Abnormal (Dysfunctional) Uterine Bleeding
- Abnormal uterine bleeding (AUB) is irregular menstrual bleeding (usually heavy, prolonged, or frequent); it is a diagnosis of exclusion after establishment of normal anatomy and the absence of other medical illnesses and pregnancy.
- May be acute or chronic (occurring >6 months)
- The International Federation of Gynecology and Obstetrics (FIGO) revised the terminology system and now uses AUB rather than dysfunctional uterine bleeding (DUB).
- Commonly associated with anovulation
Adolescent and perimenopausal women are affected most often.
5% of reproductive-aged women will see a doctor in any given year for AUB.
10–30% of reproductive-aged women have AUB.
Etiology and Pathophysiology
- Anovulation accounts for 90% of AUB.
- Loss of cyclic endometrial stimulation
- Elevated estrogen levels stimulate endometrial growth.
- No organized progesterone withdrawal bleeding
- Endometrium eventually outgrows blood supply, breaks down, and sloughs from uterus.
- 6–10% will have polycystic ovarian syndrome (PCOS).
- 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 describes structural causes of AUB, and COEIN describes nonstructural causes of AUB.
- PALM: polyp, adenomyosis, leiomyoma, and malignancy and/or hyperplasia
- COEIN: coagulopathy, ovulatory disorders, endometrial, iatrogenic, and not yet classified
- Reproductive pathology and structural disorders
- Uterus: leiomyomas, endometritis, hyperplasia, polyps, trauma
- Adnexa: salpingitis, functional ovarian cysts
- Cervix: cervicitis, polyps, STIs, trauma
- Vagina: trauma, foreign body
- Vulva: lichen sclerosus, STIs
- Malignancy of the vagina, cervix, uterus, and ovaries
- Systemic diseases
- Hematologic disorders (e.g., von Willebrand disease, thrombocytopenia)
- Diseases causing anovulation
- Adrenal disorders
- Pituitary disease (prolactinoma)
- Eating disorders
- Medications (iatrogenic causes)
- Tamoxifen (estrogen receptor antagonists)
- Hormonal medications: intrauterine devices (IUDs)
- Selective serotonin reuptake inhibitors (SSRIs)
- Antipsychotic medications
- Postmenopausal hormone therapy
- Other causes of AUB not defined in PALM-COEIN
- Pregnancy: ectopic pregnancy, threatened or incomplete abortion, or hydatidiform mole
- Advanced or fulminant liver disease
- Chronic renal disease
- Inflammatory bowel disease
- Excessive weight gain
- Increased exercise
Unclear but can include inherited disorders of hemostasis
Risk factors for endometrial cancer (which can cause AUB)
- Age >40 years
- Diabetes mellitus
- Early menarche or late menopause (>55 years of age)
- Chronic anovulation or infertility
- Unopposed estrogen therapy
- History of breast cancer or endometrial hyperplasia
- Tamoxifen use
- Family history: gynecologic, breast, or colon cancer
- Thyroid disease
No direct preventive measure for AUB; however, condom use to decrease the transmission of sexually-transmitted infections (gonorrhea, chlamydia, trichomonas) reduces the risk of pelvic inflammatory disease, a cause of AUB.
Commonly Associated Conditions
- Endometrial polyps, adenomyosis, endometriosis
- Hyperprolactinemia, perimenopause, thyroid disorders, PCOS
- Coagulopathy, eating disorders, pregnancy
- Menstrual history
- Onset, severity (quantified by pad/tampon use, presence and size of clots), timing of bleeding (unpredictable or episodic)
- Menorrhagia with onset of menarche is suggestive of a coagulation disorder.
- 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 and of bleeding disorders, stress, exercise, recent weight change, visual changes, headaches, galactorrhea.)
- Medication history: Evaluate for use of aspirin, anticoagulants, hormones, and herbal supplements (1).
Discover anatomic or organic causes of AUB.
- Evaluate for:
- Body mass index (obesity)
- Pallor, vital signs (anemia)
- Visual field defects (pituitary lesion)
- Hirsutism or acne (hyperandrogenism)
- Goiter (thyroid dysfunction)
- Galactorrhea (hyperprolactinemia)
- Purpura, ecchymosis (bleeding disorders)
- Pelvic exam
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 & InterpretationInitial Tests (lab, imaging)
- All patients: urine human chorionic gonadotropin (hCG; rule out pregnancy and/or hydatidiform mole) and complete blood count (CBC)
- For acute heavy/hemorrhagic bleeding, a type and cross should be obtained.
- If disorder of hemostasis is suspected, a partial thromboplastin time (PTT), prothrombin time (PT), activated partial thromboplastin time, and fibrinogen level are appropriate.
- If anovulation is suspected: thyroid-stimulating hormone (TSH) level, prolactin level
- Consider other tests based on differential diagnosis.
- Follicle-stimulating hormone (FSH) level to evaluate for hypo- or hypergonadotropism
- 17-Hydroxyprogesterone if congenital adrenal hyperplasia is suspected
- Testosterone and/or dehydroepiandrosterone sulfate (DHEA-S) if PCOS
- Screening for STI
- Endometrial biopsy (EMB) should be performed as part of the initial evaluation for postmenopausal uterine bleeding and in premenopausal women with risk factors for endometrial carcinoma. Medical management can be initiated in premenopausal women with low risk for malignancy (2).
- 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 <3 mm: 99.7% negative predictive value (NPV)
- ET <5 mm: 99.6% NPV for ruling out endometrial cancer (3)
- 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.
- If normal findings following imaging in patients without known risk factors for endometrial carcinoma, a biopsy should be performed if not done so previously (1)[C].
- Pap smear to screen for cervical cancer if age >21 years (1)[C]
- EMB should be performed in
- Women age >35 years with AUB to rule out cancer or premalignancy
- Postmenopausal women with ET ≥4 mm
- Women aged 18 to 35 years with AUB and risk factors for endometrial cancer (see “Risk Factors”)
- Perform on or after day 18 of cycle, if known; secretory endometrium confirms ovulation occurred.
- Dilation and curettage (D&C)
- Hysteroscopy if another intrauterine lesion is suspected
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.
Attempt to rule out other causes of bleeding prior to instituting therapy.
NSAIDs (naproxen sodium 500 mg BID, mefenamic acid 500 mg TID, ibuprofen 600 to 1,200 mg/day)
- Acute, emergent, nonovulatory bleeding
- Conjugated equine estrogen (Premarin): 25 mg IV q4h (max 6 doses) or 2.5 mg PO q6h should control bleeding in 12 to 24 hours (2)[A].
- D&C if no response after 2 to 4 doses of Premarin or sooner if bleeding >1 pad per hour (1)[C]
- Then, change to oral contraceptive pill (OCP) or progestin for cycle regulation.
- Acute, nonemergent, nonovulatory bleeding
- Combination OCP with ≥30 μg estrogen given as a taper. An example of a tapered dose: 4 pills per day for 4 days; 3 pills per day for 3 days; 2 pills per day for 2 days, daily for 3 weeks then 1 week off, then cycle on OCP for at least 3 months
- Nonacute, nonovulatory bleeding (ranked in order based on decision analysis as best option based on efficacy, cost, side effects, and consumer acceptability)
- Levonorgestrel IUD (Mirena) is the most effective form of progesterone delivery and is not inferior to surgical management (4)[A].
- 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 (6)[A].
- OCPs: 20 to 35 μg estrogen plus progesterone
- Do not use estrogen if contraindications, such as suspicion for endometrial hyperplasia or carcinoma, history of deep vein thrombosis (DVT), migraine with aura, or the presence of smoking in women >35 years of age (relative contraindication), are present.
- Leuprolide (varying doses and duration of action); gonadotropin-releasing hormone (GnRH) agonist
- Danazol (200 to 400 mg/day for a maximum of 9 months) more effective than NSAIDs but limited by androgenic side effects and cost. It has been replaced by GnRH agonists.
- Antifibrinolytics such as tranexamic acid (Lysteda) 650 mg, 2 tablets TID (max 5 days during menstruation)
- Metformin or clomifene (Clomid) alone or in combination in women with PCOS who desire ovulation and pregnancy
Issues For Referral
- If an obvious cause for vaginal bleeding is not found in a pediatric patient, refer to a pediatric endocrinologist or gynecologist.
- Patients with persistent bleeding despite medical treatment require reevaluation and possible referral.
- Antiemetics if treating with high-dose estrogen or progesterone (1)[C]
- Iron supplementation with vitamin C if anemia (usually iron deficiency) is identified
- Ulipristal acetate 5 or 10 mg (selective progesterone receptor modulator) currently under investigation for use in women with leiomyoma-associated AUB
- Hysterectomy in cases of endometrial cancer or if medical therapy fails or if other uterine pathology is found
- Endometrial ablation, less expensive than hysterectomy and associated with high patient satisfaction; failure of primary medical treatment is not necessary (2). 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
- Control of vaginal bleeding
- Once stable from acute management, recommend follow-up evaluation in 4 to 6 months for further evaluation.
- Routine follow-up with a primary care or OB/GYN provider
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
- Uterine cancer in cases of prolonged unopposed estrogen stimulation
- N91.2 Amenorrhea, unspecified
- N92.2 Excessive menstruation at puberty
- N92.3 Ovulation bleeding
- N92.4 Excessive bleeding in the premenopausal period
- N93.8 Other specified abnormal uterine and vaginal bleeding
- N93.9 Abnormal uterine and vaginal bleeding, unspecified
- 626.0 Absence of menstruation
- 626.2 Excessive or frequent menstruation
- 626.3 Puberty bleeding
- 626.5 Ovulation bleeding
- 626.8 Other disorders of menstruation and other abnormal bleeding from female genital tract
- 626.9 Unspecified disorders of menstruation and other abnormal bleeding from female genital tract
- 19155002 Dysfunctional uterine bleeding (finding)
- 237134002 Ovulatory dysfunctional bleeding (finding)
- 27585009 Anovular menstruation (finding)
- 312984006 Abnormal uterine bleeding unrelated to menstrual cycle (disorder)
- 44991000119100 Abnormal uterine bleeding (disorder)
- Anovulation accounts for 90% of AUB.
- An EMB should be performed in all women >35 years of age with AUB to rule out cancer or premalignancy, and it should be considered in women aged 18 to 35 years with AUB and risk factors for endometrial cancer.
- It is appropriate to initiate medical therapy in females <35 years of age with no apparent risk of endometrial cancer prior to performing an EMB. Surgical therapy is generally more effective than medical therapy.
Rebecca A. Lauters, MD
- 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]
- Bradley L, Gueye N. The medical management of abnormal uterine bleeding in reproductive-aged women. Am J Obstet Gynecol. 2016;214(1):31–44. [PMID:26254516]
- Wong AS, Lao TT, 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;(1):CD003855. [PMID:26820670]
- Matteson KA, Rahn DD, Wheeler TL 2nd, et al; for Society of Gynecologic Surgeons Systematic Review Group. Nonsurgical management of heavy menstrual bleeding: a systematic review. Obstet Gynecol. 2013;121(3):632–643. [PMID:23635628]
- Lethaby A, Irvine G, Cameron I. Cyclical progestogens for heavy menstrual bleeding. Cochrane Database Syst Rev. 2008;(1):CD001016. [PMID:18254075]
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