Menorrhagia

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 ^[13] or menses lasting longer than 7 days. ^[14] The World Health Organization reports that 18 million women aged 30-55 years perceive their menstrual bleeding to be exorbitant. ^[15] Reports show that only 10% of these women experience blood loss severe enough to cause anemia or be clinically defined as menorrhagia. ^{[14, 16, 17]} 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. ^[18]

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). ^[18]

Nearly 30% of all hysterectomies performed in the United States are performed to alleviate heavy menstrual bleeding. ^[11] 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.

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. ^[19]

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.

Etiologies of menorrhagia are divided into 4 categories, organic, endocrinologic, anatomic, and iatrogenic.

Organic causes

Organic causes of menorrhagia include infection, bleeding disorders, and organ dysfunction. Consider the following:

• 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. ^[20]  See more on bleeding disorders below.

• 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

Endocrine causes of menorrhagia include thyroid and adrenal gland dysfunction, pituitary tumors, anovulatory cycles, PCOS, obesity, and vasculature imbalance. Note the following:

• 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. ^[21]

• 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 causes

Anatomic etiologies for menorrhagia include uterine fibroids, endometrial polyps, endometrial hyperplasia, and pregnancy. Note the following:

• 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. ^[22]

Iatrogenic causes

Iatrogenic causes of menorrhagia include IUDs, steroid hormones, chemotherapy agents, and medications (eg, anticoagulants). Consider the following:

• 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.

Bleeding disorders

An international expert panel including obstetrician/gynecologists and hematologists has issued guidelines to assist physicians in better recognizing bleeding disorders, such as von Willebrand disease, as a cause of menorrhagia and postpartum hemorrhage and to provide disease-specific therapy for the bleeding disorder. ^[23]  Historically, a lack of awareness of underlying bleeding disorders has led to underdiagnosis in women with abnormal reproductive tract bleeding.

The panel provided expert consensus recommendations on how to identify, confirm, and manage a bleeding disorder. An underlying bleeding disorder should be considered when a patient has any of the following:

• Menorrhagia since menarche

• Family history of bleeding disorders

• Personal history of 1 or more of the following: (1) Notable bruising without known injury; (2) bleeding of oral cavity or gastrointestinal tract without obvious lesion; and/or (3) epistaxis greater than 10 minutes duration (possibly necessitating packing or cautery)

If a bleeding disorder is suspected, consultation with a hematologist is suggested.

United States statistics

Although 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. ^[17]

Age-related demographics

Any woman of reproductive age who is menstruating may develop menorrhagia. Most patients with menorrhagia are older than 30 years. ^[18]  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. ^[24]

With proper workup, diagnosis, treatment, and follow-up care, prognosis is excellent.

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. ^[21]

Complications

Complications of menorrhagia include the following:

• Treatment of menorrhagia 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.

Reassure patients that most bleeding stops, but not immediately. Provide literature on the treatment of choice, including expectations and adverse effects.

Many patients appreciate reassurance that they do not have cancer and are not alone in their plight.

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