is slower than the loop and is not as well suited for large fibroids. There are also special kinds of loops that can be used in saline solution. These are more expensive than the standard loops, so not all hospitals have them yet, but they are probably safer since there is less chance of an electrolyte imbalance compared with the standard loops.

Endometrial ablation essentially means destruction of the endometrium. This is typically done in women who have abnormal uterine bleeding were the workup is negative, i.e. the doctor can't find a cause for the bleeding. Some of the methods can also be used if there are small fibroids present. However, these methods cannot be used if there are large fibroids present or if the uterus itself is abnormally large. There are several ways of performing an endometrial ablation. The traditional method is using the electrical loop mentioned above. In this method, called endometrial resection, the electrical loop is used to systematically shave off the lining of the uterus. The pieces of endometrium are removed and sent to pathology. Alternatively the physician can use a device called rollerball, which is essentially a hot ball that is rolled along the endometrium to burn and destroy the endometrial layer. The disadvantage with this method is that there is no sample to send to pathology. However, there is also less risk of going to deep into the uterus. When this happens, it is possible to perforate the uterus, i.e. punching a hole through the uterine wall. This can be potentially dangerous, especially if other organs, such as the urinary bladder or bowel are damaged. Additionally, there is a possibility of heavy bleeding if the perforation takes place close to the blood vessels to the uterus (uterine artery). Fortunately, it is unusual for organs to be damaged with a perforation, but your doctor will want to make sure by performing a laparoscopy to look inside the abdomen. If no damage to other organs is seen and there is minimal or no bleeding, you will most likely need to take antibiotics for a week to decrease the risk of infection.

Recently, simpler endometrial ablation methods have been developed. These are designed to be user friendly and easy to master. Collectively, these methods are called global endometrial ablation. These methods can be divided in two main categories, those who destroy the endometrium using heat and those who use cold.

The following devices use heat:

• Novasure
  This is a mesh that is placed into the uterine cavity and heated for an average of 90 seconds. The advantages are that the treatment time is short, however the cervix needs to be dilated significantly to place the device into the uterus.
• Thermachoice
  A small elastic balloon is placed into the uterine cavity and inflated with hot water. The treatment time is eight minutes. Advantages; small catheter (requires minimal dilation) Disadvantages; distention of the uterine cavity causes pain
• Hydrothermablation (HTA)
  Hot water is transmitted through a hysteroscope into the uterine cavity under low pressure. The hot water then circulates inside the cavity for about 10 minutes to destroy the endometrium. The pressure is kept low so that there is little danger of fluid going through the fallopian tubes. If there is more than 10ml of fluid missing, the system shuts off automatically. Advantages; Possible to visualize the uterine cavity during treatment to monitor the treatment effect, can effectively treat a uterine cavity that is abnormally shaped, can treat small fibroids Disadvantages; requires a lot of dilation of the cervix (painful), vaginal burns have been reported
• Microwave endmetrial ablation (MEA)
  A probe that transmits microwave energy is inserted into the uterus. The microwave energy is used to "paint" the endometrium with heat. Advantages; no uterine distention, relatively short treatment time (3-4 minutes) Disadvantages; requires a lot of dilatation, cannot treat a uterus with a thin muscle wall

• HerOption (cryoablation)
  A 5.5mm probe is inserted into the uterus and the tip of the probe cools down to minus 80°C. An elliptical ice ball forms around the probe and destroys the endometrial lining. The procedure is monitored using ultrasound. Two to three ice balls are needed to completely destroy the uterine cavity. Advantages; thin probe requiring little dilatation, less pain than with heat since the cold numbs the nerves (cryoanesthesia). Disadvantages; relatively long procedure (at least 20 minutes), requires ultrasound monitoring Endometrial ablation does not prevent you from getting pregnant. It is therefore necessary for women who undergo endometrial ablation to take some contraceptive measures. This is especially important since women who do get pregnant following an endometrial ablation have significantly higher rates of complications such as abortion, abnormal placenta, preterm birth and fetal death. Endometrial ablation is effective in most women, but not all. Overall about 15% of women who undergo endometrial ablation will need to have a hysterectomy because of continued bleeding problems. This important to consider when you are choosing the best treatment option, especially when considering that minimally invasive hysterectomy has a short recovery time and is a permanent solution to the problem. In fact, a recent study that compared patient satisfaction in women undergoing laparoscopic hysterectomy and endometrial ablation for abnormal uterine bleeding found that significantly more women in the laparoscopic hysterectomy group were satisfied with the treatment outcome. With this information in mind, younger women who have finished their childbearing might be better candidates for a laparoscopic hysterectomy, since they probably have a higher risk of symptom recurrence than women who are closer to menopause. Women with abnormal uterine bleeding who are considering endometrial ablation should also consider the hormonal IUD. These two treatment options are probably equally effective, but each has distinct advantages and disadvantages;
• Hormonal IUD
  Advantages:
  1) Reversible (better suited for women who have not finished their childbearing)
  2) Easy to use (can be placed into the uterus in 1-2 minutes in the doctors office with little discomfort)
  3) Provides contraception
  Disadvantages:
  1) Needs to be replaced every 5 years
  2) Hormonal side effects in small proportion of women
  3) A "foreign object" in the uterus
• Endometrial ablation
  Advantages: 1) No risk of hormonal side effects 2) No "foreign body" in the uterus 3) Can be performed in the office in some cases 4) No need for repeated treatment in 85% of patients Disadvantages: 1) More invasive and takes longer than the IUD insertion 2) Irreversible (not suited for women who want to have more children) 3) Women still need to take some contraceptive measures 4) More potential for serious complications during treatment

The permanent treatment option for abnormal uterine bleeding is to perform a hysterectomy (see chapter on hysterectomy). All the minimally invasive treatment options mentioned above are designed to decrease the chance that a hysterectomy might be required, since this is the most invasive treatment option. In any case, an abdominal hysterectomy that is performed through a large abdominal incision is rarely required in patients with abnormal bleeding. The vast majority of them (approximately 90% depending on the patient population) should be able to have either a vaginal or a laparoscopic hysterectomy, with decreased pain and shorter recovery period.