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.
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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.
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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.
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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.
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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
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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.
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• 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
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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.
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• 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
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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.
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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.
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• 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
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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.
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• 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).
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• 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
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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
Pediatric Dose Not established
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
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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
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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
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 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
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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
Pediatric Dose Not established
ContraindicationsDocumented 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 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
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 withconcurrent use; might interfere with laboratory
determinations of DHEA, androstenedione, andtestosterone
Pregnancy X - Contraindicated in pregnancy
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
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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)
Pediatric Dose Not established
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
Pediatric Dose Not established
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
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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
Pregnancy X - Contraindicated in pregnancy
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.
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• 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:
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• 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.