Accepted Manuscript

Heavy Menstrual Bleeding in Adolescents

Fareeda Haamid, DO, Amy E. Sass, MD, MPH, Jennifer E. Dietrich, MD, MSc

PII: S1083-3188(16)30253-4
DOI: 10.1016/j.jpag.2017.01.002
Reference: PEDADO 2084

To appear in: Journal of Pediatric and Adolescent Gynecology

Received Date: 26 October 2016

Revised Date: 14 December 2016
Accepted Date: 4 January 2017

Please cite this article as: Haamid F, Sass AE, Dietrich JE, Heavy Menstrual Bleeding in Adolescents,
Journal of Pediatric and Adolescent Gynecology (2017), doi: 10.1016/j.jpag.2017.01.002.

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Manuscript Details:

Manuscript number: JPAG_2016_25

Title: Heavy Menstrual Bleeding in Adolescents

Article type: Fast track communications

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Keywords: heavy menstrual bleeding; abnormal uterine bleeding; acute management; chronic bleeding;
bleeding disorder

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Corresponding Author: Jennifer Dietrich, Baylor College of Medicine, Pavilion for Women TCH, 6651
Main St, Ste F1050, United States. Tel: 8328267464, Email: jedietri@bcm.edu

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Order of Authors: Fareeda Haamid, Amy Sass, Jennifer Dietrich

Affiliations:

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1
Department of Pediatrics, The Ohio State University College of Medicine, Nationwide Children's
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Hospital, Columbus, Ohio, USA.
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University of Colorado, Boulder, CO 80309, USA
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3
Baylor College of Medicine, Pavilion for Women TCH, 6651 Main St, Ste F1050, USA
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Heavy Menstrual Bleeding in Adolescents

This Clinical Recommendation has been prepared under the direction of the NASPAG Education

Committee, and Reviewed by the NASPAG Board and JPAG Editors

Committee Opinion NASPAG 2016

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Fareeda Haamid DO, Amy E. Sass MD, MPH, Jennifer E. Dietrich MD, MSc

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*Authors declare no conflict of interest.

The authors would like to thank Dr. Andra James MD, MPH for conducting the expert review of this

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document.

The information contained in this Clinical Recommendation reflects the currently available best evidence

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for practice at the time of publication. The information is designed to aid practitioners in making
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decisions about appropriate patient care, but should not be construed as dictating an exclusive course of

treatment or procedure. Variations in practice may be warranted based on the needs of the individual
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patient and/or based on resources and limitations unique to the institution or type of practice. This

information has been reviewed and approved by NASPAG.

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Abstract
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Heavy menstrual bleeding (HMB) is a very common gynecological condition in adolescent females and a

frequent presenting complaint of females with bleeding disorders. Recommendations have been
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established to screen for bleeding disorders in this age group where appropriate. The purpose of this

document is to impart clinical recommendations regarding HMB in adolescents. Specifically, the

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document provides a description of the epidemiology, clinical presentation, diagnostic approach, and
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treatment of HMB in adolescents.

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Level of Evidence

II-1, II-2, II-3

Grading of Recommendations

Levels B and C

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Introduction

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Clinical recommendations for the care of adolescents with heavy menstrual bleeding (HMB) is often a

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challenging clinical problem. An overview of the clinical presentation of HMB is provided as well as

diagnostic modalities and treatment strategies for this disorder. Finally, levels of evidence will be

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assigned to the literature reviewed. AN
Key Words: abnormal uterine bleeding, adolescents, dysfunctional uterine bleeding, heavy menstrual

bleeding, menorrhagia, menstrual disorders, bleeding disorders

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Background

Abnormal uterine bleeding (AUB) is the current preferred terminology to describe any aberration of
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menstrual volume, regulation, frequency, and duration according to the classification recommended
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by the International Federation of Gynecology and Obstetrics (FIGO).¹ This all-encompassing term

replaces other poorly defined and confusing terminologies used to describe menstrual abnormalities
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such as menorrhagia, metrorrhagia and dysfunctional uterine bleeding.¹ Heavy menstrual bleeding

(HMB) is used to describe the woman's perspective of increased menstrual volume, regardless of
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regularity, frequency, or duration. HMB is defined per FIGO, as excessive menstrual blood loss
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which interferes with the woman's physical, emotional, social and material quality of life, and which

can occur alone or in combination with other symptoms. ¹ HMB is a common medical condition

affecting adolescent girls. A population-based prevalence study of nearly 1,000 healthy adolescent

females revealed approximately 40% had experienced HMB.² Among adolescents with HMB, up to

20% are found to have an underlying bleeding disorder. While the exact prevalence of specific types

of bleeding disorders among adolescents varies, current literature suggests the prevalence ranges for
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the following more common bleeding disorders: von Willebrand disease (VWD) 5-36%, platelet

function defects 2-44%, thrombocytopenia 13-20%, and clotting factor deficiencies (CFD) 8-9%.3-12

Normal menstrual cycles have been regarded as a surrogate indicator of overall adolescent health.13-15

However, patients and their families may be unaware of the characteristics of normal menses. Some

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adolescents are not aware of the severity of their symptoms.16 Lack of patient awareness is potentially

compounded by provider knowledge gaps or diagnostic challenges that occur for a variety of reasons.¹

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HMB is traditionally described as bleeding greater than 7 days or blood loss that exceeds 80 mL per

menses.18-20 HMB may also be identified based on the patient’s observation of increased menstrual blood

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flow that impedes her well-being and quality of life.1 The American College of Obstetricians and

Gynecology (ACOG) and the American Academy of Pediatrics (AAP) have emphasized for over a decade

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that menstrual cycle assessment should be viewed as an additional vital sign, thus allowing for timely
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identification of normal pubertal progression and disease processes in girls and adolescents.21 The

interval between normal menstrual cycles in girls and adolescents is 21-45 days.22-26 Menstrual periods in
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this age group should last 7 days or less and require 3-6 pads or tampons daily.18, 21
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Menstrual disorders have both physical and psychological morbidities.27, 28 Therefore, clinicians should
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be attuned to parental or patient concerns about disruptions in quality of life (QOL). Health related

quality of life research has not yet been fully explored in adolescents with menstrual disorders.27, 29, 30 In a
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study involving high school students, there was a greater likelihood that QOL was unfavorably impacted
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in those with higher bleeding scores.29 Assessment of school absenteeism or marginal school
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performance, involvement in social activities and sports, and fatigue should be included in the

comprehensive evaluation of an adolescent presenting with HMB. Treatment of HMB for adult women

can result in significant healthcare costs including hospital admissions, outpatient and emergency

department visits.31, 32 Although no definitive extrapolations of these data have been applied to

adolescents, some commonalities likely exist. Provider knowledge of proper diagnostic techniques and
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effective treatment strategies for HMB may assist with more timely diagnoses and encourage proper

healthcare utilization behaviors.

Clinical Presentation

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HMB is frequently reported by patients and their caregivers as bleeding “too much.” Patients often

describe heavy menstrual flow during the majority of their menses. HMB may be associated with

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changing a pad or tampon more than every 1-2 hours or the use of double-protection (i.e. pad and

tampon), or frequent soiling of clothes or bed linens.

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Quantifying menstrual blood loss can be challenging to providers and patients for many reasons. Tools to

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improve quantification have been developed such as the pictorial blood assessment chart (PBAC), but are
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not without limitations.33, 34 The PBAC tool was validated in adult women; a score greater than 100 in

one menstrual cycle has a sensitivity and specificity of 80% for determining HMB.35 However, the
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validity of the PBAC has been debated and scores are typically inaccessible to the clinician immediately.

Furthermore, there is a paucity of literature pertaining to PBAC use among adolescents. The first study
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evaluating PBAC utilization in adolescents involved a cohort of adolescents who self-identified as having
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"light," "medium," or "heavy" menses reported that mean PBAC scores in the heavy menses group was

362 as compared to 136 in the normal menses group and 44 in the light menses group.36 The study found
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a similar 20% incidence of bleeding disorders in patients with heavy menstrual bleeding.
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Additional variables that have been shown to predict blood loss in excess of 80 mL, include changing a

pad or tampon more than hourly, passing clots larger than 1 inch diameter, and low ferritin levels.37 Iron

deficiency and increased fatigue severity scores in adolescents with HMB have also been described in the

literature.38 Revel-Vilk et al also affirm that in adolescents, underdiagnosed heavy or prolonged bleeding

is associated with underdiagnosed anemia.16

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Diagnosis
The PALM-COEIN classification system developed by the International Federation of Gynecology and

Obstetrics (FIGO) and supported by the American College of Obstetrics and Gynecology provides a

schema for the etiologies of abnormal uterine bleeding (AUB) using standardized terminology.39 (Fig. A).

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Within this system, AUB is described as either HMB (AUB/HMB) or intermenstrual bleeding

(AUB/IMB). The causes of AUB are divided into two groups: those related to structural abnormalities

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(Polyp, Adenomyosis, Leiomyoma, Malignancy and hyperplasia) and those related to nonstructural

causes (Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic, and Not yet classified).39 (Figure

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A).

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Figure A. The PALM-COEIN classification of causes for abnormal uterine bleeding in
nonpregnant women of reproductive age.
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Abnormal Uterine Bleeding:
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● Heavy menstrual bleeding

(AUB/HMB)
● Intermenstrual bleeding (AUB/IMB)
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PALM-structural causes: COEIN-nonstructural causes:

Polyp (AUB-P) Coagulopathy (AUB-C)
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Adenomyosis (AUB-A) Ovulatory dysfunction (AUB-O)

Leiomyoma (AUB-L) Endometrial (AUB-E)
Submucosal leiomyoma Iatrogenic (AUB-I)
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Other leiomyoma (AUB-LO) Not yet classified (AUB-N)

Malignancy and hyperplasia (AUB-M)
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For adolescent women, the more common etiologies of HMB are nonstructural (Table 1). Anovulatory

bleeding is the most common etiology due to the immaturity of the hypothalamic-pituitary-ovarian-

axis.40,41 Anovulatory bleeding is typically associated with disordered bleeding patterns which can present

as HMB and/or irregular menses. Pregnancy and sexually transmitted infections are other important
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causes of adolescents presenting with HMB.42 The adult literature supports an increased incidence of

Polycystic Ovarian Syndrome (PCOS) in women with an admission diagnosis of excessive menstrual

bleeding.43 Thus this diagnosis should be considered for adolescents presenting with HMB who have

classic clinical signs of PCOS such as obesity, acanthosis nigricans, hirsutism and acne.44

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Table 1. Differential Diagnoses of HMB in Adolescents45

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Endocrine Bleeding Pregnancy Infection Uterine Medication Other

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Disorders

Anovulatory von Willebrand Abortion Cervicitis Myoma Depot Trauma

bleeding Disease medroxy

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progesterone
IM or SC
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PCOS Platelet Ectopic Adenomyosis IUD Anticoagulants Foreign
dysfunction pregnancy body

Thyroid Thrombocytope Gestational Polyp Hemorrhagic

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disease nia trophoblasti ovarian cysts

c disease
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Other Clotting factor Cancer

deficiency
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Bleeding disorders such as von Willebrand disease (VWD), clotting factor deficiencies, immune

thrombocytopenia, platelet function defects, and fibrinolytic pathway defects also cause HMB in
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adolescents.3, 4, 46-53 Clinicians must be cognizant of signs and symptoms that may be suggestive of these

disorders.17, 46, 53 Evaluation for underlying bleeding disorders should be considered for patients who
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endorse any of the following: insignificant wounds that lead to prolonged bleeding; heavy, prolonged or

recurrent bleeding after surgery or dental procedures; epistaxis greater than 10 minutes in duration or

requiring medical attention; unexplained bleeding from the gastrointestinal tract; HMB with iron

deficiency; postpartum hemorrhage, and/or a family history of bleeding disorders.4 (Table 2)

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Table 2. Signs, Symptoms, and Red Flags of Bleeding Disorders4, 54, 55

Prolonged bleeding from trivial wounds lasting > 15 minutes

Heavy, prolonged or recurrent bleeding after surgery

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Heavy, prolonged or recurrent bleeding after dental procedures or tooth extraction

Bruising with minimal or no trauma, esp. resulting in a lump one to two times per month

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Nose bleeds > 10 minutes or require medical attention one to two times per month

Unexplained bleeding from gastrointestinal tract

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Anemia requiring iron therapy or transfusions

HMB (clots ≥ 1 inch, pad/tampon change more than hourly, low ferritin)

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Family history of bleeding disorders such as VWD or hemophilia, hysterectomy at young age
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Postpartum hemorrhage

Women with underlying bleeding disorders may also have HMB associated with hemorrhagic ovarian
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cysts or endometriosis.4, 56, 57 Hereditable collagen disorders such as Ehlers-Danlos and Benign Joint

Hypermobility Syndrome have been associated with various bleeding abnormalities due to capillary
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fragility. Accordingly, a history of HMB accompanied by joint hyperflexibility, joint dislocations,

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hyperextensible skin or abnormal scarring may require further investigation.58, 59 Certain medications

including hormonal contraceptives and anticoagulation medications can also cause HMB and a thorough
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medication and supplement history should be obtained. Rarer causes of HMB in adolescence include

endometrial polyps and leiomyomas. Although leiomyomas are exceedingly rare in adolescence, HMB
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associated with pelvic mass and/or pelvic pain should prompt further investigation.60, 61
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Evaluation
The first step in evaluating a patient with HMB is to determine whether the bleeding is acute or chronic

through history and physical examination and appropriate laboratory testing and radiologic imaging. The

history should elicit the quantity and quality of the bleeding and symptoms of associated anemia and
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hemodynamic stability as well as a detailed reproductive health and sexual history. Additionally,

information about associated positive review of symptoms concerning for underlying etiologies of HMB,

the presence of chronic medical illnesses associated with HMB, prescription and nonprescription

medication use and family history of health issues associated with HMB should be obtained (Table 3).

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Table 3. Focused history for evaluation of HMB 55, 62

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Bleeding pattern Quantity, frequency of changing pads or tampons, presence of clots > 1
inch, timing during menstrual cycle, impact on quality of life

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Symptoms of anemia Headache, palpitations, shortness of breath, dizziness, fatigue, pica

Sexual and reproductive Menstrual history, determination of gynecologic age, pregnancy history

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history and outcomes, possibility of current pregnancy, contraceptives use,
sexually transmitted infections, cervical screening
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Associated symptoms Fever, chills, increasing abdominal girth, pelvic pressure or pain, bowel
or bladder dysfunction, vaginal discharge or odor
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Symptoms associated with Obesity, PCOS, hypothyroidism, hyperprolactinemia, hypothalamic or

systemic cause of HMB adrenal disorder
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Chronic medical illness Inherited bleeding disorders (coagulopathy, blood dyscrasias, platelet
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function disorders), systemic lupus erythematosus or other connective

tissue diseases, liver disease, renal disease, cardiovascular disease

Medications Hormonal contraceptives, anticoagulants, SSRIs*, antipsychotics,

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tamoxifen, herbals (i.e. ginseng)

Family history Coagulation or thromboembolic disorders, hormone-sensitive cancers

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Physical Exam

The physical exam of a patient who presents with acute HMB should initially focus on signs of acute

blood loss (hypovolemia and anemia) and assessment of medical stability. In the acute setting, the

location and the amount and intensity of bleeding need to be determined through external examination of

the genitalia to identify trauma. A pelvic examination with a speculum and bimanual exam may not be
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possible with sexually inexperienced adolescents and it can be challenging to determine trauma to the

upper vagina or visualize cervical findings that could cause vaginal bleeding. Fortunately, structural

lesions in adolescents are rare. If the patient is medically stable, Table 4 lists additional exam findings

that may elucidate the underlying diagnosis i.e. obesity, acanthosis nigricans and hirsutism suggest PCOS

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or bruising and petechiae raise concern for an underlying bleeding disorder.

Table 4. Focused physical exam for evaluation of HMB 62

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Vital signs temperature, blood pressure, pulse, orthostatic vital signs, weight, BMI

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Neck thyroid exam

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Skin pallor, bruising, petechiae, hirsutism, acanthosis nigricans, acne, scarring

Abdomen distension, striae, palpable mass, tenderness, hepatomegaly

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GU inspection vulva, vagina, urethra, anus for abnormalities (bleeding source, trauma,
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prolapse, cancer), sexual maturity rating

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Speculum exam (if for further evaluation of vagina, cervix

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clinically indicated)
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Digital or Bimanual of uterus and adnexal structures for size, tenderness

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exam (if clinically

indicated)

Rectal exam (if if bleeding from anus or rectum is suspected

clinically indicated)
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Laboratory Evaluation

A tiered approach to laboratory testing for the evaluation of HMB allows for the assessment of anemia

from blood loss as well as an investigation of potential etiologies of HMB.41 (Table 5). Blood type and

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cross match must be obtained immediately for hemodynamically unstable patients. First tier labs also

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consist of a pregnancy test and complete blood cell count (CBC) with differential and platelet count to

rule out thrombocytopenia. In addition to a CBC, obtaining a ferritin level allows for the evaluation of

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iron deficiency. Standard coagulation testing (i.e., prothrombin time, activated partial thromboplastin

time, thrombin time, and fibrinogen level) allow for an assessment of hemostasis. Second tier laboratory

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testing includes testing for sexually transmitted infections for sexually experienced patients, androgen
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testing for patients with signs and symptoms of PCOS, thyroid stimulating hormone testing for patients

with signs and symptoms of thyroid disease and testing for von Willebrand disease for patients who are at
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risk of an underlying bleeding disorder. Third tier testing is reserved for the patient with a significant

bleeding history and nondiagnostic initial testing. Consulting a hematologist is recommended when
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considering further evaluation with third tier testing i.e. for platelet aggregation abnormalities.53 In
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addition, ultrasound can be helpful to rule out significant structural abnormalities of the uterus and to

assess thickness of the endometrium. Although transvaginal ultrasound is preferable, using a vaginal
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probe may not be feasible in adolescent patients and a magnetic resonance imaging has increased

sensitivity of imaging pelvic organs.

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Table 5. Tiered approach to the investigation of HMB 41, 45, 55, 63, 64

Laboratory Test Abnormalities

First Tier

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Pregnancy test Disorders of pregnancy i.e. spontaneous
miscarriage
Complete blood count (CBC) with differential Anemia, microcytosis, thrombocytopenia

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Ferritin Iron deficiency

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Prothrombin time (PT) Factor VII deficiency if prolonged

Activated partial thromboplastin time (aPTT) Factors VIII, IX, XI, XII deficiencies if
prolonged

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Thrombin time (TT) Hypofibrinogenemia dysfibrinogenemia or
heparin contamination if prolonged
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Fibrinogen Hypofibrinogenemia or dysfibrinogenemia

Second Tier
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Chlamydia trachomatis, Neisseria gonorrhoeae vaginal, cervical Sexually transmitted infection

or urine testing
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Thyroid stimulating hormone (TSH) Thyroid abnormalities

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von Willebrand profile (von Willebrand factor antigen, von Willebrand disease
Ristocetin cofactor assay, Factor VIII, multimer analysis)
(Total and free testosterone, dehydroepiandrosterone sulfate, Polycystic Ovary Syndrome and other causes
androstenedione) of hyperandrogenism
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Third Tier

Platelet function and aggregation testing Platelet aggregation and secretion

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abnormalities
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Treatment

Overview:

The treatment for heavy menstrual bleeding in adolescent females can be separated into 2 major sections:

acute treatment and maintenance treatment. The acute management of heavy bleeding is focused on the
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stability of the patient and may require hormonal and nonhormonal measures for bleeding control. The

initial focus is that of hormonal and medical interventions to control acute or chronic heavy menstrual

bleeding. Invasive measures and surgical interventions may ultimately be necessary for treatment in the

life threatening situation and in the setting of failed medical management. Once a patient has been

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stabilized from an acute heavy menstrual bleeding event, transitioning to a maintenance plan is important.

A variety of options are available, including hormonal and non-hormonal measures as well as

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combination category therapies.41

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Acute Treatment:

There are a number of options for the acute management of heavy menstrual bleeding that will result in

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bleeding cessation. It is important to note whether the patient is hemodynamically stable or not and
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whether the patient will need to be hospitalized for bleeding control.41 For the patient requiring

hospitalization, blood products should be administered as necessary for severe anemia. The first line
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medical treatment beyond transfusion products usually involves that of estrogen containing hormones or

progesterone only hormones (when there are contraindications to estrogen administration).65 In addition,
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iron therapy should be started concurrently. In the estrogen category, intravenous conjugated estrogens
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may be utilized when the patient is unable to tolerate oral therapy. A high dose 50mcg combination birth

control pill may also be utilized when a patient can tolerate oral therapy (Table 6).
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Many studies show the efficacy of these options for stabilizing the endometrium and resulting in bleeding
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cessation, in many cases within the first 24 hours of treatment initiation. There are many tapering
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regimens available as well as ultimately, patients will need to transition from high dose estrogen therapy

to a lower dose maintenance treatment. Tapering regimens may start from an initial combined estrogen

pill every 6 hours, stepping down to one pill every 8 hours for 3-7 days, one pill every 12 hours for 3-7

days then one tablet daily thereafter until the provider feels it is safe to cycle in controlled fashion. For

patients with an inability or contraindication to taking estrogen containing options, progesterone only

treatments are also available and have been shown to be effective.42, 65, 66 (Table 6). Tapering protocols
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also exist for progesterone alone therapies ranging from administration of pills every 8 hours eventually

to every 12 hours, followed by every 24 hours to a daily pill. A small percentage of patients will need

something to augment hormonal therapy. Antifibrinolytics are an excellent option in this situation when

patients have been unresponsive to hormones alone. Antifibrinolytics have been shown in several

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instances to work alone or in conjunction with other therapies to decrease HMB.67 Two choices for

antifibrinolytics are available and approved for use in North America, aminocaproic acid and tranexamic

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acid. Either therapy may be given in the oral or intravenous form (Table 6). Ultimately, when medical

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therapy fails, more invasive measures are available. A few studies have reported on the use of

intrauterine balloon tamponade as an effective means to decrease acute heavy menstrual bleeding.

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Although most of these studies have been conducted in women having post-partum hemorrhage related

bleeding, a 30 cc Foley balloon is an acceptable alternative for tamponade of the adolescent uterus.41, 66, 68
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Adolescents have not yet completed child bearing, therefore, more invasive measures, such as

endometrial ablation or hysterectomy, are avoided unless absolutely needed in the case of a life
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threatening emergency.41, 42
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Table 6. Medical and Hormonal therapies for acute HMB 41

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Therapy Dose Route Initial

Frequency

conjugated estrogen 25 mg IV every 4-6 hours

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50 mcg ethinyl estradiol combined one tablet oral every 6 hours

pill

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30-35 mcg ethinyl estradiol combined one tablet oral every 6 hours

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pill

medroxyprogesterone 10-20 mg (max 80mg/day) oral every 6-12 hours

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norethindrone acetate 5-10 mg oral every 6 hours

Tranexamic acid 10 mg/kg IV** every 6-8 hours

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Aminocaproic acid 100-200 mg/kg (max 30 IV** or every 4-6 hours

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grams/day) oral
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**IV (intravenous)

Maintenance Treatment:
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Fortunately, many maintenance treatments are available to adolescent females. These range from
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combination pills, patches and rings to progesterone alone treatments, including cyclic progesterone,
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injectables, implantables or intrauterine devices. All have been shown to work to decrease overall

bleeding with menses, result in fewer missed days from school due to heavy bleeding, increase

hemoglobin and iron levels and increase quality of life (Table 7). Iron supplementation should be given

simultaneously and continue until anemia resolves completely.66

Table 7. Options for Maintenance 66

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Therapies Hormonal Non-hormonal

Combined oral contraceptive pills Tranexamic acid orally

Progesterone only pills

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Combined patches

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Combined rings Aminocaproic acid orally

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Progesterone injections

Etonogestrel implant

Levonorgestrel IUD
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Conclusion
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HMB is a common menstrual complaint among adolescent females. Providers must have knowledge
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about normal menstrual patterns in this age group and consider both underlying pathophysiology as well

as physical and quality of life morbidities for adolescents with HMB. The assessment of a patient with
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HMB should begin with a determination of medical stability and triage to emergency care if necessary.

For medically stable patients, the evaluation should include a detailed history assessing the quantity and
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quality of menstrual bleeding, symptoms of anemia, reproductive health history and sexual behaviors,
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symptoms that may suggest the potential for an underlying bleeding disorder and a thorough focused

physical exam should be conducted. A tiered approach to laboratory and radiologic testing for the

evaluation of HMB allows for the assessment of the degree of anemia from blood loss as well as an

individualized investigation of potential etiologies of HMB. Treatment strategies are categorized into

acute and maintenance therapies prioritizing safety and fertility-preserving approaches to bleeding
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cessation, correction of anemia and subsequent regulation of menses. Consultation with a hematologist

should be considered for difficult management cases.

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Level of Evidence

Studies were reviewed and evaluated for quality according to the method outlined by the U.S. Preventive

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Services Task Force

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I Evidence obtained from at least one properly designed randomized controlled trial.

II-1 Evidence obtained from well-designed controlled trials without randomization.

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II-2 Evidence obtained from well-designed cohort or case–control analytic studies, preferably from more
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than one center or research group.
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II-3 Evidence obtained from multiple time series with or without the intervention. Dramatic results in

uncontrolled experiments also could be regarded as this type of evidence.

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III Opinions of respected authorities, based on clinical experience, descriptive studies, or re-ports of
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ex-pert committees.
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Based on the highest level of evidence found in the data, recommendations are provided and graded

according to the following categories:

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Level A—Recommendations are based on good and consistent scientific evidence.

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Level B—Recommendations are based on limited or inconsistent scientific evidence.

Level C—Recommendations are based primarily on consensus and expert opinion.

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