Uterine Bleeding, Abnormal Premenopausal

Essentials of Diagnosis

• Accurate diagnosis of abnormal uterine bleeding depends on appropriate categorization and diagnostic tests

• Pregnancy should always be ruled out as a cause of abnormal uterine bleeding in women of reproductive age

• The evaluation of abnormal bleeding depends on the age and risk factors of the patient

General Considerations

• Normal menstrual bleeding

  • Lasts an average of 5 days (range, 2–7 days)

  • Mean blood loss of 40 mL

• Abnormal uterine bleeding (AUB) refers to menstrual bleeding of abnormal quantity, duration, or schedule

• A classification system for causes of abnormal uterine bleeding uses the acronym PALM-COEIN

  • Polyp

  • Adenomyosis

  • Leiomyoma

  • Malignancy

  • Coagulopathy-Hyperplasia

  • Ovulatory dysfunction

  • Endometrial

  • Iatrogenic

  • Not yet classified

• Abnormal uterine bleeding in women aged 19–39 years is often a result of

  • Pregnancy

  • Structural lesions

  • Anovulatory cycles

  • Use of hormonal contraception

  • Endometrial hyperplasia

Symptoms and Signs

• The diagnosis depends on the following:

  • Confirming uterine source of the bleeding

  • Excluding pregnancy and confirming patient is premenopausal

  • Determining if the bleeding pattern suggests regular ovulatory bleeding or anovulatory bleeding

  • Determining contribution of structural abnormalities (PALM), including risk for malignancy/hyperplasia

  • Determining risk of medical conditions that may impact bleeding (eg, inherited bleeding disorders, endocrine disease, risk for infection)

  • Assessing contribution of current medications, including contraceptives or natural product supplements or combinations that may affect bleeding

Differential Diagnosis

• Ovulation bleeding (spotting episode between menses)

• Anovulatory cycle (dysfunctional uterine bleeding)

• Polycystic ovary syndrome (type of anovulatory cycle)

• Pregnancy

• Ectopic pregnancy

• Spontaneous abortion

• Uterine leiomyomas (fibroids)

• Endometrial polyp

• Cervicitis or pelvic inflammatory disease

• Adenomyosis (uterine endometriosis)

• Cervical cancer

• Cervical polyp

• Endometrial hyperplasia

• Endometrial cancer

• Hypothyroidism

• Hyperprolactinemia

• Diabetes mellitus

• Bleeding disorder, eg, von Willebrand disease

Laboratory Tests

• Complete blood count

• Pregnancy test

• Thyroid function tests

• Vaginal or urine samples should be obtained for polymerase chain reaction or culture to rule out infectious causes

• If indicated, cervical cytology should also be obtained

• For adolescents with heavy menstrual bleeding and adults with a positive screening history, coagulation studies (eg, prothrombin time, activated partial thromboplastin time, platelet count) should be considered

Imaging Studies

• Transvaginal ultrasound is useful to assess for presence of fibroids, suspicion of adenomyosis, and to evaluate endometrial thickness

• Sonohysterography or hysteroscopy may be used to diagnose endometrial polyps or subserous myomas

• MRI

  • Not primary imaging method for abnormal uterine bleeding

  • However, can definitively diagnose submucous myomas and adenomyosis

Diagnostic Procedures

• See Table 18–1 for sampling methods and other gynecologic diagnostic procedures

• Endometrial sampling is used to determine whether hyperplasia or carcinoma is present

• Endometrial sampling should be performed in

  • Patients aged 45 years and older with abnormal uterine bleeding

  • Younger patients with a history of unopposed estrogen exposure or failed medical management and persistent abnormal uterine bleeding

• Colposcopic-directed biopsies and endocervical curettage are usually indicated if a Pap smear abnormality requires it or if a gross cervical lesion is seen

Medications

Abnormal uterine bleeding

• Give medroxyprogesterone acetate, 10 mg once daily orally, or norethindrone acetate, 5 mg once daily orally, for 10 days, following which withdrawal bleeding occurs

• Treatment can be repeated for several cycles starting medication on day 15 of subsequent cycles, or can be reinstituted if amenorrhea or dysfunctional bleeding recurs

• In women who are bleeding actively

  • Any combination oral contraceptive can be given four times daily for 1 or 2 days followed by two pills daily through day 5 and then one pill daily through day 20

  • After withdrawal bleeding occurs, pills are taken in the usual dosage for three cycles

• Nonhormonal options

  • Nonsteroidal anti-inflammatory drugs (NSAIDs), such as naproxen or mefenamic acid, in the usual anti-inflammatory doses taken during menses

  • Tranexamic acid,1300 mg three times per day orally for up to 5 days

  • Both have been shown to decrease menstrual blood loss by about 40%, with tranexamic acid superior to NSAIDs in direct comparative studies

Heavy bleeding

• For intractable heavy bleeding, a gonadotropin-releasing hormone agonist can be used for up to 6 months to create a temporary cessation of menstruation by ovarian suppression; for example

  • Depot leuprolide, 3.75 mg monthly intramuscularly

  • Nafarelin, 0.2–0.4 mg twice daily intranasally

• For cases requiring hospitalization, intravenous conjugated estrogens, 25 mg every 4 hours for three or four doses, can be used followed by oral conjugated estrogens, 2.5 mg once daily orally, or ethinyl estradiol, 20 mcg once daily orally, for 3 weeks, with the addition of medroxyprogesterone acetate, 10 mg once daily orally for the last 10 days of treatment, or a combination oral contraceptive daily for 3 weeks

  • This will thicken the endometrium and control the bleeding

Menorrhagia

• Nonsteroidal anti-inflammatory drugs in the usual anti-inflammatory doses will often reduce blood loss in menorrhagia—even that associated with a copper intrauterine device

• Prolonged use of a progestin, as in a minipill, in injectable contraceptives, or in the therapy of endometriosis, can also lead to intermittent bleeding, sometimes severe

  • In this instance, the endometrium is atrophic and fragile

  • If bleeding occurs, it should be treated with estrogen as follows: ethinyl estradiol, 20 mcg once daily orally for 7 days, or conjugated estrogens, 1.25 mg once daily orally for 7 days

Therapeutic Procedures

• For structural lesions (eg, fibroids, adenomyosis)

  • Minimally invasive procedural options for fibroids include

    • Uterine artery embolization

    • Focused ultrasound ablation

  • Surgical options for fibroids include

    • Myomectomy

    • Hysterectomy

• For women without structural abnormalities, endometrial ablation has similar results compared to the LNG-IUD in reducing menstrual blood loss

• Hysteroscopic surgical approaches include

  • Endometrial ablation with laser photocoagulation

  • Electrocautery

• Non-hysteroscopic techniques include

  • Balloon thermal ablation

  • Cryoablation

  • Free-fluid thermal ablation

  • Impedance bipolar radiofrequency ablation

  • Microwave ablation

• Alternatives to hysterectomy

  • Endometrial ablation

  • LNG-IUD

  • Both have lower risk of complications and good short-term results compared to hysterectomy

Follow-Up

• Monitor for the development of iron deficiency anemia

Prognosis

• While short-term results with endometrial ablation and LNG-IUD are satisfactory, up to 40% of women will have had either repeat ablation procedures or a hysterectomy at 5 years

When to Refer

• If bleeding does not stop with first-line therapy

• If expertise is needed with a procedure

When to Admit

• If bleeding is uncontrollable with first-line therapy or patient is not hemodynamically stable