Dysfunctional Uterine Bleeding

Author: Amir Estephan, MD; Chief Editor: Pamela L Dyne, MD more...

Background
Abnormal uterine bleeding is a common presenting problem in the ED. Dysfunctional uterine bleeding (DUB) is defined as abnormal uterine bleeding in the absence of organic disease. Dysfunctional uterine bleeding is the most common cause of abnormal vaginal bleeding during a woman's reproductive years. Dysfunctional uterine bleeding can have a substantial financial and quality-of-life burden.[1] It affects women's health both medically and socially.

Pathophysiology
The normal menstrual cycle is 28 days and starts on the first day of menses. During the first 14 days (follicular phase) of the menstrual cycle, the endometrium thickens under the influence of estrogen. In response to rising estrogen levels, the pituitary gland secretes follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which stimulate the release of an ovum at the midpoint of the cycle. The residual follicular capsule forms the corpus luteum. After ovulation, the luteal phase begins and is characterized by production of progesterone from the corpus luteum. Progesterone matures the lining of the uterus and makes it more receptive to implantation. If implantation does not occur, in the absence of human chorionic gonadotropin (hCG), the corpus luteum dies, accompanied by sharp drops in progesterone and estrogen levels. Hormone withdrawal causes vasoconstriction in the spiral arterioles of the endometrium. This leads to menses, which occurs approximately 14 days after ovulation when the ischemic endometrial lining becomes necrotic and sloughs.[2] Terms frequently used to describe abnormal uterine bleeding:

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 - Uterine bleeding of variable amounts occurring between regular menstrual periods Midcycle spotting - Spotting occurring just before ovulation, typically from declining estrogen levels Postmenopausal bleeding - Recurrence of bleeding in a menopausal woman at least 6 months to 1 year after cessation of cycles Amenorrhea - No uterine bleeding for 6 months or longer

Dysfunctional uterine bleeding is a diagnosis of exclusion. It is ovulatory or anovulatory bleeding, diagnosed after pregnancy, medications, iatrogenic causes, genital tract pathology, malignancy, and systemic disease have been ruled out by appropriate investigations.

Approximately 90% of dysfunctional uterine bleeding cases result from anovulation, and 10% of cases occur with ovulatory cycles.[3] Anovulatory dysfunctional uterine bleeding results from a disturbance of the normal hypothalamic-pituitary-ovarian axis and is particularly common at the extremes of the reproductive years. When ovulation does not occur, no progesterone is produced to stabilize the endometrium; thus, proliferative endometrium persists. Bleeding episodes become irregular, and amenorrhea, metrorrhagia, and menometrorrhagia are common. Bleeding from anovulatory dysfunctional uterine bleeding is thought to result from changes in prostaglandin concentration, increased endometrial responsiveness to vasodilating prostaglandins, and changes in endometrial vascular structure. In ovulatory dysfunctional uterine bleeding, bleeding occurs cyclically, and menorrhagia is thought to originate from defects in the control mechanisms of menstruation. It is thought that, in women with ovulatory dysfunctional uterine bleeding, there is an increased rate of blood loss resulting from vasodilatation of the vessels supplying the endometrium due to decreased vascular tone, and prostaglandins have been strongly implicated. Therefore, these women lose blood at rates about 3 times faster than women with normal menses.[4]

Epidemiology
Frequency United States

Dysfunctional uterine bleeding is one of the most often encountered gynecologic problems. An estimated 5% of women aged 30-49 years will consult a physician each year for the treatment of menorrhagia. About 30% of all women report having had menorrhagia.[4]
International

No cultural predilection is present with this disease state.

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. Excessive menstrual bleeding accounts for two thirds of all hysterectomies and most endoscopic endometrial destructive surgery. Menorrhagia has several adverse effects, including anemia and iron deficiency, reduced quality of life, and increased healthcare costs.[1]
Race

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

Age

Dysfunctional uterine bleeding 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 cases of dysfunctional uterine bleeding in adolescent girls occur during the first 2 years after the onset of menstruation, when their immature hypothalamic-pituitary axis may fail to respond to estrogen and progesterone, resulting in anovulation. Abnormal uterine bleeding affects up to 50% of perimenopausal women. In the perimenopausal period, dysfunctional uterine bleeding 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.[2]

History

Patients often present with complaints of amenorrhea, menorrhagia, metrorrhagia, or menometrorrhagia. The amount and frequency of bleeding and the duration of symptoms, as well as the relationship to the menstrual cycle, should be established. 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 or pad absorbs 20-30 mL or vaginal effluent. Personal habits vary greatly among women; therefore, the number of pads or tampons used is unreliable. The patient should be questioned about the possibility of pregnancy.[3] A reproductive history should always be obtained, including the following: o Age of menarche and menstrual history and regularity o Last menstrual period (LMP), including flow, duration, and presence of dysmenorrhea o Postcoital bleeding o Gravida and para o Previous abortion or recent termination of pregnancy o Contraceptive use, use of barrier protection, and sexual activity (including vigorous sexual activity or trauma) o History of sexually transmitted diseases (STDs) or ectopic pregnancy Questions about medical history should include the following: o Signs and symptoms of anemia or hypovolemia (including fatigue, dizziness, and syncope) o Diabetes mellitus o Thyroid disease o Endocrine problems or pituitary tumors o Liver disease o Recent illness, psychological stress, excessive exercise, or weight change

Medication usage, including exogenous hormones, anticoagulants, aspirin, anticonvulsants, and antibiotics o Alternative and complementary medicine modalities, such as herbs and supplements An international expert panel including obstetrician/gynecologists and hematologists has issued guidelines to assist physicians to better recognize bleeding disorders, such as von Willebrand disease, as a cause of menorrhagia and postpartum hemorrhage and to provide diseasespecific therapy for the bleeding disorder.[5] 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. If a bleeding disorder is suspected, evaluation for a coagulation problem is required and consultation with a hematologist is suggested. An underlying bleeding disorder should be considered when a patient has any of the following: o Menorrhagia since menarche o Family history of bleeding disorders o Personal history of 1 or several of the following: Notable bruising without known injury Bleeding of oral cavity or GI tract without obvious lesion Epistaxis >10 min duration (possibly necessitating packing or cautery)
o

Physical

Vital signs, including postural changes, should be assessed. Initial evaluation should be directed at assessing the patient's volume status and degree of anemia. Examine for pallor and absence of conjunctival vessels to gauge anemia. An abdominal examination should be performed. Femoral and inguinal lymph nodes should be examined. Stool should be evaluated for the presence of blood. Patients who are hemodynamically stable require a pelvic speculum, bimanual, and rectovaginal examination to define the etiology of vaginal bleeding. A careful physical examination will exclude vaginal or rectal sources of bleeding. The examination should look for the following: o The vagina should be inspected for signs of trauma, lesions, infection, and foreign bodies. o The cervix should be visualized and inspected for lesions, polyps, infection, or intrauterine device (IUD). o Bleeding from the cervical os o A rectovaginal examination should be performed to evaluate the cul-de-sac, posterior wall of the uterus, and uterosacral ligaments. Uterine or ovarian structural abnormalities, including leiomyoma or fibroid uterus, may be noted on bimanual examination. Patients with hematologic pathology may also 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, acne, palpable enlarged ovaries, and acanthosis nigricans (hyperpigmentation typically seen in the folds of the skin in the neck, groin, or axilla) 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

Systemic disease, including thrombocytopenia, hypothyroidism, hyperthyroidism, Cushing disease, liver disease, diabetes mellitus, and adrenal and other endocrine disorders, can present as abnormal uterine bleeding. Pregnancy and pregnancy-related conditions may be associated with vaginal bleeding. Trauma to the cervix, vulva, or vagina may cause abnormal bleeding. Carcinomas of the vagina, cervix, uterus, and ovaries must always be considered in patients with the appropriate history and physical examination findings. Endometrial cancer is associated with obesity, diabetes mellitus, anovulatory cycles, nulliparity, and age older than 35 years. Other causes of abnormal uterine bleeding include structural disorders, such as functional ovarian cysts, cervicitis, endometritis, salpingitis, leiomyomas, and adenomyosis. Cervical dysplasia or other genital tract pathology may present as postcoital or irregular bleeding. Polycystic ovary disease results in excess estrogen production and commonly presents as abnormal uterine bleeding. Primary coagulation disorders, such as von Willebrand disease, myeloproliferative disorders, and immune thrombocytopenia, can present with menorrhagia. Excessive exercise, stress, and weight loss cause hypothalamic suppression leading to abnormal uterine bleeding due to disruption along the hypothalamus-pituitary-ovarian pathway. Bleeding disturbances are common with combination oral contraceptive pills as well as progestin-only methods of birth control. However, the incidence of bleeding decreases significantly with time. Therefore, only counseling and reassurance are required during the early months of use. 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.
[2]

Differentials

Abortion, Complete Abortion, Incomplete Abortion, Inevitable Abortion, Missed Abortion, Threatened Abruptio Placentae

Adenomyosis Anovulation Anticoagulants Antipsychotics Arteriovenous Malformations Cervical Cancer Cervicitis Coagulopathies Cushing Syndrome Endocervical Polyp Endometrial Carcinoma Endometrial Polyp Endometriosis Estrogen Therapy Fibroids (leiomyomata) Foreign body Hydatidiform Mole Hyperthyroidism Hypothyroidism Intrauterine devices Liver disease Mullerian Duct Anomalies Oral contraceptives Ovarian Cysts Pelvic Inflammatory Disease Placenta Previa Platelet Disorders Polycystic Ovarian Syndrome Pregnancy, Ectopic Prolactinoma Renal disease Trauma von Willebrand Disease Vulvovaginitis

Laboratory Studies

When evaluating a woman of reproductive age with vaginal bleeding, pregnancy must always be ruled out by urine or serum human chorionic gonadotropin. In a patient with any hemodynamic instability, excessive bleeding, or clinical evidence of anemia, a complete blood count is essential. Coagulation studies should be considered when indicated by the history or physical examination findings and in patients with underlying liver disease or other coagulopathies. In patients with suspected endocrine disorders, other laboratory studies such as thyroid function tests and prolactin levels may be helpful, although these results may not be available from the ED.

Imaging Studies

Pelvic ultrasonography is an important imaging modality for nonpregnant patients with abnormal vaginal bleeding. It may determine the etiology of

the bleeding such as a fibroid uterus, endometrial thickening, or a focal mass. o Thickened endometrium may indicate an underlying lesion or excess estrogen and may be suggestive of malignancy. An endometrial stripe measuring less than 4 mm thick is unlikely to have endometrial hyperplasia or cancer, and biopsy is often considered unnecessary before treatment. Women with a normal endometrial stripe (512 mm) may require biopsy, particularly if they have risk factors for endometrial cancer. When the endometrial stripe is larger than 12 mm, a biopsy should be performed.[6] o Depending on the urgency to determine the etiology of bleeding and on the reliability of outpatient follow-up, ultrasonography may be deferred for outpatient evaluations because for the majority of nonpregnant patients, ultrasonographic findings do not immediately affect ED decision-making.[3] Transvaginal ultrasonography may be particularly helpful in further delineating ovarian cysts and fluid in the cul-de-sac. Computed tomography is used primarily for evaluation of other causes of acute abdominal or pelvic pain. Magnetic resonance imaging is used primarily for cancer staging.

Procedures

Before instituting therapy, many consulting gynecologists perform endometrial sampling or biopsy to diagnose intrauterine pathology and to exclude endometrial malignancy. Endometrial biopsy is indicated for the following patients with abnormal uterine bleeding[6] : o Women older than 35 years o Obese patients o Women who have prolonged periods of unopposed estrogen stimulation o Women with chronic anovulation Hysteroscopy is the definitive way to detect intrauterine lesions. It offers a more complete examination of the surface of the endometrium. However, it is usually reserved for treating lesions that were detected by other less invasive means.

Emergency Department Care

Hemodynamically unstable patients with uncontrolled bleeding and signs of significant blood loss should have aggressive resuscitation with saline and blood as with other types of hemorrhagic shock. o Evaluate ABCs and address the priorities. o Initiate 2 large-bore intravenous lines (IVs), oxygen, and cardiac monitor. o If bleeding is profuse and the patient is unresponsive to initial fluid management, consider administration of IV conjugated estrogen (Premarin) 25 mg IV every 4-6 hours until the bleeding stops. o In women with severe, persistent uterine bleeding, an immediate dilation and curettage (D&C) procedure may be necessary.

Combination oral contraceptive pills may be used in women who are not pregnant and have no anatomic abnormalities. An oral contraceptive with 35 mcg of ethinyl estradiol can be taken twice a day until the bleeding stops for up to 7 days, at which time the dose is decreased to once a day until the pack is completed. They provide the additional benefits of reducing dysmenorrhea and providing contraception. Side effects include nausea and vomiting.[3] Progesterone alone can be used to stabilize an immature endometrium. It is usually successful in the treatment of women with anovulatory dysfunctional uterine bleeding (DUB) because these women have unopposed estrogen stimulation. Medroxyprogesterone acetate 10 mg is taken orally once daily for 10 days, followed by withdrawal bleeding 3-5 days after completion of the course. Currently, there is not enough evidence comparing the effect of either progesterone alone or in combination with estrogens for the treatment of dysfunctional uterine bleeding.[7] Nonsteroidal anti-inflammatory drugs (NSAIDs) are generally effective for the treatment of dysfunctional uterine bleeding and dysmenorrhea. NSAIDs inhibit cyclooxygenase in the arachidonic acid cascade, thus inhibiting prostaglandin synthesis and increasing thromboxane A2 levels. This leads to vasoconstriction and increased platelet aggregation. These medications may reduce blood loss by 20-50%. NSAIDs are most effective if used with the onset of menses or just prior to its onset and continued throughout its duration. Danazol creates a hypoestrogenic and hyperandrogenic environment, which induces endometrial atrophy resulting in reduced menstrual loss. Side effects include musculoskeletal pain, breast atrophy, hirsutism, weight gain, oily skin, and acne. Because of the significant androgenic side effects, this drug is usually reserved as a second-line treatment for shortterm use prior to surgery. Gonadotropin-releasing hormone agonists may be helpful for short-term use in inducing amenorrhea and allowing women to rebuild their red blood cell mass. They produce a profound hypoestrogenic state similar to menopause. Side effects include menopausal symptoms and bone loss with long-term use. Tranexamic acid is an antifibrinolytic drug that exerts its effects by reversibly inhibiting plasminogen. It diminishes fibrinolytic activity within endometrial vessels to prevent bleeding. It has been shown effective in reducing bleeding in up to half of women with dysfunctional uterine bleeding. Tranexamic acid is not approved for the treatment of dysfunctional uterine bleeding in the United States.[6]

Consultations

Seek an emergency gynecologic consultation for patients requiring hemodynamic stabilization. If parenteral therapy does not completely arrest vaginal bleeding in the hemodynamically unstable patient, an emergency D&C may be warranted. Consultation with or urgent referral to a gynecologist for surgical treatment may be necessary for patients who do not desire fertility and in whom medical therapy fails. Both endometrial ablation and hysterectomy are effective treatments in women with dysfunctional uterine bleeding with comparable patient satisfaction rates.[8]

Endometrial ablation may be performed using laser, electrocautery, or rollerball. Amenorrhea is seen in approximately 35% of women treated, and decreased flow is seen in another 45%; although, treatment failures increase with time following the procedure due to endometrial regeneration. A substantial number of patients receiving endometrial ablation require reoperation (30% by 48 months). Hysterectomy is the most effective treatment for bleeding. However, it is associated with more frequent and severe adverse events compared with either conservative medical or ablation procedures. Operating time, hospitalization, recovery times, and costs are also greater. Hence, hysterectomy is reserved for selected patient populations.

Summary
The management of postterm pregnancies is complicated and fraught with complex issues. The decision of whether to induce labor or to proceed with expectant management with or without antepartum fetal surveillance is not taken lightly. Data support inducing labor at 41 weeks' gestation in an accurately dated, low-risk pregnancy, regardless of cervical examination findings. This strategy, although not without its critics, averts the need for antepartum fetal surveillance and does not increase the cesarean delivery rate; in fact, it may decrease the cesarean delivery rate. References
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