Dysfunctional Uterine Bleeding ? Causes, Symptoms, Diagnosis ...

Basics

Description

• Dysfunctional uterine bleeding (DUB) is irregular (usually heavy, prolonged, or frequent) bleeding that occurs in the absence of anatomic pathology
• Associated with anovulatory menstrual cycles
• Typically a diagnosis of exclusion: Need to exclude anatomic pathology and medical illnesses
• Systems affected: Endocrine/Metabolic, Reproductive

Epidemiology

• Predominant age: 12?50 years
• Predominant gender: Female only
• Adolescents and perimenopausal women are most often affected

Incidence

Accounts for 5?10% of outpatient gynecologic visits

Prevalence

Abnormal uterine bleeding occurs in:

• ? 1 in 3 women of reproductive age
• ?1 in 10 post-menopausal women

Risk Factors

Risk factors for endometrial cancer (which can cause DUB):

• Age >40
• Obesity
• Diabetes Mellitus
• Nulliparity
• Early menarche or late menopause (>55 years)
• Hypertension
• Chronic anovulation or infertility
• Unopposed estrogen therapy
• History of breast cancer or endometrial hyperplasia
• Tamoxifen use
• Family history: Gynecologic, breast, or colon cancer

Genetics

Unclear

Pathophysiology

• Disruption of normal hormonal sequence of ovulatory menstrual cycle
• Anovulation accounts for 90% of DUB:
  • Loss of cyclic endometrial stimulation
  • Elevated estrogen levels stimulate endometrial growth
  • Endometrium does not shed and eventually outgrows blood supply
  • Tissue breaks down and sloughs from uterus

Etiology

The diagnosis of DUB is made when pathologic causes of abnormal bleeding have been ruled out:

• Pregnancy
  • Ectopic pregnancy, threatened or incomplete abortion, or hydatidiform mole
• Reproductive pathology & structural disorders
  • Uterus: leiomyomas, endometritis, hyperplasia, polyps, trauma
  • Adnexa: Salpingitis, functional ovarian cysts
  • Cervix: Cervicitis, polyps, sexually transmitted diseases (STDs), trauma
  • Vagina: Trauma, foreign body
  • Vulva: Lichen sclerosis, STDs
• Malignancy of the vagina, cervix, uterus, & ovaries
• Systemic diseases
  • Inflammatory bowel disease
  • Hematologic disorders (Von Willebrand?s disease, thrombocytopenia, etc.)
  • Advanced or fulminant liver disease
  • Chronic renal disease
• Diseases causing anovulation
  • Hyper/hypothyroidism
  • Adrenal disorders
  • Pituitary disease (prolactinoma)
  • Polycystic ovarian syndrome (PCOS)
  • Eating disorders
• Medications (iatrogenic causes)
  • Anticoagulants
  • Steroids
  • Tamoxifen
  • Hormonal medications: Intrauterine devices (IUDs)
  • Selective-serotonin reuptake inhibitors
  • Antipsychotic medications
• Other causes of abnormal uterine bleeding:
  • Excessive weight gain
  • Increased exercise
  • Stress

Diagnosis

A thorough medical, surgical, social, and family history should be obtained.

History

• History of bleeding:
  • Onset, severity (quantified in pad/tampon use, presence & size of clots)
  • Association with other factors (i.e. coitus, contraception, weight loss/gain)
• Menstrual history:
  • Unpredictable or episodic, heavy or light bleeding
  • Menstrual symptoms do not typically precede bleeding
• Review of symptoms (exclude symptoms of pregnancy, symptoms of bleeding disorders, bleeding from other orifices, stress, exercise, recent weight change, visual changes, headaches, galactorrhea)
• Medication history (evaluate for use of aspirin, anticoagulants, hormones, herbal supplements)

Alert

Postmenopausal bleeding is any bleeding that occurs >1 year after the last menstrual period; cancer must always be ruled out

Physical Exam

Discover anatomic or organic causes of DUB:

• Assess hemodynamic stability
• Evaluate for:
  • Obesity (BMI)
  • Pallor
  • Visual field defects (pituitary lesion)
  • Hirsutism or acne (hyperandrogenism)
  • Goiter
  • Galactorrhea (hyperprolactinemia)
  • Purpura, ecchymosis (bleeding disorders)
• Pelvic exam:
  • Evaluate for uterine irregularities
  • Check for foreign bodies
  • Rule out rectal or urinary tract bleeding
  • Include Pap smear and tests for STDs

Pediatric Considerations

• Premenarchal children with vaginal bleeding should be evaluated for foreign bodies, physical/sexual abuse, possible infections, and signs of precocious puberty.

Diagnostic Tests & Interpretation

Lab

Not always necessary

Initial lab tests

• Urine human chorionic gonadotropin (rule out pregnancy and/or hydatiform mole)
• Complete blood count (CBC)
• Thyroid-stimulating hormone (TSH) (1)[B]
• Prolactin level
• Consider other tests based on differential diagnosis:
  • Follicle-stimulating hormone (FSH) to evaluate for hypo/hypergonadotropism
  • Coagulation studies & factors (2)[A]
  • Liver function tests
  • 17-hydroxyprogestrone
  • Androgenic hormones
  • Neisseria gonorrhea,?Chlamydia trachomatis?tests

Imaging

Initial approach

• Transvaginal ultrasound (TVUS):
  • Indications: postmenopausal patients, suspicion of pregnancy or anatomic abnormalities, PCOS
  • High sensitivity for endometrial carcinoma in postmenopausal women (3)[A]. If ?4 mm, endometrial cancer unlikely
  • If endometrial thickness >5 mm, proceed to endometrial biopsy (EMB)
• Saline infusion sonohistogram: Often superior to TVUS in screening for anatomic abnormalities (4). Can perform if TVUS suspicious for lesion.

Diagnostic Procedures/Surgery

• Pap smear to exclude cervical cancer
• Endometrial biopsy (EMB) should be performed in women:
  • Women >35 years of age with DUB to rule out cancer or premalignancy
  • Women with endometrial thickness >5 mm
  • Women aged 18?35 with DUB and risk factors for endometrial cancer (see?Risk Factors)
  • Perform ?day 18 of cycle if known; secretory endometrium confirms ovulation occurred
  • Does not diagnose leiomyosarcoma or fibroids because lesions are deep to endometrial lining
• Dilation & curettage:
  • Performed if bleeding is heavy, uncontrolled, and/or failed emergent medical management
  • If unable to perform EMB in office
• Hysteroscopy if lesion suspected (diagnostic and therapeutic)

Pathological Findings

Pap smear could reveal carcinoma or inflammation indicative of cervicitis. Most EMBs show proliferative or dyssynchronous endometrium (suggesting anovulation)

Differential Diagnosis

See?Etiology

Treatment

Attempt to diagnose other causes of bleeding prior to instituting therapy.

Medication

First Line

• Acute, emergent, nonovulatory bleeding: (5)
  • Conjugated equine estrogen (Premarin): 25 mg IV Q4H (maximum of 6 doses) or 2.5 mg PO Q6H should control bleeding in 12?24 hours (6)[A]
  • Then change to OCP or progestin for cycle regulation
• Acute, nonemergent, nonovulatory:
  • Combination OCP with ?30 mcg estrogen given as a taper. An example of a tapered dose: 4 pills/d until bleeding stopped for 24 hours; 3 pills/d for 3 days; 2 pills/d for 3 days.
  • Then begin once-a-day regimen (7)[B]
• Nonacute, nonovulatory:
  • OCPs: 20?35 mcg estrogen plus progesterone (mono- or triphasic)
  • Progestins: Medroxyprogesterone acetate (Provera) 10 mg/d for 5?10 days each month. Daily progesterone for 21 days per cycle results in significantly less blood loss (8)[A].
  • Levonorgestrel intrauterine devices (Mirena) are most effective (9)[A].
• Do not use estrogen if contraindications are present
• Precautions:
  • Exclude endometrial hyperplasia & carcinoma before administering estrogen
  • Consider deep vein thrombosis prophylaxis when treating with high-dose estrogens
  • Failed medical treatment requires further workup
  • Smokers >35 years of age should be counselled on the risk of thromboembolic disease when using OCPs

Second Line

• Gonadotropin-releasing hormone (GnRH) agonists create a hypogonadotropic state, usually used as a bridge to definitive therapy.
• Danazol (Danocrine 200?400 mg/d) is more effective than nonsteroidal anti-inflammatory drugs (NSAIDs), but is limited by androgenic side effects & cost (10)[A]. It has been essentially replaced by GnRH agonists.
• Antifibrinolytics like tranexamic acid (Lysteda, 650mg, 2 tabs three times daily (max of 5 days during menstruation) (11)[A].

Additional Treatment

General Measures

NSAIDs (naproxen sodium 500 mg BID, mefenamic acid 500 mg TID, ibuprofen 600?1,200 mg/d):

• Decreases amount of blood loss compared to placebo (10)[A]
• Diminishes pain

Issues for Referral

• If an obvious cause for vaginal bleeding is not found in a pediatric patient, refer to a pediatric endocrinologist.
• Patients with persistent bleeding despite medical treatment require reevaluation and referral to a gynecologist.

Additional Therapies

• Antiemetics if treating with high-dose estrogen
• Iron supplementation if anemia (usually iron deficiency) is identified

Surgery/Other Procedures

• Hysterectomy if endometrial cancer, if medical therapy fails, or uterine pathology
• Endometrial ablation is less expensive than hysterectomy with high satisfaction; medical treatment does not have to fail first (12)[A]

In-Patient Considerations

Initial Stabilization

With acute bleeding, replace volume with crystalloid and blood as necessary

Admission Criteria

Significant hemorrhage causing acute anemia with signs of hemodynamic instability

Nursing

Pad counts and clot size can be helpful to determine and monitor amount of bleeding

Discharge Criteria

• Hemodynamic stability
• Control of vaginal bleeding

Ongoing Care

Follow-Up Recommendations

Routine follow-up with a primary care or ob/gyn provider

Patient Monitoring

Women treated with estrogen or OCPs should keep a menstrual diary to document bleeding patterns & their relation to therapy.

Diet

No restrictions

Patient Education

• Explain possible/likely etiologies
• Answer all questions, especially those related to cancer and fertility
• http://www.acog.org

Prognosis

• Varies with pathophysiologic process
• Most anovulatory cycles can be treated with medical therapy and do not require surgical intervention.

Complications

• Iron-deficiency anemia
• Uterine cancer in cases of prolonged unopposed estrogen stimulation

References

1.?Albers J, et al. Abnormal uterine bleeding.?Am Fam Physician.?2004;69:8.

2.?Kouides PA, et al. Hemostasis and menstruation: Appropriate investigation for underlying disorders of hemostasis in women with extensive menstrual bleeding.?Fertil Steril.?2005;84(5):1345?51.

3.?Dijkhuizen FP, et al. The accuracy of transvaginal ultrasonography in the diagnosis of endometrial abnormalities.?Obstet Gynecol.?1996;87(3):345?9.

4.?Maness DL, Reddy A, Harraway-Smith CL, Mitchell G, Givens V et al. How best to manage dysfunctional uterine bleeding.?J Fam Pract.?2010;59:449?58.

5.?Casablanca Y. Management of dysfunctional uterine bleeding.?Obstet Gynecol Clin North Am.?2008;35:219?34.

6.?DeVore GR, et al. Use of intravenous Premarin in the treatment of dysfunctional uterine bleeding: A double-blind randomized control study.Obstet Gynecol.?1982;59(3):285?91.

7.?Rimsza ME. Dysfunctional uterine bleeding.?Pediatr Rev.?2002;23(7):227?33.

8.?Lethaby A, et al. Cyclical progestogens for heavy menstrual bleeding.Cochrane Database Syst Rev.?2004.

9.?Lethaby A, et al. Progesterone or progesterone-releasing intrauterine systems for heavy menstrual bleeding.?Cochrane Database Syst Rev.?2005.

10.?Lethaby A, et al. Nonsteroidal anti-inflammatory drugs for heavy menstrual bleeding.?Cochrane Database Syst Rev.?2004.

11.?Lethaby A, et al. Antifibrinolytics for heavy menstrual bleeding.?Cochrane Database Syst Rev.?2004.

12.?Lethaby A, et al. Endometrial resection and ablation versus hysterectomy for heavy menstrual bleeding.?Cochrane Database Syst Rev.?2004.

Additional Reading

Chen EC, Danis PG, Tweed E et al. Clinical inquiries. Menstrual disturbances in perimenopausal women: what?s best??J Fam Pract.?2009;58:E3.

14.?LaCour DE, Long DN, Perlman SE et al. Dysfunctional uterine bleeding in adolescent females associated with endocrine causes and medical conditions.J Pediatr Adolesc Gynecol.?2010;23:62?70.

See Also (Topic, Algorithm, Electronic Media Element)

Menorrhagia; Dysmenorrhea

Algorithm: Menorrhagia

Codes

ICD9

626.8 Other disorders of menstruation and other abnormal bleeding from female genital tract

Snomed

19155002 Dysfunctional uterine bleeding (finding)

Clinical Pearls

• Uterine bleeding in premenarchal & postmenopausal women is always abnormal and should prompt immediate evaluation.
• Dysfunctional uterine bleeding is irregular bleeding occurring in the absence of pathology, making it a diagnosis of exclusion.
• Anovulation accounts for 90% of DUB.
• An endometrial biopsy should be performed in all women >35 years of age with DUB to rule out cancer or premalignancy, and considered in women aged 18?35 with DUB and risk factors for endometrial cancer.

Source: http://health.tipsdiscover.com/dysfunctional-uterine-bleeding-causes-symptoms-diagnosis-treatment-and-ongoing-care/

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