Abnormal (Dysfunctional) Uterine Bleeding in Pediatrics 

Updated: Jul 08, 2019
Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Andrea L Zuckerman, MD 

Overview

Background

Abnormal uterine bleeding (AUB), an updated term for dysfunctional uterine bleeding (DUB), is classically defined as excessively heavy, prolonged, or frequent bleeding of uterine origin that is not caused by pregnancy or recognizable pelvic or systemic disease.[1, 2] It usually results from disordered functioning of the hypothalamic-pituitary-ovarian (HPO) axis and is often associated with anovulatory cycles. This classic definition highlights that anovulatory uterine bleeding (as part of the etiologic spectrum of AUB) is a diagnosis of exclusion.

AUB occurs most often in the beginning and end of the reproductive years: 20% of cases occur in adolescent females, and as many as 50% of women aged 40-50 years experience AUB (see Abnormal [Dysfunctional] Uterine Bleeding and Abnormal [Dysfunctional] Uterine Bleeding in Emergency Medicine). Of these cases of AUB, about 90% are due to menstrual periods when ovulation does not occur. Adolescent females have several anovulatory cycles per year; hence, anovulatory uterine bleeding is the primary cause of AUB in the female adolescent population.[3, 4, 5]

In 2011, a revised terminology system for AUB in nongravid reproductive-age women was introduced by the International Federation of Gynecology and Obstetrics (FIGO). The FIGO classifies AUB according to the PALM-COEIN system, in which the acronym PALM represents structural causes (polyps, adenomyosis, leiomyomas, malignancy and hyperplasia) and the acronym COEIN represents nonstructural causes (coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, and not yet classified).[6]

In this system, AUB is further qualified by adding a suffix reflecting the cause of the abnormal bleeding. For example, AUB from ovulatory dysfunction is designated as AUB-O. In addition, AUB can be categorized as either AUB/heavy menstrual bleeding (HMB; ie, what has been commonly referred to as menorrhagia) or AUB/intermenstrual bleeding (IMB; ie, metrorrhagia).[7, 8]

The FIGO system was reviewed, clarified, and, where necessary, revised in late 2018; however, the fundamental structure of the system remains.[9]

It has been suggested that the term DUB should be retired and that AUB, appropriately qualified as described above, should be used instead. However, a number of medical authors have continued to use the term DUB.

Pathophysiology

The normal menstrual cycle, characterized by sequential growth, maturation, and eventual sloughing of the endometrial mucosa, is produced by the cyclic release of estrogen and progesterone from the ovary. This process (orchestrated by the HPO axis) occurs with amazing regularity throughout most of a woman's reproductive lifetime.

An understanding of the normal cyclic fluctuations of the two gonadotropins (ie, luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) and the primary female reproductive hormones (ie, estrogen and progesterone) helps clarify the hormonal abnormalities associated with anovulation.[10]

The first 14 days of a typical 28-day menstrual cycle (day 1 being defined as the first day of menstrual flow) are characterized by rising FSH levels, which stimulate ovarian follicle development and the subsequent production of estrogens (primarily estradiol). Serum progesterone levels are extremely low during this stage. LH levels climb more slowly but abruptly peak on day 12 or 13 in positive response to rising estrogen levels. (See the image below.)

Menstrual cycle. Menstrual cycle.

During that first 14-day period, the endometrium, under the influence of estrogen, undergoes proliferation. The LH surge stimulates ovulation (on or about day 14) and conversion of the ovulatory follicle to a corpus luteum, which is responsible for estrogen and progesterone production. Under the influence of this progesterone, the endometrium is converted to a secretory state in preparation for implantation, if fertilization of the ovum should occur. Progesterone is produced only if ovulation occurs.

As LH levels drop (on the assumption that fertilization and production of human chorionic gonadotropin [HCG] by the developing conceptus did not occur), the corpus luteum regresses, estrogen and progesterone levels plummet, and the endometrium deteriorates and is sloughed.

The average menstrual cycle is 28-29 days (range, 21-35 days). Initially, some teenagers can have cycles as long as 45 days. Over time, the menstrual cycle becomes fairly consistent from month to month in any given woman. Normal menstrual flow lasts for 7 days or less and produces an average total blood loss of 25-69 mL. Women who experience (1) bleeding either more frequently than every 21 days or less frequently than every 45 days, (2) a menstrual flow longer than 7 days, and (3) blood loss exceeding 80 mL are considered to have abnormal menstrual cycles.

With anovulation, estrogen levels rise as usual in the early phase of the cycle. In the absence of ovulation, a corpus luteum never forms, and progesterone is not produced. The endometrium moves into a hyperproliferative state, ultimately outgrowing its estrogen supply. This leads to irregular sloughing of the endometrium and excessive bleeding from spiral arteries that have not undergone physiologic senescence.

Etiology

Anovulation can result from dysfunction from any pathway of the HPO axis. In the pediatric age group, the vast majority of cases can be attributed to an immature HPO axis with acyclic hormonal stimulation of the endometrium. Although anovulatory bleeding can occur in any female of reproductive age, the following female patients may be at greater risk for AUB:

  • Adolescents during the first 3-5 years following menarche
  • Patients with eating disorders (eg, anorexia nervosa or bulimia)
  • Adolescents with a body mass index (BMI) higher than 30 (>95% for age in the obesity range)
  • Adolescents experiencing significant psychological stress
  • Athletes with significant exercise stress [11]

Epidemiology

United States and international statistics

The exact incidence of AUB is unknown. In the United States, the epidemiologic basis consists of case series reports from tertiary institutions citing female patients who most likely do not reflect the general population. Nearly 50% of all women have irregular periods in the first year after menarche; and of these, more than 50% of the cycles are anovulatory. Irregular periods can persist for as long as 5 years after menarche in 20% of women.[12]

International rates should reflect those seen in the US.

Age- and race-related demographics

Worldwide, the age of menarche varies and is influenced by female biology, genetic factors, and environmental factors. Geographic region, race, and ethnicity also play significant roles. The median age of menarche worldwide has been estimated at 14 years, with the premise that menarche occurs later in Asian populations than in female populations from the Western hemisphere.[13]

In the United States, the average age of menarche is 12.3 years.[14] In Canada and the United Kingdom, the average ages of menarche are 12.7 years and 12.9 years, respectively.[15, 16] Irregular and anovulatory cycles may persist for 1-5 years after menarche; however, regulation of menstrual periods typically occurs within 2 years. 

Race does not contribute significantly to the incidence of AUB.

Prognosis

Overall, adolescents with AUB have an excellent prognosis, with most outgrowing the problem within 3-5 years of menarche. Compliant patients for whom oral contraceptive pills are prescribed rarely have recurrent episodes of AUB. For patients with AUB related to systemic disease, the prognosis depends upon the underlying disease process.

Patient Education

The patient and her caregivers should be educated about the normal menstrual cycle and the generally benign nature of AUB. It is a good idea for her to record a calendar history of her menstrual cycles, noting the beginning and end dates of bleeding. The patient should be advised to return if she experiences (1) bleeding more frequently than every 21 days or less frequently than every 45 days, (2) a menstrual flow longer than 7 days, and (3) overall blood loss exceeding 80 mL (~5 tbsp), or if she cannot comply with the prescribed outpatient treatment.

For patient education resources, see the Women's Health Center, as well as Vaginal Bleeding, Amenorrhea, Anemia, and Painful Ovulation (Mittelschmerz).

 

Presentation

History

Patients with abnormal (dysfunctional) uterine bleeding (AUB) present with unexpected and often heavy vaginal bleeding. Irregular menstrual periods are common during the first few years after menarche. Because AUB is largely a diagnosis of exclusion, exploring the more common and serious possible alternatives (see Differential Diagnosis) is prudent.

Bleeding associated with complications of pregnancy

Any patient of reproductive age should be considered pregnant until proved otherwise (with a negative pregnancy test result). Frequently, adolescents do not report sexual behavior, and it is wise to assume that their histories may be less than accurate. The patient should be asked about risk factors for pregnancy and about symptoms of pregnancy, including the following:

  • Symptoms of breast tenderness, nausea, urinary frequency, and fatigue
  • Vaginal bleeding associated with severe pain or cramping
  • Vaginal bleeding associated with the passage of tissue

Coagulation defects

In adolescents with acute menorrhagia, there is the potential risk of a coagulation disorder; von Willebrand disease (vWD),[17]  idiopathic thrombocytopenic purpura (ITP), and leukemia are the more common etiologies.[18]  The incidence of coagulopathy in this setting could be as high as 20-30%. Questioning should focus on the following:

  • Family history of bleeding disorders - Information about female family members and their menstrual and childbirth history should be sought; concern arises with a history of recurrent, heavy prolonged periods or of prolonged bleeding after childbirth
  • Poor clotting response time as seen with excessive bleeding associated with minor injuries (eg, small cuts, dental procedures), phlebotomy, or menses
  • Frequent or prolonged nose bleeds
  • Easy bruising, purpura, or petechiae

Bleeding from anatomic cause

Anatomic causes of abnormal bleeding can occur anywhere along the female genital tract. Important questions to consider in quickly surveying this organ system include the following:

  • Has there been recent traumatic intercourse?
  • Is there a history of sexually transmitted infections, abnormal discharge, or pelvic pain?
  • Has there been a change in abdominal girth that raises concerns about a possible intra-abdominal or pelvic mass?

Medication-related abnormal uterine bleeding

A complete history of recent medication use should be obtained. Specific medications to look for include the following:

  • Hormonal contraceptive agents
  • Anticoagulants
  • Aspirin
  • Nonsteroidal anti-inflammatory drugs (NSAIDs)

Polycystic ovarian syndrome

Polycystic ovarian syndrome (PCOS), an endocrine disorder of hyperandrogenism, is a common cause of anovulation and oligomenorrhea and should always be considered in the differential diagnosis of AUB.[19] Physical manifestations of this syndrome (usually due to elevated androgen levels) can be prevented if appropriate treatment is begun at an early stage. Symptoms of PCOS include the following:

  • Irregular periods
  • Male-pattern hair growth, acne, or both
  • Excessive body weight
  • Infertility

Systemic disease

Systemic disease states often cause abnormal bleeding through their impact on the hypothalamic-pituitary-ovarian (HPO) axis. The patient should be asked about typical symptoms of endocrine disorders, such as diabetes or thyroid disease (hypo- or hyperthyroidism). Additional questions should be aimed at investigating the possibility that an eating disorder (eg, anorexia nervosa or bulimia) may help explain menstrual cycle irregularity or secondary amenorrhea as being due to weight fluctuations or low body mass index (BMI).

Physical Examination

The physical examination should focus on uncovering signs of the more common or serious diagnoses cited in the Differential Diagnosis list.

General physical examination

Initial steps should include the following:

  • Measurement of height and weight
  • Calculation of BMI with age percentile
  • Inquiry into the patient's pregnancy history and menstrual history, including the date of the last menstrual period, the characteristics of prior menses (if the patient has had vaginal bleeding in the past), the length of the cycle, the number of days of bleeding, the number of sanitary pads changed per day, the use of tampons, the contraceptive method used (if any), and the age at menarche in female family members

In addition, special attention should be paid to the following clinical signs:

  • Excessive weight gain or weight loss, addressing rapid fluctuations in weight without a clear etiology
  • Physical signs of a bleeding dyscrasia (eg, petechiae or purpura, excessive gum bleeding after brushing teeth)
  • Physical signs of anemia (eg, pale conjunctiva, pale coloring to the skin or nail beds, tachycardia)
  • Signs of androgen excess (eg, acne or hirsutism, thinning hair, male-pattern baldness)
  • Thyroid enlargement (eg, concern for hypo- or hyperthyroidism)
  • Tanner breast stage and presence or history of nipple discharge, such as galactorrhea (suggestive of hyperprolactinemia)
  • A palpable abdominal mass, liver enlargement, or splenic enlargement

Pelvic examination

A pelvic examination should be performed, with careful consideration of the patient's age, sexual history, and use of tampons. Every effort should be made to ensure that this portion of the examination is as comfortable and atraumatic as possible. Considerable psychological harm can result from an examination that is performed in a rushed and an insensitive manner. The following considerations should be taken into account:

  • The best setting for the pelvic examination is often in the office of the primary care clinician who has established rapport, trust, and a level of comfort with the patient
  • Potential concerns of the patient are fear of discovering abnormalities, pain, embarrassment, and uneasiness with the examiner.
  • A history of sexual abuse may affect the patient's comfort level
  • Important aspects of preparing the patient include explaining the examination, instructing the patient to stop the examination if needed, explaining relaxation techniques, and asking the patient to empty her bladder prior to the examination
  • Chaperones are recommended with the patient's permission, even if the clinician and the patient are of the same sex
  • In regard to the speculum examination, the 7/8-in.-wide Pederson speculum is typically used in sexually active young women, and the 1/2-in.-wide Huffman speculum is used in virginal young women
  • The bimanual examination (insertion of one or two fingers into the vagina with a water-based lubricant on the gloved hand) can assess cervical consistency and motion tenderness, uterus size and tenderness, and adnexal pain or masses [20]

Salient aspects of the pelvic examination are the following:

  • Tanner stage (or sexual maturity rating [SMR]), with the distribution of pubic hair noted
  • Discharge and excoriations suggesting chronic vaginal candidiasis
  • Old or acute vulvar and vaginal lacerations and the condition of the hymenal ring
  • Retained foreign bodies (eg, toilet tissue, tampons, or tampon fragments); these occasionally cause a chronic blood-tinged vaginal discharge
  • Microscopic examination of the vaginal discharge, cervical cultures or amplified DNA probe on urine samples for  Neisseria gonorrhoeae and  Chlamydia trachomatis infection, and Papanicolaou test (Pap smear), if indicated by the sexual history
  • Evidence of cervical lesions, cervical motion tenderness, or an open cervical os
  • Uterine size and any pelvic masses or tenderness

Complications

The main complication of AUB is anemia. For female adolescents, anemia is indicated when the hemoglobin level is lower than 12 g/dL (normal range, 12.1-15.1 g/dL). Acute blood loss can occasionally lead to a profound anemia. Blood product transfusion (with the attendant risks and complications) is occasionally required. Blood loss in the healthy female adolescent is rarely fatal. 

Chronic or recurrent AUB can cause in an iron-deficient state.

 

DDx

Diagnostic Considerations

In addition to the conditions cited in the differential diagnosis list, other problems to be considered include the following:

  • Pregnancy complications (eg, threatened abortion, incomplete abortion, missed abortion, ectopic pregnancy, trophoblastic neoplasia)
  • Thyroid disease
  • Diabetes
  • Cervical polyps
  • Uterine polyps
  • Exogenous hormones (eg, oral contraceptive pills)
  • Hyperprolactinemia (as due to an intracranial prolactinoma or medication use)
  • Medication misuse or abuse (eg, prolonged use of estrogen or progesterone)
  • Vaginal trauma or foreign body
  • Ovarian cysts
  • Pelvic inflammatory disease
  • Coagulation pathway disorders
  • Leukemia
  • Oncologic treatments, such as chemotherapy [21]

Differential Diagnoses

 

Workup

Laboratory Studies

Focus routine laboratory studies to discover understood complications of AUB and to also rule out serious medical conditions that can mimic AUB, as follows:

  • Complete blood count (CBC), including platelet count and white count differential - Useful for revealing anemia, thrombocytopenia, oncologic concerns, and infections
  • Prothrombin time (PT), activated partial thromboplastin time (aPTT), and bleeding time - Useful for detecting possible blood dyscrasias and clotting disorders
  • Pregnancy test - Mandatory, even in those patients who deny sexual activity
  • Cervical cultures or urine DNA probe - Ordered to test for sexually transmitted infections (STIs) such as chlamydia and gonorrhea, especially if sexual activity is suspected; the overall prevalence of chlamydial infection, the most commonly reported STI in the United States, [22]  has been underestimated

Consider the following laboratory studies for patients with AUB who are unresponsive to therapy or who have salient findings on history, physical examination, or initial laboratory studies that suggest a systemic disorder:

  • Thyroid-stimulating hormone (TSH) test and free thyroxine (fT4) concentration, to screen for thyroid disease
  • Fasting glucose, to rule out occult diabetes
  • Prolactin, to rule out hyperprolactinemia [23]
  • Dehydroepiandrosterone sulfate (DHEAS), free testosterone, and 17-hydroxyprogesterone (17 OHP), to evaluate for polycystic ovarian syndrome (PCOS)
  • vWF:Ag (von Willebrand factor [vWF] antigen), vWF:RCo (vWF ristocetin cofactor) and factor VIII, if von Willebrand disease (vWD) is suspected [24]

Imaging Studies

Pelvic imaging studies should be reserved for women who do not respond to routine management. Ultrasonography (US), either transabdominal or transvaginal (with the latter to be considered only in patients with a history of sexual intercourse or tampon use), is the method of choice for evaluation of the female pelvis.[25]  It is useful for detecting structural abnormalities of the uterus, PCOS, and ovarian neoplasms. For proper performance and interpretation of this imaging study, an experienced ultrasound technician or practitioner must be available. 

A retrospective study by Pecchioli et al questioned the value of routine pelvic US in adolescents with AUB.[26] This study involved a retrospective chart review of 230 adolescent patients younger than 18 years who presented with AUB to the gynecology clinic at the Hospital for Sick Children in Toronto, Canada. The extensive chart review cited the clinical findings on pelvic US and on any additional imaging and described the treatment approaches for these patients. Of the 230 patients, 67.8% (156/230) underwent pelvic US as part of their AUB workup.

In both those patients who were examined with US and those who were not, the most common diagnosis for AUB was an immature hypothalamic-pituitary-ovarian (HPO) axis.[26] Of the patients who underwent US, 72.4% (113/156) had normal findings, 17.9% (28/156) had incidental findings, and 6.4% (10/156) had PCOS morphology. Structural causes of AUB were found in only two (1.3%) of the adolescents imaged. In none of the patients who underwent US did the findings from imaging lead to a change in the AUB treatment plan. The results of this study strongly suggest that pelvic US should not be a required part of the initial investigation of AUB in adolescents.

Other imaging modalities that may be considered in the workup of AUB are magnetic resonance imaging (MRI) and computed tomography (CT). MRI has adequate resolution, but it is only rarely superior to US and is quite expensive. CT can be useful in the workup of adolescent females with a confirmed neoplasm. Before CT is performed, it is important to weigh the benefit against the risk so as to avoid unnecessary exposure of the pelvic region to radiation.

Procedures

Referral to a coordinated Women's Health Care/Gynecology Care Team is recommended for these treatment approaches:

  • Uterine curettage is rarely indicated in the adolescent with AUB; it is usually reserved for women with significant and prolonged hemorrhage that is unresponsive to standard medical therapy
  • Diagnostic hysteroscopy can be used to look for structural abnormalities as a cause of persistent AUB
  • Sonohysterography is a less invasive but less accurate method of evaluating the uterine cavity; it consists of injecting fluid into the uterus under US visualization [25]

Histologic Findings

Endometrial biopsy is rarely required and should be reserved for adolescents with uterine bleeding that is unresponsive to standard medical intervention. Endometrial curettage often demonstrates a disordered proliferative pattern without secretory activity (absence of progesterone effect). Findings from endometrial biopsies in patients who currently are receiving hormonal therapy can demonstrate hormonal effects and hence may interfere with biopsy interpretation.

 

Treatment

Medical Care

Patients with abnormal (dysfunctional) uterine bleeding (AUB) may present with chronic light flow in the form of irregular, prolonged, or intermenstrual bleeding. In most cases, this does not pose a significant health concern. Alternatively, patients with AUB can present with severe acute hemorrhage that warrants immediate medical attention. Patients require hospital admission for acute, poorly controlled bleeding that results in severe blood loss and, hence, symptomatic anemia; transfusion of packed red blood cells (PRBCs) should be considered for these patients.

Management must be tailored to the condition of each patient. For most patients, treatment consists of oral contraceptive pills (OCPs) and iron supplementation. Standard practice is that only patients with acute severe hemorrhage require more intensive treatment.

AUB has been classified into three categories of severity on the basis of the patient's hemoglobin (Hb) levels, as follows:

  • Mild - Hb >11 g/dL
  • Moderate - Hb 9-11 g/dL
  • Severe - Hb < 9 g/dL

Medical therapy should be addressed accordingly.[27, 28, 29]

Light-flow (mild or moderate) abnormal uterine bleeding

After obtaining a complete history, performing a physical examination, and ordering appropriate laboratory studies, the clinician should reassure the patient and discuss the usual irregular nature of an adolescent's early menstrual cycles.

Menstrual regulation in the form of OCPs or cyclic progestins should be offered if the Hb level is below 11 mg/dL or, if the irregular bleeding has a significant impact on the patient's quality of life.[30]

Oral iron supplementation should be initiated if anemia is detected or if bleeding is persistent. Iron supplements can be prescribed to any patient after evaluation, according to the physician's judgment.

Further workup is indicated only when significant bleeding is occurring or when menstrual regulation does not correct the problem.

Acute (severe) abnormal uterine bleeding

Blood loss often is significant and may be life-threatening. Actively bleeding women who have unstable vital signs require emergency department (ED) management for fluid stabilization with intravenous (IV) crystalloid fluid replacement.

The underlying problem of an anovulatory cycle is bleeding from a hyperproliferative endometrium that has outgrown its estrogen supply; therefore, the primary therapeutic goal is reestablishment of estrogen supply in the form of high-dose oral or parenteral estrogen. Secondary treatment is aimed at stabilizing the endometrium with exogenous progestin therapy.

The physiologic response to estrogen is similar, regardless of the route of administration. Therefore, parenteral therapy is reserved for unstable patients or for patients who are unable to tolerate oral medications. Rarely, progestin medications alone (eg, medroxyprogesterone) are prescribed for those patients who cannot tolerate estrogen therapy.

Although infrequently required, blood product replacement should be considered if the patient has persistent heavy bleeding with a low hematocrit or if the patient continues to be symptomatic after bleeding has been controlled.

Once the patient has been stabilized and is able to tolerate oral therapy, iron supplementation should initiated as indicated by laboratory findings, and continuity should be established with follow-up care.

Surgical Care

Patients with AUB who do not respond to medical therapy may require endometrial curettage, hysteroscopic evaluation, or both. In life-threatening circumstances where medical therapy is ineffective or contraindicated, endometrial ablation or hysterectomy may be the only reasonable alternative. In this situation, a gynecology healthcare team is required. The benefits and risks of surgical intervention and its long-term impact in relation to future childbearing must all be clearly addressed.

Complications

Complications are related to acute or chronic blood loss and the resulting anemia.

Patients who receive blood products should be onserved for transfusion-related complications, such as acute hemolytic reactions, bacterial sepsis, and viral infections.

Diet and Activity

Patients with anemia should be instructed about how to maintain a healthy diet rich in iron and folic acid.

Typically, limitation of activity is not indicated.

Prevention

Patients with a history of AUB who are sexually active and desire birth control should be placed on OCPs or cyclic progestins for menstrual cycle control. A backup birth control method (eg, condom use) is recommended.

Consultations

Consultation with a gynecologist (ideally one with expertise in adolescent medicine) is appropriate for any patient who has significant bleeding and anemia or in whom attempts at medical therapy do not resolve the problem. Abnormal laboratory findings should prompt referral to or consultation with an appropriate specialist. 

 

Long-Term Monitoring

Long-term (≥6 months) suppression of the hypothalamic-pituitary-ovarian (HPO) axis should be considered for patients with bleeding that results in significant anemia. Mild anemia responds rapidly to once-daily oral iron supplementation. Iron supplements taken orally two or three times daily can cause gastointestinal complaints (eg, nausea and constipation) and subsequent noncompliance. The Office of Dietary Supplements (ODS) of the National Institutes of Health (NIH) is an excellent resource for iron dietary enhancement and iron supplement guidelines.

 

Medication

Medication Summary

Pharmacotherapy is aimed at preventing medical complications of abnormal uterine bleeding (AUB) and includes the following:

  • Hormone therapy (eg, estrogen, combination estrogen-progestin) [31]
  • Antiprostaglandins
  • Antifibrinolytics [32]
  • Iron supplements

Therapies such as gonadotropin-releasing hormone (GnRH) agonists and selective estrogen receptor modulators (SERMs) have a limited place in the treatment of unresponsive bleeding; however, further medical investigation is warranted to support their routine use.[33]

Estrogens

Class Summary

Anovulatory bleeding occurs as the hyperproliferative endometrium, lacking a progesterone effect, outgrows its estrogen supply, leading to irregular sloughing. Rapid return of adequate estrogen levels is the quickest way to decrease bleeding. Estrogens alone are primarily used for acute dysfunctional uterine bleeding when rapid control of the bleeding is required.

Estrogen, conjugated (Premarin)

Administered PO, IM, or IV. Studies have demonstrated that similar blood levels are achieved at the same rate by any route. Parenteral therapy is reserved for patients who are unable to tolerate PO intake. Equivalent doses of other forms of estrogen (eg, estradiol, esterified estrogens, ethinyl estradiol, estropipate) are likely to be equally effective although clinical studies are lacking. Only the conjugated estrogens are approved by the FDA for this indication.

Progestins

Class Summary

Individually, progestins are used to stabilize an estrogen-primed endometrium and are administered in a cyclic fashion. Because the pathophysiology of dysfunctional uterine bleeding is based on a relative estrogen deficiency, progestins alone should not be the first-line treatment for acute bleeding. Progestins should be administered along with estrogens, and this combination is discussed under oral contraceptive pills.

Continuous use of high-dose progestins, orally or in a depo-form, can induce endometrial atrophy and amenorrhea. This approach is useful for preventing future blood loss while correcting a significant anemia or when combination contraceptive pills do not achieve adequate control of bleeding.

Medroxyprogesterone (Amen, Provera, Depo-Provera)

May be administered PO, in a cyclic or continuous fashion, or as a parenteral depot formulation. When managing acute and heavy uterine bleeding, should be administered concurrently with an estrogen preparation. Progestins alone do not address the underlying pathophysiology of a hyperproliferative endometrium that has outgrown its estrogen supply.

Norethindrone (Aygestin, Micronor)

Administered PO in a cyclic or continuous fashion. When managing acute and heavy uterine bleeding, should be administered concurrently with estrogen. Progestins alone do not address the underlying pathophysiology of a hyperproliferative endometrium that has outgrown its estrogen supply.

Oral contraceptive agents

Class Summary

Oral contraceptive agents or oral contraceptive pills (OCPs) provide a convenient method of rapidly delivering high-dose combinations of estrogen and progestin. The monophasic preparations offer the best opportunity for creating a stable endocrine environment. Most of the modern products contain 20, 30, or 35 mcg of ethinyl estradiol in combination with norethindrone or one of the second- or third-generation progestins. For all practical purposes, they are essentially equivalent.

Ethinyl estradiol and desogestrel (Desogen)

This is one example of an OCP preparation. When treating light-flow irregular bleeding, OCPs are administered in the usual contraceptive fashion (ie, 1 tab PO qd for 21 d of a typical 28-d cycle). Treatment of acute heavy uterine bleeding, multiple tab are administered PO each day and then tapered once the heavy flow has ceased. If significant anemia is present, the placebo phase (ie, days 22-28) may be omitted for several mo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Class Summary

Studies have demonstrated a prostaglandin imbalance in women with menorrhagia and a reduction in menstrual flow with administration of NSAIDs. Several drugs in this category should have similar efficacy.

Ibuprofen (Motrin, Advil, Ibuprin)

A classic example of this category of medications. For best efficacy, start the NSAID prior to the onset of flow. Have analgesic, anti-inflammatory, and antipyretic activities. Mechanism of action is nonselective inhibition of cyclooxygenases 1 and 2, resulting in reduced synthesis of prostaglandins and thromboxanes.

Antifibrinolytic agents

Class Summary

These agents inhibit fibrinolysis via inhibition of plasminogen activator substances, to a lesser degree, through antiplasmin activity.

Aminocaproic acid (Amicar)

Used for acute heavy uterine bleeding in patients with increased fibrinolytic activity. Discontinued once bleeding has stopped.

Iron salts

Class Summary

These are used to replenish iron stores lost during acute or chronic hemorrhage. The body stores iron in compounds called ferritin and hemosiderin for future use in the production of hemoglobin. Iron absorption is a variable of the existing body iron stores, the form and quantity in foods, and the combination of foods in the diet. The ferrous form of inorganic iron is more readily absorbed.

Ferrous sulfate (Feosol, Slow FE, Feostat)

This is the most common medication for iron therapy though several other formulations are available.