eMedicine Specialties > Obstetrics and Gynecology > General Gynecology
Menorrhagia: Treatment & Medication
Updated: Oct 19, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Medical therapy for menorrhagia should 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 are also considered because they may play a direct role in patient compliance.14
- Nonsteroidal anti-inflammatory drugs
- Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first-line medical therapy in ovulatory menorrhagia.
- Studies show an average reduction of 20-46% in menstrual blood flow.15
- NSAIDs reduce prostaglandin levels by inhibiting cyclooxygenase and increasing the ratio of prostacyclin to thromboxane.
- NSAIDs are ingested for only 5 days of the entire cycle, limiting their most common adverse effect of stomach upset.
- Oral contraceptive pills
- Oral contraceptive pills (OCPs) are a popular first-line therapy for women who desire contraception.
- Menstrual blood loss is reduced as effectively as NSAID's secondary to endometrial atrophy.16
- OCPs suppress pituitary gonadotropin release, preventing ovulation.
- Common adverse effects include breast tenderness, breakthrough bleeding, nausea, and, possibly, related weight gain in some individuals.
- Progestin therapy
- Progestin is the most frequently prescribed medicine for menorrhagia.
- Therapy with progestin results in a significant reduction in menstrual blood flow when used alone.
- Progestin works as an antiestrogen by minimizing the effects of estrogen on target cells, thereby maintaining the endometrium in a state of down-regulation.
- Common adverse effects include weight gain, headaches, edema, and depression.
- Levonorgestrel intrauterine system
- Reduces menstrual blood loss by as much as 97%17
- Comparable to transcervical resection of the endometrium for reduction of menstrual bleeding18
- The FDA approved a new indication for the levonorgestrel intrauterine device, Mirena, for the treatment of menorrhagia in women who use intrauterine conception. Approval was granted subsequent to a randomized, open-label, active-control (medroxyprogesterone) clinical trial of women (n=160) with established heavy menstrual bleeding. The results demonstrated that Mirena reduced menstrual blood loss significantly compared with medroxyprogesterone (p<0.001). Adverse effects of Mirena include uterine bleeding or spotting, headache, ovarian cysts, vaginitis, dysmenorrhea, and breast tenderness.19
- Gonadotropin-releasing hormone agonists
- These agents are used on a short-term basis due to high costs and severe adverse effects.
- GnRH agonists are effective in reducing menstrual blood flow.
- They inhibit pituitary release of FSH and LH, resulting in hypogonadism.
- A prolonged hypoestrogenic state leads to bone demineralization and reduction of high-density lipoprotein (HDL) cholesterol.
- Danazol
- Danazol competes with androgen and progesterone at the receptor level, causing amenorrhea in 4-6 weeks.
- Androgenic effects cause acne, decreasing breast size, and, rarely, lower voice.
- Conjugated estrogens
- These agents are given intravenously every 4 hours in patients with acute bleeding.
- A D&C procedure may be necessary if no response is noted in 24 hours.
- If menses slows, follow up with estrogen-progestin therapy for 7 days. This is followed by OCPs for 3 months.
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.
Dilatation and curettage
A D&C should be used for diagnostic purposes. It is not used for treatment because it provides only short-term relief, typically 1-2 months.
This procedure is used best in conjunction with hysteroscopy to evaluate the endometrial cavity for pathology.
It is contraindicated in patients with known or suspected pelvic infection. Risks include uterine perforation, infection, and Asherman syndrome.
Resectoscopic endometrial ablation techniques
- Transcervical resection of the endometrium20
- Transcervical resection of the endometrium (TCRE) has been considered the criterion standard cure for menorrhagia for many years.
- This procedure requires the use of a resectoscope (ie, hysteroscope with a heated wire loop), and it requires time and skill.
- The primary risk is uterine perforation.
- Roller-ball endometrial ablation21
- Roller-ball endometrial ablation essentially is the same as TCRE, except that a heated roller ball is used to destroy the endometrium (instead of the wire loop).
- It has the same requirements, risks, and outcome success as TCRE.
- Satisfaction rates are equal to those of TCRE.
- Endometrial laser ablation
- Endometrial laser ablation requires Nd:YAG equipment and optical fiber delivery system.
- The laser is inserted into the uterus through the hysteroscope while transmitting energy through the distending media to warm and eventually coagulate the endometrial tissue.
- Disadvantages include the expense of the equipment (high), the time required for the procedure (long), and the risk of excessive fluid uptake from the distending media infusion and irrigating fluid.
- This technique has largely been replaced by the nonresectoscopic systems (discussed below).
Nonresectoscopic endometrial ablation techniques
- Thermal balloon therapy22
- A balloon catheter filled with isotonic sodium chloride solution is inserted into the endometrial cavity, inflated, and heated to 87°C for 8 minutes.
- Uterine balloon therapy cannot be used in irregular uterine cavities because the balloon will not conform to the cavity.
- Studies report a 90% satisfaction rate and a 25% amenorrhea rate. Long-term studies are ongoing.
- Heated free fluid23
- HydroThermAblator (HTA) is an office procedure in which normal saline is infused into the uterus via the hysteroscope.
- The solution is heated to 194°F (90°C) for 10 minutes under direct visualization.
- This procedure requires only local anesthesia.
- HTA may be used in patients with irregularly shaped endometrial cavities and/or fibroids.
- Vaginal and skin burns are the most reported complications.
- Cryoablation24
- Cryoablation is the use of liquid nitrogen to freeze the endometrium. The procedure is performed in approximately 10 minutes under ultrasonographic guidance.
- Patients usually experience 1 week of watery vaginal discharge postprocedure.
- Risks include perforation and suboptimal ablation of the entire uterine cavity.
- Microwave endometrial ablation alternative25
- Microwave endometrial ablation (MEA) uses high-frequency microwave energy to cause rapid but shallow heating of the endometrium.
- Microwaves are selected so that they do not destroy beyond 6 mm in depth.
- MEA requires 3 minutes of time and only local anesthetic. It is proving to be as effective as TCRE.
- This procedure was developed and has been used in Europe since 1996.
- Radiofrequency electricity24
- NovaSure system is a detailed microprocessor-based unit with a bipolar gold mesh electrode array.
- It contains a system for determining uterine integrity based upon the injection of CO 2 .
- The device is placed transcervically, the array is opened and electrical energy is applied for 80-90 seconds, desiccating the endometrium.
- Myomectomy26
- Myomectomy can be useful in women who wish to retain their uterus and/or fertility.
- Since myomectomy can be associated with large blood loss, this procedure is often reserved for cases of a single or few myomas.
- Risks include large blood loss or recurrence.
- Hysterectomy6,27
- Hysterectomy provides definitive cure for menorrhagia.
- This procedure is more expensive and results in greater morbidity than ablative procedures.
- The mortality rate ranges from 0.1-1.1 cases per 1000 procedures.
- The morbidity rate is usually 40%.
- Risks include those usually associated with major surgery.
A 2005 Cochrane Review (updated in 2009) concluded that "overall the existing evidence suggests that success rates and complication profiles of newer techniques of ablation compare favourably with TCRE, although technical difficulties with new equipment need to be ironed out."25
Endometrial ablation or resection preparation
- A trial of medical therapy should have failed in patients considered for this therapy.
- The endometrium should be properly sampled and evaluated before surgery.
- Patients should be pretreated with danazol or a GnRH analogue for 4-12 weeks before surgery to atrophy the endometrium, reducing surgical difficulty and time.
- Success rates are similar to laser ablation techniques.
Medication
Acute menorrhagia requires prompt medical intervention. This is bleeding that will compromise an untreated patient (see Media file 1).
Acute menorrhagia requires prompt medical intervention. This is bleeding that will compromise an untreated patient.
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 Media files 2-4).
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.
Flow chart continued from Media file 2.
Flow chart continued from Media files 2 and 3.
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.
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
250-500 mg PO bid; give at last 2 d and first 3 d of cycle, for a total of 5 d
Pediatric
Not established
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)
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 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
Diclofenac (Cataflam)
Inhibits PG synthesis by decreasing activity of enzyme cyclooxygenase, which in turn decreases formation of PG precursors.
Adult
Initial: 100 mg PO once, then 50 mg PO tid
Pediatric
Not established
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
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
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
GI bleeding; anaphylaxis; renal or liver injury
Combination oral contraceptives
OCPs containing estrogen and progestin used to treat acute hemorrhagic uterine bleeding.
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
1 tab PO qd for 3 wk; followed by a week of inactive pills, during which a withdrawal bleed generally occurs; repeat monthly
Pediatric
Not established
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
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
Pregnancy
X - Contraindicated; benefit does not outweigh risk
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)
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.
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
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
Not established
Decreases aminoglutethimide efficacy
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)
Pregnancy
X - Contraindicated; benefit does not outweigh risk
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
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.
Leuprolide (Lupron)
Suppresses ovarian and testicular steroidogenesis by decreasing LH and FSH levels.
Adult
3.5-7.5 mg IM monthly for 3-6 mo
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; may cause menopauselike symptoms; may cause bone demineralization and/or reduction in HDL cholesterol if given for > 6 mo
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.
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
100-400 mg PO qd for 3 mo
Pediatric
Not established
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
Documented hypersensitivity; breastfeeding; seizure disorders; markedly impaired hepatic function or porphyria
Pregnancy
X - Contraindicated; benefit does not outweigh risk
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
Arginine vasopressin derivatives
Indicated in patients with thromboembolic disorders.
Desmopressin (DDAVP)
Has been used to treat abnormal uterine bleeding in patients with coagulation defects. Transiently elevates factor VIII and von Willebrand factor.
Adult
0.3 mcg/kg in 50 mL NS IV push (15 min)
Pediatric
Not established
Coadministration with demeclocycline and lithium decrease effects; fludrocortisone and chlorpropamide increase effects
Documented hypersensitivity; platelet-type von Willebrand disease
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Avoid overhydration in patients using desmopressin to benefit from its hemostatic effects; may cause platelet aggregation in von Willebrand type IIB
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.
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
Acute bleeding: 25 mg IV q4h for a maximum of 48 h; 2.5 mg PO q6h for a maximum of 48 h
Pediatric
Not established
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
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 (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
More on Menorrhagia |
| Overview: Menorrhagia |
| Differential Diagnoses & Workup: Menorrhagia |
 Treatment & Medication: Menorrhagia |
| Follow-up: Menorrhagia |
| Multimedia: Menorrhagia |
| References |
| « Previous Page | Next Page » |
References
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Further Reading
Keywords
menorrhagia, heavy menses, metrorrhagia, menometrorrhagia, polymenorrhea, dysfunctional uterine bleeding, hysterectomy, heavy menstrual bleeding, dilatation and curettage, transcervical resection of the endometrium, roller-ball endometrial ablation, endometrial laser ablation, uterine balloon therapy, myomectomy, uterine artery embolization, UAE, microwave endometrial ablation alternative, HydroThermAblator, cryoablation,
