Menorrhagia 3

MEDICATION
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) -- Inhibits PG synthesis by decreasing activity of enzyme cyclooxygenase, which in turn decreases formation of PG precursors.
Adult Dose
Initial: 100 mg PO once, then 50 mg PO tid
Pediatric Dose
Not established
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 therapyOral contraceptives can cause fluid retention (address any condition aggravated by this factor)Monitor patients with epilepsy, migraine, asthma, or renal or cardiac dysfunctionHistory 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 pancreatitisDiscontinue if jaundice developsContact lens wearers with visual changes should be examined by ophthalmologistPatients 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 monthlyProvera for atypical hyperplasia: 10 mg/d PO for 12 d onceMegestrol acetate: 40-80 mg PO for 10 d monthlyMegestrol acetate for atypical hyperplasia: 40-80 mg PO for 12 d onceDerivatives of 19-nortestosterone: Used in oral combination birth control pills; doses vary from 0.075-0.35 mg/pill depending on derivativeDerivatives 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
FOLLOW-UP
Complications:
Treatment must be individualized to treat each patient's specific symptoms. Cost, dosing, and patient compliance can play major roles.
If bleeding does not subside within the expected time frame, have the patient keep a menstrual calendar to better assess the resulting bleeding pattern.
If a specific treatment fails, investigate all possibilities, including noncompliance, medication dosing, diagnosis, patient age, and comorbid conditions.
Prognosis:
With proper workup, diagnosis, treatment, and follow-up care, prognosis is excellent.
Patient Education:
Reassure patients that most bleeding stops, but not immediately. Provide literature on the treatment of choice, including expectations and adverse effects.
Many patients appreciate reassurance that they do not have cancer and are not alone in their plight.
Reassure patients who experience a treatment failure that other options are available.
MISCELLANEOUS
Medical/Legal Pitfalls:
Every patient presenting with uterine bleeding should first undergo pregnancy testing. Threatened or incomplete abortion, ectopic pregnancy, or retained products of conception must be considered before any imaging studies may be ordered.
Every high-risk or postmenopausal patient with uterine bleeding first must be evaluated for endometrial or other gynecological malignancy.
When treating patients with progestin therapy of any form, they must be informed that this is not a form of birth control. Pregnancy is possible, especially if ovulation is induced by the cycling of the progesterone.
All medications and procedures must be administered only after informed consent of all benefits and risks.