Abnormal uterine bleeding (AUB) is a common and debilitating condition with high direct and indirect costs. AUB frequently co-exists with fibroids, but the relationship between the two remains incompletely understood and in many women the identification of fibroids may be incidental to a menstrual bleeding complaint.

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.  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 that 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.

Causes of Abnormal Uterine Bleeding

Other causes of AUB – The PALM-COEIN classification system accepts that women may have more than one underlying etiology and also that often in the case of structural abnormalities, many women may in fact be asymptomatic.

  • Polyps (AUB-P) – Endometrial polyps are epithelial proliferations arising from the endometrial stroma and glands. The majority are asymptomatic. The contribution of polyps to AUB varies widely ranging from 3.7% to 65% [rx], [rx], but it is widely accepted [rx]. The incidence of polyps as with fibroids increases with age and both pathologies may frequently co-exist, or suspected polyps visualized on transvaginal ultrasound scanning (TV-USS) may be mistaken for SM fibroids and vice-versa [rx].
  • Adenomyosis (AUB-A) – The relationship between adenomyosis and AUB remains unclear [rx], particularly with regard to wide variations in histopathological diagnosis reflecting variations in criteria used and also improved radiological diagnosis. Typically, adenomyosis is associated with increasing age and may co-exist with fibroids. Furthermore, adenomyosis maybe both focal and diffuse and it may be harder to establish a diagnosis if fibroids are also present [rx].
  • Malignancy (AUB-M) – Endometrial cancer is the most common gynecological malignancy in the western world. Historically, endometrial cancer has rarely occurred in premenopausal women; however, with increasing obesity and rising prevalence of the metabolic syndrome, the endocrine-driven subset of endometrial malignancy has markedly increased in frequency. [rx]. With the reclassification by the WHO from hyperplasia to endometrial intraepithelial neoplasia (EIN), the current prevalence of the premalignant disease is unknown. The evaluation of the endometrium may be affected by distortion of the uterine cavity by fibroids, and as such, the co-existing pathology may delay diagnosis.

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.

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 period’s 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.

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In many women, AUB is caused by a hormone imbalance. It can also occur due to the 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
  • Polyp
  • Adenomyosis
  • Leiomyoma
  • Malignancy and hyperplasia
  • Coagulopathy
  • Ovulatory dysfunction due to hypothyroidism, hyperthyroidism, prolactin-secreting tumors, PCOS
  • Endometrial
  • Iatrogenic (IUDs, chemotherapeutic agents, anticoagulants)
  • Not yet classified

It is essential for the provider to choose the most likely etiology for the effective and appropriate management of these women.

Symptoms of Abnormal Uterine Bleeding

Symptoms include vaginal bleeding that occurs irregularly, at an abnormal frequency, lasts excessively long, or is more than normal.[rx] The normal frequency of periods is 22 to 38 days. Variation in the length of time between cycles is typically less than 21 days.[rx] Bleeding typically last less than nine days and blood loss is less than 80 mL. Excessive blood loss may also be defined as that which negatively affects a person’s quality of life.[rx] Bleeding more than six months after menopause is also a concern.[rx]

AUB is unpredictable. The bleeding may be very heavy or light, and can occur often or randomly.

Symptoms of AUB may include:

  • 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

Other symptoms caused by changes in hormone levels may include:

  • Excessive growth of body hair in a male pattern (hirsutism)
  • Hot flashes
  • Mood swings
  • Tenderness and dryness of the vagina

A woman may feel tired or fatigued if she loses too much blood over time. This is a symptom of anemia.

Diagnosis of Abnormal Uterine Bleeding

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 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

Evaluation

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 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
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Your provider may recommend the following:

  • Culture to look for infection
  • Biopsy to check for precancer, cancer, or to help decide on hormone treatment
  • Hysteroscopy, performed in your provider’s office to look into the uterus through the vagina
  • Ultrasound to look for problems in the uterus or pelvis
  • Ultrasound – This uses sound waves to make images of the inside of your uterus so your doctor can look for fibroids or polyps.
  • Hysteroscopy – The doctor will look inside your uterus with a tiny lighted scope that they put in through your cervix.
  • Biopsy  – The doctor may take out a small piece of tissue and check it under a microscope for abnormal cells.
  • Magnetic resonance imaging – This test uses radio waves and powerful magnets to make detailed pictures of your uterus. It isn’t used that often, but it can help spot adenomyosis.

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.

Treatment of Abnormal Uterine Bleeding

Treatment options include iron supplementation, combined oral contraceptives (COCs), progesterone, nonsteroidal anti-inflammatory drugs (NSAIDs), antifibrinolytics, desmopressin and GnRH analogs. Management is largely based on the severity of the bleeding and anemia [rx]. If an underlying cause is identified, specific treatment is given additionally. As HMB in adolescents is mostly due to anovulatory cycles, treatment is focused on anovulatory uterine bleeding.

Drugs are usually the first thing your doctor will try. They include:

  • Hormones – Birth control pills and other hormone treatments may be able to give you regular menstrual cycles and lighter periods.
  • Gonadotropin-releasing hormone agonists (GnRHa) – These stop your body from making certain hormones. They can shrink fibroids for a while, but they’re usually used along with other treatments.
  • NSAIDS-   If you take anti-inflammatories like ibuprofen or naproxen a few days before your period starts, they may help lighten the bleeding.
  • Tranexamic acid-   This is a pill that helps your blood clot and can control heavy uterine bleeding. Tranexamic acid prevents fibrin degradation and can be used to treated acute AUB. Tamponade of uterine bleeding with a Foley bulb is a mechanical option for treatment of acute AUB.
  • IUD – For some women, an IUD that releases a hormone called progestin can stop heavy bleeding. Many women who use one don’t get a period at all.
  • Endometrial ablation – This uses heat, cold, electricity, or a laser to destroy the lining of your uterus. It may end your periods entirely. You probably won’t be able to get pregnant after having it done, but it can be dangerous if you do. You’ll need to use birth control until menopause.
  • Myomectomy or uterine artery embolization – If you have fibroids, the doctor may take them out or cut off the vessels that supply them with blood.
  • Hysterectomy-   This is when the doctor removes your uterus. You may need a hysterectomy if your fibroids are very large or you have endometrial or uterine cancer. Otherwise, it’s the last resort when other treatments haven’t worked.
  • Intravenous (IV) conjugated equine estrogen – combined oral contraceptive pills (OCPs), and oral progestins are all options for treatment of acute AUB.
  • 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.
  • 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.
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Treatment With Severity

  • Mild Anovulatory Uterine Bleeding – For girls with mild bleeding with normal hemoglobin, observation is enough, unless they report a negative change in their life quality. NSAIDs, such as ibuprofen and naproxen sodium, may help to decrease flow. If the hemoglobin is 10-12 g/dL, both observation and hormonal therapy are acceptable alternatives, as long as iron supplementation with 60 mg elemental iron per day is given. If hormonal therapy is decided on as the treatment choice, the possible regimens are the same as those for moderate anovulatory uterine bleeding, discussed below in detail. Re-evaluation should be made at three months or sooner if the bleeding persists or becomes more severe.
  • Moderate Anovulatory Uterine Bleeding – These patients can also be managed on an outpatient basis. In addition to iron supplementation, hormonal therapy is necessary to stabilize endometrial proliferation and shedding. There is no consensus on whether to treat with COCs or progestin-only regimens [rx]. In adolescents with moderate anemia who are actively bleeding, COCs are a better choice, as estrogen improves hemostasis [rx]. Monophasic COCs, containing at least 30 mcg of ethinyl E2, are preferred to prevent breakthrough bleeding. We recommend taking one pill every 8-12 hours until the bleeding stops, then to continue with one pill per day for a total of at least 21 days. If bleeding starts again dosing may be increased to twice a day for a total 21 days. 4-8 mg of ondansetron can be given if nausea occurs with high doses of E2 [rx]. At the end of 21 days, seven days of placebo or pause should be given. COCs treatment is continued for 3-6 months until the hemoglobin level reaches ≥12 g\dL. Different COCs regimens have been suggested in the literature [rx,rx,rx].
  • Severe Anovulatory Uterine Bleeding – Patients with hemoglobin levels <7 g/dL and those with hemoglobin levels <10 g/dL but who have active heavy bleeding and hemodynamic instability (tachycardia, hypotension, orthostatic vital signs) must be hospitalized. They must be promptly evaluated in case blood transfusion is necessary. Patients with hemoglobin levels of 8-10 g/dL with parents who can reliably be contacted by telephone can be followed on an ambulatory basis [rx]. All patients with severe anemia due to menstrual bleeding must be assessed for bleeding disorders. Supplementation of 60-120 mg elemental iron must be started as soon as the patient is stable enough to take oral pills.
  • 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).
  • 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.

References

  1. https://www.ncbi.nlm.nih.gov/books/NBK532913/
  2. https://www.ncbi.nlm.nih.gov/books/NBK542229/
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970656/
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6081150/
  5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2218686/
  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083466/
  7. https://www.ncbi.nlm.nih.gov/books/NBK536910/
  8. https://medlineplus.gov/ency/article/000903.htm
  9. https://medlineplus.gov/ency/article/000903.htm
  10. https://en.wikipedia.org/wiki/Abnormal_uterine_bleeding

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