Abnormal Uterine Bleeding

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Chapter 21 Abnormal Uterine Bleeding

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.

Abnormal Uterine Bleeding Terminology

The following descriptive terms are often used to describe AUB:

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.

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

Adenomyosis

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

Neoplasms

AUB can be a marker for gynecologic neoplasms. These neoplasms can be benign (e.g., leiomyoma, endometrial or endocervical polyps) or malignant (e.g., endometrial or cervical carcinoma). Focal intracavitary lesions account for up to 40% of cases of AUB.14 Ovarian neoplasms can indirectly cause irregular bleeding by interfering with ovulation Some of the most common neoplasms known to cause AUB are reviewed here.

Endometrial Polyps

Endometrial polyps are localized overgrowths of the endometrium that project into the uterine cavity. Such polyps may be broad-based (sessile) or pedunculated. Endometrial polyps are surprisingly common in both premenopausal and postmenopausal women, and are found in at least 20% of women undergoing hysteroscopy or hysterectomy.16 The incidence of these polyps rises steadily with increasing age, peaks in the fifth decade of life, and gradually declines after menopause.

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.

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.

ABNORMAL UTERINE BLEEDING UNRELATED TO UTERINE PATHOLOGY

Many women experience heavy or irregular menstrual bleeding that is not caused by an underlying anatomic abnormality of the uterus. Although anovulatory bleeding is one of the most common underlying causes, a number of other unrelated causes, such as exogenous hormones and bleeding disorders, must also be considered (Table 21-3).

Table 21-3 Causes of Abnormal Uterine Bleeding Unrelated to Uterine Pathology*

* Referred to as “dysfunctional uterine bleeding” in the past.

Exogenous Hormones

Hormonal therapy has become one of the most common causes of AUB. Irregular bleeding is one of the most common symptoms in women receiving contraceptive therapy and hormone replacement therapy (HRT) and is the most common reason for discontinuation of these therapies.

Hormone Contraceptives

Today, approximately 10 million women in the United States use some type of hormonal contraception, including combination oral contraceptives, progestin-only pills, depot medroxyprogesterone acetate injections, progestin-containing intrauterine devices, subdermal levonorgestrel implants, transdermal combination hormone patches, and intravaginal rings (see Chapter 26). In addition to being a common reason to visit primary care physicians, AUB is a major cause of contraception discontinuation and subsequent unplanned pregnancy.

During the first 3 months of combination oral contraceptive use, as many as one third of women will experience AUB. For the majority of women, the most effective treatment approach is patient reassurance and watchful waiting. As the uterus adapts to the new regimen of hormonal exposure, the monthly withdrawal bleeding becomes regular, lighter, and less painful than natural menstruation in most women.

If abnormal bleeding persists beyond 3 months, other common causes should be excluded. In young sexually active women, sexually transmitted diseases should be excluded; in one study, almost one third of women on oral contraceptives who experienced abnormal bleeding were found to have otherwise asymptomatic Chlamydia trachomatis infections.24 If no cause for AUB other than hormonal therapy is found, treatment options include the use of supplemental estrogen and changing to an oral contraceptive with a different formulation with a different progestin or higher estrogen content (see Chapter 26).

Women using progestin-only contraceptives have an even greater risk of continued AUB than those using combined oral contraceptives. Prolonged exposure to progestins results in a microscopic condition sometimes called pseudoatrophy (see Endometrial Atrophy in this chapter). When reassurance is not sufficient, administration of supplemental estrogen during bleeding episodes is sometimes useful.

Hormone Replacement Therapy

Hormone replacement therapy (HRT) after the menopause is a common iatrogenic cause of AUB. Unopposed daily estrogen therapy is associated with the highest rates of irregular bleeding and subsequent discontinuation of therapy.25 The addition of sequential or continuous oral progestins is associated with decreased irregular bleeding and reduced rate of endometrial hyperplasia. Sequential progestins result in the lowest rate of irregular bleeding during the first year of therapy, but the rate for sequential and continuous therapy is similar thereafter.

Each selective estrogen receptor modulator (SERM) is associated with a distinctive risk of AUB, which varies according to their effect on the endometrium. Tamoxifen, the first SERM used clinically as adjuvant treatment for breast cancer, exhibits antiestrogenic activity in the breast but stimulates the endometrium.26 As a result, tamoxifen has an incidence of postmenopausal vaginal bleeding similar to unopposed estrogen and likewise increases the risk of endometrial pathology, including endometrial polyps, hyperplasia, and cancer.

Raloxifene, a SERM approved for the prevention of osteoporosis, has little if any estrogenic effect on the uterus, resulting in atrophic endometrium.27 As a result, the risk of vaginal bleeding for women taking raloxifene is not increased compared to women not taking any form of HRT.

Ovulation Defects

Abnormal or absent ovulation is one of the most common causes of AUB during the reproductive years. A brief description of normal menstrual physiology (which is covered in depth in Chapter 1) is helpful in understanding anovulation as an underlying cause of AUB.