Dysfunctional uterine bleeding

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Dysfunctional Uterine Bleeding (DUB) is the most common cause of functional abnormal uterine bleeding, which is abnormal genital tract bleeding based in the uterus and found in the absence of demonstrable organic pathology.

Diagnosis must be made by exclusion, since organic pathology must first be ruled out. It can be classified as ovulatory or anovulatory, depending on whether ovulation is occurring or not.

• Uterine bleeding is deemed abnormal when there is an irregular amount or an irregular pattern of bleeding.
• Menometrorrhagia: Excessive and irregular bleeding between cycles and during menstruation
• Metrorrhagia: Irregular and more frequent bleeding
• Menorrhagia: Excessive, but regular bleeding

Ovulatory

Ovulatory DUB happens with the involvement of ovulation, and may represent a possible endocrine dysfunction, resulting in menorrhagia or metrorrhagia. Mid-cycle bleeding may indicate a transient estrogen decline, while late-cycle bleeding may indicate progesterone deficiency.

Anovulatory

Anovulatory cycle DUB happens without the involvement of ovulation. The etiology can be psychological stress, weight (obesity, anorexia, or a rapid change), exercise, endocrinopathy, neoplasm, drugs, or it may be otherwise idiopathic.

Assessment of anovulatory DUB should always start with a good medical history and physical examination. Laboratory assessment of hemoglobin, luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, T₄, thyroid stimulating hormone (TSH), pregnancy (by βhCG), and androgen profile should also happen.

More extensive testing might include an ultrasound and endometrial sampling.

Diagnosis

History and Symptoms

• History taking is an important part of diagnosis of DUB.

Physical Examination

• Complete physical exam, including pelvic and rectal examinations.

Laboratory Findings

• Pap smear
• Peripheral smear
• Complete blood count (CBC) with differential
• Prolactin
• Clotting factor assays
• human chorionic gonadotropin
• Dehydroepiandrosterone-sulfate (DHEA-S)
• Testosterone
• Estradiol
• Follicle stimulating hormone (FSH)
• Luteinizing hormone (LH)
• Thyroid stimulating hormone (TSH)
• LFTs (liver function tests)
• Blood urea nitrogen (BUN) / creatinine
• Serum progesterone

Ultrasound

• Transvaginal ultrasound more accurate than pelvic ultrasound
• Pelvic ultrasound may be indicated to reveal certain pathologies, as well as uterine masses, adnexal masses.

MRI and CT

• If malignancy is suspected, a CT scan can be helpful

Other Diagnostic Studies

• Diagnostic dilatation and curettage provides more information than biopsy, but is more invasive
• Prothrombin time / partial thromboplastin time (PT/PTT)
• Biopsy of endometrial and progesterone challenge test reveal estrogen excess
• The uterine cavirty and endometrium may be evaluated by hysteroscopy.

Differential Diagnosis of Causes of Dysfunctional uterine bleeding

• Anatomic or structural lesions

  • Uterine or cervical polyps
  • Uterine leiomyoma
  • Foreign body

• Coagulation disorders

  • Clotting factor disorder: Hemophilia, hepatic disease, anticoagulant use, renal disease, Von Willebrand's Disease
  • Platelet dysfunction: Leukemia, Thrombocytopenia, and related medications

• Pregnancy complications

  • Placental abruption
  • Ectopic Pregnancy
  • Miscarriage
  • Spontaneous abortion
  • Placenta previa

• Endometrial cancer

  • Risk Factors:

    • Diabetes Mellitus
    • Unopposed estrogen
    • Obesity
    • Older age
    • Chronic anovulation
    • Hypertension

• Endometrial hyperplasia

  • Exogenous extrogen
  • Excess of endogenous estrogen
  • DUB (dysfunctional uterine bleeding) is a diagnosis of exclusion

• Endometrioma
• Hyperprolactinemia
• Hypo- or Hyperthyroidism
• Hypothalamic lesion
• Medications (e.g., Norepinephrine)
• Nonuterine bleeding

  • Rectal
  • Urinary
  • Vaginal
  • Cervical

• Other malignancy
• Pelvic infection
• Polycystic Ovarian Syndrome (Stein Leventhal Syndrome)
• Systemic disease
• Anorexia Nervosa
• Immature hypothalamic-pituitary-ovarian axis
• Intense exercise
• Nutritional status (Very low calorie diets)
• Peri-menopause
• Psychologic stress

Treatment

Management of dysfunctional uterine bleeding predominantly consists of reassurance, though mid-cycle estrogen and late-cycle progestin can be used for mid- and late-cycle bleeding respectively. Also, non-specific hormonal therapy such as combined estrogen and progestin can be given.

The goal of therapy should be to arrest bleeding, replace lost iron to avoid anemia, and prevent future bleeding.

In general;

• IV estrogen, blood transfusion, IV fluids, curettage, hysterectomy or ligation of uterine artery are used to treat acute life-threatening bleeds.
• Treatment of underlying etiologies.

Pharmacotherapy

Acute Pharmacotherapies

• Oral contraceptives are used to treat nonacute bleeding.

  • Cyclic progesterone
  • Estrogen/progesterone
  • Other:

    • Fibrinolytic agents
    • Danazol
    • Tranexamic acid
    • Megestrol
    • GnRH analogs (Gonadotropin-releasing hormone)
    • Intrauterine progesterone

Surgery and Device Based Therapy

• Hysterectomy
• Endometrial ablation

Indications for Surgery

• Anatomic causes
• If fertility is not desired

Resources

• Merck Manual: Abnormal Uterine Bleeding