Abnormal (Dysfunctional) Uterine Bleeding
- Abnormal uterine bleeding (AUB) is uterine bleeding that is irregular in quantity, frequency, or duration.
- 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).
Adolescent and perimenopausal women are affected most often.
5% of reproductive-aged women will see a doctor in any given year for AUB.
3–30% of reproductive-aged women have AUB.
Etiology and Pathophysiology
- Anovulation accounts for 90% of AUB.
- Adolescent AUB is usually due to an immature hypothalamic-pituitary-ovarian (HPO) axis that leads to anovulatory cycles.
- 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
- 20% of patients with heavy menstrual bleeding have a bleeding disorder.
- Two most common coagulopathies involved: von Willebrand disease and thrombocytopenia
- Diseases causing ovulatory dysfunction
- Hyperparathyroidism, hypothyroidism, adrenal disorders, pituitary disease (prolactinoma), PCOS, eating disorders
- Medications (iatrogenic causes)
- Anticoagulants, steroids, tamoxifen (estrogen receptor antagonists), hormonal contraception, copper IUD, antipsychotic medications (mostly first generation), postmenopausal hormone replacement therapy, antiemetics (metoclopramide and domperidone specifically)
- 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
Unclear but can include inherited disorders of hemostasis
- Unopposed estrogen therapy (no. 1 risk factor for endometrial cancer)
- Increasing age, typically >40 years old; obesity; PCOS; diabetes mellitus; nulliparity; early menarche or late menopause (>55 years of age); chronic anovulation or infertility; history of breast cancer or endometrial hyperplasia; tamoxifen use; family history: gynecologic, breast, or colon cancer; thyroid disease
No direct preventive measure for AUB
Commonly Associated Conditions
Endometrial polyps, adenomyosis, leiomyoma, endometrial cancer, coagulopathy, PCOS, thyroid disorders, starvation (eating disorders), hyperprolactinemia, ovarian follicle decline (perimenopause), pregnancy, endometriosis
The most valuable in diagnosis and determining etiology is history.
- Menstrual history: onset, severity (quantified by pad/tampon use, presence and size of clots), timing of bleeding (unpredictable or episodic) over the last 6 months; also assess menopausal status.
- Association with other factors (e.g., coitus, contraception, weight loss/gain)
- Gynecologic history: gravidity and parity, STI history, previous Pap smear results
- Review of systems (Exclude symptoms of pregnancy, bleeding disorders, stress, exercise, recent weight change, visual changes, headaches, and galactorrhea.)
- Body mass index, pallor, vital signs, visual field defects (may suggest a pituitary lesion), vaginal discharge, hirsutism or acne, goiter, galactorrhea, purpura, ecchymosis
- Pelvic exam: uterine irregularities and Tanner stage, foreign bodies; rule out rectal or urinary tract bleeding; include Pap smear and tests for STIs (1)[C].
Premenarchal children with vaginal bleeding should be evaluated for foreign bodies, physical/sexual abuse, possible infections, and signs of precocious puberty.
See “Etiology and Pathophysiology.”
Diagnostic Tests & Interpretation
Initial Tests (lab, imaging)
- All patients: urine hCG and CBC
- For acute heavy/hemorrhagic bleeding, a blood type and crossmatch should be obtained.
- If coagulopathy is suspected, a partial thromboplastin time (PTT), prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen level; if abnormal, get von Willebrand factor, ristocetin cofactor assay, and factor VIII.
- Consider other tests based on differential diagnosis:
- Suspected hormonal abnormalities: TSH, prolactin level, follicle-stimulating hormone (FSH)
- Concern for infection: STI screening, KOH prep, vaginitis panel
- Possible congenital adrenal hyperplasia: 17-hydroxyprogesterone
- Possible PCOS: testosterone and/or dehydroepiandrosterone sulfate (DHEA-S)
- TVUS in postmenopausal AUB
- Postmenopausal endometrial thickness (ET) <4 mm does not require endometrial sampling unless bleeding is persistent or recurrent, whereas ET >4 mm should prompt further evaluation.
- ET <5 mm: 99.6% negative predictive value (NPV) for ruling out endometrial cancer (2)
- 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.
- TVUS, sonohysterography, and hysteroscopy may be similarly effective in detection of intrauterine pathology in premenopausal women with AUB.
Follow-Up Tests & Special Considerations
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 endometrial biopsy (EMB).
- Pap smear to screen for cervical cancer if age >21 years (1)[C]
- Women aged >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 (1)
- Perform on or after day 18 of cycle, if known; secretory endometrium confirms that 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%.
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.
NSAIDs (naproxen sodium 500 mg BID, mefenamic acid 500 mg TID, ibuprofen 600 to 1,200 mg/day)
- Decreases amount of blood loss and pain compared with placebo
- Acute, emergent, nonovulatory bleeding (4)
- TXA 1.3 g PO or 10 mg/kg IV (max 600 mg/dose) TID
- Intrauterine tamponade by filling 26F foley bulb with 30 mL saline
- D&C if no response after 2 to 4 doses of Premarin or sooner if bleeding >1 pad per hour (1)
- Change to oral contraceptive pill (OCP) or progestin for cycle regulation.
- Acute, nonemergent, nonovulatory bleeding:
- Monophasic combined OCPs with 35 μg of estrogen TID for 7 days shown to stop bleeding in 88% of women
- Medroxyprogesterone acetate 20 mg PO TID for 7 days shown to stop bleeding in 76% of women in 3 days
- Nonacute, nonovulatory bleeding
- OCPs: 20 to 35 μg daily estrogen plus progesterone (Consider especially for anovulatory females <18 years old who are not yet sexually active.)
- TXA 1.0 to 1.5 g PO TID; avoid in patients with hypercoagulable states.
- Do not use estrogen if contraindications exist (suspicion for endometrial hyperplasia or carcinoma, history of DVT, migraine with aura, or smoking in women >35 years of age [relative contraindication]).
- Gonadotropin-releasing hormone (GnRH) agonists
- Leuprolide (varying doses and duration of action)
- GnRH antagonists (Elagolix 300 mg BID) (6)
- FDA approved for heavy menstrual bleeding due to uterine fibroids in premenopausal women combined with add-back therapy (1 mg estradiol/0.5 mg norethindrone acetate once a day)
- Danazol (200 to 400 mg/day for a maximum of 9 months) is more effective than NSAIDs but is limited by androgenic side effects and cost; now replaced by GnRH agonists
- Metformin or clomiphene (Clomid) alone or in combination in women with PCOS who desire ovulation and pregnancy
Issues For Referral
If an obvious cause of vaginal bleeding is not found in a pediatric patient, refer to a pediatric endocrinologist or gynecologist.
- Antiemetics if treating with high-dose estrogen or progesterone (1)[C]
- Iron supplementation if anemia (usually iron deficiency) is identified
- Ulipristal acetate 5 mg or 10 mg (selective progesterone receptor modulator)
- Found to be effective but currently suspended while undergoing evaluation of possible severe liver injury
- Hysterectomy in cases of endometrial cancer, if medical therapy fails, or if other uterine pathology is found
- Endometrial ablation, less expensive than hysterectomy and associated with high patient satisfaction; this is a permanent procedure and should be avoided in patients who desire continued fertility.
- Uterine artery embolization if bleeding is refractory to medications or confirmed fibroids
Admission, Inpatient, and Nursing Considerations
- Significant hemorrhage causing acute anemia with signs of hemodynamic instability; with acute bleeding, replace volume with crystalloid and blood, as necessary.
- Pad counts and clot size can be helpful to determine and monitor amount of bleeding.
- Discharge criteria: hemodynamic stability and control of vaginal bleeding
Once stable from acute management, recommend follow-up evaluation in 4 to 6 months for further evaluation.
Women treated with estrogen or OCPs should keep a menstrual diary to document bleeding patterns and their relation to therapy.
No restrictions, although a 5% reduction in weight can induce ovulation in anovulation caused by PCOS
- Varies with pathophysiologic process
- Most anovulatory cycles can be treated with medical therapy and do not require surgical intervention.
Iron deficiency anemia, mood disorders
- Goldstein SR, Lumsden MA. Abnormal uterine bleeding in perimenopause. Climacteric. 2017;20(5):414–420. [PMID:28780893]
- Lethaby AE, Cooke I, Rees M. Progesterone or progestogen-releasing intrauterine systems for heavy menstrual bleeding. Cochrane Database Syst Rev. 2005;(4):CD002126. [PMID:16235297]
- Practice bulletin no. 136: management of abnormal uterine bleeding associated with ovulatory dysfunction. Obstet Gynecol. 2013;122(1):176–185. [PMID:23787936]
- N93.8 Other specified abnormal uterine and vaginal bleeding
- N93.9 Abnormal uterine and vaginal bleeding, unspecified
- 44991000119100 Abnormal uterine bleeding
- AUB is irregular uterine bleeding that occurs in the absence of pregnancy or pathology, making it a diagnosis of exclusion.
- Anovulation accounts for 90% of AUB.
- EMB should be performed in
- Women aged >45 years with AUB
- Women aged 18 to 45 years with AUB and a history of unopposed estrogen and failed medical management
Pratha Muthiah, MD, MPH
- 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. [PMID:22914421]
- Wong ASW, Lao TTH, Cheung CW, et al. Reappraisal of endometrial thickness for the detection of endometrial cancer in postmenopausal bleeding: a retrospective cohort study. BJOG. 2016;123(3):439–446. [PMID:25800522]
- Marjoribanks J, Lethaby A, Farquhar C. Surgery versus medical therapy for heavy menstrual bleeding. Cochrane Database Syst Rev. 2016;2016(1):CD003855. [PMID:26820670]
- ACOG committee opinion no. 557: management of acute abnormal uterine bleeding in nonpregnant reproductive-aged women. Obstet Gynecol. 2013;121(4):891–896. [PMID:23635706]
- Lethaby A, Irvine G, Cameron I. Cyclical progestogens for heavy menstrual bleeding. Cochrane Database Syst Rev. 2008;(1):CD001016. [PMID:18253983]
- Ali M, Sara AR, Al Hendy A. Elagolix in the treatment of heavy menstrual bleeding associated with uterine fibroids in premenopausal women. Expert Rev Clin Pharmacol. 2021;14(4):427–437. [PMID:33682578]
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