eMedicine Specialties > Obstetrics and Gynecology > Reproductive Endocrinology and Infertility

Dysfunctional Uterine Bleeding

Author: Millie A Behera, MD, Assistant Professor, Director of Clinical Research, Division of Reproductive Endocrinology and Fertility, Department of Obstetrics and Gynecology, Duke University Medical Center
Coauthor(s): Thomas Michael Price, MD, Associate Professor of Reproductive Endocrinology, Director of Reproductive Fellowship Training Program, Duke University Medical Center
Contributor Information and Disclosures

Updated: Jun 11, 2009

Introduction

Background

Dysfunctional uterine bleeding (DUB) 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. DUB occurs without recognizable pelvic pathology, general medical disease, or pregnancy. It is considered a diagnosis of exclusion.

Pathophysiology

Patients with dysfunctional uterine bleeding (DUB) 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 DUB. Chronic stimulation from higher levels of estrogen will lead to episodes of frequent, heavy bleeding.

Frequency

United States

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

Mortality/Morbidity

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 dysfunctional 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.

Sex

The condition only affects females.

Age

Because most cases are associated with anovulatory menstrual cycles, adolescents and perimenopausal women are particularly vulnerable. About 20% of affected individuals are in the adolescent age group, and 50% of affected individuals are aged 40-50 years.

Clinical

History

• Suspect dysfunctional uterine bleeding (DUB) when a patient presents 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.
  • Exclude the diagnosis of pregnancy first.
  • Address the presence of local and systemic disease. Rule out the presence of signs or symptoms indicative of bleeding disorders. Screening for personal and family history of easy bruising, bleeding gums, epistaxis, and excessive bleeding episodes during childbirth, surgery, or dental procedures may be useful.
  • Rule out iatrogenic causes of bleeding, including bleeding secondary to steroid hormone contraception, hormone replacement therapy, or other hormone treatments, which are common causes.
  • Most patients are adolescents or are older than 40 years.
• 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.
• Patients with adrenal enzyme defects, hyperprolactinemia, thyroid disease, or other metabolic disorders also might present with anovulatory bleeding.

Physical

The physical examination can elicit several anatomic and organic causes of abnormal uterine bleeding.

• A complete physical examination should begin with assessment of hemodynamic stability (vital signs) and proceed with evaluation of the following:
  • Obesity (BMI)
  • Signs of androgen excess (hirsutism, acne)
  • 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)
  • Signs of anemia or chronic blood loss
• A careful gynecologic examination, including Papanicolaou test (Pap smear) and sexually transmitted disease (STD) screening, is warranted.
• The hallmark of DUB is a negative pelvic examination despite the clinical history. In such cases, management might rest on a clinical diagnosis.
  • Rule out the presence of uterine fibroids or polyps.
  • Rule out endometrial hyperplasia or carcinoma.

Causes

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 DUB. 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.
  • Progesterone 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.¹ 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:
    • Notable bruising without known injury
    • Bleeding of oral cavity or gastrointestinal tract without obvious lesion
    • 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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