Introduction
Abnormal uterine bleeding (AUB) is the most common complaint among adolescents reporting to a gynecologist. They may present with bleeding that lasts for several weeks at a time or concern that they go months between periods. Young girls and their caretakers can have difficulty assessing what constitutes normal menstrual cycles or patterns of bleeding. Although some irregularity is expected around menarche, it can be hard to assess what is concerning for a more severe problem. The American College of Obstetricians and Gynecologists (ACOG) has provided guidance on what constitutes normal menses in young girls and adolescents ( Table 9.1 ). Please refer to Chapter 8 for further discussion of normal menses.
| Menarche (median age) | 12.43 |
| Mean cycle interval | 32.2 days in first gynecologic year |
| Menstrual cycle interval | Typically 21–45 days |
| Menstrual flow length | 7 days or less |
| Menstrual product use | Three to six pads or tampons per day |
Abnormal uterine bleeding
AUB refers to bleeding from the uterine corpus that is abnormal in volume, regularity, frequency, or duration and occurs in the absence of pregnancy.
Menstrual irregularities refer to a deviation in what is considered normal menstrual bleeding in adolescents or adult women. The most common menstrual irregularities are described in Table 9.2 .
| Amenorrhea (pronounced ey-men-uh-REE-uh ) |
|
| Heavy menstrual bleeding (HMB) | See section on HMB |
| Irregular menstrual periods | Cycle-to-cycle variation of more than 20 days |
| Shortened menstrual bleeding | Less than 2 days in duration |
| Intermenstrual bleeding | Episodes of bleeding that occur between normally timed periods, also known as spotting |
Prevalence
Menstrual cycles are often irregular during adolescence. Immaturity of the hypothalamic-pituitary-ovarian (HPO) axis during the early years after menarche often results in anovulation, and cycles may be somewhat irregular. However, 90% of cycles will be within the range of 21 to 45 days, although short cycles of less than 20 days and long cycles of more than 45 days may occur. By the third year after menarche, 60% to 80% of menstrual cycles are 21 to 34 days long, as is typical of adults.
There is a paucity of data in regard to the prevalence of specific menstrual irregularities (see Table 9.2 ) in the adolescent population. A cross-sectional study with 848 girls aged 12 to 18 years looked to characterize the menstrual cycle (regularity and menstrual flow length) in this population. A total of 41.3% of the girls reported irregular cycles and 17.2% reported menstrual flow length of >6 days. Irregular cycles were noted to be more prevalent among young teens ages 12 to 14 (44.6%) than among teenagers ages 15 to 18 (39.2%). Also, a higher percentage of younger teens ages 12 to 14 reported longer menstrual flow (22.9%) compared with the teenagers ages 15 to 18 (13.7%).
Etiology/pathophysiology of AUB
Causes of AUB are numerous and often multifactorial. , In an effort to create a universally accepted system of nomenclature to describe AUB in nonpregnant women, a new classification system was introduced in 2011. This system classifies AUB into heavy menstrual bleeding (HMB) or intermenstrual bleeding (IMB). From there, causes are broken down into two main categories. The PALM acronym refers to structural causes of AUB, and the COEIN acronym is reserved for nonstructural causes of AUB (See Video 9.1, Causes of Irregular Menstrual Bleeding).
Structural causes of AUB (PALM) could be the result of uterine p olyps, a denomyosis, l eiomyoma (also known as fibroids ), and m alignancy. Nonstructural causes of AUB are the case for the majority of adolescent patients—COEIN—and include c oagulopathy, o vulatory dysfunction, e ndometrial causes such as sexually transmitted infections, and i atrogenic reasons such as breakthrough bleeding from a contraception or side effect of hormone therapy. The N is the “not yet classified” subcategory where causes that do not fit well into any of the previously mentioned subcategories are located; an example of this would be arteriovenous malformations.
One of the most common reasons for AUB in the adolescent is ovulatory dysfunction. The differential diagnosis for anovulation in adolescents is broad and can be divided into physiologic versus pathologic causes. Physiologic causes of anovulation include the process of puberty or an immature HPO axis does not have the necessary hormonal feedback needed to regulate menses. Pregnancy or breastfeeding, which increases prolactin levels, can also result in anovulation.
Pathologic causes can be the result of elevated androgens such as in polycystic ovary syndrome (PCOS), congenital adrenal hyperplasia (CAH), or androgen-producing tumors. Hypothalamic dysfunction, which can occur because of eating disorders such as anorexia nervosa, and elevated prolactin from pathologic causes such as pituitary tumor, thyroid disease, and premature ovarian insufficiency (POI) are also possible causes. Iatrogenic causes stem from treatment of other ailments such as radiation to the brain or pelvis or chemotherapy with toxic effects to the ovaries. And finally, certain drugs or medications can cause increases in the prolactin level and/or menstrual disturbances such as risperidone.
See Video 9.2, Causes of Heavy Menstrual Bleeding.
Clinical presentation and classical signs
The presentation for AUB will vary depending on the etiology. Determining the etiology of AUB is essential in choosing the most appropriate and effective management for the individual, and it is accomplished by obtaining a thorough history and physical examination and ordering relevant laboratory and imaging tests ( Table 9.3 ).
| History |
|
| Physical Examination |
|
| Laboratory Tests |
|
| Imaging |
|
a Can use a menstrual calendar app for patients being expectantly managed.
Evaluation/testing
A thorough history is perhaps the most important component and should be taken in a systematic manner, while taking the clinical setting into consideration.
Direct information regarding the timing, length, and heaviness of the cycle should be elicited:
- 1.
When did you start your period?
- 2.
How often do you bleed?
- 3.
How many days do you bleed for?
- 4.
How many pads or tampons do you use per day or per hour?
All the components of a physical examination are important depending on your clinical setting. However, attention should be paid to vital signs, checking the skin for any signs of unwanted hair growth, acne, thyroid abnormalities, Tanner staging, and an external genitalia examination. Speculum examination is often not necessary and may not be well tolerated in this population. The external genital examination can be accomplished via labial retraction in a down and out manner to evaluate the introitus, and in some cases, this technique exposes the distal third of the vagina. Refer to Chapter 4 for further information on pediatric gynecologic examination.
Laboratory tests for AUB with associated ovulatory dysfunction (AUB-O) include a pregnancy test, a complete blood count (CBC) to evaluate for anemia and platelet quantity, screening for thyroid hormone (as thyroid abnormalities are associated with menstrual abnormalities), and sexually transmitted infections (when appropriate). Bleeding disorder screening should also be performed if indicated (discussed later). Structural abnormalities account for only a small minority of cases of AUB in this population; thus clinical evaluation should guide the inclusion of a pelvic ultrasound. Although the transvaginal is considered the most accurate route to assess the female reproductive structures, the majority of adolescent patients will not tolerate it, and thus transabdominal pelvic imaging is the imaging modality of choice in nonsexually active females.
See Fig. 9.1 for important aspects to look for during the physical examination and Table 9.3 for detailed history, laboratory, and imaging testing for abnormal uterine bleeding.
Treatment
Determining the etiology of AUB is essential in choosing the most appropriate and effective management for the individual ( Table 9.4 ).
| Etiology | Management |
|---|---|
| C oagulopathy a | Hormone therapy |
| O vulatory Dysfunction | |
| O varian Failure, Premature a | Hormone therapy |
| P rimary Pituitary Disease a | Treat underlying disease |
| T hyroid Disease | Treat underlying disease |
| I atrogenic: chemotherapy/radiation | Hormone therapy |
| M edications | Discuss alternatives, hormone therapy |
| Hyper A ndrogenic anovulation (PCOS,CAH) a | Hormone therapy |
| Hyperpro L actinemia | Treat underlying disease |
| H ypothalamic dysfunction (anorexia nervosa) | Treat underlying disease |
| E ndometrial (e.g., STIs) | Treat underlying disease |
| I atrogenic (e.g., BTB with contraception) | Optimize hormone therapy, offer alternatives |
| N ot yet classified | Treat underlying disease |
a Consider collaboration with hematology and endocrinology as indicated for optimal management of disease.
Hormone therapy
Hormone therapy comprises two main categories ( Tables 9.5 and 9.6 ):
- 1.
Combined hormonal therapy with estrogen and progestin
- 2.
Progestin therapy only
| Combined Hormonal Therapy (E + P) | Progestin Therapy (P Only) |
|---|---|
|
|
|
|
| Vaginal Ring | Levonorgestrel Intrauterine Device |
| Method | Strategies a |
|---|---|
| Estrogen-containing methods (combined OCPs, patch, ring) |
|
| Oral progestins b |
|
| Depot medroxyprogesterone acetate b |
|
| Implant b |
|
| Progestin-containing intrauterine device b |
|
a Evaluate for pregnancy if applicable.
b Counsel patient on alternative methods, given progestin-only methods are notorious for irregular bleeding; provide reassurance.
When counseling regarding hormonal therapy, an individualized approach with shared decision making is important, and one needs to take several factors into consideration such as the priorities, preferences (e.g., Can the patient commit to taking a pill daily or do they need a long-acting contraceptive method?), concerns of the patient, and the medical history.
Although generally safe in a healthy patient, there are some medical conditions where estrogen should be avoided such as in migraines with aura, uncontrolled hypertension, and hypercoagulable disorders, to mention a few. The US Medical Eligibility Criteria for Contraceptive Use (US MEC) was designed by the Centers for Disease Control and Prevention (CDC) to provide guidance on the safety of contraceptive options, especially in women with particular medical conditions. There is a free app that can be downloaded for quick access ( https://www.cdc.gov/reproductivehealth/contraception/contraception-app.html ). Refer to Chapter 21 for more detailed information on contraceptive choices in adolescents.
When starting hormonal therapy, it is important to discuss common side effects and set expectations regarding breakthrough bleeding, the patient should be reassured that if bothersome, there are treatment options available (see Table 9.6 ).
Heavy menstrual bleeding
HMB is defined as excessive menstrual bleeding that negatively effects emotional, social, and material quality of life. Objectively, it is described as greater than 80 mL of blood loss per cycle, which is difficult for a patient to assess, so greater than or equal to eight fully saturated pads a day and greater than or equal to 8 days of bleeding would also qualify as HMB. There are more and more menstrual products on the market including menstrual cups, sponges, and underwear, and the milliliters of blood that each product can hold is often found online.
Prevalence
The exact prevalence of HMB among adolescents is unknown, but surveys have reported that 15% to 40% of adolescents perceive their bleeding as abnormally heavy. , The frequency of HMB among adolescents with bleeding disorders is far higher. Females with von Willebrand disease (vWD), the most common bleeding disorder among women with HMB, report that HMB is the single most common bleeding symptom they experience. Approximately 95% of women with vWD report heavy menstrual bleeding, and over 50% of women with rare factor deficiencies report it. ,
Etiology/pathophysiology
There are multiple etiologies for HMB among reproductive-age women. These are well defined via the previously discussed ACOG mnemonics PALM and COEIN. Single episodes of heavy menstrual or vaginal bleeding may be attributed to trauma from abuse, foreign body or straddle injury, infections such as cervicitis, or pregnancy related. Persistent or recurrent HMB may be caused by anovulatory cycles, PCOS, or thyroid disease. Although uterine pathology such as polyps and fibroids are possible causes, they are much less common in this patient population. Medications specifically used by adolescents that may result in heavy menses include various forms of contraception (AUB section). More individuals need to use direct-acting oral anticoagulants and other blood thinners that can certainly increase bleeding of any kind, including menstrual bleeding. Patients receiving various forms of chemotherapy can experience thrombocytopenia, which may lead to HMB. Chemotherapeutic agents commonly associated with thrombocytopenia include carboplatin, cisplatin, gemcitabine, paclitaxel, and temozolomide. Finally the risk of bleeding disorders is much higher in patients with heavy menses since menarche. Although vWD is the most common bleeding disorder, factor deficiency and platelet abnormalities should also be considered. Clotting factor deficiencies are rare, including factor II, V, VII, X, and XI and hemophilia. As mentioned, thrombocytopenia can result in HMB, as can platelet dysfunction. Platelet dysfunction may be inherited such as Bernard-Soulier and Glanzmann syndromes or acquired from medication, liver disease, and myeloproliferative disorders.
Clinical presentation/classic signs
Adolescents with HMB will typically present with the complaint of bleeding too much or for too long during menstruation. Adolescents may complain of needing to be picked up from school because of soiling of their clothes or using towels at night so they do not bleed through onto their sheets. 
Classic signs or associated symptoms may help to identify the underlying etiology; for example, a history of prolonged gum bleeds may suggest an underlying bleeding disorder; fatigue and pallor reflect anemia; or skin changes and weight gain could be the presenting symptoms of thyroid disease (see Fig. 9.1 ).
Evaluation/testing
A thorough history is important to establish the amount of bleeding and frequency (see earlier) and to evaluate for underlying causes. It can be helpful to use an app that tracks cycles for more accurate and objective data. The Sisterhood app, created by the Hemophilia Federation of America ( https://www.sisterhoodapp.com/ ) can be a useful tool. The Pictorial Bleeding Assessment Tool (PBAC) has also been shown to help evaluate bleeding prospectively among patients ( https://www.rch.org.au/uploadedFiles/Main/Content/rch_gynaecology/PBAC.pdf ).
Additionally, several other menstrual products are now available, including period panties and menstrual cups. These alternatives often have estimated milliliters of blood loss that can be calculated based on use.
A bleeding-specific history should be performed ( Table 9.7 ). A family history of known bleeding disorders and heavy bleeding and need for transfusion should be elicited.
| Menses Specific | General Bleeding Symptoms | Medical History | Medication |
|---|---|---|---|
| Frequent soiling for clothes or bedding | Epistaxis >10 min | Known bleeding disorder | Anticoagulants |
| Large clots (>2 cm) | Frequent/prolonged gum bleeding | History of anemia | Chemotherapy |
| Changing saturated pad more than every 2 hours | Easy bruising | History of transfusion | Hormonal Medication |
| Excessive bleeding associated with trauma or surgery | Chronic medical illness: systemic lupus erythematosus, liver disease, renal disease | ||
| Postpartum hemorrhage |
It is recommended to use a bleeding assessment tool (BAT) to evaluate patients who warrant further laboratory evaluation. These should specifically be used when presenting to a primary care setting such as a pediatrician or family medicine clinic; they are not recommended for subspecialist referral centers such as a pediatric hematologist. Based on the sensitivity and specificity of various BATs, the ACOG recommends a bleeding disorder workup for any adolescent who meets any of the following criteria , :
- 1.
Duration of menses was greater than or equal to 7 days and reports either “flooding” or bleeding through a tampon or napkin in 2 hours or less with most periods
- 2.
A history of treatment for anemia
- 3.
A family history of a diagnosed bleeding disorder
- 4.
A history of excessive bleeding with tooth extraction, delivery or miscarriage, or surgery
Physical examination
The physical examination is also used to help elicit the cause of HMB. Evaluation of the skin may suggest a bleeding disorder with petechiae, poorly healed wounds, hematomas, or bruising ( Fig. 9.1 ). Pallor can be seen in patients with chronic or significant anemia. The physical examination can also help rule out other causes such PCOS and thyroid disease (see AUB section). An examination of the genitalia is indicated for patients who are sexually active, if there is a concern for trauma, or if the source of bleeding is not confirmed to be vaginal.
Laboratory
The initial evaluation of a patient presenting with an 
acute episode of heavy menses should include having a CBC collected. A type and screen are warranted if transfusion is being considered. Iron studies, including ferritin, thyroid-stimulating hormone, and pregnancy test, should be checked upon presentation.
Adolescents presenting with HMB who screen positive (affirmative response to any of the four BAT questions posed earlier) should undergo a bleeding disorder workup, which includes the labs in Table 9.8 .
| PT, PTT, INR |
| Fibrinogen |
|
a Historically von Willebrand factor activity was evaluated by a ristocetin cofactor activity, but because of high test result variability in addition to a nonclinically significant polymorphism, GPIbM will replace this ristocetin cofactor in the future.
If a patient requires a transfusion, these laboratory studies should be drawn before the administration of blood products. However, several aspects of the bleeding disorder workup are acute-phase reactants, which means they can be falsely elevated during an acute bleed or in cases of severe anemia. For that reason, the bleeding disorder panel should always be drawn or repeated once the patient has stabilized and hemoglobin has returned to normal.
For cases of an abnormal bleeding disorder workup or persistent heavy bleeding that fails therapy, a hematology referral is recommended. Hematology may initiate further evaluation of more rare bleeding disorders such as factor deficiency and disorders of platelet function.
Imaging
Ultrasound may be indicated for adolescents with HMB. In general, it is not part of the initial evaluation because structural causes such as cancer, polyps, and fibroids are so rare. However, it should be considered in individuals who fail initial medical management or in individuals who have a palpable abdominal mass or concern for müllerian or vaginal anomaly. Transabdominal ultrasound is usually sufficient to assess ovarian and uterine structures. Magnetic resonance imaging (MRI) can be considered in cases of anomalous or complex anatomy.
Treatment/management
Treatment can be divided into acute versus maintenance therapy. Several institutions have published protocols for acute heavy menses that are publicly available and can be accessed online, such as the ED Guidelines for Heavy Menstrual Bleeding https://www.choa.org/-/media/Files/Childrens/medical-professionals/clinical-practice-guidelines/heavy-menstrual-bleeding-ed.pdf .
Acute
Patients who are hemodynamically compromised or severely anemic (<8 g/dL) with active bleeding should be admitted, transfused as appropriate, and started on hormone therapy. Hormone therapy may include intravenous (IV) estrogen or a combined oral contraceptive pill or high-dose progesterone ( Table 9.9 ). Several tapers exist, but there is little evidence to support one as being more effective than the other ( Table 9.10 ).
