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MENORRHAGIA
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Menorrhagia

Introduction

Background

Menorrhagia is defined as menstruation at regular cycle intervals but with excessive flow and duration and is one of the most common gynecologic complaints in contemporary gynecology. Clinically, menorrhagia is defined as total blood loss exceeding 80 mL per cycle or menses lasting longer than 7 days.1  The World Health Organization reports that 18 million women aged 30-55 years perceive their menstrual bleeding to be exorbitant.2 Reports show that only 10% of these women experience blood loss severe enough to cause anemia or be clinically defined as menorrhagia.1,3,4 In practice, measuring menstrual blood loss is difficult. Thus, the diagnosis is usually based upon the patient's history.

A normal menstrual cycle is 21-35 days in duration, with bleeding lasting an average of 7 days and flow measuring 25-80 mL.5

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).5

Nearly 30% of all hysterectomies performed in the United States are performed to alleviate heavy menstrual bleeding.6 Historically, definitive surgical correction has been the mainstay of treatment for menorrhagia. Modern gynecology has trended toward conservative therapy both for controlling costs and the desire of many women to preserve their uterus. 

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 is usually 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 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, also known 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 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 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 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 cycle itself.

Frequency

United States

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.4

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 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.7

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.5 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.

Clinical

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:

  • Exclusion of pregnancy
    • This is the most common cause of irregular bleeding in women of reproductive age.
    • 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 bleeding.
    • Quality of bleeding involves the presence of clots and their size.
  • Age
    • 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 age.
  • Sexual activity
    • 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.
    • 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 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 rule out a pituitary tumor.
  • Systemic illnesses (hepatic/renal failure or diabetes)
    • As explained in the Introduction, 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 menorrhagia (hypothyroidism).
  • 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 care.
    • 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 Presence of hirsutism).
    • 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:
    • Visual fields
    • Bleeding gums
    • Thyroid evaluation
    • Galactorrhea
    • 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:
    • 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 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 organ dysfunction.
    • 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.8
    • 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.
    • 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.7
    • 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 manifests.
    • 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 the ovaries.
    • 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 endometrial vasculature.
  • 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 2.8 compared to nonusers. 9
    • 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 irritation effects.
    • 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 reversible.

Introduction

Background

Menorrhagia is defined as menstruation at regular cycle intervals but with excessive flow and duration and is one of the most common gynecologic complaints in contemporary gynecology. Clinically, menorrhagia is defined as total blood loss exceeding 80 mL per cycle or menses lasting longer than 7 days.1  The World Health Organization reports that 18 million women aged 30-55 years perceive their menstrual bleeding to be exorbitant.2 Reports show that only 10% of these women experience blood loss severe enough to cause anemia or be clinically defined as menorrhagia.1,3,4 In practice, measuring menstrual blood loss is difficult. Thus, the diagnosis is usually based upon the patient's history.

A normal menstrual cycle is 21-35 days in duration, with bleeding lasting an average of 7 days and flow measuring 25-80 mL.5

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).5

Nearly 30% of all hysterectomies performed in the United States are performed to alleviate heavy menstrual bleeding.6 Historically, definitive surgical correction has been the mainstay of treatment for menorrhagia. Modern gynecology has trended toward conservative therapy both for controlling costs and the desire of many women to preserve their uterus. 

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 is usually 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 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, also known 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 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 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 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 cycle itself.

Frequency

United States

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.4

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 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.7

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.5 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.

Clinical

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:

  • Exclusion of pregnancy
    • This is the most common cause of irregular bleeding in women of reproductive age.
    • 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 bleeding.
    • Quality of bleeding involves the presence of clots and their size.
  • Age
    • 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 age.
  • Sexual activity
    • 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.
    • 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 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 rule out a pituitary tumor.
  • Systemic illnesses (hepatic/renal failure or diabetes)
    • As explained in the Introduction, 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 menorrhagia (hypothyroidism).
  • 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 care.
    • 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 Presence of hirsutism).
    • 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:
    • Visual fields
    • Bleeding gums
    • Thyroid evaluation
    • Galactorrhea
    • 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:
    • 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 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 organ dysfunction.
    • 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.8
    • 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.
    • 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.7
    • 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 manifests.
    • 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 the ovaries.
    • 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 endometrial vasculature.
  • 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 2.8 compared to nonusers. 9
    • 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 irritation effects.
    • 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 reversible.
 
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