RISK FACTORS: Obesity, Anovulation, Estrogen administration (without progestin), Prior treatment with progestational agents or oral contraceptives, Increases the risk of endometrial atrophy, but decreases the risk of endometrial hyperplasia
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.
Nonsteroidal anti-inflammatory drugs
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first-line medical therapy in ovulatory menorrhagia.
Studies show an average reduction of 25-35% in menstrual blood flow.
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 much as 60% due to endometrial atrophy.
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 15% reduction in menstrual blood flow when used alone.
If administered to a patient with an IUD, the reduction in blood loss is as high as 86%.
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.
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, although studies have shown that less than 50% of the endometrium is sampled during a D&C. 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.
Transcervical resection of the endometrium
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 but achieves an 84% satisfaction or success rate.
The primary risk is uterine perforation.
Roller-ball endometrial ablation
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.
Of patients, 50% have amenorrhea and another 30% have hypomenorrhea, resulting in an overall success rate of nearly 80%.
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.
Uterine balloon therapy
A balloon catheter filled with isotonic sodium chloride solution is inserted into the endometrial cavity, inflated, and heated to 87Β°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. This success rate is slightly higher than the other techniques described above, but the rate is based on short-term studies. Long-term studies are in place but have not been completed because this technique has not been available for as long as the others.
Hysterectomy
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 usually is 40%.
Risks include those usually associated with major surgery.
Myomectomy
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.
Uterine artery embolization
Uterine artery embolization (UAE) is an efficient remedy for menorrhagia due to fibroids or acute bleeding unrelated to myomas.
Substances such as gelatin microspheres (trisacryl gelatin) or polyvinyl alcohol (PVA) are injected into the uterine arteries to immediately slow or stop blood flow.
Fibroids usually begin to quickly necrose and any active bleeding commonly subsides.
Risks include procedure failure, incomplete fibroid resolution, or necrosis associated abdominal and/or pelvic pain.
UAE is associated with less blood loss than hysterectomy and myomectomy and is generally performed by interventional radiologists.
Microwave endometrial ablation alternative
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.
HydroThermAblator
HydroThermAblator (HTA) is an office procedure in which normal saline is infused into the uterus via the hysteroscope.
The solution is heated to 194Β°F/90Β°C for 10 minutes under direct visualization.
This procedure requires only local anesthesia and reportedly has an 87% satisfaction rate.
HTA may be used in patients with irregularly shaped endometrial cavities and/or with fibroids.
Vaginal and skin burns are the most reported complications.
Cryoablation
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.
Studies indicate that 50-70% of patients report complete amenorrhea.
DRUG TREATMENT : 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.
1. NSAIDS -- 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
- DICLOFENAC
2. COMBINATION ORAL CONTRACEPTIVES : OCPs containing estrogen and progestin used to treat acute hemorrhagic uterine bleeding.
- ETHINYL ESTRADIOL & PROGESTIN DERIVATIVES
3. 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.
3. 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.
- LEUPROLIE
4. 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 : 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.
5. ARGININE VASOPRESSIN DERIVATIVES : Indicated in patients with thromboembolic disorders.
- DESMOPRESSIN
6. 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 ESTROGENS ( PREMARIN ) : Only controls bleeding acutely but does not treat underlying cause. Appropriate long-term therapy can be administered once the acute episode has passed.
DRUG(S) OF CHOICE
. For acute control of severe bleeding:
. Estrogen, conjugated (Premarin) 25 mg IV every 4 hours up to 6 doses until bleeding abates
. For less severe bleeding or after control of acute bleeding:
. Medroxyprogesterone acetate (Provera) 10-30 mg daily for 5-10 days
. Any combination oral contraceptive, (usually one of the high dose oral contraceptives) one tablet 4 times a day for 5-7 days
. To prevent heavy bleeding in subsequent cycles:
. Medroxyprogesterone acetate 10-20 mg daily for 10 days per month
. Usual cyclic dose of a combination oral contraceptive
. For endometrial atrophy in postmenopausal woman:
. Estrogen plus progesterone replacement therapy
Contraindications:
. To estrogen, oral contraceptives, or progestins:
. Pregnancy
. Breast or endometrial cancer
. Thromboembolic disease, past or present
. Impaired liver function
ALTERNATIVE DRUGS
β’ Non-steroidal prostaglandin-synthetase inhibitors (naproxen, mefenamic acid, ibuprofen, and others) can
reduce blood loss with ovulatory cycles and reduce Dysmenorrhea
β’ Norethindrone acetate (Aygestin) 2.5-10 mg daily for 10 days per month, during the assumed latter half of menstrual cycle
β’ Danazol and GnRH agonists are also effective therapies, but more likely to have adverse side effects
β’ Megestrol acetate (Megace) 40 mg daily for 10 days per month (caution required to prevent progression to
endometrial carcinoma)
β’ Megestrol acetate (Megace) 40 mg daily continuously to treat atypical hyperplasia
PATIENT MONITORING
β’ Varies with cause of bleeding
β’ Medical treatment of hyperplastic/dysplastic endometrium should be followed by repeat biopsy to confirm that histologic structure has returned to normal
PREVENTION/AVOIDANCE Pap smear and pelvic examination annually
POSSIBLE COMPLICATIONS Anemia
EXPECTED COURSE/PROGNOSIS
β’ Varies with cause of bleeding
β’ Most patients with hormonal causes will respond to hormonal manipulation