AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Dysfunctional uterine bleeding (DUB) is the most common cause of abnormal vaginal bleeding during a woman's reproductive years. The diagnosis of DUB should be used only when other organic and structural causes for abnormal vaginal bleeding have been ruled out.

A normal menstrual cycle occurs every 21-35 days with menstruation for 2-7 days. The average blood loss is 35-150 mL total, which represents 8 or fewer soaked pads per day with usually no more than 2 heavy days.

Pathophysiology

During the normal menstrual cycle, the first day corresponds to the first day of menses. The menstrual phase usually lasts 4 days and involves the disintegration and sloughing of the functionalis layer of the endometrium. The proliferation (follicular) phase extends from day 5 to day 14 of the typical cycle. It is marked by endometrial proliferation brought on by estrogen stimulation. The estrogen is produced by the developing ovarian follicles under the influence of follicle-stimulating hormone (FSH). Cellular proliferation of the endometrium is marked, and the length and convolutedness of the spiral arteries increases. This phase ends as estrogen production peaks, triggering the FSH and luteinizing hormone (LH) surge.

Rupture of the ovarian follicle follows, with release of the ovum (ovulation). The secretory (luteal) phase is marked by production of progesterone and less potent estrogens by the corpus luteum. It extends from day 15 to day 28 of the typical cycle. The functionalis layer of the endometrium increases in thickness, and the stroma becomes edematous. If pregnancy does not occur, the estrogen and progesterone feedback to the hypothalamus, and FSH and LH production falls. The spiral arteries become coiled and have decreased flow. At the end of the cycle, they alternately contract and relax, causing a breakdown of the functionalis layer and menses to begin.

Approximately 90% of DUB results from anovulation, and 10% occur with ovulatory cycles. During an anovulatory cycle, the corpus luteum fails to form, which causes failure of normal cyclical progesterone secretion. This results in continuous unopposed production of estradiol, stimulating overgrowth of the endometrium. Without progesterone, the endometrium proliferates and eventually outgrows its blood supply, leading to necrosis. The end result is overproduction of uterine blood flow.

In ovulatory DUB, prolonged progesterone secretion causes irregular shedding of the endometrium. This probably is related to a constant low level of estrogen that is around the bleeding threshold. This causes portions of the endometrium to degenerate and results in spotting. Progesterone causes the enzymatic conversion of estradiol to estrone, a less potent estrogen. The changes in the endometrium remain secretory within the glands. Patients who exhibit these symptoms in the reproductive years often have ovulatory cycles or secondary reasons for altered hypothalamic function (eg, polycystic ovary disease).

Dysfunctional bleeding from the uterus can be described as follows:

• Menorrhagia - Prolonged (>7 d) or excessive (>80 mL daily) uterine bleeding occurring at regular intervals
• Metrorrhagia - Uterine bleeding occurring at irregular and more frequent than normal intervals
• Menometrorrhagia - Prolonged or excessive uterine bleeding occurring at irregular and more frequent than normal intervals
• Intermenstrual bleeding (spotting) - Uterine bleeding of variable amounts occurring between regular menstrual periods
• Polymenorrhea - Uterine bleeding occurring at regular intervals of less than 21 days
• Oligomenorrhea - Uterine bleeding occurring at intervals of 35 days to 6 months
• Amenorrhea - No uterine bleeding for 6 months or longer

The major categories of DUB include the following:

• Estrogen breakthrough bleeding
• Estrogen withdrawal bleeding
• Progestin breakthrough bleeding

Frequency

United States

As many as 10% of women with normal ovulatory cycles reportedly have experienced DUB. Obese females tend to have irregularities in their menstrual cycles due to nonovarian endogenous production of estrogen often related to their degree of adipose tissue. This usually results in prolonged cycles of amenorrhea that alternate with cycles of metrorrhagia or menometrorrhagia.

International

No cultural predilection is present with this disease state. However, note that countries, including the United States, that have a large population of female athletes have more recognition of this entity. In athletes, a loss of the LH surge, as well as, a luteal phase deficiency tends to be present. This is characterized by a shortened luteal phase from insufficient progesterone production or effect. This inadequate progesterone stimulation may be coexistent with high, low, or normal estrogen levels and often results in similar problems in anovulatory cycles such as amenorrhea.

Mortality/Morbidity

Morbidity is related to the amount of blood loss at the time of menstruation, which occasionally is severe enough to cause hemorrhagic shock.

Although, DUB in itself is rarely fatal, distinguishing this presentation from that of endometrial cancer is important. Development of endometrial cancer is related to estrogen stimulation and endometrial hyperplasia. Symptoms include postmenopausal bleeding, which is usually considered cancer until proven otherwise.

Race

DUB has no predilection for race; however, black women have a higher incidence of leiomyomas and higher levels of estrogen. As a result, they are prone to experiencing more episodes of abnormal vaginal bleeding.

Age

DUB is most common at the extreme ages of a woman's reproductive years, either at the beginning or near the end, but it may occur at any time during her reproductive life.

• Most severe cases of DUB occur in adolescent girls during the first 18 months after the onset of menstruation, when their immature hypothalamic-pituitary axis may fail to respond to estrogen and progesterone, resulting in anovulation.
• In the perimenopausal period, DUB may be an early manifestation of ovarian failure causing decreased hormone levels or responsiveness to hormones, thus also leading to anovulatory cycles. In patients who are 40 years or older, the number and quality of ovarian follicles diminishes. Follicles continue to develop but do not produce enough estrogen in response to FSH to trigger ovulation. The estrogen that is produced usually results in late-cycle estrogen breakthrough bleeding.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Patients often present with complaints of amenorrhea, oligomenorrhea, menorrhagia, or metrorrhagia. Ask patients to compare the number of pads or tampons used per day in a normal menstrual cycle to the number used at the time of presentation. The average tampon holds 5 mL of blood; the average pad holds 5-15 mL of blood.
• Occasionally, bleeding is profuse with associated signs and symptoms of hypovolemia, including hypotension, tachycardia, diaphoresis, and pallor. These patients usually do not have vaginal or pelvic pain associated with bleeding episodes, and other systemic symptoms rarely are noted unless vaginal bleeding has an organic cause.
• A reproductive history should always be obtained, including the following:
• • Menstrual regularity
  • Last menstrual period (LMP), including flow and duration
  • Gravida and para
  • Previous abortion or recent termination of pregnancy
  • Contraceptive use
• Questions about medical history should include the following:
• • Signs and symptoms of hypovolemia
  • Diabetes mellitus
  • Hypertension
  • Hypothyroidism, hyperthyroidism
  • Liver disease
  • Medication usage, including exogenous hormones, anticoagulants, aspirin, anticonvulsants, and antibiotics
  • Alternative and complementary medicine modalities, such as herbs and supplements

Physical

• Initial evaluation should be directed at assessing patient's volume status and degree of anemia. Examine for pallor and absence of conjunctival vessels to gauge anemia.
• Patients who are hemodynamically stable require a pelvic speculum and bimanual examination to define the etiology of vaginal bleeding. The examination should look for the following:
• • Trauma to the vaginal walls or cervix
  • Retained foreign body
  • Cervical or vaginal laceration
  • Bleeding from the cervical os
• Uterine or ovarian structural abnormalities may be noted on bimanual examination, but a negative examination is insensitive for finding abnormalities.
• Patients with hematologic pathology also may have cutaneous evidence of bleeding diathesis. Physical findings include petechiae, purpura, and mucosal bleeding (eg, gums) in addition to vaginal bleeding.
• Patients with liver disease that has resulted in a coagulopathy may manifest additional symptomatology because of abnormal hepatic function. Evaluate patients for spider angioma, palmar erythema, splenomegaly, ascites, jaundice, and asterixis.
• Women with polycystic ovary disease present with signs of hyperandrogenism, including hirsutism, obesity, and palpable enlarged ovaries.
• Hyperactive and hypoactive thyroid can cause menstrual irregularities. Patients may have varying degrees of characteristic vital sign abnormalities, eye findings, tremors, changes in skin texture, and weight change. Goiter may be present.

Causes

• Multiple organic pathologies can present as abnormal vaginal bleeding, including thrombocytopenia, hypothyroidism, hyperthyroidism, Cushing disease, liver disease, hypertension, diabetes mellitus, and adrenal disorders.
• Pregnancy may be associated with vaginal bleeding that the patient may report as "abnormal" for her in terms of timing, amount, or duration.
• Trauma to the cervix, vulva, or vagina may cause abnormal bleeding.
• Carcinomas of the vagina, cervix, uterus, and ovaries always must be considered in patients with the appropriate history and physical exam.
• Other causes of DUB include structural disorders, such as functional ovarian cysts, cervicitis, endometritis, salpingitis, and leiomyomas.
• Polycystic ovary disease, vaginal infection, polyps, ectopic pregnancy, hydatidiform mole, blood dyscrasias, excessive weight gain, increased exercise performance, or stress may also contribute to DUB.
• Breakthrough bleeding may occur in patients taking oral contraceptives that have inadequate doses of estrogen and progestin for the patient.
• • Intermenstrual bleeding may occur secondary to missed pills, varied ingestion times, and drug interactions.
  • The most common drug interactions with OCPs occur with phenobarbital, carbamazepine, some penicillins, tetracycline, and trimethoprim-sulfamethoxazole.
  • Breakthrough bleeding can indicate reduced birth control efficiency; therefore, advise using additional birth control methods until the next menstrual cycle begins.
• An iatrogenic cause of DUB is the use of progestin-only compounds for birth control. Medroxyprogesterone acetate (Depo-Provera), a long-acting injection given every 3 months, inhibits ovulation. An adverse effect of this drug is prolonged uterine breakthrough bleeding; this may continue after discontinuation of the drug because of persistent anovulation. The Norplant system (surgically implanted levonorgestrel), which acts to block some but not all ovulatory cycles, has the same adverse effects as Depo-Provera.
• Contraceptive intrauterine devices (IUDs) can cause variable vaginal bleeding for the first few cycles after placement and intermittent spotting subsequently. The progesterone impregnated IUD (Mirena) is associated with less menometrorrhagia and usually results in secondary amenorrhea.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Advanced liver disease
Anabolic steroids
Cervical cancer
Cervicitis
Cervical polyps
Cirrhosis
Endometrial cancer
Leiomyoma
Leukemia
Postcoital bleeding
Salpingitis
Thrombocytopenia
Uterine cancer
Uterine leiomyomas
Vaginal lacerations
Von Willebrand disease

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• A detailed workup for DUB is beyond the scope of the ED, yet several studies are required to ensure hemodynamic stability in patients presenting with vaginal bleeding.
• In the patient with unstable vital signs, perform a CBC with platelets, prothrombin time (PT), activated partial thromboplastin time (aPTT), liver function tests (if other signs indicate liver disease), and type and cross-match.
• Pregnancy must be ruled out by urine and/or serum human chorionic gonadotropin, before consideration of any imaging studies or further referral or detailed examination.
• Consider thyroid function tests. FSH, TSH, DHEAS, and prolactin levels should be considered, although these results may not be available from the ED.

Imaging Studies

• Workup by the gynecologist should include pelvic ultrasonography to evaluate for fibroids or other structural lesions that may cause abnormal vaginal bleeding.
• Transvaginal ultrasonography (TVUS): Consider TVUS if the patient may be pregnant or may have anatomic problems or polycystic ovarian syndrome.
• Dilatation and curettage (D&C) can be both therapeutic and diagnostic. It may be the treatment of choice when bleeding is severe, and it allows more extensive sampling of the uterine cavity and also has a higher sensitivity than endometrial biopsy.
• Although mostly an office or intraoperative procedure, hysteroscopy can be used in place of D&C and allows direct visualization of the endometrial cavity with directed biopsy.

Procedures

• Pelvic examination
• Before instituting therapy, many consulting gynecologists perform an endometrial sampling or endometrial biopsy to diagnose intrauterine pathology and to exclude endometrial malignancy.
• Perform endometrial biopsy for the following patients:
• • All patients older than 35 years
  • Obese patients
  • Patients with diabetes mellitus
  • Patients with hypertension
  • Patients with suspected polycystic ovarian disease
• D&C is indicated in the following situations:
• • Consider D&C in patients at high risk for endometrial hyperplasia and carcinoma.
  • Consider D&C rather than endometrial biopsy if suspected diagnosis is endometritis, atypical hyperplasia, or carcinoma.
  • Perform in patients having heavy, uncontrolled bleeding.
  • Perform if histologic examination is required but biopsy is contraindicated.
  • Perform if medical curettage fails.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Emergency Department Care

• Hemodynamic instability
• • Evaluate ABCs and address the priorities.
  • Initiate 2 large-bore intravenous lines (IVs), oxygen, and cardiac monitor.
  • If bleeding is profuse and the patient is unresponsive to initial fluid management, consider administration of IV conjugated estrogen (Premarin) 25 mg. Repeat doses if necessary until bleeding stops, which is usually within 1-5 hours.
• If bleeding continues after instituting IV estrogen, insert a pediatric Foley catheter into the cervical os and inflate to tamponade the bleeding. The balloon is distended with saline until the bleeding stops. If the patient has an unusually large uterus, a larger balloon (15-30 mL) may be needed. The Foley catheter may need to be clamped to reinforce the tamponade if blood begins to exit through a large-caliber catheter. The balloon is left in place for 12-24 hours to control bleeding.
• For older, hemodynamically stable (hematocrit 25-35%) patients with a known history of DUB, iron-deficiency anemia, and moderate amount of prolonged bleeding, administer an oral contraceptive containing a combination of high doses of estrogen and synthetic progesterone (eg, Ortho-Novum 1/50) 4 times per day for 7 days to arrest bleeding. Oral contraceptives may aggravate an already suppressed hypothalamic-ovarian axis in young postmenarchal patients; therefore, use them only in patients with an established menstrual history. Exclude pregnancy prior to initiating therapy. Appropriate oral contraceptives include the following:
• • Modicon 21 (ethinyl estradiol, norethindrone)
  • Ortho-Novum 1/35 (ethinyl estradiol, norethindrone)
  • Ortho-Novum 1/50 (mestranol, norethindrone)
  • Levlen 21,28 (ethinyl estradiol, levonorgestrel)
  • Lo/Ovral (ethinyl estradiol, norgestrel)
  • Ortho-Cept 21 (ethinyl estradiol, desogestrel)
  • Demulen 1/30,50 (ethinyl estradiol, ethynodiol diacetate)
• Progestins alone are the drug of choice to treat anovulatory DUB and should be reserved for patients with a clear-cut diagnosis. These can be started safely in the ED after the severe acute bleeding episode is curtailed with IV estrogen and pregnancy has been ruled out.

Consultations

• Seek an emergency gynecologic consultation for patients requiring hemodynamic stabilization. Should parenteral therapy not completely arrest vaginal bleeding in the hemodynamically unstable patient, an emergency D&C may be warranted.
• Consult a gynecologist if administering combination therapy to a mature patient with a history of DUB, moderate bleeding, and a negative pregnancy test.
• Consult a surgeon for acute hemorrhage with hemodynamic instability. One of the following procedures may be necessary:
• • D&C
  • Hysterectomy (rare)
  • Endometrial ablation

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Although definitive therapy is beyond the scope of the emergency physician, knowledge of these regimens will help patients with intermittent recurrences of symptoms.

Drug Category: Steroid hormones

These agents are used because of their hemodynamic effects in the uterus.

Drug Name	Medroxyprogesterone acetate (Provera)
Description	DOC for most patients with anovulatory DUB. After acute bleeding episode controlled, can be used alone in patients with adequate amounts of endogenous estrogen to cause endometrial growth. Progestin therapy in adolescents produces regular cyclic withdrawal bleeding until positive feedback system matures. Progestins stop endometrial growth and support and organize endometrium to allow organized sloughing after their withdrawal. Bleeding ceases rapidly because of an organized slough to the basalis layer. These drugs usually do not stop acute bleeding episodes, yet produce a normal bleeding episode following their withdrawal.
Adult Dose	10 mg PO qd for first 10-12 d of menstrual cycle Depo-medroxyprogesterone (Depo-Provera) as 150 mg IM q3mo Progestin-only oral contraceptive pills: Daily after acute phase of bleeding For acute moderate bleeding: Oral contraceptive pills qid for 5-7 d or until bleeding stops
Pediatric Dose	Not recommended
Contraindications	Documented hypersensitivity; cerebral apoplexy; undiagnosed vaginal bleeding; thrombophlebitis; liver dysfunction
Interactions	May decrease effects of aminoglutethimide
Pregnancy	X - Contraindicated; benefit does not outweigh risk
Precautions	Caution in asthma, depression, renal or cardiac dysfunction, or thromboembolic disorders

Drug Category: Nonsteroidal anti-inflammatory drugs (NSAIDS)

These agents can decrease DUB through inhibition of prostaglandin synthesis. Bleeding is controlled; NSAIDS need only to be taken during menstruation.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• All patients with abnormal vaginal bleeding who are discharged from the ED receive follow-up from their family physician or gynecologist.

In/Out Patient Meds

• Patients with bleeding heavy enough to decrease hematocrit may be given ferrous sulfate tablets (325 mg tid).
• Hormone regimens, including combination oral contraceptives and cyclic progestins, should be continued for several months under the supervision of the consulting gynecologist.

Complications

• Anemia
• Adenocarcinoma of the uterus (if prolonged, unopposed estrogen stimulation)
• Significant adverse effects of individual oral contraceptive preparations

Prognosis

• Most patients do well once a diagnosis is established and an appropriate hormone regimen is started by a gynecologist. Hormonal regulation has a 90% cure rate among those with anovulatory bleeding.
• Prognosis varies with pathophysiologic process.
• In young women, most anovulatory cycles can be treated confidently and successfully with physiologically sound therapeutic regimens without surgical intervention.

Patient Education

• Instruct patients to continue prescribed medications, although bleeding may still be occurring during the early part of the cycle. If the patient is taking a combination of estrogens for the first 25 days and a progesterone during the last 10 days of their cycle, they should be told to expect menses after cessation of the regimen.
• Young patients with small amounts of irregular bleeding need reassurance and observation only prior to instituting drug regimen. Express to patients that pharmacologic intervention will not be necessary once menstrual cycles become regular.
• Discuss ways patient can avoid prolonged stress and emotional turmoil.
• For excellent patient education resources, visit eMedicine's Women's Health Center. Also, see eMedicine's patient education articles Vaginal Bleeding and Mittelschmerz.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• All patients should be examined for pregnancy complications, threatened or incomplete abortion, and ectopic pregnancy. DUB is a diagnosis of exclusion and should be considered only after other causes of abnormal vaginal bleeding have been investigated.
• Patients older than 35 years or those with other risk factors for endometrial cancer should have endometrial biopsy within 1 week of starting hormonal manipulation.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Bayer SR, DeCherney AH. Clinical manifestations and treatment of dysfunctional uterine bleeding. JAMA. Apr 14 1993;269(14):1823-8. [Medline].
• Herbst A, Mishell D, Stenchever M. Abnormal uterine bleeding. In: Comprehensive Gynecology. 2^nd ed. Mosby-Year Book; 1992:1083-1097.
• Johnson CA. Making sense of dysfunctional uterine bleeding. Am Fam Physician. Jul 1991;44(1):149-57. [Medline].
• Physician's Desk Reference. 50^th ed. Medical Economics Books; 1996.
• Pritchard JA, MacDonald PC, Gant NF. Complications of pregnancy. In: William's Obstetrics. 19^th ed. McGraw-Hill Professional Publishing; 1993:819-820.
• Rosenfeld JA. Treatment of menorrhagia due to dysfunctional uterine bleeding. Am Fam Physician. Jan 1996;53(1):165-72. [Medline].
• Seamen C, Slovis C. Abnormal vaginal bleeding in the nonpregnant patient. Emerg Med Rep. 1996;17:219-226. [Medline].

Article Last Updated: Nov 12, 2007