BACKGROUND AND DEFINITIONS

Abnormal uterine bleeding (AUB) is among the most common diagnostic and therapeutic challenges faced by gynecologists. Complaints of AUB account for more than a third of gynecology visits.¹ An indication of how difficult this problem can be to treat is that AUB remains the indication for half the hysterectomies performed in the United States. The inability to find any pathologic abnormality in 20% of these hysterectomy specimens suggests that AUB is often caused by potentially treatable hormonal or systemic conditions.²

Each gynecologist needs to develop an approach to AUB that is expedient, cost-effective, and successful. Focused evaluation and appropriate treatment depend on knowing the most likely causes of AUB and their most common presenting symptoms.

Definition

Abnormal uterine bleeding is an all-inclusive term used to describe any uterine bleeding outside the parameters of normal menstruation that occurs during the reproductive years. It does not include bleeding that originates lower in the genital tract (i.e., the vagina or vulva). It usually does include bleeding originating from either the uterine fundus or cervix, because these causes are difficult to distinguish clinically, and should both be considered in all patients presenting with bleeding from the uterus. Abnormal bleeding can occur during childhood or after the menopause. However, because the differential diagnoses and thus the diagnostic approach are markedly different during these time periods, bleeding in these age groups is considered separately in Chapters 13 and 24.

Normal Menstruation

Exactly what is considered normal menstruation is somewhat subjective and often varies between individual women and certainly between cultures. However, normal menstruation (eumenorrhea) can be defined as bleeding that occurs after ovulatory cycles every 21 to 35 days, lasts 3 to 7 days, and is not excessive. The total amount of blood lost during a normal menstrual period has been found to be no more than 80mL, although this is difficult to estimate clinically, because much of the menstrual effluent is dissolved endometrium.³ Normal menses do not cause severe pain, do not include passage of identifiable clots, and do not require the patient to change pads or tampons more than once per hour. It follows that AUB is any bleeding that falls outside these parameters.

Abnormal Uterine Bleeding Terminology

The following descriptive terms are often used to describe AUB:

• Dysmenorrhea—painful menstruation

• Polymenorrhea—frequent menstruation with bleeding intervals shorter than 21 days

• Menorrhagia—excessive menstrual bleeding, in terms of flow (<80mL) and/or duration (<7 days). This implies regular ovulatory cycles.

• Metrorrhagia—irregular menstruation intervals

• Menometrorrhagia—irregular menstruation intervals with excessive flow and/or duration

• Oligomenorrhea—menstruation fewer than 9 times per year (i.e., average bleeding intervals <40 days)

• Hypomenorrhea—very light or short duration menstruation

• Intermenstrual bleeding—uterine bleeding in between apparently ovulatory menses

• Amenorrhea —absence of menses for at least 6 months, or three cycles

• Postmenopausal bleeding—uterine bleeding more than 12 months after cessation of menses.

These various types of characteristic bleeding patterns can give clues as to the etiology and help guide the diagnostic workup. However, because of the marked variation in presentation and the common existence of multiple potential causes of bleeding, presentation alone cannot be used clinically to exclude common conditions.

Dysfunctional Uterine Bleeding: An Obsolete Diagnostic Term

Dysfunctional uterine bleeding is a traditional term that was used for years to refer to excessive uterine bleeding in cases where no uterine pathology could be identified.⁴ However, the development of a greater understanding of AUB and the continuing development of more sophisticated diagnostic techniques has made this term outdated.

In most cases, bleeding unrelated to uterine pathology can be determined to be due to chronic anovulation (polycystic ovary syndrome and related conditions), exogenous steroid hormones (contraceptives or hormone replacement therapy), or hemostatic disorders (e.g., von Willebrand’s disease). In many cases that would have been referred to as dysfunctional uterine bleeding in the past, modern diagnostic techniques identify uterine or systemic pathologies that (1) result in anovulation (e.g., hypothyroidism), (2) result from anovulation (e.g., endometrial hyperplasia or cancer), or (3) coexist with anovulatory bleeding but may or may not be causal (e.g., leiomyomata).

Clinically, treatment will always be the most effective when specific causes of AUB can be identified. Because grouping widely divergent causes of AUB together in a poorly defined group is unlikely to improve diagnosis or treatment, a national consensus group has recently concluded that dysfunctional uterine bleeding no longer has any usefulness in clinical medicine.⁵

ABNORMAL UTERINE BLEEDING CAUSED BY UTERINE CONDITIONS

Different causes of AUB can be grouped according to their basic pathophysiology (Tables 21-1 and 21-2). The clinician must keep in mind that any individual patient can simultaneously have two or more causes of uterine bleeding. For this reason, the workup must evaluate patients simultaneously for the most likely and most serious anatomic and systemic etiologies based on clinical presentation.

Table 21-1 Common Uterine Conditions Associated with Abnormal Uterine Bleeding

Table 21-2 Incidence of Endometrial Polyps and the Risk of Associated Malignancies as a Function of Age.

Age Group (Years of age)	Incidence of Endometrial Polyps	Risk of Associated Malignancy
25–35	9%	2%
36–45	27%	11%
46–55	29%	15%
56–65	18%	17%
>65	17%	55%

Data from Hileeto D, Fadare O, Martel M, Zheng W: Age-dependent association of endometrial polyps with increased risk of cancer involvement. World J Surg Oncol 3:8, 2005.

Pregnancy

Normal pregnancies, spontaneous abortions, and ectopic pregnancies together represent the most common causes of AUB in the reproductive-age group. First-trimester bleeding occurs in up to 25% of all pregnancies and is associated with an increased risk of several common complications.⁶ In approximately half of these cases, bleeding will be an early symptom of impending spontaneous abortion, whereas the remaining half will ultimately prove to have a viable pregnancy. Ectopic pregnancies, which currently make up 2% of all pregnancies, will commonly present with AUB as one of the symptoms as well.⁷ Gestational trophoblastic disease is another pregnancy-related problem that presents as AUB in more than 80% of cases.⁸ Pregnancy must be ruled out in every case of AUB in reproductive-age women, no matter how obvious any alternative causal diagnoses might be.

Uterine Pathology

An important and expected priority for gynecologists is to precisely identify uterine pathology that might contribute to uterine bleeding (see Table 21-1). Most of these diagnoses can be determined to be related to infection and neoplasm. An additional common uterine pathology related to AUB is adenomyosis.

Infection

Infection is a surprisingly common cause of AUB and is often the basis of what appears to be AUB. In obvious cases of pelvic inflammatory disease (see Chapter 33), approximately 40% of the patients will present with vaginal bleeding.⁹ An underrecognized cause of uterine bleeding is endometritis. Although chronic endometritis was classically diagnosed only when plasma cells were found on endometrial biopsy, recent studies have found an association between AUB and reactive changes in the surface endometrium, but no association with the presence of a particular type of inflammatory cell.¹⁰ Other studies have verified that subclinical endometritis is a common finding in patients diagnosed with AUB and can be related to any of a number of pathogens.¹¹

Cervicitis is another common cause of AUB characterized by postcoital spotting. In addition to common sexually transmitted diseases (i.e., chlamydia and gonorrhea), other vaginal flora and pathogens can be involved.¹² Postcoital bleeding is the most common presenting symptom in women found to have chlamydia infections.¹³

Studies have found that from 5% to 33% of premenopausal women complaining of AUB will be found to have endometrial polyps.^17,¹⁸ Endometrial polyps are commonly found in patients with a long history of anovulatory bleeding, suggesting that polyps might be the result of chronic anovulation in some women. Polyps are also found in women complaining of postmenstrual spotting or bleeding in ovulatory cycles or during cyclic hormonal therapy.

Although endometrial polyps in premenopausal women are usually benign, the risk of associated endometrial malignancy increases significantly with age, such that in women older than age 65 the risk of malignancy is greater than 50% (see Table 21-2).¹⁶ In one pathologic study of 513 women with endometrial polyps, associated carcinomas were endometrioid in 58, serous in 6, carcinosarcoma in 1, and clear cell in 1.¹⁶

Endometrial Cancer

The single most important disease to identify early in the evaluation of a perimenopausal or postmenopausal woman is endometrial cancer. In women age 40 to 49, the incidence of endometrial carcinoma is 36 per 100,000.¹⁹ After the menopause, approximately 10% of women with AUB will be found to have endometrial cancer, and the incidence increases with each decade of life thereafter.

Endocervical Polyps

These soft, fleshy growths originate from the mucosal surface of the endocervical canal. They usually hang from a stalk and protrude through the cervical os, although some are broad based. They usually range in size from 3 to 20 mm, but are occasionally even larger.

The cause of endocervical polyps is unclear, but they are known to be more frequent in women on oral contraceptives or with chronic cervicitis. Microscopically, endocervical polyps consist of a vascular core surrounded by a glandular mucous membrane and may be covered completely or partially with stratified squamous epithelium. In some cases, the connective tissue core may be relatively fibrous. Endocervical polyps removed from women taking oral contraceptives often show a pattern of microglandular hyperplasia.²⁰

Endocervical polyps are relatively common in sexually active women and are rare before menarche. Many endocervical polyps are asymptomatic and are discovered incidentally on visual examination of the cervix. When symptomatic, these polyps usually manifest as intramenstrual or postcoital spotting.

Cervical Cancer

As many as 17% of women presenting with postcoital spotting will be found to have cervical dysplasia; 4% will have invasive cancer.²¹ In the absence of a visible lesion, Papanicolaou smears and colposcopy (if indicated) are important diagnostic tools. In the presence of a visible cervical lesion, biopsy is the most important technique for confirming the clinical diagnosis.