Menorrhagia is menstruation at regular cycle intervals but
with excessive flow and duration. It is defined 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 pathology findings from
hysterectomies for menorrhagia are free of disease and histopathologic
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 perceives to 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), which induce the ovaries to produce estrogen and
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, also known as the secretory phase, progesterone causes endometrial
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 is asynchronous 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 blood can 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 is dependent on the location and size of the
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 disturbances result 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
- 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’s 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 to medical therapy may require surgical intervention to control the
- 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.
- Only females are affected by menorrhagia.
- 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 common cause 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 laboratory tests.
Considering the lengthy list of possible etiologies that contribute to
menorrhagia, taking a detailed patient history is imperative. Inquiries should
include the following:
- This is the most common cause of irregular bleeding in women of
- Pregnancy should be the first diagnosis to be excluded before further
testing or medications are instituted.
- Quantity and quality of bleeding
- 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 mL and 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
- Quality of bleeding involves the presence of clots and their size.
- 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.
- 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.
- Postmenopausal women with any uterine bleeding should receive an
immediate workup for endometrial cancer.
- Endometrial hyperplasia must be considered in women who are obese, aged
70 or older, nulliparous, or have diabetes.
- Pelvic pain and pathology
- Knowing if a patient has any long-standing diagnosis or known pathology
(eg, fibroids) is helpful.
- Records from other physicians or hospitalizations may prevent redundancy
in ordering lab work or diagnostic imaging.
- Menses pattern from menarche
- If a young patient has had irregular menses since menarche, the most
common etiology of her bleeding is anovulation.
- Anovulatory bleeding is most common in young girls (aged 12-18 y) and
common in obese females of any reproductive age.
- If a patient's bleeding normally occurs at regular intervals and the
irregularity is new in onset, pathology must be ruled out, regardless of
- 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
- Chlamydia is a common cause of postpartum endometritis, leading to
vaginal bleeding in the weeks following a delivery.
- A postpartum infection (eg, endometritis) also may be due to organisms
unrelated to sexual activity.
- Contraceptive use (intrauterine device or hormones)
- Commonly, an intrauterine device (IUD) causes increased uterine cramping
and menstrual flow.
- 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)
- 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.
- The etiology of this is explained in the
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 rule out a pituitary tumor.
- Systemic illnesses (hepatic/renal failure or diabetes)
- As explained in the
organic diseases may affect either the hormonal or hematologic pathways that
are involved in the manifestation of menorrhagia.
- 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
- Excessive bruising or known bleeding disorders
- This is especially important in a young patient who does not stop
bleeding during her first menses.
- This is a very common presentation for an undiagnosed bleeding disorder
(von Willebrand disease) in a young girl.
- Current medications (hormones or anticoagulants)
- Any medication that prolongs bleeding time may cause menorrhagia.
- 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:
- Signs of severe volume depletion (eg, anemia): This may help confirm the
patient's history of very heavy bleeding and/or prompt immediate inpatient
- 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).
- Signs of androgen excess (eg, hirsutism): This usually points to
polycystic ovarian syndrome (PCOS), leading to anovulatory bleeding (see
- Ecchymosis: This usually is a sign of trauma or a bleeding disorder.
- Purpura: This also is a sign of trauma or a possible bleeding disorder.
- Pronounced acne: This is a sign of PCOS.
- General examination should include evaluation of the following:
- Pelvic examination should evaluate for the presence of external genital
- Vaginal/cervical discharge: Look for a copious discharge indicating
infection, and confirm the actual site of the bleeding (if present). Assess as
- 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 proven otherwise.
- 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 it can lead to pelvic adhesions and infertility.
- 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. Any suspicion of an adnexal mass should prompt an immediate
Causes: Etiologies of menorrhagia are divided into 4
categories, organic, endocrinologic, anatomic, and iatrogenic.
- Organic causes of menorrhagia include infection, bleeding disorders, and
- 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 the workup, especially in the postmenopausal woman who has
negative findings after a workup for vaginal bleeding.
- 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; idiopathic thrombocytopenia purpura (ITP); and thromboasthenia.
- 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
- 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
- Prolactin-producing pituitary tumors cause menorrhagia by disrupting (GnRH)
secretion. This leads to decreased LH and FSH levels, which ultimately cause
hypogonadism. Interim stages of menorrhagia result until hypogonadism
- 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.
- The hallmarks of PCOS are anovulation, irregular menses, obesity, and
hirsutism. Insulin resistance is common and increases androgen production by
- Hyperinsulinemia is a direct consequence of obesity. This overproduction
of insulin leads to ovarian production of androgens, as occurs in PCOS.
- 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
- Anatomic etiologies for menorrhagia include uterine fibroids, endometrial
polyps, endometrial hyperplasia, and pregnancy.
- 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.
- 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 to the surrounding endometrium and is thought to function
independently. This blood supply is greater than the endometrial supply and
may have impeded venous return, causing pooling in the areas of the fibroid.
Heavy pooling is thought to weaken the endometrium in that area, and
break-through bleeding ensues.
- 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.
- 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 takes unopposed 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).
- IUDs can cause increased menstrual bleeding and cramping due to local
- Steroid hormones and chemotherapy agents disrupt the normal menstrual
cycle, which is restored easily upon cessation of the products.
- Anticoagulants decrease clotting factors needed to cease any normal
blood flow, including menses. This type of menorrhagia also is easily
- The CBC count may be used as a baseline for hemoglobin and hematocrit or
to rule out anemia.
- 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 threatened abortion, 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
- Order liver function tests (LFTs) when liver disease is suspected, such
as in persons with alcoholism or hepatitis.
- BUN and creatinine tests assess renal function.
- Dysfunction of either organ can alter coagulation factors and/or the
metabolism of hormones.
- LH, FSH, and androgen levels help diagnose patients with suspected PCOS.
- 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
- 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
- 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).
- Papanicolaou (Pap) smear test results for cervical cytology should be
- Cervical specimens should be obtained if the patient is at risk for an
- 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
- 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
- This technique is used to directly visualize the endometrial cavity by
- A biopsy sample should be taken, regardless of the endometrial
- The histologic diagnosis is missed in less than 2% of patients who
undergo hysteroscopy with directed biopsy.
- This procedure is used in women who are at risk for endometrial
carcinoma, polyps, or hyperplasia.
- 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).
- 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 EMB and 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
Endometrial hyperplasia with atypia (especially atypical adenomatous
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’s age, coexisting medical
diseases, family history, and desire for fertility. Medication cost and adverse
effects also are factored in because they may play a direct role in patient
- Nonsteroidal anti-inflammatory drugs
- Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first-line medical
therapy in ovulatory menorrhagia.
- Studies show an average reduction of 25-35% in menstrual blood flow.
- NSAIDs reduce prostaglandin levels by inhibiting cyclooxygenase and
increasing the ratio of prostacyclin to thromboxane.
- NSAIDs are ingested for only 5 days of the entire cycle, limiting their
most common adverse effect of stomach upset.
- Oral contraceptive pills
- Oral contraceptive pills (OCPs) are a popular first-line therapy for
women who desire contraception.
- Menstrual blood loss is reduced as much as 60% due to endometrial
- OCPs suppress pituitary gonadotropin release, preventing ovulation.
- Common adverse effects include breast tenderness, breakthrough bleeding,
nausea, and, possibly, related weight gain in some individuals.
- Progestin therapy
- Progestin is the most frequently prescribed medicine for menorrhagia.
- Therapy with progestin results in a 15% reduction in menstrual blood
flow when used alone.
- If administered to a patient with an IUD, the reduction in blood loss is
as high as 86%.
- Progestin works as an antiestrogen by minimizing the effects of estrogen
on target cells, thereby maintaining the endometrium in a state of
- Common adverse effects include weight gain, headaches, edema, and
- Gonadotropin-releasing hormone agonists
- These agents are used on a short-term basis due to high costs and severe
- GnRH agonists are effective in reducing menstrual blood flow.
- They inhibit pituitary release of FSH and LH, resulting in hypogonadism.
- A prolonged hypoestrogenic state leads to bone demineralization and
reduction of high-density lipoprotein (HDL) cholesterol.
- Danazol competes with androgen and progesterone at the receptor level,
causing amenorrhea in 4-6 weeks.
- Androgenic effects cause acne, decreasing breast size, and, rarely,
- Conjugated estrogens
- These agents are given intravenously every 4 hours in patients with
- A D&C procedure may be necessary if no response is noted in 24 hours.
- If menses slows, follow up with estrogen-progestin therapy for 7 days.
This is followed by OCPs for 3 months.
Surgical Care: Surgical management has been the standard of
treatment in menorrhagia due to organic causes (eg, fibroids) or when medical
therapy fails to alleviate symptoms. Surgical treatment ranges from a simple D&C
to a full hysterectomy.
- Dilatation and curettage
- A D&C should be used for diagnostic purposes, although studies have
shown that less than 50% of the endometrium is sampled during a D&C. It is
not used for treatment because it provides only short-term relief, typically
- This procedure is used best in conjunction with hysteroscopy to evaluate
the endometrial cavity for pathology.
- It is contraindicated in patients with known or suspected pelvic
infection. Risks include uterine perforation, infection, and Asherman
- Transcervical resection of the endometrium
- Transcervical resection of the endometrium (TCRE) has been considered
the criterion standard cure for menorrhagia for many years.
- This procedure requires the use of a resectoscope (ie, hysteroscope with
a heated wire loop), and it requires time and skill but achieves an 84%
satisfaction or success rate.
- The primary risk is uterine perforation.
- Roller-ball endometrial ablation
- Roller-ball endometrial ablation essentially is the same as TCRE, except
that a heated roller ball is used to destroy the endometrium (instead of the
- It has the same requirements, risks, and outcome success as TCRE.
- Satisfaction rates are equal to those of TCRE.
- Endometrial laser ablation
- Endometrial laser ablation requires Nd:YAG (neodymium-doped:yttrium
aluminum garnet) laser equipment and optical fiber delivery system.
- The laser is inserted into the uterus through the hysteroscope while
transmitting energy through the distending media to warm and eventually
coagulate the endometrial tissue.
- Disadvantages include the expense of the equipment (high), the time
required for the procedure (long), and the risk of excessive fluid uptake
from the distending media infusion and irrigating fluid.
- Of patients, 50% have amenorrhea and another 30% have hypomenorrhea,
resulting in an overall success rate of nearly 80%.
- Endometrial ablation or resection preparation
- A trial of medical therapy should have failed in patients considered for
- The endometrium should be properly sampled and evaluated before surgery.
- Patients should be pretreated with danazol or a GnRH analogue for 4-12
weeks before surgery to atrophy the endometrium, reducing surgical
difficulty and time.
- Success rates are similar to laser ablation techniques.
- Uterine balloon therapy
- A balloon catheter filled with isotonic sodium chloride solution is
inserted into the endometrial cavity, inflated, and heated to 87°C for 8
- Uterine balloon therapy cannot be used in irregular uterine cavities
because the balloon will not conform to the cavity.
- Studies report a 90% satisfaction rate and a 25% amenorrhea rate. This
success rate is slightly higher than the other techniques described above,
but the rate is based on short-term studies. Long-term studies are in place
but have not been completed because this technique has not been available
for as long as the others.
- Hysterectomy provides definitive cure for menorrhagia.
- This procedure is more expensive and results in greater morbidity than
- The mortality rate ranges from 0.1-1.1 cases per 1000 procedures.
- The morbidity rate usually is 40%.
- Risks include those usually associated with major surgery.
- Microwave endometrial ablation alternative
- Microwave endometrial ablation (MEA) uses high-frequency microwave
energy to cause rapid but shallow heating of the endometrium.
- Microwaves are selected so that they do not destroy beyond 6 mm in
- MEA requires 3 minutes of time and only local anesthetic. It is proving
to be as effective as TCRE.
- This procedure was developed and has been used in Europe since 1996.
Acute menorrhagia requires prompt medical
intervention. This is bleeding that will compromise an untreated patient (see
Successful treatment of chronic menorrhagia is highly dependent on a thorough
understanding of the exact etiology. For instance, acute bleeding postpartum
does not respond to progesterone therapy, while anovulatory bleeding worsens
with high-dose estrogen (see
Picture 3, and
Drug Category: Nonsteroidal anti-inflammatory drugs
-- Block formation of prostacyclin, an antagonist of thromboxane, which
is a substance that accelerates platelet aggregation and initiates coagulation.
Prostacyclin is produced in increased amounts in menorrhagic endometrium.
Because NSAIDs inhibit blood prostacyclin formation, they might effectively
decrease uterine blood flow.
|Naproxen (Anaprox, Naprelan, Naprosyn)
-- Used for relief of mild to moderate pain. Inhibits inflammatory reactions
and pain by decreasing activity of cyclooxygenase, which is responsible for
||250-500 mg PO bid; give at last 2 d and
first 3 d of cycle, for a total of 5 d
||Documented hypersensitivity; peptic
ulcer disease; recent GI bleeding or perforation; renal insufficiency
||Probenecid may increase toxicity of
NSAIDs; coadministration with ibuprofen might decrease effects of loop
diuretics; coadministration with anticoagulants might prolong PT (watch for
signs of bleeding); might increase serum lithium levels and risk of
methotrexate toxicity (eg, stomatitis, bone marrow suppression,
||B - Usually safe but benefits must
outweigh the risks.
||Category D in third trimester of
pregnancy; acute renal insufficiency, interstitial nephritis, hyperkalemia,
hyponatremia, and renal papillary necrosis might occur; patients with
preexisting renal disease or compromised renal perfusion risk acute renal
failure; leukopenia occurs rarely, is transient, and usually returns to
normal during therapy; persistent leukopenia, granulocytopenia, or
thrombocytopenia warrants further evaluation and might require
||Initial: 100 mg PO once, then 50 mg PO
||Use in persons with allergic reaction
to aspirin/NSAIDs, such as swelling, asthma, hives, urticaria, or any forms
of angioedema; active GI bleed; active ulcer
||Reports suggest that NSAIDs may
diminish the antihypertensive effect of ACE inhibitors, concomitantly with
ACE inhibitors; concomitant administration of low-dose aspirin may result in
increased rate of GI ulceration or other complications compared to use of
NSAIDs alone; clinical studies and postmarketing observations show that
NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some
patients, and this response has been attributed to inhibition of renal
prostaglandin synthesis; NSAIDs have produced an elevation of plasma lithium
levels and a reduction in renal lithium clearance
||C - Safety for use during pregnancy has
not been established.
||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
|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
||1 tab PO qd for 3 wk; followed by a
week of inactive pills, during which a withdrawal bleed generally occurs;
||Documented hypersensitivity; pregnancy;
active or inactive thrombophlebitis or thromboembolic disorders, cerebral
vascular disease, myocardial infarction, coronary artery disease, or a past
history of these disorders; known or suspected breast cancer; known or
suspected genital cancer; history of cholestatic jaundice in pregnancy or
jaundice with prior pill use; past or present liver tumors
||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
||X - Contraindicated in pregnancy
||Complete physical examination,
documentation of recent Pap smear test, and family history recommended; pay
special attention to blood pressure, breasts, abdomen, and pelvic organs;
repeat physical examination annually as long as patient is on hormonal
Oral contraceptives can cause fluid retention (address any condition
aggravated by this factor)
Monitor patients with epilepsy, migraine, asthma, or renal or cardiac
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
Discontinue if jaundice develops
Contact lens wearers with visual changes should be examined by
Patients might develop hypertension secondary to increase in angiotensinogen
production (reevaluate blood pressure approximately 3 mo after initiating
therapy in all patients)
Drug Category: Progestins -- Occasional
anovulatory bleeding that is not profuse or prolonged can be treated with
progestins, antiestrogens given in pharmacologic doses. Inhibit
estrogen-receptor replenishment and activate 17-hydroxysteroid dehydrogenase in
endometrial cells, converting estradiol to the less-active estrone.
acetate/19-nortestosterone derivative -- Provera: Short-acting synthetic
progestin. Works as an antiestrogen by minimizing estrogen effects on target
cells. Endometrium is maintained in an atrophic state. Effective against
hyperplasia and has modest effects on serum lipids (ie, lowering HDL)
Megestrol acetate: May be substituted for Provera. Is active against
hyperplasia without significantly altering serum lipid levels.
Derivatives of 19-nortestosterone: Potent progestins used in oral
contraceptives. Have partial androgenic properties and lower HDL cholesterol
||Provera: 10 mg/d PO for 10 d monthly
Provera for atypical hyperplasia: 10 mg/d PO for 12 d once
Megestrol acetate: 40-80 mg PO for 10 d monthly
Megestrol acetate for atypical hyperplasia: 40-80 mg PO for 12 d once
Derivatives of 19-nortestosterone: Used in oral combination birth control
pills; doses vary from 0.075-0.35 mg/pill depending on derivative
Derivatives of 19-nortestosterone for atypical hyperplasia: 5 mg/d for 12 d
||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)
||Decreases aminoglutethimide efficacy
||X - Contraindicated in pregnancy
||Caution in asthma, depression, renal or
cardiac dysfunction, or thromboembolic disorders; perform complete physical
examination, document recent Papanicolaou smear, and take family history
before therapy; give special attention to blood pressure, breasts, abdomen,
and pelvic organs; repeat physical examination annually; progestins can
cause fluid retention (address any condition aggravated by this factor);
monitor patients with epilepsy, migraine, asthma, renal or cardiac
dysfunction, and history of psychic depression
Drug Category: Gonadotropin-releasing hormone agonists
-- Work by reducing concentration of GnRH receptors in the pituitary via
receptor down-regulation and induction of postreceptor effects, which suppress
gonadotropin release. After an initial gonadotropin release associated with
rising estradiol levels, gonadotropin levels fall to castrate levels, with
resultant hypogonadism. This form of medical castration is very effective in
inducing amenorrhea, thus breaking the ongoing cycle of abnormal bleeding in
many anovulatory patients.
|Leuprolide (Lupron) -- Suppresses
ovarian and testicular steroidogenesis by decreasing LH and FSH levels.
||3.5-7.5 mg IM monthly for 3-6 mo
undiagnosed vaginal bleeding and spinal cord compression
||X - Contraindicated in pregnancy
||Urinary tract obstruction, tumor flare,
and bone pain may occur; monitor patients for weakness and paresthesias; may
cause menopauselike symptoms; may cause bone demineralization and/or
reduction in HDL cholesterol if given for >6 mo
Drug Category: Androgens -- Certain androgenic
preparations have been used historically to treat mild-to-moderate bleeding,
particularly in ovulatory patients with abnormal uterine bleeding. Use might
stimulate erythropoiesis and clotting efficiency. Alters endometrial tissue so
that it becomes inactive and atrophic.
|Danazol (Danocrine) -- Synthetic
steroid analog with strong antigonadotropic activity (inhibits LH and FSH)
and weak androgenic action. Competes with androgen and progesterone at
receptor level, resulting in amenorrhea within 3 mo.
||100-400 mg PO qd for 3 mo
breastfeeding; seizure disorders; markedly impaired hepatic function or
||Prolongation of PT occurs in patients
who are on warfarin; carbamazepine levels might rise with concurrent use;
might interfere with laboratory determinations of DHEA, androstenedione, and
||X - Contraindicated in pregnancy
||Caution in renal, hepatic (may elevate
serum transaminase levels), or cardiac insufficiency and in seizure
disorders; androgen effects may cause hirsutism, acne, lowering of voice, or
decreased breast size
Drug Category: Arginine vasopressin derivatives
-- Indicated in patients with thromboembolic disorders.
|Desmopressin (DDAVP) -- Has been used
to treat abnormal uterine bleeding in patients with coagulation defects.
Transiently elevates factor VIII and von Willebrand factor.
||0.3 mcg/kg in 50 mL NS IV push (15 min)
platelet-type von Willebrand disease
||Coadministration with demeclocycline
and lithium decrease effects; fludrocortisone and chlorpropamide increase
||B - Usually safe but benefits must
outweigh the risks.
||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
|Conjugated equine estrogen (Premarin)
-- Only controls bleeding acutely but does not treat underlying cause.
Appropriate long-term therapy can be administered once the acute episode has
||Acute bleeding: 25 mg IV q4h for a
maximum of 48 h; 2.5 mg PO q6h for a maximum of 48 h
||Documented hypersensitivity; known or
suspected pregnancy; breast cancer, undiagnosed abnormal genital bleeding,
active thrombophlebitis, or thromboembolic disorders; history of
thrombophlebitis, thrombosis, or thromboembolic disorders associated with
previous estrogen use (except when used in treatment of breast or prostatic
||May reduce hypoprothrombinemic effect
of anticoagulants; coadministration of barbiturates, rifampin, and other
agents that induce hepatic microsomal enzymes may reduce estrogen levels;
pharmacologic and toxicologic effects of corticosteroids may occur as a
result of estrogen-induced inactivation of hepatic P450 enzyme; loss of
seizure control has been noted when administered concurrently with
||X - Contraindicated in pregnancy
||Certain patients may develop
undesirable manifestations of excessive estrogenic stimulation (eg, abnormal
or excessive uterine bleeding, mastodynia); may cause some degree of fluid
retention (exercise caution); prolonged unopposed estrogen therapy may
increase risk of endometrial hyperplasia
- 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
- If a specific treatment fails, investigate all possibilities, including
noncompliance, medication dosing, diagnosis, patient age, and comorbid
- With proper workup, diagnosis, treatment, and follow-up care, prognosis is
- Reassure patients that most bleeding stops, but not immediately. Provide
literature on the treatment of choice, including expectations and adverse
- 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
- 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.
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