Abnormal uterine bleeding is a common but complicated clinical presentation. One national study (1) found that menstrual disorders were the reason for 19.1 percent of 20.1 million visits to physician offices for gynecologic conditions over a two-year period. Furthermore, a reported 25 percent of gynecologic surgeries involve abnormal uterine bleeding. (2)
Except for self-limited, physiologic withdrawal bleeding that occurs in some newborns, vaginal bleeding before menarche is abnormal. (3) In women of childbearing age, abnormal uterine bleeding includes any change in menstrual-period frequency or duration, or amount of flow, as well as bleeding between cycles. (4) (Amenorrhea, or the cessation of menses for six months or more in nonmenopausal women, is beyond the scope of this article.) In postmenopausal women, abnormal uterine bleeding includes vaginal bleeding 12 months or more after the cessation of menses, or unpredictable bleeding in postmenopausal women who have been receiving hormone therapy for 12 months or more. (5)
This article presents a practical approach to determining the cause of abnormal uterine bleeding and briefly reviews medical and surgical management.
Etiology and Evaluation of Abnormal Uterine Bleeding
BEFORE MENARCHE
Malignancy, trauma, and sexual abuse or assault are potential causes of abnormal uterine bleeding before menarche. A pelvic examination (possibly under anesthesia) should be performed, because a reported 54 percent of cases involve focal lesions of the genital tract, and 21 percent of these lesions may be malignant. (3)
CHILDBEARING YEARS
The menstrual cycle has three phases. During the follicular phase, follicle-stimulating hormone levels increase, causing a dominant follicle to mature and produce estrogen in the granulosa cells. With estrogen elevation, menstrual flow ceases, the endometrium proliferates, and positive feedback is exerted on luteinizing hormone (LH), resulting in the ovulatory phase. During the luteal phase, progesterone elevation halts proliferation of the endometrium and promotes its differentiation; progesterone production by the corpus luteum diminishes, causing endometrial shedding, or menstruation. A menstrual cycle of fewer than 21 days or more than 35 days or a menstrual flow of fewer than two days or more than seven days is considered abnormal. (6)(pp201-38)
Pregnancy is the first consideration in women of childbearing age who present with abnormal uterine bleeding (Table 1).7,8 Potential causes of pregnancy-related bleeding include spontaneous pregnancy loss (miscarriage), ectopic pregnancy, placenta previa, abruptio placentae, and trophoblastic disease. Patients should be questioned about cycle patterns, contraception, and sexual activity. A bimanual pelvic examination (seeking uterine enlargement), a beta-subunit human chorionic gonadotropin test, and pelvic ultrasonography are useful in establishing or ruling out pregnancy and pregnancy-related disorders.
Next, iatrogenic causes of abnormal uterine bleeding should be explored. Bleeding may be induced by medications, including anticoagulants, selective serotonin reuptake inhibitors, antipsychotics, corticosteroids, hormonal medications, and tamoxifen (Nolvadex). Herbal substances, including ginseng, ginkgo, and soy supplements, may cause menstrual irregularities by altering estrogen levels or clotting parameters. (9)
Once pregnancy and iatrogenic causes have been excluded, patients should be evaluated for systemic disorders, particularly thyroid, hematologic, hepatic, adrenal, pituitary, and hypothalamic conditions (Table 2).Menstrual irregularities are associated with both hypothyroidism (23.4 percent of cases) and hyperthyroidism (21.5 percent of cases).10 [Strength of recommendation (SOR) B. Consistent cohort studies] Thyroid function tests may help the physician determine the etiology.
Inherited coagulopathy has been shown to be the underlying cause of abnormal uterine bleeding in 18 percent of white women and 7 percent of black women with menorrhagia. (11) These patients may present in adolescence with severe menstrual bleeding or frequent bruising. A complete blood count with platelet count should be obtained. If a coagulation defect is suspected, consultation with a hematologist may be the most cost-effective option in the absence of reasonable screening tests for specific abnormalities. (11) Because jaundice and hepatomegaly may suggest underlying acquired coagulopathy, liver function tests should be considered.
Obesity, acne, hirsutism, and acanthosis nigricans may be signs of polycystic ovary syndrome or diabetes mellitus. Polycystic ovary syndrome is associated with unopposed estrogen stimulation, elevated androgen levels, and insulin resistance, and is a common cause of anovulation. (6)(p499), (12)
The presence of galactorrhea, as determined by the history or physical examination, may indicate underlying hyperprolactinemia, which can cause oligo-ovulation or eventual amenorrhea. A prolactin level confirms the diagnosis of hyperprolactinemia. Hypothalamic suppression secondary to eating disorders, stress, or excessive exercise may induce anovulation, which sometimes manifests as irregular and heavy menstrual bleeding or amenorrhea.
Genital tract pathology may be associated with intermenstrual, postcoital, and heavy menstrual bleeding. (4) Any history of abnormal Papanicolaou (Pap) smears, sexually transmitted disease, gynecologic surgery, trauma, or sexual abuse should be elicited. Uterine fibroids, endometrial polyps, adenomyosis, endometrial hyperplasia and atypia, and endometrial cancer should be excluded. (13)
The evaluation of postmenarchal women who present with abnormal uterine bleeding includes a pelvic examination, as well as a Pap smear if appropriate, to look for vulvar or vaginal lesions, signs of trauma, and cervical polyps or dysplasia. Cervical dysplasia seldom causes abnormal uterine bleeding, but it may be associated with postcoital bleeding. (14) Cervical cultures may be indicated if the patient is at risk for infection or if symptoms of infection are present. A bimanual examination in the postmenarchal woman may reveal tenderness associated with infection, an adnexal mass consistent with an ovarian neoplasm or cyst, or uterine enlargement consistent with fibroids, pregnancy, or a tumor.
Because endometrial abnormalities are present in 31 percent of patients with a Pap result of "atypical glandular cells of undetermined significance, favor endometrial origin," endometrial biopsy is indicated. (15) [SOR B, observational studies] Transvaginal ultrasonography may be useful in delineating the underlying cause of abnormal uterine bleeding that is associated with uterine enlargement or an adnexal mass. Even if the pelvic examination is normal, further evaluation of the endometrium may be required to eliminate less obvious abnormalities.
Dysfunctional uterine bleeding, with both anovulatory and, less commonly, ovulatory (4) causes, occurs during the childbearing years. It is a diagnosis of exclusion and is made only after pregnancy, iatrogenic causes, systemic conditions, and obvious genital tract pathology have been ruled out (Figure 1). (2,16)
[FIGURE 1 OMITTED]
Anovulatory dysfunctional uterine bleeding is a disturbance of the hypothalamic-pituitary-ovarian axis that results in irregular, prolonged, and sometimes heavy menstrual bleeding. It may occur immediately after menarche but before maturation of the hypothalamic-pituitary-ovarian axis, or it may occur during perimenopause, when declining estrogen levels fail to regularly stimulate the LH surge and resulting ovulation.
Unopposed estrogen stimulation may lead to endometrial proliferation and hyperplasia. Without sufficient progesterone to stabilize and differentiate the endometrium, this mucous membrane becomes fragile and sloughs irregularly. Estrogen also affects uterine vascular tone, angiogenesis, prostaglandin formation, and endometrial nitric oxide production. (4)
Ovulatory dysfunctional bleeding may include polymenorrhea, oligomenorrhea, midcycle spotting, and menorrhagia (Table 3). (6)(pp575-9) Polymenorrhea, a presumed lutealphase dysfunction, results in shortened cycles (less than 21 days), whereas oligomenorrhea, a prolonged follicular-phase dysfunction, results in lengthened cycles (more than 35 days). Midcycle spotting occurs before ovulation as the estrogen levels decline. (6) Menorrhagia is regularly occurring heavy menstrual bleeding (more than 80 mL per cycle) and may result from the loss of local endometrial hemostasis.
Further Evaluation Based on Risk Factors for Endometrial Cancer
