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Menorrhagia

para>Metrorrhagia: irregular or frequent flow, noncyclic
  • Menometrorrhagia: frequent, excessive, irregular flow in amount and duration (menorrhagia plus metrorrhagia)

  • Polymenorrhea: frequent flow, cycles of ≤21 days

  • Intermenstrual bleeding: bleeding between regular menses

  • Abnormal uterine bleeding (AUB): abnormal endometrial bleeding of hormonal and other causes related to pregnancy, anovulation (estrogen breakthrough), estrogen or progesterone excess or withdrawal, thyroid disorders, adenomyosis, endometriosis, malignancy, as well as infection and bleeding disorders

  • System affected: reproductive

  • Epidemiology


    Prevalence
    • The prevalence of menorrhagia is estimated at 30% in the general population during reproductive years and increases with age.
      • Menarche to menopause; ’ ˆ Ό50% of cases occur in patients age >40 years.

      • Menorrhagia is fairly common in adolescence and in the perimenopausal period.

      • In adolescence, irregular or heavy bleeding due to anovulation and immaturity of the hypothalamic " “pituitary " “ovarian axis is common.

      • In adolescence, severe menorrhagia may be associated with a bleeding disorder up to 40% of the time, with platelet function defects and von Willebrand disease being the most common.


    Pediatric Considerations
    Genital bleeding before puberty can result from trauma, foreign bodies, vaginal infection due to abuse, or exogenous hormone administration but is not considered menorrhagia by definition. ‚  
    Pregnancy Considerations
    Bleeding in pregnancy is not menorrhagia. But menorrhagia in a period a couple days late could be a miscarriage. ‚  

    Etiology and Pathophysiology


    • Hypothyroidism if regular menses
    • Endometrial proliferation//hyperplasia
      • Anovulation; oligo-ovulation frequently associated with heavy, prolonged, painful periods; called menorrhagia if occurring regularly

      • Ovarian tumor or other estrogen-producing tumor

      • Prolonged use of oral combination pill formulated to allow menses

      • Polycystic ovarian syndrome, (PCOS) (although menses often irregular)

      • Local factors:

      • Abnormal endometrial prostaglandin levels

      • Endometrial polyps

      • Endometrial neoplasia

      • Adenomyosis/endometriosis

      • Uterine myomata (fibroids)

      • Intrauterine device (IUD)

      • Uterine sarcoma

    • Coagulation disorders:
      • Thrombocytopenia, platelet disorders

      • von Willebrand disease, factor deficiencies

      • Leukemia

      • Ingestion of aspirin/acetylsalicylic acid or anticoagulants

      • Renal failure/dialysis leading to uremic platelet dysfunction


    Risk Factors


    • Obesity due to estrogen excess
    • Infertility/nulliparity
    • Anovulation due to chronic unopposed estrogen stimulation (menses usually irregular)
    • Family history of endometrial or colon cancer

    General Prevention


    Combined oral contraceptives help prevent menorrhagia when progesterone is dominant. Lower estrogen doses result in less menstrual bleeding. Ibuprofen inhibits prostaglandin production without permanently affecting platelets and is also noted to decrease blood loss at menses. Progesterone-only contraceptives reduce blood loss but can often convert menorrhagia to unpredictable (although lighter) uterine bleeding. ‚  

    Commonly Associated Conditions


    Endometriosis, adenomyosis, fibroids, low-grade infection ‚  

    Diagnosis


    History


    • Excessive menstrual flow is defined subjectively and varies greatly from woman to woman (1).
    • Useful features: Regular bleeding substantially heavier than usual flow (or >80 mL/cycle, if quantified, or changing pads or tampons every 1 " “2 hours as quantified by patient) lasting >7 days.
      • Significant clotting

      • Symptomatic anemia with no other cause but menses

    • Symptoms that suggest cycles are ovulatory:
      • Regular menstrual interval

      • Midcycle pain (mittelschmerz)

      • Premenstrual symptoms: breast soreness, mood changes

    • Abdominal pain or cramps at other times of the cycle may be associated with structural causes:
      • Myomas

      • Polyps

      • Ovarian tumors

      • Endometriosis

    • Symptoms that may indicate a more general bleeding disorder:
      • Epistaxis, bleeding gums

      • Easy bruising

      • Family history of bleeding disorder

    • Review of medications
      • Anticoagulant use in women of childbearing age due to hypercoagulable states


    Physical Exam


    • Hirsutism, acne, or obesity may accompany chronic anovulation such as with PCOS.
    • Signs of nongenital or general bleeding, bruising, petechiae
    • Pelvic/rectal examination to detect/exclude other causes of bleeding:
      • Cervical or vaginal bleeding

      • Pelvic or adnexal masses

      • Signs of pelvic infection

      • Urethral trauma

      • Gastrointestinal bleeding


    Differential Diagnosis


    • Pregnancy complications
      • Early threatened abortion

      • Early incomplete abortion

    • Nonendometrial bleeding
      • Cervical neoplasia/polyp

      • Cervical or vaginal trauma/foreign body

    • Pelvic inflammatory disease
      • Endometritis

      • Tuberculosis


    Diagnostic Tests & Interpretation


    Initial Tests (lab, imaging)
    • Pregnancy test: Always exclude pregnancy first.
    • CBC with differential to assess severity of blood loss and to rule out thrombocytopenia and leukemia
    • In selected cases:
      • Thyroid-stimulating hormone test, prolactin

      • If suspected anovulation, DHEAS

      • Coagulation panel, with platelet function testing if screen is abnormal

      • Creatinine, BUN to rule out uremia

      • Serum progesterone: 5 " “20 ng/mL (15.9 " “63.6 nmol/L) in luteal phase, <1 ng/mL (<3.18 nmol/L) in follicular phase or anovulatory cycle

      • If infectious cause is suspected, aerobic genital culture, wet and KOH preps for microscopic evaluation, or bacterial vaginosis panel and PCR for gonorrhea and chlamydia

    • Transvaginal ultrasonography can help distinguish bleeding caused by structural abnormalities versus anovulatory bleeding via assessment of endometrial stripe.
    • Abdominopelvic ultrasonography to evaluate suspected adnexal masses or myomas
    • Saline infusion sonography for evaluation of small lesions frequently missed on transvaginal ultrasound
    • Hysteroscopy to evaluate structural abnormalities more closely (2)[A]
    • CT may be used to investigate potentially malignant pelvic masses if needed after ultrasound.

    Diagnostic Procedures/Other
    • Endometrial biopsy detects hyperplasia, dysplasia, or atrophy. If done before expected menses, it may also help confirm the diagnosis of anovulation or luteal phase defect.
    • All women older than age 40 years with unexplained menorrhagia or older than age 35 years with unexplained menometrorrhagia should undergo an endometrial biopsy to rule out cancer.
    • Progestins used before endometrial biopsy may cause decidualization but rarely obscure correct diagnosis and often are valuable as an empiric test.

    Treatment


    Medication


    First Line
    • For acute control of severe bleeding:
      • Estrogen, conjugated (Premarin): 25 mg IV q4h up to 6 doses or 10 " “20 mg/day PO in four divided doses until bleeding abates; not for use in patients with estrogen contraindications (give with antiemetics).

      • Tranexamic acid 650 mg (3) 3 ƒ — daily for up to 5 days, expensive but as effective, nonestrogenic but not for those with clotting disorder

    • For less severe bleeding (usual case) or after control of acute bleeding has been achieved:
      • Medroxyprogesterone acetate (Provera): 10 " “30 mg/day for 5 " “10 days

      • Any combination oral contraceptive (i.e., usually a high-dose oral contraceptive) 1 tablet QID for 5 " “7 days (usually poorly tolerated, give with antiemetic)

    • To prevent heavy bleeding in subsequent cycles:
      • Medroxyprogesterone acetate: 5 " “10 mg/day for 10 days/month if the problem is due to estrogen excess (2)[A]

      • Cyclic dose of a combination oral contraceptive usually with ≤35 Ž Όg of estrogen


    Second Line
    • Nonsteroidal prostaglandin-synthetase inhibitors (e.g., naproxen, mefenamic acid, ibuprofen) can reduce blood loss ’ ˆ Ό25% with ovulatory cycles and reduce dysmenorrhea.
    • Norethindrone acetate (Aygestin): 2.5 " “10 mg/day for 10 " “21 days/month if anovulatory
    • Levonorgestrel intrauterine system (Mirena IUD) causes amenorrhea in around 50% and irregular spotting in the other half. A few women experience heavier bleeding.

    Surgery/Other Procedures


    • Endometrial ablation by laser or electrosurgical, microwave, or thermal means is a conservative alternative to hysterectomy and usually successful, although some patients require additional therapy in the long term (4)[B].
    • Uterine artery embolization is a conservative method to treat leiomyomata (5,6)[A].
    • Hysterectomy when indicated to treat coexisting conditions (myomas, endometrial dysplasia) or for bleeding unresponsive to other measures

    Inpatient Considerations


    Admission Criteria/Initial Stabilization
    • Bleeding leading to orthostatic hypotension
    • Hematocrit <25% or hemoglobin <8 and symptomatic
    • Most cases can be managed as outpatient in an office or emergency department.
    • Rule out pregnancy complications and nonuterine bleeding.
    • Treat severe or life-threatening bleeding acutely:
      • Circulatory support; transfusion, if necessary

      • IV Premarin (estrogen), tranexamic acid PO

      • Curettage, if necessary

      • Uterine tamponade and hysterectomy in extreme cases


    Ongoing Care


    Follow-up Recommendations


    Proceed to identify the underlying cause of bleeding, and treat to prevent recurrence: ‚  
    • Hormonal therapy
    • Dilatation and curettage for cases that fail to respond to hormone therapy
    • Consider endometrial ablation, uterine fibroid embolization, or hysterectomy in persistent cases in which fertility is not a concern (4).
    • Specific treatment for neoplasia, polyps, systemic disease
    • Patients desiring fertility may also need appropriate treatment for anovulation, endometriosis, and myomas (surgical) (1,4,6)[A].

    Patient Monitoring
    Medical treatment of hyperplastic/dysplastic endometrium should be followed by a repeat biopsy to confirm that histologic structure has returned to normal. ‚  

    Diet


    Iron supplementation may help correct for increased blood loss. ‚  

    Patient Education


    Information about side effects of medications should be provided as well as risks and benefits of procedures. ‚  

    Prognosis


    Most patients with hormonal imbalances will respond to hormonal manipulation. ‚  

    Complications


    • Anemia
    • Asherman syndrome from vigorous dilation and curettage
    • Estrogen may precipitate acute, intermittent porphyria or cholestatic jaundice in susceptible patients.
    • Prolonged treatment with Depo-Provera may lead to bone loss, but clinical significance is uncertain; rapid regain after discontinuation is usual.
    • Even with acute bleeding, estrogen should not be used in patients with coronary artery disease, significant carotid narrowing, active liver disease, thrombophilias, estrogen-dependent cancer history, or pregnancy.

    References


    1.Matteson ‚  KA, Munro ‚  MG, Fraser ‚  IS. The structured menstrual history: developing a tool to facilitate diagnosis and aid in symptom management. Semin Reprod Med.  2011;29(5):423 " “435. ‚  [View Abstract]2.Sweet ‚  MG, Schmidt-Dalton ‚  TA, Weiss ‚  PM, et al. Evaluation and management of uterine bleeding in premenopausal women. Am Fam Physician.  2012;85(1):35 " “43. ‚  [View Abstract]3.Bouchard ‚  P. Current and future medical treatments for menometrorrhagia during the premenopause. Gynecol Endocrinol.  2011;27(Suppl 1):1120 " “1125. ‚  [View Abstract]4.Karimi-Zarichi ‚  M, Dehghani-Firoozabadi ‚  R, Tabatabaie ‚  A, et al. A comparison of the effect of levonorgestrel IUD with oral medroxyprogesterone acetate on abnormal uterine bleeding with simple endometrial hyperplasia and fertility preservation. Clin Exp Obstet Gynecol.  2013;40(3):421 " “424. ‚  [View Abstract]5.Osayande ‚  AS, Mehulic ‚  S. Diagnosis and initial management of dysmenorrhea. Am Fam Physician.  2014;89(5):341 " “346. ‚  [View Abstract]6.van der Kooij ‚  SM, Bipat ‚  S, Hehenkamp ‚  WJ, et al. Uterine artery embolization versus surgery in the treatment of symptomatic fibroids: a systematic review and metaanalysis. Am J Obstet Gynecol.  2011;205(4):317.e1 " “317.e18. ‚  [View Abstract]

    Additional Reading


    See Also


    • Abnormal Pap and Cervical Dysplasia; Amenorrhea; Cervical Malignancy; Cervical Polyps; Cervicitis, Ectropion, and True Erosion; Abnormal (Dysfunctional) Uterine Bleeding; Dysmenorrhea; Menopause; Polycystic Ovarian Syndrome (PCOS); Uterine Myomas
    • Algorithm: Menorrhagia (Excessive Bleeding)

    Codes


    ICD10


    • N92.0 Excessive and frequent menstruation with regular cycle
    • N92.1 Excessive and frequent menstruation with irregular cycle
    • N93.8 Other specified abnormal uterine and vaginal bleeding

    ICD09


    • 626.2 Excessive or frequent menstruation
    • 626.8 Other disorders of menstruation and other abnormal bleeding from female genital tract
    • 626.6 Metrorrhagia

    SNOMED


    • 386692008 Menorrhagia (finding)
    • 314631008 menometrorrhagia (finding)
    • 19155002 Dysfunctional uterine bleeding (finding)
    • 52754008 polymenorrhea (finding)

    Clinical Pearls


    • Menorrhagia is defined as an excessive amount or duration of menstrual flow at regular intervals.
    • Pregnancy should be ruled out as part of the initial evaluation.
    • Because endometrial carcinoma is a significant cause of bleeding in women age >35 years, an endometrial biopsy to rule out endometrial carcinoma is recommended if the bleeding remains undiagnosed, especially if not confined to regular cyclic menses.
    • Remember that estrogen should not be used in patients with coronary artery disease, carotid stenosis, liver disease, thrombophilias, and family history of estrogen-dependent cancer (breast and endometrial).
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