Abnormal (Dysfunctional) Uterine Bleeding

Descriptive text is not available for this image Basics

Description

  • Abnormal uterine bleeding (AUB) is uterine bleeding that is abnormal in terms of menstrual regularity, frequency, duration, or volume (1).
  • May be acute or chronic (occurring >6 months)
  • The International Federation of Gynecology and Obstetrics (FIGO) now uses AUB rather than dysfunctional uterine bleeding (DUB).

Epidemiology

Adolescent and perimenopausal women are affected most often.

Incidence

5% of reproductive-aged women will see a doctor in any given year for AUB.

Prevalence

10–30% of reproductive-aged women have AUB (1).

Etiology and Pathophysiology

  • The breakdown of etiologies for AUB varies by population and age. Anovulation accounts for 90% of AUB among adolescents related to an immature hypothalamic pituitary ovarian (HPO) axis.
  • The mnemonic PALM-COEIN was developed to describe AUB in reproductive-aged women.
  • PALM (structural causes): Polyp, Adenomyosis, Leiomyoma, and Malignancy and/or hyperplasia
  • COEIN (nonstructural causes): Coagulopathy, Ovulatory disorders, Endometrial, Iatrogenic, and Not yet classified
  • Coagulopathy
    • Approximately 20% of patients with heavy menstrual bleeding have a bleeding disorder.
    • von Willebrand disease and platelet dysfunction are the most common coagulopathies associated with AUB.
  • Diseases causing ovulatory dysfunction: hyperprolactinemia, immature hypothalamic-pituitary-adrenal axis (adolescence), intense exercise/stress, polycystic ovary syndrome (PCOS), starvation (including eating disorders), thyroid disorders
  • Medications (iatrogenic causes): anticoagulants, antipsychotic medications (mostly first generation), copper intrauterine device, hormonal contraception or other hormone therapy, tamoxifen (estrogen receptor antagonists),
  • Other causes of AUB not defined in PALM-COEIN: ectopic pregnancy, threatened or incomplete abortion or hydatidiform mole, upper genital tract infections, advanced or fulminant liver disease, chronic renal disease, nutritional deficiencies, inflammatory bowel disease, excessive weight gain, increased exercise

Genetics

Inherited bleeding disorders such as von Willebrand disease and rare inherited clotting factor deficiencies and platelet function defects

Risk Factors

  • Bleeding disorders are a major risk factor.
  • Among adolescents, conditions including PCOS, thyroid disease, stress, and eating disorders increase the risk of an immature HPO axis.

General Prevention

There is no known direct preventive measure for AUB.

Descriptive text is not available for this image Diagnosis

Definitions of normal and AUB; the FIGO recommendations on terminologies and definitions for normal and AUB

Menstrual Cycle TermsDescriptive TermsDefinition
Frequency (interval between the start of each menstrual cycle)Infrequent>38 days
Normal≥24 and ≤38 days
Frequent<24 days
Regularity (variation of menstrual cycle length, measured over 12 months)RegularRegular: shortest to longest cycle variation ≤7 to 9 days
IrregularIrregular: shortest to longest cycle variation ≥10 rays
Duration of menstruationShortened<4.5 days
Normal≤8 days
Prolonged>8 days
Volume (total blood loss each menstrual cycle)LightPatient considers light
NormalPatient considers normal
HeavyPatient considers heavy

History

  • Menstrual history: onset, frequency, regularity and volume; volume should be quantified by pad/tampon use, presence and size of clots; passing blood clots or changing pads/tampons at least hourly suggest heavy menstrual bleeding (1).
  • A history of postcoital bleeding may indicate cervicitis, ectropion, or rarely cervical cancer.
  • Associated abdominopelvic pain may suggest infection, structural lesions, or endometriosis.
  • Gynecologic history: gravidity and parity, STI history, previous Pap smear results
  • Family history of abnormal bleeding or personal history of heavy menstrual bleeding since menarche, or symptoms such as frequent bruising, bleeding gums, epistaxis, postpartum hemorrhage, or bleeding with surgical and dental procedures.
  • Review of systems (Exclude symptoms of pregnancy, bleeding disorders, stress, exercise, recent weight change, visual changes, headaches, galactorrhea)
ALERT

Postmenopausal bleeding is any bleeding that occurs >1 year after the last menstrual period; cancer must always be ruled out (1).

Physical Exam

Evaluate for:

  • Signs of PCOS (i.e., hirsutism and acne)
  • Signs of thyroid disease (i.e., thyroid nodules)
  • Signs of insulin resistance (i.e., acanthosis nigricans)
  • Signs of pituitary lesions (i.e., visual field defects, galactorrhea)
  • Findings suggestive of bleeding disorder include petechiae, ecchymosis, skin pallor, or swollen joints (although absence does not exclude the possibility of underlying bleeding condition) (2).
  • Pelvic exam: Examine all potential bleeding sites, including the urethra, perineum, and anus.
  • Perform cervical cancer screening if not up-to-date.

Pediatric Considerations

  • Premenarchal children with vaginal bleeding should be evaluated for foreign bodies, physical/sexual abuse, possible infections, and signs of precocious puberty.
  • Pelvic examination can be deferred in adolescents if the patient is not sexually active, neither trauma nor infection is suspected, and the response to initial treatment is adequate (1).

Differential Diagnosis

See “Etiology and Pathophysiology.”

Diagnostic Tests & Interpretation

Initial Tests (lab, imaging)

  • All patients: pregnancy test and complete blood count
  • If coagulopathy is suspected: prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen level; note that these results may be normal in women with von Willebrand or other bleeding disorders.
  • Consider other tests based on differential diagnosis and risk factors:
    • Suspected hormonal abnormalities: TSH, prolactin level
    • Age ≥45 years or elevated risk of endometrial carcinoma: endometrial biopsy (EMB)
    • Concern for infection: STI screening (GC/CT, trichomonas), KOH prep, vaginitis panel
    • Suspected congenital adrenal hyperplasia: 17-hydroxyprogesterone
    • Suspected PCOS: Consider testosterone and/or dehydroepiandrosterone sulfate (DHEA-S).
  • Imaging
    • Indications for pelvic imaging include abnormalities palpated on bimanual exam or symptoms that persist despite initial treatment.
    • Transvaginal ultrasound is the first-line approach for most patients.
  • Procedures: endometrial sampling/biopsy for certain patients (see “Diagnostic Procedures/Others”)

Follow-Up Tests & Special Considerations

  • Depending on results of initial tests, or if a patient’s medical history is suggestive of underlying bleeding condition, specific tests for von Willebrand disease or other coagulopathies may be indicated, including von Willebrand-ristocetin cofactor activity, von Willebrand factor antigen, and factor VIII (2).
  • If transvaginal ultrasound imaging is not adequate or further evaluation of cavity is necessary, then sonohysterography (also known as saline infusion sonohysterography) or hysteroscopy is recommended.
  • It is appropriate to initiate medical therapy in females <35 years of age if low risk of uterine anatomic/histologic abnormality or adenomyosis prior to performing an EMB.
  • American College of Obstetricians and Gynecologists (ACOG) recommends endometrial sampling for post-menopausal women with AUB, but states that a thin, homogeneous endometrial thickness (ET) <4 mm does not require endometrial sampling unless bleeding is persistent or recurrent, whereas ET >4 mm should prompt further evaluation (based on ACOG 2018 guidance). Sampling of thin endometrium is often unsatisfactory for histologic evaluation.
  • Incidentally found endometrial measurement >4 mm without associated bleeding in postmenopausal women should not trigger evaluation; however, assessment based on individual risk factors is appropriate.

Diagnostic Procedures/Other

  • EMB
    • Women age >45 years with AUB to rule out cancer or premalignancy
    • Postmenopausal women with ET ≥4 mm
    • Women aged 18 to 45 years with AUB, a history of unopposed estrogen and failed medical management
    • Women of any age without risk factors if they have abnormal findings following imaging
    • Perform on or after day 18 of cycle, if known; secretory endometrium confirms ovulation occurred.
  • Hysteroscopy with targeted biopsy if suspected intrauterine lesion with negative EMB; NPV for endometrial cancer with negative hysteroscopy at any age is 99.5%.

Test Interpretation

Pap smear could reveal carcinoma or inflammation indicative of cervicitis. Most EMBs show proliferative or dyssynchronous endometrium (suggesting anovulation) but can show simple or complex hyperplasia without atypia, hyperplasia with atypia, or endometrial adenocarcinoma.

Descriptive text is not available for this image Treatment

Medication

First Line

  • Management should be directed at the suspected cause of the AUB. For those with known structural, infectious, or endocrine etiologies, appropriate medical or surgical therapies should be selected. Those with unknown etiologies can be triaged into acute or chronic bleeding.
  • Acute bleeding
    • Conjugated equine estrogen
      • Hemodynamically unstable: 25 mg IV q4–6h for 24 hours); shown to stop bleeding in 72% of participants within 8 hours of administration compared with 38% of participants treated with placebo (3)
      • Hemodynamically stable: 2.5 mg conjugated equine estrogen (Premarin) PO q6h for 21 days should control bleeding in 12 to 24 hours (2)[A].
    • Oral contraceptive pills (OCPs): 1 monophasic pill containing 35 μg of ethinyl estradiol PO 3 times daily for 7 days (3)
    • Tranexamic acid (TXA) 10 mg/kg IV (max 600 mg/dose) q8h or 20 to 25 mg/kg PO q8h (3)
    • Intrauterine tamponade by filling 26F Foley bulb with 30 mL saline
    • Dilation and curettage (D&C) if no response after 2 to 4 doses of Premarin or sooner if bleeding >1 pad per hour
  • Chronic bleeding:
    • The 20-μg-per-day formulation of levonorgestrel-releasing intrauterine system (Mirena) is the most effective for decreasing heavy menstrual bleeding (71–95% reduction in blood loss) and performs similarly to hysterectomy with quality-adjusted life years considered (1).
    • Progestins: medroxyprogesterone acetate (Provera) 10 mg/day for 5 to 10 days each month; daily progesterone for 21 days per cycle results in significantly less blood loss; medroxyprogesterone acetate (Depo-Provera) 150 mg q12w.
    • OCPs: 1 monophasic pill containing 35 μg daily estrogen plus progesterone
    • TXA (Lysteda) 1.0 to 1.5 g by mouth 3 times a day.
    • NSAIDs (naproxen sodium 500 mg BID, ibuprofen 600 to 1,200 mg/day) decrease amount of blood loss and pain compared with placebo.
  • Additional considerations:
    • Do not use estrogen if contraindications exist including breast cancer, suspicion for endometrial hyperplasia or carcinoma, history of DVT, liver disease, migraine with aura, or smoking in women >35 years of age (relative contraindication).
    • Do not use TXA in patients at increased risk of thrombosis.
    • Both TXA and NSAIDs are effective, well-tolerated, non-hormonal choices that are taken only when patient is bleeding. TXA is safe to use while patient is attempting to conceive.
    • The need for surgical treatment depends on clinical stability of patient, severity of bleeding, contraindications to medical management, and response to medical management (3).

Issues for Referral

If an obvious cause for vaginal bleeding is not found in a pediatric patient, refer to a pediatric endocrinologist or pediatric/adolescent gynecologist.

Additional Therapies

  • Antiemetics if treating with high-dose estrogen or progesterone
  • Iron supplementation if anemia (usually iron deficiency) is identified.

Surgery/Other Procedures

Surgical options include D&C, endometrial ablation, uterine artery embolization, and hysterectomy (3).

Admission, Inpatient, and Nursing Considerations

  • Admission for inpatient care recommended if there is significant hemorrhage causing acute anemia with signs of hemodynamic instability; with acute bleeding, replace volume with crystalloid and blood, as necessary.
  • Discharge criteria: hemodynamic stability and control of vaginal bleeding

Descriptive text is not available for this image Ongoing Care

Follow-up Recommendations

Once stable from acute management, recommend follow-up evaluation in 2 to 4 months for further evaluation.

Patient Monitoring

Women should keep a menstrual diary to document bleeding patterns and their response to therapy.

Diet

No dietary restrictions, although a 5% reduction in weight can induce ovulation in anovulation caused by PCOS

Patient Education

https://www.acog.org/womens-health/faqs/abnormal-uterine-bleeding

Prognosis

  • Varies with pathophysiologic process
  • Most anovulatory cycles can be treated with medical therapy and do not require surgical intervention.

Complications

Iron deficiency anemia, impaired quality of life, hemodynamic instability

Authors

Alexandra Renee Zaballa, MD
Jenny T. Giang-Griesser, MD

References

  1. Wouk N, Helton M. Abnormal uterine bleeding in premenopausal women. Am Fam Physician. 2019;99(7):435–443.  [PMID:30932448]
  2. Committee on Practice Bulletins—Gynecology. Practice bulletin no. 128: diagnosis of abnormal uterine bleeding in reproductive-aged women. Obstet Gynecol. 2012;120(1):197–206. doi:10.1097/AOG.0b013e318262e320.  [PMID:22914421]
  3. ACOG committee opinion no. 557: management of acute abnormal uterine bleeding in nonpregnant reproductive-aged women. Obstet Gynecol. 2013;121(4):891–896. doi:10.1097/01.AOG.0000428646.67925.9a. [PMID:23635706]

Descriptive text is not available for this image Codes

ICD-10

  • N93.9 Abnormal uterine and vaginal bleeding, unspecified
  • N93.8 Other specified abnormal uterine and vaginal bleeding

SNOMED

44991000119100 Abnormal uterine bleeding

Clinical Pearls

  • AUB is a clinical diagnosis defined by deviations in normal menstrual parameters cause by many etiologies. PALM-COEIN is a commonly used diagnostic algorithm for AUB.
  • Approximately 20% of AUB is caused by bleeding disorders. Anovulation accounts for 90% of AUB in adolescents.
  • EMB should be performed in:
    • Women age >45 years with AUB
    • Women aged 18 to 45 years with AUB and a history of unopposed estrogen and failed medical management

Last Updated: 2027

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