Abnormal uterine bleeding

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Abnormal uterine bleeding (AUB) refers to abnormal menstruation in nonpregnant individuals of reproductive age. The FIGO-AUB system 1 classifies AUB according to bleeding characteristics, i.e., frequency, regularity, duration, volume of bleeding, and intermenstrual bleeding. The PALM-COEIN system classifies AUB by structural causes (e.g., endometrial polyps, leiomyomas) and nonstructural causes (e.g., coagulopathy, ovulatory dysfunction). Initial diagnostic evaluation involves exclusion of pregnancy, gynecological examination, and basic laboratory tests (e.g., CBC, coagulation tests). Emergency treatment for patients with acute AUB with significant blood loss and/or hemodynamic instability includes immediate hemodynamic support, intrauterine hemostatic control, high-dose IV conjugated estrogen, and, in refractory cases, surgical intervention. In stable patients, acute and long-term management may include hormonal and/or nonhormonal pharmacotherapy and treatment of the underlying cause of AUB.

This article addresses AUB in nonpregnant individuals of reproductive age. For bleeding in pregnancy, postmenopausal bleeding, and bleeding in children and adolescents, see “Vaginal bleeding.”

The following applies to nonpregnant individuals of reproductive age.

International Federation of Gynecology and Obstetrics (FIGO) definition [2]

• FIGO defines AUB using descriptive terms used in the FIGO-AUB system 1.
• The term dysfunctional uterine bleeding and other historical terminology are no longer recommended.

Historical terminology

No longer recommended by FIGO [2]

• Menorrhagia or hypermenorrhea: abnormally high volume menstrual bleeding (now termed heavy menstrual bleeding)
• Metrorrhagia: abnormal bleeding between menstrual periods (now termed intermenstrual bleeding)
• Menometrorrhagia: heavy and/or prolonged, irregular menstruation
• Oligomenorrhea: infrequent menstruation with cycle intervals > 38 days
• Polymenorrhea: frequent menstruation with cycle intervals < 24 days
• Hypomenorrhea: light menstruation

The following applies to nonpregnant individuals of reproductive age. For other patients, see “Vaginal bleeding.”

PALM-COEIN system [2]

AUB may have one or more of the following causes.

• Structural causes (PALM)
  • Polyp (endometrial polyp)
  • Adenomyosis
  • Leiomyoma (uterine leiomyoma)
  • Malignancy and hyperplasia
• Nonstructural causes (COEIN)
  • Coagulopathy (AUB-C): e.g., Von Willebrand disease [3][4]
  • Ovulatory dysfunction (anovulatory bleeding; AUB-O): e.g., secondary to hyperprolactinemia, thyroid disorders, PCOS, obesity
  • Endometrial (AUB-E): endometrial dysfunction in a structurally normal uterus with regular cycles (diagnosis of exclusion) [3][5]
  • Iatrogenic (AUB-I): e.g., estrogens, progestins, IUD, antithrombotic agents
  • Not otherwise classified (AUB-N): e.g., cesarean scar defect, uterine arteriovenous malformations (AVM) [6][7]

In patients with acute AUB and menarche within the last year, consider anovulatory bleeding due to immaturity of the hypothalamic-pituitary-gonadal axis. [8]

Causes by menstrual abnormality

Clinical criteria [2]

One of the following bleeding abnormalities described in the FIGO-AUB classification system 1 must be present: [2]

• Abnormal bleeding frequency, duration, regularity, and/or volume
• Intermenstrual bleeding
• Unscheduled bleeding

Associated features [2][3][4][11]

These vary depending on the underlying cause of AUB and can include:

• Other menstrual cycle abnormalities, e.g., dysmenorrhea
• Abdominal and/or pelvic pain
• Postcoital bleeding
• Signs of anemia
• Signs of bleeding disorders
• Signs of hyperandrogenism
• Red flags for sexual assault
• Clinical features of sexually transmitted infections (STIs)
• Clinical features of cervical cancer

FIGO classifies AUB in nonpregnant individuals of reproductive age using the FIGO-AUB system 1 and FIGO-AUB system 2. [12]

FIGO-AUB system 1: bleeding characteristics [2]

Frequency

• Definition: the number of days in the cycle interval
• Classification
  • Normal: 24–38 days
  • Absent (amenorrhea): no bleeding days
  • Infrequent (formerly oligomenorrhea): > 38 days
  • Frequent (formerly polymenorrhea): < 24 days

Regularity

• Definition: variation between shortest and longest cycle menstrual cycle length
• Classification
  • Normal: ≤ 7–9 days (i.e., normal cycle length ± 4 days)
  • Irregular: ≥ 8–10 days

Duration

• Definition: the length of menstruation
• Classification
  • Normal: ≤ 8 days
  • Prolonged: > 8 days

Volume

• Definition: the amount of bleeding as described by the patient
• Classification
  • Normal
  • Light menstrual bleeding (formerly hypomenorrhea)
  • Heavy menstrual bleeding (formerly hypermenorrhea or menorrhagia): excessive menstrual bleeding that interferes with quality of life [13]

Intermenstrual bleeding [2]

Formerly metrorrhagia

• Definition: bleeding between regular menstrual periods
• Classification
  • Normal: none
  • Random: occurs unpredictably
  • Cyclic: predictable bleeding during early, mid, or late cycle

Unscheduled bleeding (breakthrough bleeding) [2][5][14]

• Definition: endometrial bleeding that occurs on unexpected days while taking hormonal contraceptives
• Classification
  • Not applicable: not on hormonal contraceptives
  • None: on hormonal contraceptives with no unscheduled bleeding
  • Present

FIGO-AUB system 2: underlying cause [2]

See “PALM-COEIN system” for details.

• Structural causes: generally identifiable on imaging or histopathology
• Nonstructural causes: generally not identifiable on imaging or histopathology

Other classifications [2][15]

• Acute AUB: : an episode of AUB requiring immediate measures to prevent further blood loss
• Chronic AUB: AUB persisting for most of the preceding 6 months
• Ovulatory AUB: abnormal bleeding associated with ovulatory cycles; typically occurs at regular intervals
• Anovulatory AUB: bleeding associated with recurrent anovulatory cycles; typically occurs irregularly and/or infrequently

The following applies to nonpregnant individuals of reproductive age, including adolescents. For other patients, see “Vaginal bleeding.”

Approach [2][3][4][11][16]

• Rule out pregnancy and nonuterine sources of bleeding.
• Establish a clinical diagnosis of AUB and classify the type and severity of uterine bleeding (see “FIGO-AUB system 1”).
• Identify the underlying cause of AUB, e.g., via the PALM-COIEN system.
• Screen for bleeding disorders using a bleeding assessment tool.

A speculum examination is not routinely required for initial assessment of adolescents with AUB who are not sexually active. [3][16]

Do not delay resuscitation of hemodynamically unstable patients with acute AUB for diagnostic evaluation.

Routine laboratory studies [3][4][11][16]

• β-hCG (urine or serum): to rule out pregnancy
• CBC and serum ferritin: to evaluate for anemia, thrombocytopenia, and iron deficiency
• TSH
• Type and screen, crossmatch: in severe acute bleeding
• PT, PTT, and fibrinogen: if a bleeding disorder is suspected and in all adolescents with heavy menstrual bleeding [16]
• Age-appropriate cervical cancer screening
• Chlamydia testing, with additional STI testing in patients with symptoms and/or risk factors for STI [11]

Further evaluation [2][3][4][11][16][17]

Further testing is based on clinical suspicion of potential causes, as guided by the PALM-COEIN system.

• Additional laboratory tests: : e.g., prolactin, gonadotropins, diagnostic workup of bleeding disorders
• Pelvic ultrasound: : to evaluate endometrial thickness and rule out structural abnormalities (e.g., leiomyoma, adnexal mass)
  • Transvaginal ultrasound (TVUS): test of choice for initial imaging of the uterus in most patients
  • Transabdominal ultrasound: alternative test for adolescents or complementary imaging if transvaginal views are insufficient
• Additional imaging (e.g., sonohysterography, hysteroscopy): Consider if previous imaging is inconclusive and/or further evaluation is required.
• Endometrial sampling: indicated in patients with AUB and increased risk of endometrial hyperplasia or cancer [3][4][18]
  • All patients ≥ 45 years of age
  • Patients < 45 years of age with any of the following:
    • Persistent bleeding despite medical management
    • Unopposed estrogen (e.g., due to obesity or polycystic ovary syndrome)
    • Other risk factors for endometrial cancer: type 2 diabetes, tamoxifen therapy, Lynch syndrome
  • See “Indications for endometrial biopsy.”

Pelvic ultrasound (preferably TVUS) is the initial imaging method of choice for evaluation of AUB. [11]

• Other causes of vaginal bleeding (including genitourinary trauma, infections, and pregnancy-related complications)
• Other menstrual cycle abnormalities
• Gastrointestinal bleeding
• Hematuria

The differential diagnoses listed here are not exhaustive.

The following applies to nonpregnant individuals of reproductive age, including adolescents. For other patients, see “Vaginal bleeding.”

Approach [3][19]

Do not delay immediate hemodynamic support and emergency transfusion of unstable patients with AUB.

Hemodynamically unstable patients

• Fluid resuscitation and emergency transfusion
• Urgent OB/GYN consult
• Bedside hemostatic control, e.g., intrauterine balloon tamponade or gauze packing
• High-dose IV conjugated equine estrogen and tranexamic acid (See “Pharmacotherapy of AUB” for dosages.)
• Refractory bleeding: urgent surgical interventions for AUB

All other patients

• AUB treatment
  • Pharmacotherapy for AUB (first-line for most patients): hormonal and/or nonhormonal medications [3]
  • Surgical treatment of AUB: if pharmacotherapy is ineffective or contraindicated or for specific underlying causes
• Definitive treatment of underlying causes of AUB
• Treatment of iron-deficiency anemia
• Consult hematology if a bleeding disorder is suspected. [16]

Pharmacological treatment of AUB [3][16][19][20]

Acute AUB [3][16][19]

• Hormonal therapy: Consider contraindications for hormonal contraceptives when selecting the agent.
  • Unstable patients: high-dose IV conjugated equine estrogen (off-label) [16][19][21]
  • Stable patients
    • Combined oral contraceptive: e.g., ethinyl estradiol/norgestimate (off-label) [16][19]
    • Oral progestin: e.g., medroxyprogesterone acetate (off-label) , norethindrone (off-label) [3][16][19]
    • Oral conjugated equine estrogen (off-label) [3]
• Nonhormonal therapy: oral or IV tranexamic acid (off-label) [19][16]

Chronic AUB [3][16][20]

Consult specialists (e.g., gynecology, hematology) for the management of chronic AUB in individuals with a bleeding disorder. [16]

• Hormonal therapy once an underlying cause has been identified: Consider contraindications when selecting the agent. [19]
  • Depot medroxyprogesterone acetate (off-label) [3]
  • Combined oral contraceptive: e.g., ethinyl estradiol/norgestimate (off-label) [3]
  • Oral progestin: e.g., norethindrone [3]
  • Progestin intrauterine device
• Nonhormonal therapy: used only during bleeding episodes as first-line therapy and/or if hormonal treatment is contraindicated [3][20]
  • NSAIDs: e.g., naproxen (off-label) [3]
  • Oral tranexamic acid (off-label) [3][19]

Seek expert advice and review the CDC medical eligibility criteria for contraceptive use before administering hormonal therapy. [19]

Surgical treatment of AUB [3][19]

Indications

• Severe bleeding and/or hemodynamic instability
• Lack of response or contraindications to pharmacotherapy
• Structural causes requiring surgical intervention (e.g., endometrial cancer)

Procedures

Choice is based on the patient's clinical status, the underlying cause of AUB, and desire for future fertility.

• Transcatheter uterine artery embolization [6][22]
  • Can be used for AUB caused by fibroids or uterine arteriovenous malformations
  • Data on post-procedure fertility is limited. [23]
• Hysteroscopic polypectomy or myomectomy [3]
  • May provide acute and long-term control of bleeding due to endometrial polyps or uterine fibroids
  • Preserves fertility
• Dilation and curettage (D&C) with hysteroscopy [19]
  • Diagnostic and therapeutic
  • Used to identify intrauterine pathologies, take tissue samples, and remove excess uterine lining
  • Preserves fertility [24]
• Endometrial ablation [19][25]
  • Only indicated if other treatments have been ineffective or are contraindicated
  • Provides long-term improvement of uterine bleeding symptoms by destroying the endometrium
  • Contraindications include:
    • Desire to have children: Endometrial ablation does not preserve fertility. [26]
    • Pregnancy
    • Endometrial hyperplasia or endometrial cancer
    • History of transmyometrial uterine surgery
• Hysterectomy [19]
  • Reserved for AUB that does not respond to any other treatment
  • Does not preserve fertility

Disposition [27]

• Severe acute AUB: immediate gynecologic consultation and hospitalization
• Stable patients: Imaging and further investigations may be done on an outpatient basis.