BY LINDA D. BRADLEY, MD Abnormal uterine bleeding A QUICK GUIDE TO EVALUATION AND TREATMENT After vaginitis, abnormal bleeding is the main reason women consult a gynecologist. Fortunately, the armamentarium is as broad as the range of etiologies. alf of all hysterectomies in the United systemic disease, or pregnancy. States are performed to treat abnor- Abnormal bleeding is associated with an Hmal uterine bleeding. Of these, array of symptoms. Frequent complaints approximately 20% are performed in women include heavy or prolonged menstrual flow, with a normal uterine size.1 However, when social embarrassment, diminished quality of the uterus appears nor- life, sexual compromise, and the need to Linda D. Bradley, MD mal, without adeno- alter lifestyle. Pain is not a common present- myosis or uterine pathol- ing symptom unless it is associated with the ogy, it is imperative that passage of large blood clots. the clinician perform a The following menstrual patterns are asso- thorough evaluation ciated with DUB: before resorting to hys- •Oligomenorrhea. A cycle length of more terectomy. than 35 days Abnormal uterine •Polymenorrhea. A cycle length of less than bleeding is defined as 21 days The physical must excessive, erratic, or •Amenorrhea. The absence of menses for 6 irregular bleeding in the months or 3 consecutive cycles be comprehensive, presence or absence of •Menorrhagia. Heavy or increased flow even in the intracavitary or uterine occurring at regular intervals, or a loss of pathology. It may be more than 80 mL of blood presence of heavy associated with structural •Metrorrhagia. Irregular episodes of bleeding bleeding. or systemic abnormali- •Menometrorrhagia. A longer duration of ties. In contrast, dysfunc- flow occurring at unpredictable intervals ••• tional uterine bleeding •Postmenopausal bleeding. Bleeding that (DUB) is associated with occurs more than 12 months after the last anovulatory menstrual cycles. It is not menstrual cycle caused by pelvic pathology, medications, Prevalence and pathophysiology Dr. Bradley is director of hysteroscopic services, Although we lack precise figures regard- department of OBG, at the Cleveland Clinic ing the prevalence of abnormal uterine Foundation in Cleveland, Ohio. She also serves bleeding, it is estimated that 9% to 30% of on the OBG MANAGEMENT board of editors. reproductive-age women have menstrual 26 OBG MANAGEMENT • APRIL 2002 Abnormal uterine bleeding irregularities requiring medical evaluation.2 tuations in the hypothalamic-pituitary-ovari- Approximately 15% to 20% of office gyneco- an axis that lead to denudation and slough- logic visits are scheduled for the evaluation ing of the endometrium. This hemorrhage is of abnormal uterine bleeding, which is followed by prompt hemostasis and repair. exceeded only by vaginitis as a chief com- Low physiologic levels of estrogen prime the plaint. In addition, 25% to 50% of gyneco- endometrium, while the normal secretion of logic surgical procedures are performed to progesterone from the corpus luteum stabi- address menstrual dysfunction. lizes it, decreasing vascular fragility and sup- Normal menstruation is triggered by fluc- porting the endometrial stroma. Platelets and fibrin are necessary for endometrial hemo- Causes of menstrual dysfunction stasis. Deficiencies in either factor may result in heavier menstruation. TABLE 1 TABLE A NATOMIC DUB occurs when there is inadequate Polyps progesterone secretion to stabilize the Fibroids endometrium. Anovulatory bleeding can be Adenomyosis episodic or continuous. Patients with anovu- Vaginitis Endometritis latory cycles typically do not experience pre- Retained products of conception menstrual tension, breast discomfort, Endometriosis increased mucoid vaginal discharge, or Hyperplasia Malignancy cramping and bloating, all characteristic of ovulatory cycles. Although ovulatory cycles E NDOCRINE are predictable, erratic bleeding may occur when they coexist with intracavitary lesions, Thyroid dysfunction Elevated prolactin levels including polyps and fibroids. Adrenal dysfunction Anovulatory cycles typically are associated Hypothalamic/pituitary dysfunction with puberty and the perimenopausal years. Estrogen-producing tumors In puberty, the immature hypothalamic-pitu- itary-ovarian axis has not yet developed the H EMATOLOGIC necessary hormonal feedback to sustain the Anemia endometrium. In perimenopause, the de- Coagulopathy cline of inhibin and rise in follicle-stimulat- • von Willebrand’s disease • Platelet disorders ing hormone (FSH) levels reflect the loss of Leukemia follicular activity and competence. In some cases, severe anemia can cause S YSTEMIC incessant menstrual blood loss. Typical com- Renal impairment plaints of anemia include fatigue, unusual Liver disorders food cravings (pica), and headaches. Severe Obesity Anorexia anemia also can cause fainting, exercise- Chronic illness induced fatigue, shortness of breath, conges- Rapid fluctuations in weight tive heart failure, and/or the inability to per- form routine activities. Unless it is a chronic M EDICATIONS condition, DUB is rarely associated with the Anticoagulants need for a blood transfusion. Hemorrhagic Steroids shock and death are rare sequelae. Progesterone withdrawal Herbal and soy products Diagnosis M ISCELLANEOUS Diagnosis involves 3 main components: Smoking •A detailed medical history and review of Depression Excessive alcohol intake systems. This should alert the physician Sexually transmitted diseases to the possible etiology of a patient’s menstrual dysfunction (Table 1). continued on page 33 28 OBG MANAGEMENT • APRIL 2002 Abnormal uterine bleeding Inherited and acquired disorders of coag- •Partial time (PT) and partial thromboplas- ulation, as well as liver and renal dis- tin time (PTT) eases, frequently present with symptoms •Complete blood count (CBC) with of abnormal uterine bleeding. platelets •A physical examination. The exam must Successful medical therapies for von be comprehensive, even in the presence Willebrand’s disease include oral contracep- of heavy bleeding, focusing on the vagi- tives (OCs), which have an 88% success rate; na, cervix, uterus, and adnexa to exclude desmopressin acetate; antifibrinolytic agents; pathology. and plasma-derived concentrates rich in the •Appropriate laboratory studies based on high-molecular-weight multimers of von the focused clinical history and any phys- Willebrand factor (vWf).4 ical findings. Pregnancy testing is neces- Perimenopausal women. Women entering peri- sary in all sexually active premenopausal menopause may have recurrent bouts of women. In addition, women with profuse DUB and associated physical complaints due menorrhagia and a normal uterine size to changes in the hypothalamic-pituitary- should be screened for von Willebrand’s ovarian axis. The hormonal milieu is associat- disease, since 13% to 20% of women ed with decreased inhibin, variable estradiol, offered surgical intervention have the normal FSH, and menstrual cycles that can be subtle form of Type I disease. (In episodically ovulatory.5 Many menstrual com- women, von Willebrand’s disease most plaints occur in perimenopausal women, commonly presents as DUB.) Obviously, including menometrorrhagia, amenorrhea, medical therapy is paramount for women and oligomenorrheic cycles. Decreased men- with von Willebrand’s disease; hysterec- tal clarity and concentration, vaginal dryness, tomy or other surgical treatment should hot flushes, and night sweats are classic not be the first option. symptoms of perimenopause. Liberal use of endometrial For anovulatory abnormal uterine bleeding, medical therapy biopsy is encouraged in women over 35 years of age with oral contraceptives or progesterone is the standard. with risk factors for endometri- al hyperplasia and cancer. Risk factors Oral contraceptive (OC) therapy is quite include diabetes, prolonged steroid use, useful in these women and should be the first obesity, a long history of irregular cycles, line of intervention, rather than conventional unopposed estrogen therapy, and suspected hormone replacement therapy (HRT).6 The polycystic ovary syndrome (PCOS). usual postmenopausal doses of HRT do not suppress ovulation or prevent pregnancy, Special populations while OCs do. In healthy, nonsmoking Adolescents. Teens with irregular heavy women over 35 years of age, OCs regulate menses should be evaluated for coagu- menstrual cycles, decrease vasomotor symp- lopathies, since 20% to 30% have a major toms, improve bone mineral density (BMD), bleeding diathesis.3 This is especially true if and reduce the need for surgical intervention the patient presents with a hemoglobin level for DUB. They also reduce endometrial and of less than 10 g/dL or if hospitalization is ovarian cancer rates. required. Specifically, adolescents should be Postmenopausal patients. Bleeding that occurs evaluated for von Willebrand’s disease with with HRT or tamoxifen use more than 1 year the ristocetin cofactor assay, the single best after the cessation of menses requires thor- screening test for the disease. This prevents ough evaluation. While the most common false-negative results. Other laboratory tests cause of postmenopausal bleeding is atro- should include: phy, it is important to rule out intracavitary •Serum human chorionic gonadotropin pathology, endometrial hyperplasia, and (hCG) cancer. Approximately 10% of women with •Bleeding time postmenopausal bleeding have endometrial APRIL 2002 • OBG MANAGEMENT 33 Abnormal uterine bleeding cancer. Because the risk of this cancer