Updated: Jun 9, 2009
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.
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:
The major categories of DUB include the following:
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.
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.
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.
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.
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.
| Abdominal Trauma, Blunt | Endometriosis |
| Abdominal Trauma, Penetrating | Hypothyroidism and Myxedema Coma |
| Abortion, Complete | Idiopathic Thrombocytopenic Purpura |
| Abortion, Complications | Ovarian Cysts |
| Abortion, Incomplete | Ovarian Torsion |
| Abortion, Inevitable | Pelvic Inflammatory Disease |
| Abortion, Missed | Pregnancy, Ectopic |
| Abortion, Septic | Pregnancy, Postpartum Hemorrhage |
| Abortion, Threatened | Pregnancy, Trauma |
| Abruptio Placentae | Shock, Hemorrhagic |
| Anemia, Acute | Shock, Hypovolemic |
| Anemia, Chronic | Thrombocytopenic Purpura |
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
Although definitive therapy is beyond the scope of the emergency clinician, knowledge of these regimens will help patients with intermittent recurrences of symptoms.
These agents are used because of their hemodynamic effects in the uterus.
Causes vasospasm of uterine arteries and initiates several coagulation-related functions, which decrease uterine bleeding. Use in pharmacologic doses also causes rapid growth of endometrial tissue over denuded and raw epithelial surface.
Severe uncontrolled bleeding with problems of hemostasis: 25 mg IV slowly over 10-15 min q4-6h until bleeding stops; not to exceed 4 doses
Moderate bleeding: 2.5 mg PO qd for days 1-25, followed by progesterone on days 16-25
Not established; use judiciously in children whose bone growth is not yet complete because of effects on epiphyseal closure
May reduce hypoprothrombinemic effect of anticoagulants; barbiturates, rifampin, and other agents that induce hepatic microsomal enzymes may reduce levels; pharmacologic and toxicologic effects of corticosteroids may occur as a result of estrogen-induced inactivation of hepatic P450 enzyme; loss of seizure control has been noted when administered concurrently with hydantoins
Documented hypersensitivity; known or suspected pregnancy; breast cancer; undiagnosed abnormal genital bleeding; active thrombophlebitis or thromboembolic disorders; history of thrombophlebitis, thrombosis, or thromboembolic disorders associated with previous estrogen use (except when used in treatment of breast or prostatic malignancy)
X - Contraindicated; benefit does not outweigh risk
Certain patients may develop undesirable manifestations of excessive estrogenic stimulation, such as abnormal or excessive uterine bleeding or mastodynia; may cause some degree of fluid retention (exercise caution); prolonged unopposed estrogen therapy may increase risk of endometrial hyperplasia
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.
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
Not recommended
May decrease effects of aminoglutethimide
Documented hypersensitivity; cerebral apoplexy; undiagnosed vaginal bleeding; thrombophlebitis; liver dysfunction
X - Contraindicated; benefit does not outweigh risk
Caution in asthma, depression, renal or cardiac dysfunction, or thromboembolic disorders
These agents can decrease DUB through inhibition of prostaglandin synthesis. Bleeding is controlled; NSAIDS need only to be taken during menstruation.
For relief of mild to moderate pain; inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which is responsible for prostaglandin synthesis.
NSAIDs decrease intraglomerular pressure and decrease proteinuria.
For moderate bleeding: 500 mg PO bid (with foods)
<12 years: Not established
>12 years: 2.5 mg/kg/dose PO; not to exceed 10 mg/kg/d
Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia, and renal papillary necrosis may occur; patients with preexisting renal disease or compromised renal perfusion risk acute renal failure; leukopenia occurs rarely, is transient, and usually returns to normal during therapy; persistent leukopenia, granulocytopenia, or thrombocytopenia warrants further evaluation and may require discontinuation of drug
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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. 2nd 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].
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Pritchard JA, MacDonald PC, Gant NF. Complications of pregnancy. In: William's Obstetrics. 19th 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].
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DUB, abnormal vaginal bleeding, menorrhagia, metrorrhagia, menometrorrhagia, ovulatory DUB, amenorrhea, oligomenorrhea, polycystic ovary disease, hyperandrogenism, hirsutism,obesity, enlarged ovaries, thrombocytopenia, hypothyroidism, hyperthyroidism, liver disease, hypertension, diabetes mellitus, adrenal disorders, vaginal carcinoma, cervical cancer, uterinecancer, ovarian cancer, functional ovarian cysts, cervicitis, endometritis, salpingitis, leiomyomas, vaginal infection, polyps, ectopic pregnancy, hydatidiform mole, blooddyscrasias, excessive weight gain, increased exerciseperformance
Nedra R Dodds, MD, Medical Director, Opulence Aesthetic Medicine
Nedra R Dodds, MD is a member of the following medical societies: American Academy of Anti-Aging Medicine, American Academy of Cosmetic Surgery, American College of Emergency Physicians, American Medical Association, National Medical Association, and Society for Academic Emergency Medicine
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Richard H Sinert, DO, Associate Professor of Emergency Medicine, Clinical Assistant Professor of Medicine, Research Director, State University of New York College of Medicine; Consulting Staff, Department of Emergency Medicine, Kings County Hospital Center
Richard H Sinert, DO is a member of the following medical societies: American College of Physicians and Society for Academic Emergency Medicine
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Steven A Conrad, MD, PhD, Chief, Department of Emergency Medicine; Chief, Multidisciplinary Critical Care Service, Professor, Department of Emergency and Internal Medicine, Louisiana State University Health Sciences Center
Steven A Conrad, MD, PhD is a member of the following medical societies: American College of Chest Physicians, American College of Critical Care Medicine, American College of Emergency Physicians, American College of Physicians, International Society for Heart and Lung Transplantation, Louisiana State Medical Society, Shock Society, Society for Academic Emergency Medicine, and Society of Critical Care Medicine
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Mark Zwanger, MD, MBA is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and American Medical Association
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John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
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Pamela L Dyne, MD, Professor of Clinical Medicine/Emergency Medicine, David Geffen School of Medicine at UCLA; Attending Physician, Department of Emergency Medicine, Olive View-UCLA Medical Center
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