Abnormal Uterine Bleeding – Causes, Symptoms, Treatment

Abnormal Uterine Bleeding (AUB) is a broad term that describes irregularities in the menstrual cycle involving frequency, regularity, duration, and volume of flow outside of pregnancy. Up to one-third of women will experience abnormal uterine bleeding in their life, with irregularities most commonly occurring at menarche and perimenopause. A normal menstrual cycle has a frequency of 24 to 38 days, lasts 7 to 9 days, with 5 to 80 milliliters of blood loss. Variations in any of these 4 parameters constitute abnormal uterine bleeding. Older terms such as oligomenorrhea, menorrhagia, and dysfunctional uterine bleeding should be discarded in favor of using simple terms to describe the nature of the abnormal uterine bleeding. Revisions to the terminology were first published in 2007, followed by updates from the International Federation of Obstetrics and Gynecology (FIGO) in 2011 and 2018. The FIGO systems first define the abnormal uterine bleeding, then give an acronym for common etiologies. These descriptions apply to chronic, nongestational AUB. In 2018, the committee added intermenstrual bleeding and defined irregular bleeding as outside the 75th percentile.

Abnormal uterine bleeding can also be divided into acute versus chronic. Acute AUB is excessive bleeding which requires immediate intervention to prevent further blood loss. Acute AUB can occur on its own or superimposed on chronic AUB, which refers to irregularities in menstrual bleeding for most of the previous 6 months.

Pathophysiology

The uterine and ovarian arteries supply blood to the uterus. These arteries become the arcuate arteries; then the arcuate arteries send off radial branches which supply blood to the 2 layers of the endometrium, the functionalis, and basalis layers. Progesterone levels fall at the end of the menstrual cycle, leading to enzyme breakdown of the functionalis layer of the endometrium. This breakdown leads to blood loss and sloughing which makes up menstruation. Functioning platelets and thrombin, and vasoconstriction of the arteries to the endometrium control blood loss. Any derangement in the structure of the uterus (such as leiomyoma, polyps, adenomyosis, malignancy or hyperplasia), derangements to the clotting pathways (coagulopathies or iatrogenically), or disruption of the hypothalamic-pituitary-ovarian axis (through ovulatory/endocrine disorders or iatrogenically) can affect menstruation and lead to abnormal uterine bleeding.

Causes of Abnormal Uterine Bleeding

Every woman’s period (menstrual cycle) is different.

  • On average, a woman’s period occurs every 28 days.
  • Most women have cycles between 24 and 34 days apart. It usually lasts 4 to 7 days.
  • Young girls may get their periods anywhere from 21 to 45 days or more apart.
  • Women in their 40s may start to have their period less often or have the interval between their periods decrease.

For most women, female hormone levels change every month. The hormones estrogen and progesterone are released as part of the process of ovulation. When a woman ovulates, an egg is released.

AUB can occur when the ovaries do not release an egg. Changes in hormone levels cause your period to be later or earlier. Your period may sometimes be heavier than normal.

AUB is more common in teenagers or in premenopausal women. Women who are overweight also may be more likely to have AUB.

In many women, AUB is caused by a hormone imbalance. It can also occur due to following causes:

  • Thickening of the uterine wall or lining
  • Uterine fibroids
  • Uterine polyps
  • Cancers of ovaries, uterus, cervix, or vagina
  • Bleeding disorders or problems with blood clotting
  • Polycystic ovary syndrome
  • Severe weight loss
  • Hormonal birth control, such as birth control pills or intrauterine devices (IUD)
  • Excessive weight gain or loss (more than 10 pounds or 4.5 kilograms)
  • Infection of the uterus or cervix

PALM-COEIN is a useful acronym provided by the International Federation of Obstetrics and Gynecology (FIGO) to classify the underlying etiologies of abnormal uterine bleeding. The first portion, PALM, describes structural issues. The second portion, COEI, describes non-structural issues. The N stands for “not otherwise classified.”

  • P: Polyp
  • A: Adenomyosis
  • L: Leiomyoma
  • M: Malignancy and hyperplasia
  • C: Coagulopathy
  • O: Ovulatory dysfunction
  • E: Endometrial disorders
  • I:- Iatrogenic
  • N: Not otherwise classified

One or more of the problems listed above can contribute to a patient’s abnormal uterine bleeding. Some structural entities, such as endocervical polyps, endometrial polyps, or leiomyomas, may be asymptomatic and not the primary cause of a patient’s AUB.

In the 2018 FIGO system, AUB secondary to anticoagulants was moved from the coagulopathy category to the iatrogenic category.

AUB not otherwise classified contains etiologies that are rare, and include arteriovenous malformations (AVMs), myometrial hyperplasia, and endometritis.

Others Possible causes fall into the following three areas:
  • Uterine-related problems
    1. Growths or tumors of the uterus that are not cancer; these can be called uterine fibroids or polyps.
    2. Cancer of the uterus or cervix.
    3. Certain types of birth control—for example, an intrauterine device (IUD).
    4. Problems related to pregnancy, such as a miscarriage or ectopic pregnancy, can cause abnormal bleeding. A miscarriage is when an unborn baby (also called a fetus) dies in the uterus. An ectopic pregnancy is when a baby starts to grow outside the womb (uterus), which is not safe.
  • Hormone-related problems
  • Other illnesses or disorders
    1. Bleeding-related disorders, such as von Willebrand disease (VWD) or platelet function disorder.
    2. Nonbleeding-related disorders such as liver, kidney, or thyroid disease; pelvic inflammatory disease; and cancer.
  • Problems with ovulation
  • Fibroids and polyps
  • A condition in which the endometrium grows into the wall of the uterus
  • Bleeding disorders
  • Problems linked to some birth control methods, such as an intrauterine device (IUD) or birth control pills
  • Miscarriage
  • Ectopic pregnancy
  • Certain types of cancer, such as cancer of the uterus
You Might Also Like   Recurrent Miscarriage - Causes, Symptoms, Treatment

Symptoms of Abnormal Uterine Bleeding

You might have menorrhagia if you:

  • Bleeding or spotting from the vagina between periods
  • Periods that occur less than 28 days apart (more common) or more than 35 days apart
  • Time between periods changes each month
  • Heavier bleeding (such as passing large clots, needing to change protection during the night, soaking through a sanitary pad or tampon every hour for 2 to 3 hours in a row)
  • Bleeding that lasts for more days than normal or for more than 7 days
  • Excessive growth of body hair in a male pattern (hirsutism)
  • Hot flashes
  • Mood swings
  • Tenderness and dryness of the vagina
  • Have a menstrual flow that soaks through one or more pads or tampons every hour for several hours in a row.
  • Need to double up on pads to control your menstrual flow.
  • Need to change pads or tampons during the night.
  • Have menstrual periods lasting more than 7 days.
  • Have a menstrual flow with blood clots the size of a quarter or larger.
  • Have a heavy menstrual flow that keeps you from doing the things you would do normally.
  • Have constant pain in the lower part of the stomach during your periods.
  • Are tired, lack energy, or are short of breath.

Diagnosis of Abnormal Uterine Bleeding

History and Physical

The clinician should obtain a detailed history from a patient who presented with complaints related to menstruation. Specific aspects of the history include:

  • Menstrual history

    • Age at menarche
    • Last menstrual period
    • Menses frequency, regularity, duration, volume of flow

      • Frequency can be described as frequent (less than 24 days), normal (24 to 38 days), or infrequent (greater than 38 days)
      • Regularity can be described as absent, regular (with a variation of +/- 2 to 20 days), or irregular (variation greater than 20 days)
      • Duration can be described as prolonged (greater than 8 days), normal (approximately 4 to 8 days), or shortened (less than 4 days)
      • Volume of flow can be described as heavy (greater than 80 mL), normal (5 to 80 mL), or light (less than 5 mL of blood loss)

        • Exact volume measurements are difficult to determine outside research settings; therefore, detailed questions regarding frequency of sanitary product changes during each day, passage and size of any clots, need to change sanitary products during the night, and a “flooding” sensation are important
    • Intermenstrual and postcoital bleeding
  • Sexual and reproductive history

    • Obstetrical history including the number of pregnancies and mode of delivery
    • Fertility desire and subfertility
    • Current contraception
    • History of sexually transmitted infections (STIs)
    • PAP smear history
  • Associated symptoms/Systemic symptoms

    • Weight loss
    • Pain
    • Discharge
    • Bowel or bladder symptoms
    • Signs/symptoms of anemia
    • Signs/symptoms or history of a bleeding disorder
    • Signs/symptoms or history of endocrine disorders
  • Current medications
  • Family history, including questions concerning coagulopathies, malignancy, endocrine disorders
  • Social history, including tobacco, alcohol, and drug uses; occupation; impact of symptoms on quality of life
  • Surgical history

The physical exam should include:

  • Vital signs, including blood pressure and body mass index (BMI)
  • Signs of pallor, such as skin or mucosal pallor
  • Signs of endocrine disorders

    • Examination of the thyroid for enlargement or tenderness
    • Excessive or abnormal hair growth patterns, clitoromegaly, acne that could indicate hyperandrogenism
    • Moon facies, abnormal fat distribution, striae that could indicate Cushing’s
  • Signs of coagulopathies, such as bruising or petechiae
  • Abdominal exam to palpate for any pelvic or abdominal masses
  • Pelvic exam: Speculum and bimanual

    • PAP smear if indicated
    • STI screening (such as for gonorrhea and chlamydia) and wet prep if indicated
    • Endometrial biopsy, if indicated

Lab Tests

Your provider will rule out other possible causes of irregular bleeding. You will likely have a pelvic exam and Pap/HPV test. Other tests that may be done include:

  • Complete blood count (CBC)
  • Blood clotting profile
  • Liver function tests (LFT)
  • Fasting blood glucose
  • Hormone tests, for FSH, LH, male hormone (androgen) levels, prolactin, and progesterone
  • Pregnancy test
  • Thyroid function tests

Laboratory testing can include but is not limited to a urine pregnancy test, complete blood count, ferritin, coagulation panel, thyroid function tests, gonadotropins, prolactin.

Your doctor might tell you that one or more of the following tests will help find out if you have a bleeding problem:

  • Blood test – In this test, your blood will be taken using a needle. It will then be looked at to check for anemia, problems with the thyroid, or problems with the way the blood clots.
  • Pap test – For this test, cells from your cervix are removed and then looked at to find out if you have an infection, inflammation, or changes in your cells that might be cancer or might cause cancer.
  • Endometrial biopsy – Tissue samples are taken from the inside lining of your uterus or “endometrium” to find out if you have cancer or other abnormal cells. You might feel as if you were having a bad menstrual cramp while this test is being done. But, it does not take long, and the pain usually goes away when the test ends.
  • Ultrasound – This is a painless test using sound waves and a computer to show what your blood vessels, tissues, and organs look like. Your doctor then can see how they are working and check your blood flow.

Using the results of these first tests, the doctor might recommend more tests, including,

  • Sonohysterogram – This ultrasound scan is done after fluid is injected through a tube into the uterus by way of your vagina and cervix. This lets your doctor look for problems in the lining of your uterus. Mild to moderate cramping or pressure can be felt during this procedure.
  • Hysteroscopy – This is a procedure to look at the inside of the uterus using a tiny tool to see if you have fibroids, polyps, or other problems that might be causing bleeding. You might be given drugs to put you to sleep (this is known as “general anesthesia) or drugs simply to numb the area being looked at (this is called “local anesthesia”).
  • Dilation and Curettage (D&C) – This is a procedure (or test) that can be used to find and treat the cause of bleeding. During a D&C, the inside lining of your uterus is scraped and looked at to see what might be causing the bleeding. A D&C is a simple procedure. Most often it is done in an operating room, but you will not have to stay in the hospital afterwards. You might be given drugs to make you sleep during the procedure, or you might be given something that will numb only the area to be worked on.
You Might Also Like   Trophoblast Development /Second Week of Development

Imaging studies can include transvaginal ultrasound, MRI, hysteroscopy. Transvaginal ultrasound does not expose the patient to radiation and can show uterus size and shape, leiomyomas (fibroids), adenomyosis, endometrial thickness, and ovarian anomalies. It is an important tool and should be obtained early in the investigation of abnormal uterine bleeding. MRI provides detailed images that may be useful in surgical planning, but it is costly and not the first-line choice for imaging in patients with AUB. Hysteroscopy and sonohysterography (transvaginal ultrasound with intrauterine contrast) are helpful in situations where endometrial polyps are noted, images from transvaginal ultrasound are inconclusive, or submucosal leiomyomas are seen. Hysteroscopy and sonohysterography are more invasive, but can often be performed in office settings.

Endometrial tissue sampling may not be necessary for all women with AUB but should be performed on women at high risk for hyperplasia or malignancy. An endometrial biopsy is considered the first-line test in women with AUB who are 45 years or older. Endometrial sampling should also be performed in women younger than 45 with unopposed estrogen exposure, such as women with obesity and/or polycystic ovarian syndrome (PCOS), as well as a failure of treatment, or persistent bleeding.

Treatment of Abnormal Uterine Bleeding

Treatment of abnormal uterine bleeding depends on multiple factors, such as the etiology of the AUB, fertility desire, the clinical stability of the patient, and other medical comorbidities. Treatment should be individualized based on these factors. In general, medical options are preferred as initial treatment for AUB.

Medications often are tried first to treat irregular or heavy menstrual bleeding. The medications that may be used include the following:

Drug Therapy
  • Iron supplements –To get more iron into your blood to help it carry oxygen if you show signs of anemia.
  • Ibuprofen (Advil) – To help reduce pain, menstrual cramps, and the amount of bleeding. In some women, NSAIDS can increase the risk of bleeding.
  • Desmopressin Nasal Spray (Stimate) – To stop bleeding in people who have certain bleeding disorders, such as von Willebrand disease and mild hemophilia, by releasing a clotting protein or “factor”, stored in the lining of the blood vessels that helps the blood to clot and temporarily increasing the level of these proteins in the blood.
  • Antifibrinolytic medicines (tranexamic acid, aminocaproic acid) – To reduce the amount of bleeding by stopping a clot from breaking down once it has formed.
  • Hormonal birth control methods – Birth control pills, the skin patch, and the vaginal ring contain hormones. These hormones can lighten menstrual flow. They also help make periods more regular.
  • Gonadotropin-releasing hormone (GnRH) agonists – These drugs can stop the menstrual cycle and reduce the size of fibroids.
  • Nonsteroidal anti-inflammatory drugs – These drugs, which include ibuprofen, may help control heavy bleeding and relieve menstrual cramps.
  • Antibiotics – If you have an infection, you may be given an antibiotic.
  • Special medications—If you have a bleeding disorder, your treatment may include medication to help your blood clot.
  • Intrauterine device (IUD) – Your doctor may suggest an IUD. An IUD is a small, plastic device that your doctor inserts into your uterus through your vagina to prevent pregnancy. One type of IUD releases hormones. This type can significantly reduce abnormal bleeding. Like birth control pills, sometimes IUDs can actually cause abnormal bleeding. Tell your doctor if this happens to you.
  • Birth control pills – Birth control pills contain hormones that can stop the lining of your uterus from getting too thick. They also can help keep your menstrual cycle regular and reduce cramping. Some types of birth control pills, especially the progestin-only pill (also called the “mini-pill”) can actually cause abnormal bleeding for some women. Let your doctor know if the pill you’re taking doesn’t control your abnormal bleeding.
  • A D&C, or dilation and curettage – A D&C is a procedure in which the opening of your cervix is stretched just enough so a surgical tool can be put into your uterus. Your doctor uses this tool to scrape away the lining of your uterus. The removed lining is checked in a lab for abnormal tissue. A D&C is done under general anesthesia (while you’re in a sleep-like state). If you’re having heavy bleeding, your doctor may perform a D&C both to find out the problem and to treat the bleeding. The D&C itself often makes heavy bleeding stop. Your doctor will decide if this procedure is necessary.
You Might Also Like   The Embolization of Uterine Leiomyomata

Surgery

  • Dilation and Curettage (D&C) – A procedure in which the top layer of the uterus lining is removed to reduce menstrual bleeding. This procedure might need to be repeated over time.
  • Operative hysteroscopy – A surgical procedure, using a special tool to view the inside of the uterus, that can be used to help remove polyps and fibroids, correct abnormalities of the uterus, and remove the lining of the uterus to manage heavy menstrual flow.
  • Endometrial ablation or resection – Two types of surgical procedures using different techniques in which all or part of the lining of the uterus is removed to control menstrual bleeding. While some patients will stop having menstrual periods altogether, others may continue to have periods but the menstrual flow will be lighter than before. Although the procedures do not remove the uterus, they will prevent women from having children in the future.
  • Hysterectomy – A major operation requiring hospitalization that involves surgically removing the entire uterus. After having this procedure, a woman can no longer become pregnant and will stop having her period.
  • Hysterectomy – This type of surgery removes the uterus. If you have a hysterectomy, you won’t have any more periods and you won’t be able to get pregnant. Hysterectomy is major surgery that requires general anesthesia and a hospital stay. It may require a long recovery period. Talk to your doctor about the risks and benefits of hysterectomy.
  • Endometrial ablation – is a surgical procedure that destroys the lining of the uterus. Unlike a hysterectomy, it does not remove the uterus. Endometrial ablation may stop all menstrual bleeding in some women. However, some women still have light menstrual bleeding or spotting after endometrial ablation. A few women have regular menstrual periods after the procedure. Women who have endometrial ablation still need to use some form of birth control even though, in most cases, pregnancy is not likely after the procedure.

For acute abnormal uterine bleeding, hormonal methods are first-line in medical management. Intravenous (IV) conjugated equine estrogen, combined oral contraceptive pills (OCPs), and oral progestins are all options for treatment of acute AUB. Tranexamic acid prevents fibrin degradation and can be used to treated acute AUB. Tamponade of the uterine bleeding with a Foley bulb is a mechanical option for treatment of acute AUB. It is important to assess the clinical stability of the patient and replace volume with intravenous fluids and blood products while attempting to stop the acute abnormal uterine bleeding. Desmopressin, administered intranasally, subcutaneously, or intravenously, can be given for acute AUB secondary to the coagulopathy von Willebrand disease.

Based on the PALM-COEIN acronym for etiologies of chronic AUB, specific treatment options for each category are listed below:

Polyps are treated through surgical resection.

Adenomyosis is treated via hysterectomy. Less often, adenomyomectomy is performed.

Leiomyomas (fibroids) can be treated through medical or surgical management depending on the patient’s desire for fertility, medical comorbidities, pressure symptoms, and distortion of the uterine cavity. Surgical options include uterine artery embolization, endometrial ablation, or hysterectomy. Medical management options include a levonorgestrel-releasing intrauterine device (IUD), GnRH agonists, systemic progestins, and tranexamic acid with non-steroidal anti-inflammatory drugs (NSAIDs).

Malignancy or hyperplasia can be treated through surgery, +/- adjuvant treatment depending on the stage, progestins in high doses when surgery is not an option, or palliative therapy, such as radiotherapy.

Coagulopathies leading to AUB can be treated with tranexamic acid or desmopressin (DDAVP).

Ovulatory dysfunction can be treated through lifestyle modification in women with obesity, PCOS, or other conditions in which anovulatory cycles are suspected. Endocrine disorders should be corrected with the use of appropriate medications, such as cabergoline for hyperprolactinemia and levothyroxine for hypothyroidism.

Endometrial disorders have no specific treatment as mechanisms are not clearly understood.

Iatrogenic causes of AUB should be managed based on the offending drug and/or drugs. If a certain method of contraception is the suspected culprit for AUB, alternative methods can be considered, such as the levonorgestrel-releasing IUD, combined oral contraceptive pills (in monthly or extended cycles), or systemic progestins. If other medications are suspected and cannot be discontinued, the aforementioned methods can also be helpful to control AUB. Individual therapy should be tailored based on a patient’s reproductive wishes and medical comorbidities.

Not otherwise classified causes of AUB include entities such as endometritis and AVMs. Endometritis can be treated with antibiotics and AVMs with embolization.

References