Dysfunctional Uterine Bleeding

Author: Amir Estephan, MD,, Resident Physician, Department of Emergency Medicine, Kings County Hospital Center, Brooklyn
Coauthor(s): 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

Introduction

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

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

Clinical

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: 
    • Age of menarche and menstrual history and regularity
    • Last menstrual period (LMP), including flow, duration, and presence of dysmenorrhea
    • Postcoital bleeding
    • Gravida and para
    • Previous abortion or recent termination of pregnancy
    • Contraceptive use, use of barrier protection, and sexual activity (including vigorous sexual activity or trauma)
    • History of sexually transmitted diseases (STDs) or ectopic pregnancy
  • Questions about medical history should include the following: 
    • Signs and symptoms of anemia or hypovolemia (including fatigue, dizziness, and syncope)
    • Diabetes mellitus
    • Thyroid disease
    • Endocrine problems or pituitary tumors
    • Liver disease
    • Recent illness, psychological stress, excessive exercise, or weight change
    • Medication usage, including exogenous hormones, anticoagulants, aspirin, anticonvulsants, and antibiotics
    • 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 disease-specific 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:
    • Menorrhagia since menarche
    • Family history of bleeding disorders
    • 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)

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: 
    • The vagina should be inspected for signs of trauma, lesions, infection, and foreign bodies.
    • The cervix should be visualized and inspected for lesions, polyps, infection, or intrauterine device (IUD).
    • Bleeding from the cervical os
    • 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

Differential Diagnoses

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

Workup

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.
    • 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 (5–12 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
    • 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 bleeding6 :
    • Women older than 35 years
    • Obese patients
    • Women who have prolonged periods of unopposed estrogen stimulation
    • 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.

Treatment

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. 
    • 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 IV every 4-6 hours until the bleeding stops.
    • 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 short-term 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.

Medication

The goals of pharmacotherapy are to control the bleeding, reduce morbidity, and prevent complications.

Steroid hormones

These agents may help control bleeding. Some of them are used when bleeding is profused and the patient is unresponsive to initial fluid management.

 

Ethinyl estradiol 35 μg and norethindrone 1mg (Necon 1/35, Nortrel 1/35, Ortho-Novum 1/35, Norinyl 1 + 35)

Reduces secretion of LH and FSH from pituitary by decreasing amount of GnRH.

Contraceptive pills containing estrogen and progestin have been advocated for nonsmoking patients with DUB who desire contraception. Therapy also used to treat acute hemorrhagic uterine bleeding but not as effective as other treatments perhaps because may take longer to induce endometrial proliferation when progestin is present.
Suggested mechanisms by which hormonal therapy might affect bleeding include improvement in coagulation, alterations in the microvascular circulation, and improvements in endothelial integrity. In long-term management of DUB, combination oral contraceptives are very effective.

Adult

1 tab PO bid for 1 wk until bleeding stops, followed by 1 tab PO qd for 2 wk; followed by a week of inactive pills, during which a withdrawal bleed generally occurs.

Pediatric

Not established

Phenobarbital, phenytoin, paramethadione, carbamazepine, troglitazone, rifampicin, and griseofulvin induce enzymes that decrease levels of contraceptive steroids; oral anticoagulants may increase thromboembolic potential; antibiotics may alter GI flora and cause a reduction in absorption of oral contraceptives, which may reduce efficacy

Documented hypersensitivity, endometrial, and hepatic cancer; thromboembolic disorders; undiagnosed vaginal bleeding; smokers >35 y; cardiovascular disease

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Caution in patients diagnosed with hepatic impairment, migraine, seizure disorders, cerebrovascular disorders, breast cancer, or thromboembolic disease

 

Danazol

Synthetic steroid analog, derived from ethisterone, with strong antigonadotropic activity (inhibits LH and FSH) and weak androgenic action without adverse virilizing and masculinizing effects. Increases levels of C4 component of the complement. May push the resting hematopoietic stem cells into cycle, making them more responsive to differentiation by hematopoietic growth factors. May also stimulate endogenous secretion of erythropoietin.
May impair clearance of immunoglobulin-coated platelets and decreases autoantibody production.
Certain androgenic preparations have been used historically to treat mild-to-moderate bleeding, particularly in ovulatory patients with abnormal uterine bleeding. These regimens offer no real advantage over other regimens and might cause irreversible signs of masculinization in the patient. They seldom are used for this indication today.
Use of androgens might stimulate erythropoiesis and clotting efficiency. Androgens alter endometrial tissue so that it becomes inactive and atrophic.

Adult

100-200 mg/d PO in divided doses

Pediatric

Not established

Decreases insulin requirements and increases effects of anticoagulants; may increase carbamazepine and cyclosporine levels

Documented hypersensitivity; seizure disorders; renal or hepatic insufficiency, cardiac disease; lactation; conditions influenced by edema; undiagnosed genital bleeding; porphyria

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Caution in renal, hepatic or cardiac insufficiency, and seizure disorders

 

Estrogens, conjugated (Premarin)

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.

Adult

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

Pediatric

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)

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

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

 

Medroxyprogesterone acetate (Provera)

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

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

Not recommended

May decrease effects of aminoglutethimide

Documented hypersensitivity; cerebral apoplexy; undiagnosed vaginal bleeding; thrombophlebitis; liver dysfunction

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Caution in asthma, depression, renal or cardiac dysfunction, or thromboembolic disorders

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

These agents can decrease DUB through inhibition of prostaglandin synthesis. NSAIDs only need to be taken during menstruation.

 

Naproxen (Naprosyn, Aleve, Naprelan)

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.

Adult

For moderate bleeding: 500 mg PO bid (with foods)

Pediatric

<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

Pregnancy

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

Precautions

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

Gonadotropin Releasing Hormone Analog

These agents are generally used for short-term use to induce amenorrhea and allow the rebuilding of the red blood cell mass.

 

Leuprolide acetate (Lupron, Eligard)

Suppresses ovarian and testicular steroidogenesis by decreasing LH and FSH levels.
Works by reducing concentration of GnRH receptors in the pituitary via receptor down regulation and induction of postreceptor effects, which suppress gonadotropin release. After an initial gonadotropin release associated with rising estradiol levels, gonadotropin levels fall to castrate levels, with resultant hypogonadism. This form of medical castration is very effective in inducing amenorrhea, thus breaking ongoing cycle of abnormal bleeding in many anovulatory patients. Because prolonged therapy with this form of medical castration is associated with osteoporosis and other postmenopausal side effects, many practitioners add a form of low-dose hormonal replacement to the regimen. Because of the expense of these drugs, they usually are not used as a first-line approach but can be used to achieve short-term relief from a bleeding problem, particularly in patients with renal failure or blood dyscrasia.

Adult

3.5-7.5 mg IM qmo; not to exceed 6 mo without addition of low-dose estrogen and progestin therapy

Pediatric

Not established

Follow-up

Further Inpatient Care

  • Patients with severe, acute abnormal uterine bleeding and hemodynamic instability will require urgent gynecologic consultation and hospitalization.

Further Outpatient Care

  • Most patients with abnormal uterine bleeding without hemodynamic compromise should be referred to a gynecologist for definitive management on an outpatient basis.

Inpatient & Outpatient Medications

  • 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, may be continued for several months under the supervision of the consulting gynecologist.

Complications

  • Anemia (may become severe)
  • Adenocarcinoma of the uterus (if prolonged, unopposed estrogen stimulation)

Prognosis

  • Hormonal contraceptives reduce blood loss by 40-70% when used long term.
  • Although medical therapy is generally used first, over half of women with menorrhagia undergo hysterectomy within 5 years of referral to a gynecologist.2

Patient Education

  • Instruct patients to continue prescribed medications, although bleeding may still be occurring during the early part of the cycle. Also, patients 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 a drug regimen. Express to patients that pharmacologic intervention will not be necessary once menstrual cycles become regular.
  • Discuss ways the patient can avoid prolonged emotional stress and maintain a normal body mass index.

Miscellaneous

Medicolegal Pitfalls

  • All patients should be examined for pregnancy complications, threatened or incomplete abortion, and ectopic pregnancy. Dysfunctional uterine bleeding (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

  1. Frick KD, Clark MA, Steinwachs DM, et al. Financial and quality-of-life burden of dysfunctional uterine bleeding among women agreeing to obtain surgical treatment. Womens Health Issues . Jan-Feb 2009;19(1):70-8. [Medline] .

  2. Schorge JO, Schaffer JI, Halvorson LM, Hoffman BL, Bradshaw KD, Cunningham FG. Abnormal uterine bleeding. In: Williams Gynecology . McGraw-Hill; 2008:Chap 8.

  3. Tibbles CD. Selected gynecologic disorders. In: Marx JA, Hockberger RS, Walls RM, Adams JG. Rosen's Emergency Medicine: Concepts and Clinical Practice . Vol 1. 7th ed. Mosby (Elsevier); 2009:Chap 98.

  4. Pitkin J. Dysfunctional uterine bleeding. BMJ . May 26 2007;334(7603):1110-1. [Medline] .

  5. [Guideline] James AH, Kouides PA, Abdul-Kadir R, et al. Von Willebrand disease and other bleeding disorders in women: consensus on diagnosis and management from an international expert panel. Am J Obstet Gynecol . Jul 2009;201(1):12.e1-8. [Medline] .

  6. Casablanca Y. Management of dysfunctional uterine bleeding. Obstet Gynecol Clin North Am . Jun 2008;35(2):219-34, viii. [Medline] .

  7. [Best Evidence] Hickey M, Higham J, Fraser IS. Progestogens versus oestrogens and progestogens for irregular uterine bleeding associated with anovulation. Cochrane Database Syst Rev . Oct 17 2007;CD001895. [Medline] .

  8. Dickersin K, Munro MG, Clark M, et al. Hysterectomy compared with endometrial ablation for dysfunctional uterine bleeding: a randomized controlled trial. Obstet Gynecol . Dec 2007;110(6):1279-89. [Medline] .

Mon, 19 Jul 2010 @17:29

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