Learning Objectives:After participating in this continuing professional development activity, the provider should be better able to:
1. Identify adolescents who require evaluation for heavy menstrual bleeding and associated medical, social, and psychological risks.
2. Explain appropriate diagnostic evaluation of adolescents with heavy menstrual bleeding.
3. Suggest evidence-based treatment for adolescents with heavy menstrual bleeding.
Heavy menstrual bleeding (HMB) is a common problem in adolescents. Untreated HMB may result in deleterious medical, psychological, and social consequences. Patients often benefit from a multidisciplinary team, which can include an obstetrician/gynecologist, adolescent medicine specialist or pediatrician, hematologist, and mental health provider.
A multispecialty clinic or coordinated team approach is ideal for using medical resources most efficiently to address both quality of life and the complexity of these patients, especially given the high likelihood of an underlying bleeding disorder. The purpose of this article is to provide up-to-date guidance on evaluating, diagnosing, and managing HMB in adolescents.
Background
Definition of Heavy Menstrual Bleeding
Understanding what constitutes HMB is the first step in identifying adolescents who may require evaluation and treatment. Historically, menstrual bleeding has been quantified by volume: typical menstrual bleeding is considered to be 30 mL per cycle or 3 to 6 pads or tampons per day.1 HMB has been generally defined as menses lasting longer than 7 days2 or blood loss over 80 mL during the menstrual period. This definition was drawn from a 1966 population study of 458 Swedish women aged 15 to 50 years. Spectrophotometric analysis of the hemoglobin concentration in menstrual blood was used to calculate blood loss, and subjects' hemoglobin and plasma iron concentrations were measured. Study participants who lost more than 80 mL of menstrual blood were more likely to have hemoglobin concentrations less than 12 g/dL and plasma iron concentrations less than 80 [micro]g/100 mL.3
In practice, accurately quantifying menstrual bleeding is challenging. Subjective estimation of blood loss is imprecise. Pad or tampon counts can be unreliable due to recall bias, and the amount of blood held in menstrual products varies widely based on frequency of pad or tampon changes and by brand. Further, although the proportion of actual blood in menstrual fluid averages 36%, the range has been estimated to be from 1.6% to 81%, with vaginal or cervical secretions and endometrial tissue comprising the remainder.4 Rather than relying on direct quantification, validated bleeding assessment tools (BATs) developed by hematologists and implemented in primary care settings can be used to estimate the volume of blood loss. Examples include the Pictorial Blood Loss Assessment Chart (PBAC), which has been reported to have a sensitivity and specificity of approximately 80%,5 and the newer Phillips BAT or International Society on Thrombosis and Haemostasis-Blood Assessment Tool (ISTH-BAT)6,7
Contemporary guidelines define HMB more broadly. The American College of Obstetricians and Gynecologists (ACOG)8 and the International Federation of Gynecology and Obstetrics (FIGO)9 have adopted the patient-centered definition of HMB from the United Kingdom's National Institute of Health and Clinical Excellence: "excessive menstrual blood loss that interferes with a woman's physical, social, emotional, or material quality of life."10 Aside from meeting criteria in a BAT, signs of excessive bleeding include saturating a pad or tampon every 1 to 2 hours for several hours, passing clots larger than 1 cm in diameter, or bleeding lasting more than 7 days.1,11 The Menstrual Bleeding Questionnaire (MBQ), a recently developed tool that has been validated in adults,12 and the adolescent MBQ (aMBQ), which was adapted for and validated in adolescents with HMB,13 estimate both blood loss and its effect on quality of life.
Epidemiology and Relevance
HMB is common in adolescence, although studies show a broad range in prevalence. According to a 2006 population-based study in Sweden, up to 37% of 1000 adolescents aged 15 to 20 years experienced HMB.14 Population studies in Nigeria and Hong Kong reported an HMB prevalence of 12%15 and 18%,16 respectively.
Despite the high prevalence, HMB is likely underreported, underdiagnosed, and therefore potentially undertreated, resulting in medical, psychological, and social consequences. In an Australian cross-sectional, population-based study of 1051 adolescent girls between the ages of 15 and 19 years, 93% reported menstrual pain or symptoms, and 69% of those girls reported moderate to severe pain. However, only one-third of those reporting pain sought care from their primary physicians17; possibly these individuals were embarrassed or afraid due to little education about or scant preparation for menstruation. Without a good understanding of normal menses, adolescents may not recognize that HMB is abnormal or may assume that there are no treatment options, and thus may omit menstrual history when speaking to health care providers.18
Medical complications of untreated HMB in adolescents include symptomatic iron deficiency with or without anemia, which may cause fatigue, weakness, and deficits in attention and concentration. According to a 2016 retrospective study of 114 adolescents between 9 and 19 years old who were referred to a Young Women's Hematology clinic for symptoms related to HMB, hemoglobin or complete blood count (CBC) did not show anemia in half of the adolescents with abnormal ferritin levels and iron deficiency.19 Adolescents with HMB may present with severe iron-deficiency anemia, requiring blood transfusion, urgent care and emergency department visits, and hospitalization.20 HMB may also be the presenting, or only, symptom of a bleeding disorder.21 Lastly, adolescents with HMB experience psychosocial consequences. In a 2010 study of 184 adolescents between the ages of 13 and 18 years with menstrual concerns referred to a tertiary care center, questionnaire results revealed physical and psychosocial health scores similar to those of children with other chronic illness, such as cystic fibrosis.22
Causes of Heavy Menstrual Bleeding
FIGO recommends classifying HMB based on the PALM (structural)-COEIN (nonstructural) system. This is an acronym to describe the various causes of bleeding: Polyp, Adenomyosis, Leiomyoma, Malignancy-Coagulopathy, Ovulatory Dysfunction, Endometrial Dysfunction, Iatrogenic, and Not Otherwise Classified.2
The PALM-COEIN system is generally geared toward adult patients, but may be applied to adolescents, if the age of the patient is thoughtfully considered. In adolescents, structural etiologies of HMB are rare, whereas ovulatory dysfunction and bleeding disorders are relatively common. Adolescents often experience anovulation and irregular menstrual cycles in the first 2 to 3 years after menarche due to an immature hypothalamic-pituitary-ovary axis. Anovulatory cycles lead to unopposed estrogen stimulation, continuous endometrial proliferation and instability, and resultant HMB.
Importantly, HMB that begins in adolescence may represent a bleeding disorder.23 Although the prevalence of a bleeding disorder in the general population is approximately 1% to 2%, it is closer to 20% in adolescents presenting for outpatient evaluation of HMB, and up to 33% in adolescents hospitalized for HMB.8,24,25 Adolescents presenting to the emergency department for HMB are also more likely to be diagnosed with a bleeding disorder.24 Approximately half of adolescents with a bleeding disorder will present with HMB at menarche; others may present later, after cycles become ovulatory.4 The most common bleeding disorders in this population are von Willebrand disease, platelet dysfunction, thrombocytopenia, and clotting factor deficiencies.8
Rarer causes of HMB in adolescents include physical trauma to the genital tract or foreign bodies, vascular malformations, hematologic or gynecologic malignancies, cancer treatments that induce myelosuppression and thrombocytopenia, endometriosis, polycystic ovarian syndrome, connective tissue disorders such as Ehlers-Danlos or Marfan syndrome, which can cause collagen, fibrin and matrix protein abnormalities, and medications including antithrombotic therapy, depot medroxyprogesterone, or an intrauterine device (IUD). Endocrine disorders including thyroid disease, diabetes, and Cushing's syndrome may cause hypothalamic and pituitary disruptions that result in bleeding abnormalities. Chronic renal or hepatic disease may cause hypothalamic disruption or alterations in the clotting cascade.
Screening for Heavy Menstrual Bleeding
As adolescents may not spontaneously share menstrual concerns or know how to seek medical evaluation for HMB, it is important for primary care providers and obstetrician/gynecologists to routinely ask about menstrual history and provide education to patients and families about what is normal. ACOG recommends treating menstruation as a "vital sign"26 by asking about the first day of the last menstrual cycle and menstrual patterns at every office visit. Normalizing menses as a standard component of overall health may alleviate anxiety about menstruation and elicit history that an adolescent may otherwise omit.22 For example, counseling adolescents that menstrual cycles are not typically very regular at that stage of development can be very reassuring. Conversely, adolescents who report that their bleeding requires them to change their menstrual pad every hour or floods their clothes, or that their period lasts 8 or 10 days should be evaluated rather than reassured.
ACOG suggests a screening tool with the following 4 criteria to identify HMB that warrants further evaluation27:
* Menses longer than 7 days and "flooding" or "gushing" sensation or bleeding through pad or tampon in 2 hours;
* History of anemia;
* Family history of bleeding disorder; and/or
* History of bleeding disorder after hemostatic challenge (eg, a tooth extraction, surgery, or delivery).
Because of the high prevalence of bleeding disorders in adolescents presenting with HMB, an international working group was convened between 2016 and 2019 to determine care considerations for this population. A joint project between the ISTH and Standardization Subcommittees for Pediatric and Neonatal Thrombosis and Hemostasis and Women's Health Issues in Thrombosis and Hemostasis recommended in 2020 that adolescents with symptoms suggestive of a bleeding disorder or who have a family history of bleeding disorder would benefit from early consultation with a hematologist, even with normal initial laboratory testing.28
Evaluation
History and Review of Systems
A thorough menstrual history should be obtained including age of menarche, cycle length and regularity, number of days of bleeding, and presence or absence of dysmenorrhea. Quantifying menstrual bleeding can be estimated by counting how many tampons, pads, or other menstrual products are required daily or with a formal assessment tool such as the PBAC, Phillips BAT, ISTH-BAT,7 or aMBQ.13 Newer mobile applications, such as the online version of the pictorial blood assessment chart or period tracking apps, may be especially helpful for adolescents.6 Headaches, fatigue, depressed mood, anxiety, decreased cognition, or syncopal episodes may be signs of iron deficiency and/or anemia. A family or personal history of gingival bleeding, bleeding after a hemostatic challenge (eg, a surgery), or excessive bruising suggests an underlying bleeding disorder. Family or personal history of thyroid disease or androgen excess should also be elicited.
Physical Examination, Imaging, and Laboratory Evaluation
Vital signs can reveal hemodynamic instability and should include orthostatic blood pressure measurements and pulse rate. A thorough physical examination should assess for capillary refill time longer than 2 seconds, pallor, excessive bruising, abdominal distension, and abdominal or pelvic masses. As structural causes of HMB are less likely in an adolescent, a speculum examination is not usually required, but the choice to perform a trauma-informed external genital examination with a lubricated cotton swab or a single digital vaginal examination can be tailored to the individual.23
Likewise, imaging is not routinely recommended for initial screening, as it is unlikely to change management and incurs an increase in cost. Transabdominal pelvic ultrasound may be considered if initial management is not effective4 or there is pain or concern for an anatomic abnormality or mass. Initial laboratory evaluation includes a CBC, thyroid-stimulating hormone with consideration of free thyroxine (T4), prothrombin time, partial thromboplastin time, internalized normal ratio, fibrinogen, von Willebrand factor activity and antigen, and factor VIII activity. Ferritin is a useful measure of iron stores and is recommended for evaluation of iron deficiency. Urine human chorionic gonadotropin and testing for gonorrhea and chlamydia should be obtained to exclude pregnancy and sexually transmitted infections. In emergent settings with severe anemia or hemodynamic instability, blood typing and cross-matching are indicated before transfusion of blood or blood products.8
Management of Heavy Menstrual Bleeding
Acute Management
HMB is acutely managed based on severity. For adolescents presenting with normal vital signs and a hemoglobin level higher than 8 g/dL, guidelines are outlined in the "Chronic Management" section next. For these patients, scheduled follow-up after the initial visit is recommended within 1 to 7 days depending on the level of bleeding and rate of improvement.
When anemia is severe (hemoglobin <8 g/dL or hematocrit <25%), or if there is hemodynamic instability as evidenced by orthostatic hypotension, or active, profuse bleeding (saturating more than 1 pad every hour), inpatient admission is appropriate. The first step in an urgent or emergent setting should be resuscitation with IV fluids and blood products as necessary. Obtaining laboratory testing before blood product infusion is ideal,4,8 as transfusion may distort test results. However, one should not wait for the result of the CBC before starting fluid resuscitation. Imaging such as ultrasound can be considered as indicated by the situation. Concurrent iron replacement is also recommended if the patient is iron deficient. Platelet transfusion is indicated only for severe thrombocytopenia more than 50,000 or a known platelet disorder.21 Urgent hematology consultation is recommended for these patients.
After the initial resuscitation, hormonal medication is typically used as a first-line treatment to stabilize the endometrium and stop or diminish active bleeding. Examples of medications with dosing, special considerations, and contraindications can be found in Table 1. There is no evidence to support the superiority of one regimen over another, therefore decision-making is individualized. Hormones are usually administered as first-line therapy in the form of combined oral contraceptive (COC) pills, which contain an estrogen and a progestin. If oral medication is not tolerated or if severe bleeding continues after 2 doses,11 IV conjugated estrogen can be considered. If laboratory testing was not done before treatment, it should be noted that high doses of estrogen can elevate von Willebrand factor levels, although the effect of standard low-dose oral contraceptives on baseline low von Willebrand factor (mild disease) is less clear. If necessary, a von Willebrand factor level can be measured after estrogen has been tapered and administered at a low dose for about 3 months.29 As nausea and vomiting are common side effects of high-dose estrogen, prophylactic antiemetics should be administered.
If estrogen is contraindicated, for example, if there is a known thrombophilia, progestins alone can be initiated. These have similar efficacy and fewer side effects.4 The most commonly prescribed oral progestins are medroxyprogesterone acetate or norethindrone acetate (see Table 1). Oral hormone therapy is administered 2 to 4 times a day for 24 to 48 hours, at which time bleeding is usually diminished. The dose is then gradually tapered over several days to once daily dosing, which is maintained until resolution of HMB, hemoglobin normalization, or evaluation reveals an etiology indicating a different specific therapy. Another option is leuprolide acetate, an injectable gonadotropin-releasing hormone agonist less commonly used for controlling HMB in adolescents due to poorly tolerated side effects. Furthermore, the initial agonistic response to a gonadotropin releasing-hormone (GnRH) analog such as leuprolide stimulates gonadotropin and ovarian secretory activity and can exacerbate bleeding until downregulation occurs in 10 to 14 days.
Antifibrinolytic therapy can be added if hormonal therapy is not successful, or may be used as monotherapy. Oral or IV tranexamic acid (TXA) or aminocaproic acid can be administered during the initial management of acute bleeding and continued for a maximum of 5 days. TXA can also be taken orally every 8 hours for 5 days during menstrual periods. TXA is specifically approved for HMB2 in menarchal patients, although data are limited in children younger than 12 years. Although there is a theoretical increased risk of thrombosis when antifibrinolytics are administered with estrogen, an actual increase in thrombotic events has not been documented, and combined therapy may be appropriate in an acute setting when other therapies have not controlled the bleeding.4,8 For those with type 1 and some patients with type 2 von Willebrand disease, mild factor VIII deficiency, some platelet dysfunction syndromes, and some hypermobility syndromes, desmopressin (DDAVP) may be helpful. Hematology input is essential in developing a treatment plan for such patients.
Although invasive or surgical interventions are generally not required, a 30-mL Foley balloon catheter inserted into the uterus and inflated to physically tamponade intrauterine vessels is an option for severe bleeding as medications take effect, or if severe bleeding persists after medications are administered. Dilation and curettage, endometrial ablation, uterine artery embolization, or hysterectomy is generally not helpful or necessary for adolescent patients and thus should only be considered as last resorts in a life-threatening event.
Chronic Management
Chronic management starts after outpatient evaluation of HMB in a stable patient, or after hormonal medication is tapered to once-daily dosing after an acute intervention. ACOG Committee Opinion 785, "Screening and Management of Bleeding Disorders in Adolescents With Heavy Menstrual Bleeding," describes examples of how medication might be tapered to once-daily dosing.8
Estrogen and progesterone/progestin, or progesterone/progestin alone, are again the mainstays of therapy and are available in a variety of formulations. A combination of estrogen and progestin can be administered in pills, patches, or intravaginal rings. Progestin alone can be prescribed as pills, intramuscular or subcutaneous injections, implants, and levonorgestrel eluting IUDs (LNG-IUDs).
A method is chosen with shared decision-making between the provider, the adolescent, and the family. All of these medications have been shown to decrease menstrual bleeding, reduce number of school days missed due to HMB, and improve quality of life.30 Continuous or extended dosing that prevents withdrawal bleeding can be considered.4 If breakthrough bleeding occurs, doubling the COC dose may be preferable to allowing a withdrawal bleed. Antifibrinolytics such as TXA or aminocaproic acid can be used for a maximum of 5 days during menses as alternatives if there is a contraindication to hormone use, if patients are unable to tolerate hormones, or as an adjunct if hormonal therapy alone is insufficient.8
Although many patients take COCs to control HMB, other hormonal delivery systems have efficacy and acceptability among teens. A 2018 retrospective chart review of 76 adolescents with a mean age of 14.4 years suggested that transdermal combination patches were superior to COCs for controlling bleeding, and LNG-IUDs were also effective for controlling bleeding, but were chosen by adolescents less often.31 In a 2022 study of 47 adolescents with HMB managed by an integrated complex family planning and pediatric hematology clinic, the investigators observed that most patients began HMB treatment with COCs, but after 24 months, more patients were using implants or IUDs. This study suggested that adolescents with HMB will often choose long-acting reversible contraceptives if they are offered.32 Of note, an etonogestrel implant is generally not recommended as first-line treatment for HMB, as breakthrough bleeding is a common side effect.
The LNG-IUD is FDA approved for the management of HMB in adults. Although there are less data for adolescents, LNG-IUDs, in particular those with 52-mg LNG, have been shown to effectively treat HMB, even in the setting of bleeding disorders, including von Willebrand disease.8,27,33 Careful discussion with an adolescent about the IUD insertion procedure is important for consent and complete understanding. Most adolescents have not experienced an internal genital examination. Providers can help patients determine whether IUD insertion is best performed in the office or under sedation in a procedure suite or operating room. Consultation with hematology regarding the LNG-IUD insertion and postinsertion period is recommended for patients with bleeding disorders to reduce the risk of excessive bleeding and consider whether a hemostatic bridge with desmopressin acetate or antifibrinolytics is indicated during the IUD insertion process.8 However, a 2022 study of 35 adolescents and young adults (23 with an inherited bleeding disorder and 12 with Ehlers-Danlos syndrome) demonstrated similar bleeding complications after IUD insertion with and without additional hemostatic support. The rate of IUD expulsion, which is more likely to occur in the setting of heavy bleeding and within the first 21 days after insertion, was 9% in this study, which is similar to the expulsion rate for adults with HMB without a bleeding disorder.33 None of the 12 patients in this study with hypermobile Ehlers-Danlos syndrome experienced uterine perforation, despite theoretical concerns that a disorder of collagen synthesis increases the risk for perforation.
In adolescents with iron deficiency, increased iron intake via iron-rich foods is encouraged and oral iron therapy should be initiated. Daily or every other day dosing of 60 to 120 mg is continued for 3 to 6 months until anemia symptoms resolve and ferritin levels normalize to greater than 15 [micro]g/L. For patients who do not tolerate or are unresponsive to oral iron, IV iron can be considered. During iron therapy, stool softeners are usually recommended to reduce constipation. Treatment response can also be monitored with hemoglobin, hematocrit, and routine BATs to estimate reduction in blood loss and quality-of-life improvement.
The FIGO definition of HMB includes the impact on social and emotional well-being; thus, psychosocial support is important. A 2022 retrospective cohort of 1168 adolescents 9 to 18 years old revealed that 50.9% of patients seen by pediatricians for HMB were diagnosed with depression. In contrast, only 24.2% of patients in this cohort seen for a well visit were diagnosed with depression. These observations suggest that HMB may independently contribute to the development of depression in affected adolescents. Of the adolescents with both HMB and depression, 88% were diagnosed with depression at the same time or after they were given an HMB diagnosis is a risk factor for the development of depression.34 Quality-of-life surveys from adolescents with HMB show that school is the most affected domain, manifesting as missed school days, decreased concentration and increased fatigue in class, decreased participation in sports and physical activity, increased feelings of isolation from peers, and anxiety.22,34 Screening for depression and anxiety and timely initiation of mental health support may alleviate the psychological and social burdens of HMB.
Conclusion
HMB is prevalent among adolescents. Approximately 20% of adolescents with HMB have an underlying bleeding disorder. HMB negatively affects self-esteem, school attendance, and participation in sports, and results in an increase in anemia, iron deficiency, depression, fatigue, and emergency department utilization. Thoughtful screening by using menstruation as a "vital sign" can help prevent complications, provide education to patients and families, and identify adolescents who would benefit from a health care team that includes pediatric and adolescent gynecology or adolescent medicine, hematology, and mental health specialists. Hormonal and antifibrinolytic medications are the mainstays of acute and chronic therapies for HMB, with an emphasis on improving the individual's quality of life by reducing bleeding and improving symptoms of anemia with or without iron deficiency.
Practice Pearls
* HMB is excessive bleeding that interferes with an individual's physical, social, emotional, or material quality of life, menses lasting longer than 7 days, saturating 1 pad or tampon every 1 to 2 hours for several hours, or passing clots greater than 1 cm.
* Adolescents may assume HMB is normal or may not seek care due to embarrassment; therefore, asking about menses routinely as a "vital sign" may reveal HMB warranting further evaluation.
* Online and paper resources to quantify blood loss include the PBAC, Phillips BAT, ISTH-BAT, and aMBQ.
* HMB in adolescents is commonly due to hypothalamic-pituitary-ovarian axis immaturity; however, 20% to 33% of teens with HMB have an underlying bleeding disorder.
* Acute HMB is managed with hemodynamic stabilization followed by high-dose oral or IV hormonal therapy and/or antifibrinolytics. Chronic bleeding management is tailored to the adolescent's preference and lifestyle.
References