ABNORMAL UTERINE BLEEDING (AUB)

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DEFINITION
The evaluation of abnormal uterine bleeding (AUB) requires characterization and quantification of the bleeding,specifically the onset, duration, frequency, amount,and pattern which is occurring both within and outside the menstrual cycle.

MENSTRUAL DIMENSIONS
Normal 24-35 days

Menstrual Frequency

Oligomenorrhea > 35 days

Polymenorrhea < 24 days

MENSTRUAL DIMENSIONS (2)

Normal blood loss 5-80 mL Regular cycles 2-20 days > 12 months Light cycle < 5 mL blood loss The volume of menstrual blood loss and cycle regularity Menorrhagia > 80 mL blood loss Metrorrhagia irregular bleeding

Menometrorrhagia Withdrawal bleeding

Breakthrough bleeding

MENSTRUAL DIMENSIONS (3)

Duration of menstrual bleeding

Normal 4 to 6 days

Prolonged > 7 days

Shortened < 3 days

DIFFERENTIAL DIAGNOSIS OF AUB

Tabel 1. Differential Diagnosis of AUB by Age Group
Children a. b. c. d. e. f. g. h. Physiologic Vulvovaginitis Trauma Urethral prolapse Endocrinopat hies Precocious puberty Ovarian cyst Genital tract neoplasm a.

b. c. d. e. f. g. h.

Perimenopausal Anovulatory due a. Pregnancy a. Anovulatory to immaturity of related b. Endometrial hypothalamicb. Anovulatory hyperplasia pituitary-ovarian c. Vaginal/pelvic c. Endometrial axis infection polyps Coagulopathy d. Pelvic tumor d. Leiomyomas Pregnancy e. Endocrinopathie e. Adenomyosis Vaginal/pelvic s f. Genital tract infection f. Coagulopathy neoplasm Benign lesions Medications Mllerian anomalies Genetic abnormality

Adolescent

Reproductive

Menopausal a. Atrophy b. Endometrial carcinoma c. Endometrial hyperplasia d. Endometrial polyp e. Leiomyomas f. Hormone replacement therapy

Adapted from Shwayder JM. Pathophysiology of abnormal uterine bleeding. Obstet Gynecol Clin North Am 2000;27:219-234, with permission.

DIFFERENTIAL DIAGNOSIS OF AUB (2)

Diagnostic Testing
Order laboratory serum testing for human chorionic gonadotropin (-hCG), thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH), prolactin, and complete blood count (CBC). In women with risk factors for neoplastic processes a tissue diagnosis is required. If anovulatory bleeding and pregnancy have been ruled out, evaluate for coagulation disorders.

EVALUATION OF AUB
ULTRASONOGRAFI Transvaginal Ultrasonografi (TVUS) TVUS is useful to evaluated for the presens of fibroids, intrauterine pregnancy and ectopic pregnancy. Saline Infusion Sonografi It is the most sensitive non invasive method of diagnosis for endometrial polyps and submucous myomata. But, it does not distinguish between benign and malignant processes. HYSTEROSCOPY The advantage of this procedure is that it provide direct visualization of the endometrial cavity and can be performed in the operating room. MAGNETIC RESONANCE IMAGING (MRI) Can be useful in the diagnosis adenomiosis and can accurately localize and measure fibroids, faciltating determination of the best treatment.

EVALUATION OF AUB (2)

ENDOMETRIAL SAMPLING

Recommended for a women over age 35 years with anovulatory bleeding and considered in younger women with a history of chronic anovulatory bleeding or risk endometrial carcinoma. The advantage is a rapid, safe, and cost effective. A potential drawback is that the biopsy does not sample the entire endometrium and a localized lesion may be missed.
DILATION and CURRETAGE Can be both diagnostic and therapeutic,but incurs the cost of an operating room and carries the risks of anasthesia. Its also can be indicated in women with nondiagnostic endometrial biopsi.

SPECIFIC CAUSES OF AUB

Pregnancy Associated Bleeding

Dysfunctional uterine bleeding (DUB)

Pregnancy Associated Bleeding

Pregnancy should be suspected in any woman in her reproductive years. If urine -hCG is positive, a pelvic examination must be performed and an ultrasonographic study obtained. Any patient who is hemodynamically unstable, bleeding heavily, or septic requires surgical intervention. Women with missed or incomplete abortions who are stable and not bleeding heavily may be treated medically with misoprostol

Dysfunctional uterine bleeding (DUB)

DEFINITION
Dysfunctional uterine bleeding (DUB) is a diagnosis of exclusion for AUB without a demonstrable pathologic cause and is found in approximately one third of all patients evaluated.

ETIOLOGY
The predominant causes of DUB are anovulation or oligoovulation. Anovulation is multifactorial and related to alterations of the hypothalamic-pituitaryovarian axis. long-term anovulation estrogen production occurs without the progesterone produced from the corpus luteum thus creating an unopposed estrogen state risk for endometrial hyperplasia Anovulation is also associated with polycystic ovary syndrome, which also places women at risk for endometrial hyperplasia. Morbid obesity Peripheral conversion of androstenedione to estrone occurs in adipose tissue producing elevated estrogen levels Occasionally, DUB may be associated with ovulatory cycles.

Dysfunctional uterine bleeding (DUB) (2)

MANAGEMENT
Administration of progestins

The levonorgestrel-releasing intrauterine system (Mirena)

OCPs also regulate menses and often decrease flow. Nonsteroidal anti-inflammatory drugs (NSAIDs) Danazol

Antifibrinolytic
Gonadotropin-releasing hormone (GnRH) agonists

SURGICAL TREATMENT
Endometrial ablation is designed to ablate the full thickness of the endometrium. Before performing endometrial ablation in a woman with anovulatory bleeding, endometrial hyperplasia or carcinoma must be ruled out. overall success rate is 80% to 90%, with 30% to 50% of women reporting amenorrhea 6 months postprocedure. Still, within 5 years, 15% will have a second ablation and 20% will have a hysterectomy. Endometrial ablation is not recommended in women who desire future fertility.

Pharmacologic Management of Abnormal Uterine Bleeding

Progestins
a. Medroxyprogesterone (Provera) 10 mg 3/d for 14 d (days 12-25); or for 5-10 d b. Norethindrone acetate (Aygestin) 5 mg 3/d for 14 d (days 12 and 25) for anovulatory bleeding; or on days 5-25 for ovulatory bleeding c. Medroxyprogesterone acetate injection (Depo Provera) 150 mg IM every 12 wk d. Levonorgestrel-releasing intrauterine system (Mirena)

Hormonal Management

a. Oral contraceptives Combined estrogen and b. Transdermal preparations c. Vaginal ring progestins

d. Hormone replacement therapy Danazol 200 mg/d

Androgenic steroids

GnRH agonists

a. Leuprolide (Lupron) 3.75 mg IM/mo or 11.25 mg every 3 mo b. Goserelin (Zoladex) 3.6 mg SQ every 4 wk

Pharmacologic Management of Abnormal Uterine Bleeding (2)

Nonsteroidal Anti-inflammatory Drugs (NSAIDs) a. b. c. d. Mefenamic acid 500 mg 3/d Ibuprofen 600-800 mg every 6 hr Meclofenamate sodium 100 mg 3/d Naproxen sodium 550 mg 1, then 275 mg every 6 hr

Antifibrinolytic Agents

Tranexamic acid 1 g 4/d on days 1 to 5; or 1.5 g 3/d

Coagulation Disorders
Menorrhagia during adolescence should be attributed to a coagulation disorder until proven otherwise. Bleeding from multiple sites (e.g., nose, gingiva, intravenous sites, gastrointestinal, and genitourinary tracts) may suggest coagulopathy. There is a higher prevalence of bleeding disorders in women with menorrhagia.

Von Willebrand Disease

Von Willebrand disease is the most common inherited bleeding disorder, affecting 1% to 2% of the population In women with vWD, menorrhagia is the most common manifestation, occurring in 60% to 95% beginning at menarche. Women with vWD are also likely to report postpartum or postoperative bleeding. Other coagulopathies may also cause AUB, including platelet abnormalities, idiopathic thrombocytopenic purpura, and hematologic malignancy (e.g., leukemia). Testing for vWD should be considered in women with a history of unexplained menorrhagia beginning at menarche. Screening for vWD in adolescents with severe menorrhagia before starting hormonal therapy and in adult women with significant unexplained menorrhagia.

ENDOCRINE DISORDERS
Endocrinopathies can cause anovulation, producing an estrogen without progesteron. the endometrium eventually breaks down, which may or may not lead to the formation of hyperplasia.

Hepatic Dysfunction
Decreased metabolism of estrogen and decreased clotting factor synthesis are common ramifications of liver failure. Anovulation may also ensue. Menometrorrhagia is common. Liver function tests are necessary to make the diagnosis, finding of jaundice, ascites, hepatosplenomegaly, palmar erythema, pruritus, and spider angioma are suggestive of liver failure.

Medication Side Effects

Psychotropic Medications a. Certain medications used in the treatment of psychiatric patients b. Antipsychotic medications (i.e., dopamine antagonists) Phenothiazines and antidepressants Hormone Medications a. Medroxyprogesterone acetate b. Combination OCPs c. Progestational agents Other Medications a. Anticoagulants b. Digitalis, phenytoin, and corticosteroids Intrauterine Devices a. Copper-containing intrauterine devices, unlike the levonorgestrelreleasing Mirena intrauterine system b. Such bleeding is often treated successfully with NSAIDs.

Benign Pathology
Leiomyomata Leiomyomata (fibroids) are the most common uterine neoplasm, and is the number one indication for hysterectomy in the United States. Endometrial Polyps Generally, benign endometrial lesions tend to be asymptomatic but may be present in 10% to 33% of women with complaints of bleeding, typically metrorrhagia.
Endometrial Hyperplasia
Endometrial hyperplasia, a precursor to endometrial carcinoma, is classified into simple or complex, based on architectural features, and typical or atypical, based on cytologic features.

Malignancy
Endometrial Cancer Endometrial carcinoma is rare in patients younger than age 40. Postmenopausal bleeding, should be assumed to represent endometrial cancer until proven otherwise. Cervical Cancer a. Cervical carcinoma is a disease of both the relatively young and the old it cause abnormal bleeding. b. The most common bleeding patterns associated with cervical carcinoma are intermenstrual and postcoital bleeding Ovarian Cancer Estrogen-producing ovarian tumors, such as a granulosatheca cell tumor, can produce endometrial hyperplasia and AUB.

SUGGESTED READINGS
Management of Anovulatory Bleeding. ACOG Practice Bulletin Number 14. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet 2001;72(3):263-271. Von Willebrand Disease in Women. ACOG Committee Opinion Number 451. American College of Obstetricians and Gynecologists. Obstet Gynecol 2009;114:1439-1443. Lacey JV Jr, Chia VM. Endometrial hyperplasia and the risk of progression to carcinoma. Maturitas 2009;63(1):39-44. Casablanca Y. Management of dysfunctional uterine bleeding. Obstet Gynecol Clin North Am 2008;35(2):219-234, viii.