Perimenopausal and Postmenopausal Bleeding

The most probable etiology of abnormal uterine bleeding relates to the patient’s reproductive age, as does the likelihood of serious endometrial pathology. The specific diagnostic approach depends on whether the patient is premenopausal, perimenopausal or postmenopausal. In premenopausal women with normal findings on physical examination, the most likely diagnosis is dysfunctional uterine bleeding (DUB) secondary to anovulation, and the diagnostic investigation is targeted at identifying the etiology of anovulation. In perimenopausal patients, endometrial biopsy and other methods of detecting endometrial hyperplasia or carcinoma must be considered early in the investigation. Uterine pathology, particularly endometrial carcinoma, is common in postmenopausal women with abnormal uterine bleeding. Thus, in this age group, endometrial biopsy or transvaginal ultrasonography is included in the initial investigation. Premenopausal women with DUB may respond to oral contraceptives, cyclic medroxyprogesterone therapy or cyclic clomiphene. Perimenopausal women may also be treated with low-dose oral contraceptives or medroxyprogesterone. Erratic bleeding during hormone replacement therapy in postmenopausal women with no demonstrable pathology may respond to manipulation of the hormone regimen.

Abnormal uterine bleeding is a common reason for women of all ages to consult their family physicians. Terms used to describe patterns of abnormal uterine bleeding are based on periodicity and quantity of flow (Table 1). Dysfunctional uterine bleeding (DUB), defined as abnormal uterine bleeding not caused by pelvic pathology, medications, systemic disease or pregnancy, is the most common cause of abnormal uterine bleeding but remains a diagnosis of exclusion. Other causes of abnormal uterine bleeding are listed in Table 2.

TABLE 1

Terminology Used to Describe Abnormal Uterine Bleeding

TERM DEFINITION

Menorrhagia

Prolonged or excessive bleeding at regular intervals

Metrorrhagia

Irregular, frequent uterine bleeding of varying amounts but not excessive

Menometrorrhagia

Prolonged or excessive bleeding at irregular intervals

Polymenorrhea

Regular bleeding at intervals of less than 21 days

Oligomenorrhea

Bleeding at intervals greater than every 35 days

Amenorrhea

No uterine bleeding for at least 6 months

Intermenstrual

Uterine bleeding between regular cycles

TABLE 2

Differential Diagnosis of Abnormal Uterine Bleeding

Complications of pregnancy

Intrauterine pregnancy

Ectopic pregnancy

Spontaneous abortion

Gestational trophoblastic disease

Placenta previa

Infection

Cervicitis

Endometritis

Trauma

Laceration, abrasion

Foreign body

Malignant neoplasm

Cervical

Endometrial

Ovarian

Benign pelvic pathology

Cervical polyp

Endometrial polyp

Leiomyoma

Adenomyosis

Systemic disease

Hepatic disease

Renal disease

Coagulopathy

Thrombocytopenia

von Willebrand’s disease

Leukemia

Medications/iatrogenic

Intrauterine device

Hormones (oral contraceptives, estrogen, progesterone)

Anovulatory cycles

Hypothyroidism

Hyperprolactinemia

Cushing’s disease

Polycystic ovarian syndrome

Adrenal dysfunction/tumor

Stress (emotional, excessive exercise)

An understanding of normal menstruation is essential to investigating the complaint of abnormal vaginal bleeding. The intervals of the menstrual cycle, the duration of flow and the volume of flow remain relatively constant during a woman’s reproductive years. In the first part of the cycle, estrogen halts menstrual flow and promotes endometrial proliferation. After ovulation, progesterone stops endometrial growth, then promotes differentiation. If pregnancy does not occur, the corpus luteum regresses, progesterone production falls, the endometrium sheds its lining and menstrual bleeding follows.

The cause of DUB is usually related to one of three hormonal-imbalance conditions: estrogen breakthrough bleeding, estrogen withdrawal bleeding and progesterone breakthrough bleeding.1Estrogen breakthrough bleeding occurs when excess estrogen stimulates the endometrium to proliferate in an undifferentiated manner. With insufficient progesterone to provide structural support, portions of the endometrial lining slough at irregular intervals. The usual progesterone-guided vasoconstriction and platelet plugging do not take place, often resulting in profuse bleeding.

Estrogen withdrawal bleeding results from a sudden decrease in estrogen levels, such as occurs following bilateral oophorectomy, cessation of exogenous estrogen therapy or just before ovulation in the normal menstrual cycle. Estrogen withdrawal bleeding is usually self-limited and tends not to recur if estrogen levels remain low.

Progesterone breakthrough bleeding occurs when the progesterone-to-estrogen ratio is high, such as occurs with progesterone-only contraceptive methods. The endometrium becomes atrophic and ulcerated because of a lack of estrogen and is prone to frequent, irregular bleeding.

History and Physical Examination

If abnormal uterine bleeding is not severe and does not require emergent intervention, evaluation begins with a careful medical history, including the usual menstrual pattern, the extent of recent bleeding, sexual activity, trauma and symptoms of infection or systemic disease. A complete physical examination, supplemented by laboratory testing, should uncover any signs of systemic disease.

The pelvic examination consists of careful inspection of the lower genital tract for lacerations, vulvar or vaginal pathology and cervical lesions or polyps. Bimanual uterine examination may reveal enlargement from uterine fibroids, adenomyosis or endometrial carcinoma.

Laboratory investigation includes pregnancy testing in all patients of reproductive age. A complete blood count provides a measure of blood loss and platelet adequacy. Cervical cultures and a Papanicolaou smear are appropriate initial steps to evaluate for the presence of sexually transmitted diseases or cervical dysplasia.

Premenopausal Women

An approach to the premenopausal woman with abnormal uterine bleeding is outlined in Figure 1. If the reproductive-age woman is not pregnant and has a normal physical examination, abnormal uterine bleeding is usually dysfunctional in nature and can be managed with hormonal therapy.

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FIGURE 1.

Algorithm for the diagnostic evaluation of abnormal uterine bleeding in premenopausal patients. (CBC = complete blood count; β-HCG = beta human chorionic gonadotropin; OCPs = oral contraceptive pills; IUD = intrauterine device; TSH = thyroid-stimulating hormone; LH = luteinizing hormone; FSH = follicle-stimulating hormone; DHEA-S = dihydroepiandrosterone sulfate)

ANOVULATORY BLEEDING

The first step in identifying the etiology of abnormal uterine bleeding is to determine the patient’s ovulatory status (Table 3). Anovulation is the most common cause of DUB in reproductive-age women and is especially common in adolescents. Up to 80 percent of menstrual cycles are anovulatory in the first year after menarche. Cycles become ovulatory an average of 20 months after menarche. If anovulatory bleeding is not heavy or prolonged, no treatment is necessary. If the adolescent is distressed by the irregularity of her menses or has been anovulatory for more than a year, oral contraceptive pills are the treatment of choice.

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