Background: Menorrhagia is menstruation at regular cycle intervals but with excessive flow and duration. It is defined clinically as total blood loss exceeding 80 mL per cycle or menses lasting longer than 7 days. Menorrhagia is one of the most common gynecologic complaints in contemporary gynecology. Current gynecological surveys report that 30% of all premenopausal women perceive their menses to be excessive. The World Health Organization recently reported that 18 million women aged 30-55 years perceive their menstrual bleeding to be exorbitant. Reports show that only 10% of these women experience blood loss severe enough to be defined clinically as menorrhagia.

A normal menstrual cycle is 21-35 days in duration, bleeding lasting an average of 7 days, and flow between 25 and 80 mL.

Menorrhagia must be distinguished clinically from other common gynecologic diagnoses. These include metrorrhagia (flow at irregular intervals), menometrorrhagia (frequent, excessive flow), polymenorrhea (bleeding at intervals <21 d), and dysfunctional uterine bleeding (abnormal uterine bleeding without any obvious structural or systemic abnormality).

Nearly 30% of all hysterectomies performed in the United States are performed to alleviate heavy menstrual bleeding. Definitive surgical correction has been the mainstay of treatment for menorrhagia. Modern gynecology dictates the trend toward conservative therapy for cost containment and because many women desire to preserve their uteruses. Alternatives to hysterectomy also are the result of statistics revealing that nearly 50% of uterine pathology findings from hysterectomies for menorrhagia are free of disease and histopathologic abnormalities.

Heavy menstrual bleeding is a subjective finding, making the exact problem definition difficult. Treatment regimens must address the specific facet of the menstrual cycle the patient perceives to be abnormal, (ie, cycle length, quantity of bleeding). Finally, treatment success usually is evaluated subjectively by each patient, making positive outcome measurement difficult.


Pathophysiology: Knowledge of normal menstrual function is imperative in understanding the etiologies of menorrhagia. Four phases constitute the menstrual cycle, follicular, luteal, implantation, and menstrual.

In response to gonadotropin-releasing hormone (GnRH) from the hypothalamus, the pituitary gland synthesizes follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which induce the ovaries to produce estrogen and progesterone.

During the follicular phase, estrogen stimulation results in an increase in endometrial thickness. This also is known as the proliferative phase.

The luteal phase is intricately involved in the process of ovulation. During this phase, also known as the secretory phase, progesterone causes endometrial maturation.

If fertilization occurs, the implantation phase is maintained. Without fertilization, estrogen and progesterone withdrawal results in menstruation.

Etiologic causes are numerous and often unknown. Factors contributing to menorrhagia can be sorted into several categories, including organic, endocrinologic, anatomic, and iatrogenic.

If the bleeding workup does not provide any clues to the etiology of the menorrhagia, a patient often is given the diagnosis of dysfunctional uterine bleeding (DUB). Most cases of DUB are secondary to anovulation. Without ovulation, the corpus luteum fails to form, resulting in no progesterone secretion. Unopposed estrogen allows the endometrium to proliferate and thicken. The endometrium finally outgrows its blood supply and degenerates. The end result is asynchronous breakdown of the endometrial lining at different levels. This also is why anovulatory bleeding is heavier than normal menstrual flow.

Hemostasis of the endometrium is directly related to the functions of platelets and fibrin. Deficiencies in either of these components results in menorrhagia for patients with von Willebrand disease or thrombocytopenia. Thrombi are seen in the functional layers but are limited to the shedding surface of the tissue. These thrombi are known as "plugs" because blood can only partially flow past them. Fibrinolysis limits the fibrin deposits in the unshed layer. Following thrombin plug formation, vasoconstriction occurs and contributes to hemostasis.

Anatomic defects or growths within the uterus can alter either of the aforementioned pathways (endocrinologic/hemostatic), causing significant uterine bleeding. The clinical presentation is dependent on the location and size of the gynecologic lesion.

Organic diseases also contribute to menorrhagia in the female patient. For example, in patients with renal failure, gonadal resistance to hormones and hypothalamic-pituitary axis disturbances result in menstrual irregularities. Most women in this renal state are amenorrheic, but others also develop menorrhagia. If uremic coagulopathy ensues, it usually is due to platelet dysfunction and abnormal factor VIII function. The resulting prolonged bleeding time causes menorrhagia that can be very tenuous to treat.

Due to the overwhelming factors that can contribute to the dysfunction of either the endocrine or hematological pathways, in-depth knowledge of an existing organic disease is just as imperative as understanding the menstrual cycle itself.


Mortality/Morbidity: Infrequent episodes of menorrhagia usually do not carry severe risks to women’s general health.




History: Symptoms related by a patient with menorrhagia often can be more revealing than laboratory tests. Considering the lengthy list of possible etiologies that contribute to menorrhagia, taking a detailed patient history is imperative. Inquiries should include the following:

Physical: The physical examination should be tailored to the differential diagnoses formulated by the results of the patient's history.

Causes: Etiologies of menorrhagia are divided into 4 categories, organic, endocrinologic, anatomic, and iatrogenic.


Lab Studies:

Imaging Studies:

Other Tests:


Histologic Findings: Understanding EMB results is essential for any physician treating menorrhagia.

If no tissue is returned after an EMB is performed, most likely the endometrium is atrophic and requires estrogen.

Simple proliferative endometrium is normal and does not require treatment.

Endometrial hyperplasia (except atypical adenomatous) requires progesterone on timed 12-day regimens outlined in the Treatment. Endometrial hyperplasia with atypia (especially atypical adenomatous hyperplasia) generally is considered equivalent to an intraepithelial malignancy, and hysterectomy usually is advised.

Any biopsy that reveals endometrial carcinoma should prompt immediate referral to a gynecologic oncologist for treatment outlined by current oncology protocols associated with the grade and stage of the cancer.


Medical Care: Medical therapy must be tailored to the individual. Factors taken into consideration when selecting the appropriate medical treatment include the patient’s age, coexisting medical diseases, family history, and desire for fertility. Medication cost and adverse effects also are factored in because they may play a direct role in patient compliance.

Surgical Care: Surgical management has been the standard of treatment in menorrhagia due to organic causes (eg, fibroids) or when medical therapy fails to alleviate symptoms. Surgical treatment ranges from a simple D&C to a full hysterectomy.


Acute menorrhagia requires prompt medical intervention. This is bleeding that will compromise an untreated patient (see Picture 1).

Successful treatment of chronic menorrhagia is highly dependent on a thorough understanding of the exact etiology. For instance, acute bleeding postpartum does not respond to progesterone therapy, while anovulatory bleeding worsens with high-dose estrogen (see Picture 2, Picture 3, and Picture 4).

Drug Category: Nonsteroidal anti-inflammatory drugs -- Block formation of prostacyclin, an antagonist of thromboxane, which is a substance that accelerates platelet aggregation and initiates coagulation. Prostacyclin is produced in increased amounts in menorrhagic endometrium. Because NSAIDs inhibit blood prostacyclin formation, they might effectively decrease uterine blood flow.

Drug Name
Naproxen (Anaprox, Naprelan, Naprosyn) -- Used for relief of mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing activity of cyclooxygenase, which is responsible for prostaglandin synthesis.
Adult Dose 250-500 mg PO bid; give at last 2 d and first 3 d of cycle, for a total of 5 d
Pediatric Dose Not established
Contraindications Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency
Interactions Probenecid may increase toxicity of NSAIDs; coadministration with ibuprofen might decrease effects of loop diuretics; coadministration with anticoagulants might prolong PT (watch for signs of bleeding); might increase serum lithium levels and risk of methotrexate toxicity (eg, stomatitis, bone marrow suppression, nephrotoxicity)
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Category D in third trimester of pregnancy; acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia, and renal papillary necrosis might 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 might require discontinuation
Drug Name
Diclofenac (Cataflam)
Adult Dose Initial: 100 mg PO once, then 50 mg PO tid
Contraindications Use in persons with allergic reaction to aspirin/NSAIDs, such as swelling, asthma, hives, urticaria, or any forms of angioedema; active GI bleed; active ulcer
Interactions Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE inhibitors, concomitantly with ACE inhibitors; concomitant administration of low-dose aspirin may result in increased rate of GI ulceration or other complications compared to use of NSAIDs alone; clinical studies and postmarketing observations show that NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some patients, and this response has been attributed to inhibition of renal prostaglandin synthesis; NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions GI bleeding; anaphylaxis; renal or liver injury; pregnancy category D if given at third trimester

Drug Category: Combination oral contraceptives -- OCPs containing estrogen and progestin used to treat acute hemorrhagic uterine bleeding.

Drug Name
Ethinyl estradiol and a progestin derivative (Ovral, Ortho-Novum, Ovcon, Genora) -- Reduce secretion of LH and FSH from the pituitary by decreasing amount of GnRH. Reduce pituitary production of gonadotropins and result in reduced LH and FSH with no ovulation.
Adult Dose 1 tab PO qd for 3 wk; followed by a week of inactive pills, during which a withdrawal bleed generally occurs; repeat monthly
Pediatric Dose Not established
Contraindications Documented hypersensitivity; pregnancy; active or inactive thrombophlebitis or thromboembolic disorders, cerebral vascular disease, myocardial infarction, coronary artery disease, or a past history of these disorders; known or suspected breast cancer; known or suspected genital cancer; history of cholestatic jaundice in pregnancy or jaundice with prior pill use; past or present liver tumors
Interactions Hepatotoxicity might occur with concurrent administration of cyclosporine; concomitant use of rifampin, barbiturates, phenylbutazone, phenytoin sodium, and, possibly, griseofulvin, ampicillin, and tetracyclines might influence efficacy of oral contraceptives and increase amount of breakthrough bleeding and menstrual irregularity
Pregnancy X - Contraindicated in pregnancy
Precautions Complete physical examination, documentation of recent Pap smear test, and family history recommended; pay special attention to blood pressure, breasts, abdomen, and pelvic organs; repeat physical examination annually as long as patient is on hormonal therapy
Oral contraceptives can cause fluid retention (address any condition aggravated by this factor)
Monitor patients with epilepsy, migraine, asthma, or renal or cardiac dysfunction
History of psychic depression might be aggravated (observe patient closely)
Progestin compounds might elevate LDL levels, making control of hyperlipidemia more difficult (observe closely); certain forms of congenital hypertriglyceridemia might be aggravated by oral contraceptives, with resultant pancreatitis
Discontinue if jaundice develops
Contact lens wearers with visual changes should be examined by ophthalmologist
Patients might develop hypertension secondary to increase in angiotensinogen production (reevaluate blood pressure approximately 3 mo after initiating therapy in all patients)

Drug Category: Progestins -- Occasional anovulatory bleeding that is not profuse or prolonged can be treated with progestins, antiestrogens given in pharmacologic doses. Inhibit estrogen-receptor replenishment and activate 17-hydroxysteroid dehydrogenase in endometrial cells, converting estradiol to the less-active estrone.

Drug Name
Medroxyprogesterone (Provera)/megestrol acetate/19-nortestosterone derivative -- Provera: Short-acting synthetic progestin. Works as an antiestrogen by minimizing estrogen effects on target cells. Endometrium is maintained in an atrophic state. Effective against hyperplasia and has modest effects on serum lipids (ie, lowering HDL)
Megestrol acetate: May be substituted for Provera. Is active against hyperplasia without significantly altering serum lipid levels.
Derivatives of 19-nortestosterone: Potent progestins used in oral contraceptives. Have partial androgenic properties and lower HDL cholesterol levels.
Adult Dose Provera: 10 mg/d PO for 10 d monthly
Provera for atypical hyperplasia: 10 mg/d PO for 12 d once
Megestrol acetate: 40-80 mg PO for 10 d monthly
Megestrol acetate for atypical hyperplasia: 40-80 mg PO for 12 d once
Derivatives of 19-nortestosterone: Used in oral combination birth control pills; doses vary from 0.075-0.35 mg/pill depending on derivative
Derivatives of 19-nortestosterone for atypical hyperplasia: 5 mg/d for 12 d once
Pediatric Dose Not established
Contraindications Documented hypersensitivity; cerebral apoplexy; undiagnosed vaginal bleeding; thrombophlebitis; liver dysfunction; missed abortion; known or suspected malignancy of breast or genital tract; active or past history of thrombophlebitis, thromboembolic disorders, or cerebral apoplexy (based on past experience with combination oral contraceptive medications; little data suggest that progestin therapy used without estrogen is associated with an increased risk of thrombotic events)
Interactions Decreases aminoglutethimide efficacy
Pregnancy X - Contraindicated in pregnancy
Precautions Caution in asthma, depression, renal or cardiac dysfunction, or thromboembolic disorders; perform complete physical examination, document recent Papanicolaou smear, and take family history before therapy; give special attention to blood pressure, breasts, abdomen, and pelvic organs; repeat physical examination annually; progestins can cause fluid retention (address any condition aggravated by this factor); monitor patients with epilepsy, migraine, asthma, renal or cardiac dysfunction, and history of psychic depression

Drug Category: Gonadotropin-releasing hormone agonists -- Work 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 the ongoing cycle of abnormal bleeding in many anovulatory patients.

Drug Name
Leuprolide (Lupron) -- Suppresses ovarian and testicular steroidogenesis by decreasing LH and FSH levels.
Adult Dose 3.5-7.5 mg IM monthly for 3-6 mo
Pediatric Dose Not established
Contraindications Documented hypersensitivity; undiagnosed vaginal bleeding and spinal cord compression
Interactions None reported
Pregnancy X - Contraindicated in pregnancy
Precautions Urinary tract obstruction, tumor flare, and bone pain may occur; monitor patients for weakness and paresthesias; may cause menopauselike symptoms; may cause bone demineralization and/or reduction in HDL cholesterol if given for >6 mo

Drug Category: Androgens -- Certain androgenic preparations have been used historically to treat mild-to-moderate bleeding, particularly in ovulatory patients with abnormal uterine bleeding. Use might stimulate erythropoiesis and clotting efficiency. Alters endometrial tissue so that it becomes inactive and atrophic.

Drug Name
Danazol (Danocrine) -- Synthetic steroid analog with strong antigonadotropic activity (inhibits LH and FSH) and weak androgenic action. Competes with androgen and progesterone at receptor level, resulting in amenorrhea within 3 mo.
Adult Dose 100-400 mg PO qd for 3 mo
Pediatric Dose Not established
Contraindications Documented hypersensitivity; breastfeeding; seizure disorders; markedly impaired hepatic function or porphyria
Interactions Prolongation of PT occurs in patients who are on warfarin; carbamazepine levels might rise with concurrent use; might interfere with laboratory determinations of DHEA, androstenedione, and testosterone
Pregnancy X - Contraindicated in pregnancy
Precautions Caution in renal, hepatic (may elevate serum transaminase levels), or cardiac insufficiency and in seizure disorders; androgen effects may cause hirsutism, acne, lowering of voice, or decreased breast size

Drug Category: Arginine vasopressin derivatives -- Indicated in patients with thromboembolic disorders.

Drug Name
Desmopressin (DDAVP) -- Has been used to treat abnormal uterine bleeding in patients with coagulation defects. Transiently elevates factor VIII and von Willebrand factor.
Adult Dose 0.3 mcg/kg in 50 mL NS IV push (15 min)
Pediatric Dose Not established
Contraindications Documented hypersensitivity; platelet-type von Willebrand disease
Interactions Coadministration with demeclocycline and lithium decrease effects; fludrocortisone and chlorpropamide increase effects
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Avoid overhydration in patients using desmopressin to benefit from its hemostatic effects; may cause platelet aggregation in von Willebrand type IIB

Drug Category: Estrogens -- Effective in controlling acute, profuse bleeding. Exerts a vasospastic action on capillary bleeding by affecting the level of fibrinogen, factor IV, and factor X in blood and platelet aggregation and capillary permeability. Estrogen also induces formation of progesterone receptors, making subsequent treatment with progestins more effective.

Drug Name
Conjugated equine estrogen (Premarin) -- Only controls bleeding acutely but does not treat underlying cause. Appropriate long-term therapy can be administered once the acute episode has passed.
Adult Dose Acute bleeding: 25 mg IV q4h for a maximum of 48 h; 2.5 mg PO q6h for a maximum of 48 h
Pediatric Dose Not established
Contraindications 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)
Interactions May reduce hypoprothrombinemic effect of anticoagulants; coadministration of barbiturates, rifampin, and other agents that induce hepatic microsomal enzymes may reduce estrogen 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
Pregnancy X - Contraindicated in pregnancy
Precautions Certain patients may develop undesirable manifestations of excessive estrogenic stimulation (eg, abnormal or excessive uterine bleeding, mastodynia); may cause some degree of fluid retention (exercise caution); prolonged unopposed estrogen therapy may increase risk of endometrial hyperplasia



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