Basics
Description
- Abnormal uterine bleeding (AUB) is defined as changes in menstrual frequency, duration, and volume, regardless of diagnosis or cause.
- Anovulatory, or dysfunctional, uterine bleeding (DUB) is a diagnosis of exclusion and is defined as noncyclic menstrual bleeding, with or without excessive flow, derived from the uterine endometrium, and due to anovulatory sex steroid production in the absence of a structural uterine lesion.
Clinical definitions
- Oligomenorrhea: Cycle intervals >35 days
- Polymenorrhea: Cycle intervals <21 days
- Menorrhagia: Heavy or prolonged menstrual bleeding at regular intervals (>80 mL; >7 days)
- Metrorrhagia, or intermenstrual, bleeding: Light-to-heavy bleeding at irregular intervals
- Menometrorrhagia: Heavy, prolonged bleeding at irregular intervals
- Hypomenorrhea: Scant menses, <2 days
- Break-through bleeding: Unscheduled, irregular bleeding in steroid contraception or hormone therapy users
Characteristics of normal menstruation
- Flow duration of 3-7 days, volume of 30-50 mL, and cycle interval length of 21-35 days.
- Menstrual volume >80 mL each month can result in iron-deficiency anemia.
Epidemiology
Incidence
- 30% of women report a history of heavy menses.
- 5% of women aged 30-49 years seek gynecologic care annually for heavy menses.
Prevalence
Increases with age; peaks prior to menopause.
Risk Factors
- Vaginal, pelvic, or abdominal trauma
- Personal or family history of bleeding diathesis or endocrinologic disease
- Medication use
- Severe stress (medical or psychiatric illness, eating disorders, excessive exercise)
Pathophysiology
Normal menstruation requires an intact hypothalamic-pituitary-ovarian (HPO) axis as well as endometrial hemostasis. Disruption of cyclic ovulation and/or local hemostasis can cause AUB.
Etiology
- Etiology varies based on patient age.
- Anovulation - most common cause in the perimenarchal and perimenopausal age groups due to HPO axis immaturity and waning ovarian function, respectively.
- Structural uterine anomalies, infection, and pregnancy complications are the most common causes in reproductive-aged women.
Diagnosis
History
Menstrual history
- Bleeding onset and temporal patterns; last normal menstrual period, cycle intervals, volume, and duration of flow
- ±Molimina (premenstrual symptoms)
Associated symptoms
- Pain, fever, and/or vaginal discharge
- Fatigue, dyspnea, lightheadedness
- Changes in bowel or bladder function
Medical history
- Personal or family history of bleeding disorder: Menorrhagia since menarche; bruising with minimal to no trauma; mucous membrane bleeding (nose, gums, rectum) 1-2 times per month; bleeding with surgery, dental extraction, or childbirth; anemia requiring transfusion
- Medications
- Weight changes, exercise, chronic illness
- Galactorrhea or hirsutism
- Other factors (e.g., trauma, sexual activity)
Physical Exam
General
- Signs of systemic illness, obesity, thyromegaly, galactorrhea
- Signs of bleeding disorder: Ecchymoses >5 cm, petechiae, skin pallor, swollen joints
- Signs of hyperandrogenism: Hirsutism, acne, male pattern baldness, acanthosis nigricans
- Abdominal mass
Speculum exam
- Evaluate vulva, vagina, cervix, urethra, and anus for bleeding site, mass, laceration, ulceration, discharge, atrophy, or foreign body
- Additional testing, if indicated:
- Pap test (≥age 21 regardless of age of onset of sexual intercourse)
- Saline microscopy
- Chlamydia or gonorrhea nucleic acid amplification test
Bimanual exam
Assess uterus and adnexa for size, contour, consistency, and tenderness.
Digital rectal examination
Assess for hemorrhoids, anal fissure, masses, and fecal occult blood testing, if indicated.
Tests
- Evaluation for AUB must differentiate bleeding due to anovulation or endometrial atrophy from structural uterine pathology.
- Initial evaluation includes ruling out pregnancy and determining ovulatory status.
- Ovulatory cycles have regular intervals with molimina and dysmenorrhea, while anovulatory cycles are irregular and lack molimina and dysmenorrhea.
- Methods to determine ovulatory status:
- Menstrual cycle chart
- Basal body temperature chart
- Random serum progesterone"‚>3 ng/mL
- Biopsy with secretory endometrium
- Urinary luteinizing hormone predictor test
Lab
Baseline labs, if normal physical examination
- Urine or serum pregnancy test
- CBC with platelets
- Thyroid-stimulating hormone
Additional labs, if history or clinical features suggest condition
- Urinalysis, if hematuria
- Prolactin (fasting), if galactorrhea, amenorrhea, metrorrhagia, or hypomenorrhea in a nonpregnant woman
- Follicle-stimulating hormone, if suspected premature ovarian failure or hypothalamic suppression
- Coagulation profile (aPTT, PT, platelet function assay), if suspected bleeding diathesis
- Liver function tests, if liver or renal disease
- Total testosterone, 17-hydroxyprogesterone, DHEAS, if hyperandrogenism (polycystic ovary syndrome [PCOS]) or abrupt onset of virilization (ovarian or adrenal tumor)
- Von Willebrand testing (factor VIII coagulant activity, vWD factor antigen, vWD: Ristocetin cofactor activity), if positive history (1)[B]
Imaging
Perform uterine imaging if history and/or other evaluations suggest anatomic cause, such as:
- Regular cycles with menorrhagia OR metrorrhagia without a vaginal or cervical lesion
- AUB despite evidence of ovulation:
- Random serum progesterone"‚>3 ng/mL
- Biopsy with secretory endometrium
- Failed empirical medical management
Transvaginal ultrasound (TVUS)
- Provides indirect visualization of the endometrial cavity, myometrium, and adnexa
- Assesses for structural anomalies and endometrial thickness:
- Detects polyps and submucous myomas with sensitivity of 80% and specificity of 69%
- Less effective than SIS for identification of intracavitary lesions
Saline infusion sonography (SIS)
- Infusion of sterile saline into the uterine cavity during simultaneous transvaginal sonography
- Indicated for further evaluation of a poorly visualized or thickened, indistinct endometrial echo on TVUS
- Differentiates among no anatomic pathology (no biopsy indicated), globally thickened endometrium (blind biopsy appropriate), and focal abnormalities (hysteroscopic biopsy appropriate) (2)[B]
Surgery
Indications for endometrial sampling
- All women ≥35 years with AUB
- All women (ages 19-34) with chronic anovulation (unopposed estrogen exposure increases risk for endometrial hyperplasia or cancer): PCOS, obesity personal or family history of endometrial, ovarian, breast, or colon cancer, tamoxifen use
- Adolescents (ages 13-18) with a 2-3 year history of untreated anovulatory bleeding
- New onset heavy, irregular bleeding
- Persistent bleeding after 3 months of therapy
Dilatation and curettage
- Outpatient, blind surgical procedure
- Indicated if office biopsy not feasible (e.g., cervical stenosis) or nondiagnostic
- May miss 10% of focal lesions (e.g., polyps)
Endometrial biopsy
- Office-based, blind, suction-piston biopsy
- Sensitivity range: 67-97.5% (2)[B]
- Higher sensitivity with diffuse rather than focal intrauterine process
Hysteroscopy
- Directly visualizes the endometrial cavity
- Directly biopsy or excise lesions with higher detection rate of anomalies compared to dilatation and curettage
Differential Diagnosis
- Pregnancy complications
- Abortion, ectopic pregnancy, gestational trophoblastic disease
- Retained products, placental site involution, lactation
- Anovulation
- Perimenarchal or perimenopausal
- Hyperandrogenic (PCOS, congenital adrenal hyperplasia, androgen-producing tumor)
- Hypothyroidism
- Hyperprolactinemia
- Premature ovarian failure
- Hypothalamic dysfunction (stress, weight changes, obesity, excessive exercise)
- Uterine leiomyoma
- Endometrial or cervical polyp
- Adenomyosis
- Chronic endometritis or pelvic inflammatory disease
- Endometrial hyperplasia or malignancy
- Cervical or vaginal neoplasia
- Blood dyscrasia
- Iatrogenic or medications
- Systemic disease
Must exclude bleeding from the GI and urinary tracts.
Treatment
Medication
- Consider patient age, bleeding severity, desire for future fertility, preexisting co-morbidities, and patient preferences.
- Treatment of choice for anovulatory bleeding is oral contraceptives or cyclic oral progestins.
- If medical therapy does not resolve anovulatory bleeding, then reevaluate for anatomic cause or bleeding disorder.
- Anatomic causes may require surgical intervention.
First Line
NSAIDs
- Reduces menstrual blood loss (MBL) 20-50%
- Reduces dysmenorrhea by 70%
- No effect on cycle frequency or duration
- Initiate at onset of menses for 3-5 days
Steroid contraception (estrogen/progestin combination)
Reduces MBL (50%) and dysmenorrhea, and provides cycle control
Oral progestins
- Significantly reduces MBL but is less effective than danazol, tranexamic acid, and LNG-IUS for ovulatory menorrhagia (3)[A]
- Long-course therapy (cycle days 5-26) is more effective than short-course (cycle days 16-26) for reducing MBL (3)[A].
- Medroxyprogesterone acetate (MPA) 5-20 mg daily up to t.i.d.
- Norethindrone 2.5-10 mg daily up to t.i.d.
Levonorgestrel intrauterine system (LNG-IUS)
- Reduces MBL greater than all other medical treatments (4)[A].
- Effective treatment for menorrhagia due to leiomyomata, but may have higher rates of expulsion and vaginal spotting (5)[B].
Second Line
Antifibrinolytics
- Reduces MBL (40%) but no effect on dysmenorrhea (6)[A]
- Tranexamic acid (Lystedaâ„¢) two 650 mg tablets PO t.i.d. with menses for maximum 5 days
GnRH agonists
- Induces reversible hypoestrogenic state and amenorrhea
- Decreases leiomyoma volume by 35-65% within 3 months of treatment
Surgery
Surgery or uterine artery embolization may be necessary if a patient is refractory to or has contraindications to medical therapy, and/or has an anatomic lesion.
In-Patient Considerations
Acute, severe, or life-threatening menorrhagia requires in-patient management.
Initial Stabilization
- Evaluate for anemia, hypovolemia, orthostatic hypotension, and/or actively bleeding lesion
- Transfuse and correct any coagulopathy
- Options for medical therapy:
- Conjugated equine estrogens: 2.5-5 mg PO or 25 mg IV q4h to q6h for 24 hours (7)[A]
- Combined oral contraception: 35 μg ethinyl estradiol pill, 1 tablet PO t.i.d. for 7 days, then 1 tablet daily for 21 days
- MPA 20 mg PO t.i.d. for 7 days, then 1 tablet PO daily for 21 days (8)[A]
- Tamponade with intrauterine 30 cc Foley balloon catheter until medical therapy initiated
Ongoing Care
Prognosis
Most women will have improvement and/or resolution of symptoms.
Complications
- Iron-deficiency anemia and volume depletion
- Hemorrhagic shock
- Endometrial hyperplasia or cancer
- Infertility
References
1James AH, Manco-Johnson MJ, Yawn BP. Von Willebrand disease: Key points from the 2008 National Heart, Lung, and Blood Institute guidelines. Obstet Gynecol. 2009;114:674-678. [View Abstract]2Goldstein SR Modern evaluation of the endometrium. Obstet Gynecol. 2010;116:168-176. [View Abstract]3Lethaby A, Irvine GA, Cameron IT Cyclical progestogens for heavy menstrual bleeding. Cochrane Database Syst Rev. 2008, Issue 1.4Kaunitz AM, Bissonnette F, Monteiro I. Levonorgestrel-releasing intrauterine system or medroxyprogesterone for heavy menstrual bleeding: A randomized controlled trial. Obstet Gynecol. 2010;116:625-632. [View Abstract]5Mercorio F, De Simone R, Di Spiezio Sardo A. The effect of a levonorgestrel-releasing intrauterine device in the treatment of myoma-related menorrhagia. Contraception. 2003;67:277-280. [View Abstract]6Lukes SL, Moore KA, Muse KN. Tranexamic acid treatment for heavy menstrual bleeding: A randomized controlled trial. Obstet Gynecol. 2010;116:865-875.7, Odell O, Kase N. Use of intravenous premarin in the treatment of dysfunctional uterine bleeding - a double-blind randomized controlled study. Obstet Gynecol. 1982;59:285-291.8Munro MG, Mainor N, Basu R. Oral medroxyprogesterone acetate and combination oral contraceptives for acute uterine bleeding: A randomized controlled trial. Obstet Gynecol. 2006;108:924-929. [View Abstract]
Codes
ICD9
- 626.1 Scanty or infrequent menstruation
- 626.2 Excessive or frequent menstruation
- 626.8 Other disorders of menstruation and other abnormal bleeding from female genital tract
- 626.6 Metrorrhagia
- 628.0 Infertility, female, associated with anovulation
ICD10
- N91.5 Oligomenorrhea, unspecified
- N92.0 Excessive and frequent menstruation with regular cycle
- N93.8 Other specified abnormal uterine and vaginal bleeding
- N92.1 Excessive and frequent menstruation with irregular cycle
- N97.0 Female infertility associated with anovulation
SNOMED
- 19155002 dysfunctional uterine bleeding (finding)
- 52073004 oligomenorrhea (finding)
- 52754008 polymenorrhea (finding)
- 386692008 menorrhagia (finding)
- 64996003 intermenstrual bleeding - irregular (finding)
- 314631008 menometrorrhagia (finding)
- 64206003 hypomenorrhea (finding)
- 251663001 anovulatory (finding)
Clinical Pearls
- Anovulatory bleeding occurs most commonly in perimenarchal girls and perimenopausal women. Perimenopausal women are also more likely to have structural uterine lesions.
- 20% of women who present with menorrhagia at any time of life will have a bleeding diathesis. Platelet disorders and von Willebrand disease are the most common ones.