men orr hagia

7/14/2019 Men Orr Hagia

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Menorrhagia

Background:

Menorrhagia is menstruation at regular cycle intervals but with excessive flow and duration. It isdefined 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 pathologyfindings 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 perceivesto 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), whichinduce 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, alsoknown 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 isasynchronous 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 bloodcan 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 isdependent 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 disturbancesresult 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.



Frequency:

　

• In the US: While menorrhagia remains a leading reason for gynecologic office visits,

only 10-20% of all menstruating women experience blood loss severe enough to be

defined clinically as menorrhagia.

Mortality/Morbidity: Infrequent episodes of menorrhagia usually do not carry severe risks to

women general health.

• Patients who lose more than 80 mL of blood, especially repetitively, are at risk for

serious medical sequelae. These women are likely to develop iron-deficiency anemia as a

result of their blood loss. Menorrhagia is the most common cause of anemia in

premenopausal women. This usually can be remedied by simple ingestion of ferrous

sulfate to replace iron stores. If the bleeding is severe enough to cause volume depletion, patients may experience shortness of breath, fatigue, palpitations, and other related

symptoms. This level of anemia necessitates hospitalization for intravenous fluids and possible transfusion and/or intravenous estrogen therapy. Patients who do not respond tomedical therapy may require surgical intervention to control the menorrhagia.

• Other sequelae associated with menorrhagia usually are related to the etiology. For

example, with hypothyroidism, patients may experience symptoms associated with a low-functioning thyroid (eg, cold intolerance, hair loss, dry skin, weight gain) in addition to

the effects of significant blood loss.

Sex:

•

Only females are affected by menorrhagia.

Age:

• Any woman of reproductive age who is menstruating may develop menorrhagia. Most

patients with menorrhagia are older than 30 years. This is because the most commoncause of heavy menses in the younger population is anovulatory cycles, in which

bleeding does not occur at regular intervals.

History:

Symptoms related by a patient with menorrhagia often can be more revealing than laboratorytests. Considering the lengthy list of possible etiologies that contribute to menorrhagia, taking a

detailed patient history is imperative. Inquiries should include the following:

• Exclusion of pregnancy

o This is the most common cause of irregular bleeding in women of reproductive

age.



　

o Pregnancy should be the first diagnosis to be excluded before further testing or

medications are instituted.

•

Quantity and quality of bleeding

o Quantity is a very subjective issue when considering vaginal bleeding. Best

estimates usually are the only source clinicians have available to consider. Helpful

references for totaling blood loss may include that the average tampon holds 5 mLand the average pad holds 5-15 mL of blood. Asking the patient what type of pad

(liner vs overnight) was used and if it was soaked may add some insight into what

the patient believes to be heavy bleeding.

o Quality of bleeding involves the presence of clots and their size.

• Age

o Young patients, from menarche to the late-teen years, most commonly have

anovulatory bleeding due to the immaturity of their hypothalamic-pituitary axis. If bleeding does not respond to usual therapy in this age group, a bleeding disorder

must be considered.

o Women aged 30-50 years may have organic or structural abnormalities. Fibroids

or polyps are frequent anatomical findings. Organic causes can be anything from

thyroid dysfunction to renal failure.

o Postmenopausal women with any uterine bleeding should receive an immediate

workup for endometrial cancer.

o Endometrial hyperplasia must be considered in women who are obese, aged 70 or

older, nulliparous, or have diabetes.

• Pelvic pain and pathology

o Knowing if a patient has any long-standing diagnosis or known pathology (eg,

fibroids) is helpful.

o Records from other physicians or hospitalizations may prevent redundancy in

ordering lab work or diagnostic imaging.

• Menses pattern from menarche

o If a young patient has had irregular menses since menarche, the most common

etiology of her bleeding is anovulation.

o Anovulatory bleeding is most common in young girls (aged 12-18 y) and common

in obese females of any reproductive age.



o If a patient's bleeding normally occurs at regular intervals and the irregularity is

new in onset, pathology must be ruled out, regardless of age.

• Sexual activity

o Simple vaginitis (eg, candidal, bacterial vaginosis) may cause intermenstrual bleeding, while gonorrhea and chlamydia may present with heavier bleeding

attributed primarily to the copious discharge mixed with the blood.

o Chlamydia is a common cause of postpartum endometritis, leading to vaginal

bleeding in the weeks following a delivery.

o A postpartum infection (eg, endometritis) also may be due to organisms unrelated

to sexual activity.

• Contraceptive use (intrauterine device or hormones)

o Commonly, an intrauterine device (IUD) causes increased uterine cramping andmenstrual flow.

o If a patient has recently discontinued birth control pills, she may return to her

"natural" menses and report an increase in flow. This actually is normal because

most oral birth control pills decrease the flow and duration of a woman's menses.

• Presence of hirsutism (polycystic ovarian syndrome)

o These patients commonly are obese and in an anovulatory state. When they do

have a period, it may be very heavy and cause concern for the patient.

o The etiology of this is explained in the Introduction to this article.

• Galactorrhea (pituitary tumor): Any patient complaining of a milky discharge from either

breast (while not pregnant, postpartum, or breastfeeding) needs a prolactin level to ruleout a pituitary tumor.

• Systemic illnesses (hepatic/renal failure or diabetes)

o As explained in the Introduction, organic diseases may affect either the hormonal

or hematologic pathways that are involved in the manifestation of menorrhagia.

o If either the hypothalamic-pituitary axis or the coagulation paths are disrupted,heavy bleeding may result.

• Symptoms of thyroid dysfunction: The alteration of the hypothalamic-pituitary axis may

create either amenorrhea (hyperthyroidism) or menorrhagia (hypothyroidism).

• Excessive bruising or known bleeding disorders

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o This is especially important in a young patient who does not stop bleeding during

her first menses.

o This is a very common presentation for an undiagnosed bleeding disorder (von

Willebrand disease) in a young girl.

• Current medications (hormones or anticoagulants)

o Any medication that prolongs bleeding time may cause menorrhagia.

o A patient treated with any progestin therapy may have a withdrawal bleed after

cessation of the medication. This bleeding often is heavy and worrisome to

patients if they are not forewarned.

• Previous medical or surgical procedures/diagnoses: This also is helpful in preventing

duplication of testing.

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

• Initial inspection should include evaluation for the following:

o Signs of severe volume depletion (eg, anemia): This may help confirm the

patient's history of very heavy bleeding and/or prompt immediate inpatient care.

o Obesity: This is an independent risk factor for endometrial cancer. Adipose tissue

is a locale for estrogen conversion. Therefore, the larger the patient, the more

increased the risk (and the higher the unopposed estrogen level on the

endometrium).

o Signs of androgen excess (eg, hirsutism): This usually points to polycystic ovarian

syndrome (PCOS), leading to anovulatory bleeding (see Presence of hirsutism).

o Ecchymosis: This usually is a sign of trauma or a bleeding disorder.

o Purpura: This also is a sign of trauma or a possible bleeding disorder.

o Pronounced acne: This is a sign of PCOS.

• General examination should include evaluation of the following:

o Visual fields

o Bleeding gums

o Thyroid evaluation





o Galactorrhea

o Enlarged liver or spleen

• Pelvic examination should evaluate for the presence of external genital lesions.

• Vaginal/cervical discharge: Look for a copious discharge indicating infection, and

confirm the actual site of the bleeding (if present). Assess as follows:

o Uterine size, shape, and contour: An enlarged irregularly shaped uterus suggests

fibroids if the patient is aged 30-50 years. An enlarged uniformly shaped uterus in

a postmenopausal patient with bleeding suggests endometrial cancer until provenotherwise.

o Cervical motion tenderness: This is a common symptom of pelvic inflammatory

disease (PID) that usually is caused by gonorrhea or chlamydia. This is an

important diagnosis to exclude, especially in young nulliparous women, because itcan lead to pelvic adhesions and infertility.

o Adnexal tenderness or masses: This is especially concerning in patients older than

40 years. Ovarian cancer may present with intermenstrual bleeding as its only

symptom. Rare but deadly ovarian tumors also can present in teenage girls. Anysuspicion of an adnexal mass should prompt an immediate pelvic ultrasound.

Causes: Etiologies of menorrhagia are divided into 4 categories, organic, endocrinologic,

anatomic, and iatrogenic.

• Organic causes of menorrhagia include infection, bleeding disorders, and organdysfunction.

o Infections can be of any genitourinary origin. The aforementioned sexually

transmitted diseases are of greater concern in the teenage and early adult

population. Bleeding from the urethra or rectum always must be considered in theworkup, especially in the postmenopausal woman who has negative findings after

a workup for vaginal bleeding.

o Coagulation disorders can evade diagnosis until menarche, when heavy menstrual

bleeding presents as an unrelenting disorder. These include von Willebrand

disease; factor II, V, VII, and IX deficiencies; prothrombin deficiency; idiopathicthrombocytopenia purpura (ITP); and thromboasthenia.

o Organ dysfunction causing menorrhagia includes hepatic or renal failure. Chronic

liver disease impairs production of clotting factors and reduces hormone

metabolism (eg, estrogen). Either of these problems may lead to heavy uterine

bleeding.



• Endocrine causes of menorrhagia include thyroid and adrenal gland dysfunction, pituitary

tumors, anovulatory cycles, PCOS, obesity, and vasculature imbalance.

o Both hypothyroidism and hyperthyroidism result in menorrhagia. Even

subclinical cases of hypothyroidism produce heavy uterine bleeding in 20% of

patients. Menorrhagia usually resolves with correction of the thyroid disorder.

o Prolactin-producing pituitary tumors cause menorrhagia by disrupting (GnRH)

secretion. This leads to decreased LH and FSH levels, which ultimately causehypogonadism. Interim stages of menorrhagia result until hypogonadism

manifests.

o The most common etiology of heavy uterine bleeding is anovulatory cycles. The

finding of menorrhagia at irregular intervals without any known organic etiology

confirms the clinical diagnosis. This is most common in adolescent and

perimenopausal populations.

o The hallmarks of PCOS are anovulation, irregular menses, obesity, and hirsutism.

Insulin resistance is common and increases androgen production by the ovaries.

o Hyperinsulinemia is a direct consequence of obesity. This overproduction of

insulin leads to ovarian production of androgens, as occurs in PCOS.

o Vasculature imbalance is theorized to be the result of a discrepancy between the

vasoconstricting and aggregating actions of prostaglandin F2 (alpha) and

thromboxane A2 and the vasodilating actions of prostaglandin E2 and prostacyclin

on the myometrial and endometrial vasculature.

• Anatomic etiologies for menorrhagia include uterine fibroids, endometrial polyps,

endometrial hyperplasia, and pregnancy.

o Fibroids and polyps are benign structures that distort the uterine wall and/or

endometrium. Either may be located within the uterine lining, but fibroids may

occur almost anywhere on the uterus.

o The mechanism by which endometrial polyps or fibroids cause menorrhagia is not

well understood. The blood supply to the fibroid or polyp is different compared tothe surrounding endometrium and is thought to function independently. This

blood supply is greater than the endometrial supply and may have impededvenous return, causing pooling in the areas of the fibroid. Heavy pooling is

thought to weaken the endometrium in that area, and break-through bleedingensues.

o Fibroids located within the uterine wall may inhibit muscle contracture, thereby

preventing normal uterine attempts at hemostasis. This also is why intramural

fibroids may cause a significant amount of pain and cramping. Fibroids may



enlarge to the point that they outgrow their blood supply and undergo necrosis.

This also causes a great deal of pain for patients.

o Endometrial hyperplasia usually results from unopposed estrogen production,

regardless of the etiology. Endometrial hyperplasia can lead to endometrial cancer

in 1-2% of patients with anovulatory bleeding, but it is a diagnosis of exclusion in postmenopausal bleeding (average age at menopause is 51 y). If a woman takesunopposed estrogen (without progesterone), her relative risk of endometrial

cancer is 2.3 compared to nonusers and 9.5 if taken for 10 years or longer.

• Iatrogenic causes of menorrhagia include IUDs, steroid hormones, chemotherapy agents,

and medications (eg, anticoagulants).

o IUDs can cause increased menstrual bleeding and cramping due to local irritation

effects.

o Steroid hormones and chemotherapy agents disrupt the normal menstrual cycle,which is restored easily upon cessation of the products.

o Anticoagulants decrease clotting factors needed to cease any normal blood flow,

including menses. This type of menorrhagia also is easily reversible

Lab studies:

• Complete blood count

o The CBC count may be used as a baseline for hemoglobin and hematocrit or to

rule out anemia.

o Use the platelet count in conjunction with a peripheral smear if a coagulation

defect is suspected.

• Iron studies: Total iron-binding capacity (TIBC) and total iron are used to assess iron

stores.

• Coagulation factors: These studies are used to rule out von Willebrand disease; ITP; and

factor II, V, VII, or IX deficiency. These tests should be ordered sparingly because they

are expensive tests for rare disorders.

• Human chorionic gonadotropin: Pregnancy remains the most common cause of abnormal

uterine bleeding in patients of reproductive age. Bleeding usually denotes threatenedabortion, incomplete abortion, or ectopic pregnancy.

• Thyroid function tests and prolactin level: These tests can rule out hyperthyroidism or

hypothyroidism and hyperprolactinemia. All of these conditions cause ovarian

dysfunction leading to possible menorrhagia.



• Liver function and/or renal function tests

o Order liver function tests (LFTs) when liver disease is suspected, such as in

persons with alcoholism or hepatitis.

o BUN and creatinine tests assess renal function.

o Dysfunction of either organ can alter coagulation factors and/or the metabolism of

hormones.

• Hormone assays

o LH, FSH, and androgen levels help diagnose patients with suspected PCOS.

o Adrenal function tests (eg, cortisol, 17-alpha hydroxyprogesterone [17-OHP])

delineate hyperandrogenism in women with suspected adrenal tumors. Congenital

adrenal hyperplasia (CAH) is diagnosed primarily by testing 17-OHP.

Imaging Studies:

　

• Small, focal, irregular, or eccentrically located endometrial lesions may be missed by an

in-office endometrial biopsy (EMB). The findings yielded from pelvic examinations may

be limited if patients are obese. These limitations can lead to further imaging studies to

inspect the uterus, endometrium, and/or adnexa.

• Pelvic ultrasound is the best noninvasive imaging study to assess uterine shape, size, and

contour; endometrial thickness; and adnexal areas.

• Sonohysterography (saline-infusion sonography): Fluid infused into the endometrial

cavity enhances intrauterine evaluation. One advantage is the ability to differentiate

polyps from submucous leiomyomas (ie, fibroids).

Other Tests:

　

• Papanicolaou (Pap) smear test results for cervical cytology should be current.

• Cervical specimens should be obtained if the patient is at risk for an infection.

Procedures:

　

• Because routine EMB and conventional imaging studies may miss small or laterally

displaced lesions, superior methods of assessment must be used in high-risk patients. In



addition, performing an in-office biopsy or imaging studies may be limited by patient

problems such as obesity or cervical stenosis.

• Hysteroscopy: This can be done in the office but may require anesthesia if the patient has

a low pain tolerance or adequate visualization is not obtainable.

o This technique is used to directly visualize the endometrial cavity by close

contact.

　

o A biopsy sample should be taken, regardless of the endometrial appearance.

　

o The histologic diagnosis is missed in less than 2% of patients who undergo

hysteroscopy with directed biopsy.

• Endometrial biopsy

o This procedure is used in women who are at risk for endometrial carcinoma,

polyps, or hyperplasia.

o High-risk patients who should be biopsied include those with hypertension,

diabetes, chronic anovulation (eg, PCOS), obesity, atypical glandular cells

(AGUS) on Pap smear, new-onset menorrhagia, and those older than 70 years or any woman older than 35 years with new-onset irregular bleeding (especially if

nulliparous).

o EMB findings are used to assess the stage and proliferation of the endometrial

stroma and glands. Many studies have been done to compare the results of EMBand dilatation and curettage (D&C). Both tests are accepted as equal in value and

are approximately 98% accurate.

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 atypicaladenomatous 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

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

　

o Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first-line medical therapy

in ovulatory menorrhagia.

o Studies show an average reduction of 25-35% in menstrual blood flow.

o NSAIDs reduce prostaglandin levels by inhibiting cyclooxygenase and increasing

the ratio of prostacyclin to thromboxane.

o NSAIDs are ingested for only 5 days of the entire cycle, limiting their most

common adverse effect of stomach upset.

• Oral contraceptive pills

o Oral contraceptive pills (OCPs) are a popular first-line therapy for women who

desire contraception.

o Menstrual blood loss is reduced as much as 60% due to endometrial atrophy.

o OCPs suppress pituitary gonadotropin release, preventing ovulation.

o Common adverse effects include breast tenderness, breakthrough bleeding,

nausea, and, possibly, related weight gain in some individuals.

• Progestin therapy

o Progestin is the most frequently prescribed medicine for menorrhagia.

o Therapy with progestin results in a 15% reduction in menstrual blood flow when

used alone.

o If administered to a patient with an IUD, the reduction in blood loss is as high as86%.

o Progestin works as an antiestrogen by minimizing the effects of estrogen on target

cells, thereby maintaining the endometrium in a state of down-regulation.

o Common adverse effects include weight gain, headaches, edema, and depression.



• Gonadotropin-releasing hormone agonists

o These agents are used on a short-term basis due to high costs and severe adverse

effects.

o GnRH agonists are effective in reducing menstrual blood flow.

o They inhibit pituitary release of FSH and LH, resulting in hypogonadism.

o A prolonged hypoestrogenic state leads to bone demineralization and reduction of

high-density lipoprotein (HDL) cholesterol.

• Danazol

　

o Danazol competes with androgen and progesterone at the receptor level, causing

amenorrhea in 4-6 weeks.

o Androgenic effects cause acne, decreasing breast size, and, rarely, lower voice.

• Conjugated estrogens

　

o These agents are given intravenously every 4 hours in patients with acute

bleeding.

o A D&C procedure may be necessary if no response is noted in 24 hours.

o 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 toorganic 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

o 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.

o This procedure is used best in conjunction with hysteroscopy to evaluate the

endometrial cavity for pathology.

o It is contraindicated in patients with known or suspected pelvic infection. Risks

include uterine perforation, infection, and Asherman syndrome.

• Transcervical resection of the endometrium



o Transcervical resection of the endometrium (TCRE) has been considered the

criterion standard cure for menorrhagia for many years.

o 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.

o The primary risk is uterine perforation.

• Roller-ball endometrial ablation

　

o 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).

o It has the same requirements, risks, and outcome success as TCRE.

o Satisfaction rates are equal to those of TCRE.

• Endometrial laser ablation

　

o Endometrial laser ablation requires Nd:YAG (neodymium-doped:yttrium

aluminum garnet) laser equipment and optical fiber delivery system.

o 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.

o

Disadvantages include the expense of the equipment (high), the time required for the procedure (long), and the risk of excessive fluid uptake from the distendingmedia infusion and irrigating fluid.

o Of patients, 50% have amenorrhea and another 30% have hypomenorrhea,

resulting in an overall success rate of nearly 80%.

• Endometrial ablation or resection preparation

　

o A trial of medical therapy should have failed in patients considered for this

therapy.

o The endometrium should be properly sampled and evaluated before surgery.

o 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.

o Success rates are similar to laser ablation techniques.



• Uterine balloon therapy

　

o A balloon catheter filled with isotonic sodium chloride solution is inserted into the

endometrial cavity, inflated, and heated to 87 　 for 8 minutes.

o Uterine balloon therapy cannot be used in irregular uterine cavities because the balloon will not conform to the cavity.

o 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

　

o

Hysterectomy provides definitive cure for menorrhagia.

o This procedure is more expensive and results in greater morbidity than ablative

procedures.

o The mortality rate ranges from 0.1-1.1 cases per 1000 procedures.

o The morbidity rate usually is 40%.

o Risks include those usually associated with major surgery.

• Microwave endometrial ablation alternative

o Microwave endometrial ablation (MEA) uses high-frequency microwave energy

to cause rapid but shallow heating of the endometrium.

o Microwaves are selected so that they do not destroy beyond 6 mm in depth.

o MEA requires 3 minutes of time and only local anesthetic. It is proving to be as

effective as TCRE.

o This procedure was developed and has been used in Europe since 1996

• 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-doseestrogen (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 menorrhagicendometrium. Because NSAIDs inhibit blood prostacyclin formation, they might

effectively decrease uterine blood flow.

Drug Name

Naproxen (Anaprox, Naprelan, Naprosyn) -- Usedfor relief of mild to moderate pain. Inhibits

inflammatory reactions and pain by decreasing

activity of cyclooxygenase, which is responsible

for prostaglandin synthesis.

Adult Dose250-500 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; renalinsufficiency

Interactions

Probenecid may increase toxicity of NSAIDs;

coadministration with ibuprofen might decrease

effects of loop diuretics; coadministration with

anticoagulants might prolong PT (watch for signsof bleeding); might increase serum lithium levels

and risk of methotrexate toxicity (eg, stomatitis,

bone marrow suppression, nephrotoxicity)

PregnancyB - Usually safe but benefits must outweigh the

risks.

Precautions

Category D in third trimester of pregnancy; acuterenal 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 toaspirin/NSAIDs, such as swelling, asthma, hives,

urticaria, or any forms of angioedema; active GI

bleed; active ulcer



Interactions

Reports suggest that NSAIDs may diminish theantihypertensive effect of ACE inhibitors,

concomitantly with ACE inhibitors; concomitant

administration of low-dose aspirin may result inincreased 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 effectof 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

PregnancyC - 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 Dose1 tab PO qd for 3 wk; followed by a week of inactive pills, during which a withdrawal bleed

generally occurs; repeat monthly


Contraindications

Documented hypersensitivity; pregnancy; active or

inactive thrombophlebitis or thromboembolicdisorders, 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 jaundicewith 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 historyrecommended; 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 developsContact lens wearers with visual changes should be

examined by ophthalmologist

Patients might develop hypertension secondary toincrease 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 andhas 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 cholesterollevels.

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 monthlyMegestrol acetate for atypical hyperplasia: 40-80

mg PO for 12 d once

Derivatives of 19-nortestosterone: Used in oralcombination birth control pills; doses vary from

0.075-0.35 mg/pill depending on derivative

Derivatives of 19-nortestosterone for atypicalhyperplasia: 5 mg/d for 12 d once


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


Precautions

Caution in asthma, depression, renal or cardiac

dysfunction, or thromboembolic disorders; perform

complete physical examination, document recent

Papanicolaou smear, and take family history beforetherapy; give special attention to blood pressure,

breasts, abdomen, and pelvic organs; repeat

physical examination annually; progestins cancause fluid retention (address any condition

aggravated by this factor); monitor patients with

epilepsy, migraine, asthma, renal or cardiacdysfunction, 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 tocastrate 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 andtesticular steroidogenesis by decreasing LH and

FSH levels.Adult Dose 3.5-7.5 mg IM monthly for 3-6 mo


ContraindicationsDocumented hypersensitivity; undiagnosed vaginal bleeding and spinal cord compression

Interactions None reported


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 abnormaluterine 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 LHand 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


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 withconcurrent use; might interfere with laboratory

determinations of DHEA, androstenedione, andtestosterone


Precautions Caution in renal, hepatic (may elevate serum

transaminase levels), or cardiac insufficiency andin 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 withcoagulation defects. Transiently elevates factor VIII and von Willebrand factor.

Adult Dose 0.3 mcg/kg in 50 mL NS IV push (15 min)


ContraindicationsDocumented hypersensitivity; platelet-type von

Willebrand disease

Interactions

Coadministration with demeclocycline and lithium

decrease effects; fludrocortisone and

chlorpropamide increase effects

PregnancyB - Usually safe but benefits must outweigh therisks.

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 treatunderlying cause. Appropriate long-term therapy

can be administered once the acute episode has

passed.

Adult DoseAcute bleeding: 25 mg IV q4h for a maximum of

48 h; 2.5 mg PO q6h for a maximum of 48 h


Contraindications Documented hypersensitivity; known or suspected

pregnancy; breast cancer, undiagnosed abnormalgenital bleeding, active thrombophlebitis, or

thromboembolic disorders; history of

thrombophlebitis, thrombosis, or thromboembolicdisorders 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 whenadministered concurrently with hydantoins


Precautions

Certain patients may develop undesirablemanifestations of excessive estrogenic stimulation

(eg, abnormal or excessive uterine bleeding,

mastodynia); may cause some degree of fluid

retention (exercise caution); prolonged unopposedestrogen therapy may increase risk of endometrial

hyperplasia

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.

Medical/Legal Pitfalls:

• Every patient presenting with uterine bleeding should first undergo pregnancy testing.

Threatened or incomplete abortion, ectopic pregnancy, or retained products of conceptionmust 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.

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 intheir plight.

• Reassure patients who experience a treatment failure that other options are available.

Medical/LegalPitfalls:



• 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.

men orr hagia

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