Abnormal (Dysfunctional) Uterine Bleeding

Updated: Oct 27, 2017
  • Author: Millie A Behera, MD; Chief Editor: Richard Scott Lucidi, MD, FACOG  more...
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Overview

Practice Essentials

Abnormal uterine bleeding (formerly, dysfunctional uterine bleeding [DUB] [1] ) is irregular uterine bleeding that occurs in the absence of recognizable pelvic pathology, general medical disease, or pregnancy. It reflects a disruption in the normal cyclic pattern of ovulatory hormonal stimulation to the endometrial lining. The bleeding is unpredictable in many ways. It may be excessively heavy or light and may be prolonged, frequent, or random.

About 1-2% of women with improperly managed anovulatory bleeding eventually may develop endometrial cancer.

Signs and symptoms

AUB should be suspected in patients with unpredictable or episodic heavy or light bleeding despite a normal pelvic examination. Typically, the usual moliminal symptoms that accompany ovulatory cycles will not precede bleeding episodes.

Pathologic causes of anovulatory bleeding

Because AUB is considered a diagnosis of exclusion, the presence or absence of signs and symptoms of other causes of anovulatory bleeding must be determined.

Patients who report irregular menses since menarche may have polycystic ovarian syndrome (PCOS). PCOS is characterized by anovulation or oligo-ovulation and hyperandrogenism. These patients often present with unpredictable cycles and/or infertility, hirsutism with or without hyperinsulinemia, and obesity.

Other signs of underlying pathology include the following:

  • Thyroid enlargement or manifestations of hyperthyroidism or hypothyroidism
  • Galactorrhea: May suggest hyperprolactinemia
  • Visual field deficits: Raise suspicion of intracranial/pituitary lesion
  • Ecchymosis, purpura: Signs of bleeding disorder

See Clinical Presentation for more detail.

Diagnosis

Laboratory studies

Studies used to exclude a pathologic source of anovulatory bleeding include the following:

  • Human chorionic gonadotropin (HCG)
  • Complete blood count (CBC)
  • Papanicolaou test (Pap smear)
  • Endometrial sampling
  • Thyroid functions and prolactin
  • Liver functions
  • Coagulation studies/factors
  • Other hormone assays, as indicated

Imaging studies

In obese patients with a suboptimal pelvic examination or in patients with suspected ovarian or uterine pathology, pelvic ultrasonographic evaluation may be helpful. Ultrasonography can be used to identify uterine fibroids, as well as endometrial conditions, including hyperplasia, carcinoma, and polyps.

Procedures

Rule out endometrial carcinoma in all patients at high risk for the condition, including those with the following characteristics:

  • Morbid obesity
  • Diabetes or chronic hypertension
  • Age over 35 years
  • Longstanding, chronic eugonadal anovulation

Traditionally, carcinoma was ruled out by endometrial sampling via dilation and curettage (D&C). However, endometrial sampling in the office via aspiration, curetting, or hysteroscopy has become popular and is also relatively accurate.

Histology

Most endometrial biopsy specimens will show proliferative or dyssynchronous endometrium.

See Workup for more detail.

Management

Pharmacologic treatment

  • Oral contraceptives: Suppress endometrial development, reestablish predictable bleeding patterns, decrease menstrual flow, and lower the risk of iron deficiency anemia
  • Estrogen: Prolonged uterine bleeding suggests the epithelial lining of the cavity has become denuded over time; estrogen administered alone will rapidly induce a return to normal endometrial growth
  • Progestins: Chronic management of AUB requires episodic or continuous exposure to a progestin
  • Desmopressin: A synthetic analogue of arginine vasopressin, desmopressin has been used as a last resort to treat abnormal uterine bleeding in patients with documented coagulation disorders

Hysterectomy

Abdominal or vaginal hysterectomy may be necessary in patients who have failed or declined hormonal therapy, who have symptomatic anemia, and who are experiencing a disruption in their quality of life from persistent, unscheduled bleeding.

Endometrial ablation

Endometrial ablation is an alternative for patients who wish to avoid hysterectomy or who are not candidates for major surgery.

See Treatment and Medication for more detail.

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Background

Abnormal uterine bleeding (AUB) is irregular uterine bleeding that occurs in the absence of pathology or medical illness. It reflects a disruption in the normal cyclic pattern of ovulatory hormonal stimulation to the endometrial lining. The bleeding is unpredictable in many ways. It might be excessively heavy or light, prolonged, frequent, or random.

This condition usually is associated with anovulatory menstrual cycles but also can present in patients with oligo-ovulation. AUB occurs without recognizable pelvic pathology, general medical disease, or pregnancy. It is considered a diagnosis of exclusion.

AUB is a common diagnosis, making up 5-10% of cases in the outpatient clinic setting.

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Pathophysiology

Patients with abnormal uterine bleeding (AUB) have lost cyclic endometrial stimulation that arises from the ovulatory cycle. As a result, these patients have constant, noncycling estrogen levels that stimulate endometrial growth. Proliferation without periodic shedding causes the endometrium to outgrow its blood supply. The tissue breaks down and sloughs from the uterus. Subsequent healing of the endometrium is irregular and dyssynchronous.

Chronic stimulation by low levels of estrogen will result in infrequent, light AUB. Chronic stimulation from higher levels of estrogen will lead to episodes of frequent, heavy bleeding.

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Etiology

In ovulatory cycles, progesterone production from the corpus luteum converts estrogen primed proliferative endometrium to secretory endometrium, which sloughs predictably in a cyclic fashion if pregnancy does not occur. Heavy but regular uterine bleeding implies ovulatory bleeding and should not be diagnosed as abnormal uterine bleeding (AUB). Subtle disturbances in endometrial tissue mechanisms, other forms of uterine pathology, or systemic causes might be implicated.

Anovulatory cycles are associated with a variety of bleeding manifestations. Estrogen withdrawal bleeding and estrogen breakthrough bleeding are the most common spontaneous patterns encountered in clinical practice. Iatrogenically induced anovulatory uterine bleeding might occur during treatment with oral contraceptives, progestin-only preparations, or postmenopausal steroid replacement therapy.

Estrogen breakthrough bleeding

Anovulatory cycles have no corpus luteal formation. Progesterone is not produced. The endometrium continues to proliferate under the influence of unopposed estrogen.

Eventually, this out-of-phase endometrium is shed in an irregular manner that might be prolonged and heavy. This pattern is known as estrogen breakthrough bleeding and occurs in the absence of estrogen decline.

Estrogen withdrawal bleeding

This frequently occurs in women approaching the end of reproductive life. In older women, the mean length of menstrual cycle is shortened significantly due to aberrant follicular recruitment, resulting in a shortened proliferative phase. Ovarian follicles in these women secrete less estradiol. Fluctuating estradiol levels might lead to insufficient endometrial proliferation with irregular menstrual shedding. This bleeding might be experienced as light, irregular spotting.

Eventually, the duration of the luteal phase shortens, and, finally, ovulation stops. Dyssynchronous endometrial histology with irregular menstrual shedding and eventual amenorrhea result.

Oral contraceptives, progestin-only preparations, or postmenopausal steroid replacement therapy

Treatment with oral contraceptives, progestin-only preparations, or postmenopausal steroid replacement therapy might be associated with iatrogenically induced uterine bleeding.

Progesterone breakthrough bleeding occurs in the presence of an unfavorably high ratio of progestin to estrogen.

Intermittent bleeding of variable duration can occur with progestin-only oral contraceptives, depo-medroxyprogesterone, and depo-levonorgestrel.

rogesterone withdrawal bleeding can occur if the endometrium initially has been primed with endogenous or exogenous estrogen, exposed to progestin, and then withdrawn from progestin. Such a pattern is seen in cyclic hormonal replacement therapy.

Adolescents

The primary defect in the anovulatory bleeding of adolescents is failure to mount an ovulatory luteinizing hormone (LH) surge in response to rising estradiol levels. Failure occurs secondary to delayed maturation of the hypothalamic-pituitary axis. Because a corpus luteum is not formed, progesterone levels remain low.

The existing estrogen primed endometrium does not become secretory. Instead, the endometrium continues to proliferate under the influence of unopposed estrogen. Eventually, this out-of-phase endometrium is shed in an irregular manner that might be prolonged and heavy, such as that seen in estrogen breakthrough bleeding.

Climacteric

Anovulatory bleeding in menopausal transition is related to declining ovarian follicular function.

Estradiol levels will vary with the quality and state of follicular recruitment and growth. Bleeding might be light or heavy depending on the individual cycle response.

Bleeding disorders

An international expert panel including obstetrician/gynecologists and hematologists has issued guidelines to assist physicians in better recognizing bleeding disorders, such as von Willebrand disease, as a cause of menorrhagia and postpartum hemorrhage and to provide disease-specific therapy for the bleeding disorder. [2]  Historically, a lack of awareness of underlying bleeding disorders has led to underdiagnosis in women with abnormal reproductive tract bleeding. The panel provided expert consensus recommendations on how to identify, confirm, and manage a bleeding disorder.

An underlying bleeding disorder should be considered when a patient has any of the following:

  • Menorrhagia since menarche
  • Family history of bleeding disorders
  • Personal history of 1 or more of the following: (1) Notable bruising without known injury; (2) bleeding of the oral cavity or gastrointestinal tract without obvious lesion; or (3) epistaxis greater than 10 minutes duration (possibly necessitating packing or cautery)

If a bleeding disorder is suspected, consultation with a hematologist is suggested.

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Epidemiology

Abnormal uterine bleeding is a common diagnosis, making up 5-10% of cases in the outpatient clinic setting.

Because most cases are associated with anovulatory menstrual cycles, adolescents [3]  and perimenopausal women [4]  are particularly vulnerable. About 20% of affected individuals are in the adolescent age group, and 50% of affected individuals are aged 40-50 years. In a study of 400 perimenopausal women, the most common type of bleeding pattern was menorrhagia (67.5%), and the most common pathology was simple endometrial hyperplasia without atypia (31%). [4]

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Prognosis

Morbidity/mortality

Single episodes of anovulatory bleeding generally carry a good prognosis.

Patients who experience repetitive episodes might experience significant consequences. Frequent uterine bleeding will increase the risk for iron deficiency anemia. Flow can be copious enough to require hospitalization for fluid management, transfusion, or intravenous hormone therapy. Chronic unopposed estrogenic stimulation of the endometrial lining increases the risk of both endometrial hyperplasia and endometrial carcinoma. Timely and appropriate management will prevent most of these problems.

Many individuals with abnormal uterine bleeding are exposed to unnecessary surgical intervention, such as repeated uterine curettage, endometrial ablative therapy, or hysterectomy, before adequate workup and a trial of medical therapy can be completed.

  • Iron deficiency anemia: Persistent menstrual disturbances might lead to chronic iron loss in up to 30% of cases. Adolescents might be particularly vulnerable. Up to 20% of patients in this age group presenting with menorrhagia might have a disorder of hemostasis.
  • Endometrial adenocarcinoma: About 1-2% of women with improperly managed anovulatory bleeding eventually might develop  endometrial cancer.
  • Infertility associated with chronic anovulation, with or without excess androgen production, is frequently seen in these patients. Patients with  polycystic ovarian syndrome, obesity, chronic hypertension, and insulin-resistant diabetes mellitus particularly are at risk.
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Patient Education

The goals of therapy for abnormal uterine bleeding (AUB) are to control and prevent recurrent bleeding, correct or treat any pathology present, and induce ovulation in patients who desire pregnancy. Age, past history, and bleeding amount influence management.

After initial treatment and resolution of an episode of AUB, patients need to be educated that most often chronic therapy is mandatory to prevent further episodes.

Reassure patients that most bleeding stops with the appropriate hormonal therapy. Explain the physiologic reason for the anovulatory bleeding pattern. This is particularly true for the adolescent patient who establishes a predictable ovulatory type of menstrual pattern over time.

Perhaps the best measure of successful treatment is a good menstrual calendar. Encourage patients to keep a calendar to record daily bleeding patterns. This will serve to document severity of blood loss and impact on daily activities.

For patient education resources, see Women's Health Center and Pregnancy Center, as well as Vaginal BleedingBirth Control OverviewBirth Control Methods, and Pap Smear.

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