eMedicine Specialties > Emergency Medicine > Obstetrics & Gynecology
Dysfunctional Uterine Bleeding: Treatment & Medication
Updated: Feb 1, 2010
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
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
None reported
Documented hypersensitivity; undiagnosed vaginal bleeding, and spinal cord compression
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Urinary tract obstruction, tumor flare, and bone pain may occur; monitor patients for weakness and paresthesias
More on Dysfunctional Uterine Bleeding |
| Overview: Dysfunctional Uterine Bleeding |
| Differential Diagnoses & Workup: Dysfunctional Uterine Bleeding |
 Treatment & Medication: Dysfunctional Uterine Bleeding |
| Follow-up: Dysfunctional Uterine Bleeding |
| References |
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References
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].
Schorge JO, Schaffer JI, Halvorson LM, Hoffman BL, Bradshaw KD, Cunningham FG. Abnormal uterine bleeding. In: Williams Gynecology. McGraw-Hill; 2008:Chap 8.
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.
Pitkin J. Dysfunctional uterine bleeding. BMJ. May 26 2007;334(7603):1110-1. [Medline].
[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].
Casablanca Y. Management of dysfunctional uterine bleeding. Obstet Gynecol Clin North Am. Jun 2008;35(2):219-34, viii. [Medline].
[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].
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].
Further Reading
Keywords
dysfunctional uterine bleeding, DUB, dysfunctional uterine bleeding symptoms, dysfunctional uterine bleeding causes, abnormal uterine bleeding, abnormal vaginal bleeding, menorrhagia, metrorrhagia, menometrorrhagia, amenorrhea, oligomenorrhea, vaginal carcinoma, cervical cancer, uterine cancer, ovarian cancer, functional ovarian cysts, cervicitis, endometritis, salpingitis, vaginal infection
