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Managing heavy menstrual bleeding in adolescents


Heavy menstrual bleeding (HMB) is one of the most common adolescent gynecologic complaints, with prevalence rates ranging widely from 12.1% to 37%.1,2The differential diagnosis is broad: anovulatory bleeding is common, and hypothyroidism should be considered. Bleeding disorders may be the underlying cause in approximately 20% of cases.3–5The importance of early recognition of HMB and its underlying cause is underscored by the negative impact on quality of life, which may include missed school days, lifestyle disruption, development of iron deficiency, and fatigue.6,7HMB is objectively defined as prolonged (>7 days) or excess blood loss of more than 80 mL per menstrual cycle.8

Estimating menstrual blood loss is difficult: a pictorial bleeding assessment calendar (PBAC) score has been developed and validated in adult women, with more than 80% sensitivity and specificity for scores higher than 100 being associated with blood loss of more than 80 mL.The PBAC experience in an adolescent population is limited,10 leading some clinicians to question its use and interpretation in the clinical setting. Clinical characteristics that predict HMB include clots larger than 1 inch, low serum ferritin, the need to change a pad or tampon because it is saturated more than hourly, or flooding.8

Differential diagnosis

HMB in adolescents is often related to an immature hypothalamic-pituitary-ovarian (HPO) axis, resulting in anovulatory cycles. Up to 85% of cycles are anovulatory in the first year after menarche and up to 44% of cycles at 4 years after menarche.11 However, when a patient presents with significant bleeding, an astute clinician will still entertain a bleeding diathesis superimposed on the HPO immaturity/anovulation mechanism. Polycystic ovary syndrome occurs in 5% to 10% of adolescents12and may result in HMB episodes due to prolonged periods between menses and over-thickening of the endometrial lining. Other endocrinopathies, such as hyper/hypothyroidism and Cushing syndrome, can also result in HMB. Because up to 62.3% of teens are sexually active by grade 12,pregnancy-related complications need to be considered and ruled out. Anatomic abnormalities, such a duplication of the Müllerian system and double vagina, may present with the perception of tampon overflow. Polyps and fibroids are rare causes of bleeding in this age group.

The differential diagnosis should guide the features of the physical examination and the investigations chosen. These may include: a speculum examination, a pregnancy test, cervical swabs for trichomonas, Neisseria gonorrhoeae, and Chlamydia trachomatis, and an ultrasound of the pelvis. A speculum examination is not always indicated, especially when the teen is precoital and the bleeding is unlikely to be from the lower genital tract. If a more complete examination is indicated in a young teenager or “tween,” vaginoscopy is a valuable tool and less traumatic than a speculum exam.

A complete blood count and platelet count are important to rule out anemia or thrombocytopenia. Serum ferritin is useful to rule out iron deficiency. Thyroid-stimulating hormone screening should be performed in all patients because hypothyroidism can result in HMB. It is important to note that a normal blood count, platelet count, or coagulation studies (prothrombin time/interational normalized ratio  and partial thromboplastin time do not exclude most bleeding disorders.

Menorrhagia and bleeding disorders

A congenital bleeding disorder is suspected when there is a personal or family history of bleeding. An acquired bleeding problem may be suspected with anticoagulant therapy, medications that inhibit platelet function, or when there are comorbidities such as renal disease, liver disease, and hypothyroidism. No single bleeding symptom is pathognomonic of a specific bleeding disorder, and significant overlap exists among the clinical manifestations of all the bleeding disorders (Table 1). Among patients with bleeding disorders, HMB is very common and may be the only bleeding symptom in 20% of adolescents.6

Philipp et al developed a screening tool with sensitivity of 82% for women with HMB to try to better identify an underlying bleeding disorder. The screen is positive if the patient reports (1) duration of menses ≥ 7 days, “flooding” or impairment of daily activities with menses; (2) a history of treatment for anemia; (3) a family history of a diagnosed bleeding disorder; or (4) a history of excessive bleeding with tooth extraction, tonsillectomy, adenoidectomy, delivery, or miscarriage, or bleeding complications from surgery.13Combining this screen with a positive PBAC increases sensitivity to 95%. In addition, women who meet the criteria summarized in Table 2 should be evaluated for a bleeding disorder.14Because an adolescent will not have been exposed to many hemostatic challenges such as delivery or surgery, a history of significant bleeding in the patient’s mother may indicate an unrecognized bleeding disorder and should prompt investigations. Frequently diagnosed bleeding disorders in women with HMB include von Willebrand disease (VWD), mild platelet function disorders (PFD), and mild factor deficiencies (eg, Factor XI).

The approach to investigation is outlined in Table 3. Intra-patient variation in coagulation studies, particularly von Willwbrand factor (VWF), is influenced by physiologic stressors and hormones. Testing should be avoided in stressed, ill, or pregnant patients, including in the context of acute severe hemorrhage. Serial testing (on ≥ 2 different occasions) for VWD is often required to make the diagnosis. Platelet function testing is poorly standardized and most abnormalities are mild and difficult to interpret. Thus, bleeding disorder investigations should be ordered and interpreted in collaboration with a hematologist.

HMB may also be multifactorial. Therefore, a gynecologic etiology does not rule out an underlying bleeding disorder. In fact, women with bleeding disorders and HMB may experience other gynecologic conditions at an increased frequency. In a case-control study, Kirtava et al found that 30% of women with VWD reported a history of endometriosis and 52% reported a history of ovarian cysts, as compared to 13% and 22% of controls.15On the other hand, a retrospective review of adult women with bleeding disorders failed to demonstrate the same degree of gynecologic burden.16Regardless, a low index of suspicion is required in the approach to investigation of HMB.

Treatment

In all patients with HMB, iron deficiency should be assessed and treated. No one iron preparation is more effective than another, so a patient should be encouraged to try different preparations if adverse effects are limiting. The target dose is in the range of 150 mg/day to 200 mg/day of elemental iron in 1 to 3 divided doses/day. To aid in absorption, iron supplements should be taken on an empty stomach with a glass of orange juice. The duration of replacement should extend at least 3 months beyond normalization of hemoglobin to allow for replenishment of iron stores.

Treatment of HMB will be determined by the underlying etiology, the patient’s need for contraception, her adherence or compliance capabilities, and the acceptability of adverse effects, costs, and interventions. There is a significant overlap in the management of patients with and without bleeding disorders.4,14,17Combined hormonal contraception such as oral contraceptive pills, the transdermal patch, and the vaginal ring are effective in the treatment of HMB. Eighty-six percent of adolescents with VWD will have a significant decrease in their PBAC scores using combined hormonal contraception.18Both cyclic and continuous use of combined hormonal contraception are efficacious, with adolescents often preferring an extended cycle.19Oral progestin therapy can be effective but is often poorly tolerated and therefore rarely used.4,19After an informed discussion about impact on bone density, potential for nuisance irregular bleeding or amenorrhea, and possible weight gain, long-acting injectable or subcutaneous progestins can be considered.

Finally, the levonorgestrel-releasing intrauterine system has been demonstrated to be effective in reducing menstrual blood loss. Despite initial concerns regarding safety and acceptability in adolescents, it appears to be safe and well-tolerated in properly selected teens.4,14,19

In patients who do not tolerate hormonal therapies or wish to be fertile, antifibrinolytic inhibitors, such astranexamic acid, 1-1.5 g, 3 to 4 times per day, have been shown to be useful for treatment of HMB in a wide range of clinical situations, including VWD and PFD and in those with no bleeding disorder. Desmopressin acetate (DDAVP) induces secretion of VWF from endothelial cells and results in an increase in VWF and FVIII. The best defined indications for DDAVP are VWD20and Hemophilia A,21where in mild-to-moderate disease, DDAVP raises factor levels 3- to 10-fold. DDAVP is also clinically useful in PFDs.22DDAVP use is associated with response rates of 77% in HMB18but is limited by tachyphylaxis and issues surrounding fluid retention and hyponatremia.

Use of multiple modalities (such as combination hormonal contraception and tranexamic acid or DDAVP) or replacement of the missing coagulation factors to gain adequate control of menstruation (such as with VWF concentrate in severe VWD) may be necessary in women with severe or refractory cases.

A multidisciplinary approach, with involvement of a hematologist, is recommended. Surgical intervention, including dilation and curettage and Foley balloon tamponade, is rarely necessary and should be reserved for refractory or life-threatening HMB that is unresponsive to medical and less-invasive therapies.

Summary

HMB is a common complaint in adolescence. The differential diagnosis is broad and requires a low threshold for investigation, particularly for bleeding disorders. A multidisciplinary approach with involvement by both gynecologists and hematologists can be beneficial in making the diagnosis of a bleeding disorder and is invaluable in the management of these patients.

References

1. Barr F, Brabin L, Agbaje S, et al. Reducing iron deficiency anaemia due to heavy menstrual blood loss in Nigerian rural adolescents. Public Health Nutr. 1998;1:249–257.

2. Friberg B, Ornö AK, Lindgren A, Lethagen S. Bleeding disorders among young women: a population-based prevalence study. Acta Obstet Gynecol Scand. 2006;85:200–206.

3. Frishman GN. Evaluation and treatment of menorrhagia in an adolescent population. J Minim Invasive Gynecol. 15:682–688.

4. Sokkary N, Dietrich JE. Management of heavy menstrual bleeding in adolescents. Curr Opin Obstet Gynecol. 2012;24:275–280.

5. James AH. Bleeding disorders in adolescents. Obstet Gynecol Clin North Am. 2009;36:153–162.

6. Chi C, Pollard D, Tuddenham EGD, Kadir RA. Menorrhagia in adolescents with inherited bleeding disorders. J Pediatr Adolesc Gynecol. 2010;23:215–222.

7. Wang W, Bourgeois T, Klima J, et al. Iron deficiency and fatigue in adolescent females with heavy menstrual bleeding. Haemophilia. 2013;19:225–230.

8. Warner PE, Critchley HOD, Lumsden MA, et al. Menorrhagia I: measured blood loss, clinical features, and outcome in women with heavy periods: a survey with follow-up data. Am J Obstet Gynecol. 2004;190:1216–1223.

9. Higham JM, O’Brien PM, Shaw RW. Assessment of menstrual blood loss using a pictorial chart. Br J Obstet Gynaecol. 1990;97:734–739.

10. Sanchez J, Andrabi S, Bercaw JL, Dietrich JE. Quantifying the PBAC in a pediatric and adolescent gynecology population. Pediatr Hematol Oncol. 2012;29:479–484.

11. Read GF, Wilson DW, Hughes IA, Griffiths K. The use of salivary progesterone assays in the assessment of ovarian function in postmenarcheal girls. J Endocrinol. 1984;102:265–268.

12. Gray SH, Emans SJ. Abnormal vaginal bleeding in adolescents. Pediatr Rev. 2007;28:175–182.

13. Philipp CS, Faiz A, Dowling NF, et al. Development of a screening tool for identifying women with menorrhagia for hemostatic evaluation. Am J Obstet Gynecol. 2008;198:163.e1–8.

14. James AH, Kouides PA, Abdul-Kadir R, et al. Von Willebrand disease and other bleeding disorders in women: consensus on diagnosis and management from an international expert panel. Am J Obstet Gynecol. 2009;201:12.e1–8.

15. Kirtava A, Drews C, Lally C, Dilley A, Evatt B. Medical, reproductive and psychosocial experiences of women diagnosed with von Willebrand’s disease receiving care in haemophilia treatment centres: a case-control study. Haemophilia. 2003;9:292–297.

16. Byams VR, Kouides P a, Kulkarni R, et al. Surveillance of female patients with inherited bleeding disorders in United States haemophilia treatment centres. Haemophilia. 2011;17 Suppl 1:6–13.

17. James AH. Obstetric management of adolescents with bleeding disorders. J Pediatr Adolesc Gynecol. 2010;23:S31–37.

18. Mikhail S, Kouides P. Von Willebrand disease in the pediatric and adolescent population. J Pediatr Adolesc Gynecol. 2010;23:S3–10.

19. Wilkinson JP, Kadir RA. Management of abnormal uterine bleeding in adolescents. J Pediatr Adolesc Gynecol. 2010;23:S22–30.

20. Federici AB. The use of desmopressin in von Willebrand disease: the experience of the first 30 years (1977-2007). Haemophilia. 2008;14 Suppl 1:5–14.

21. Franchini M, Zaffanello M, Lippi G. The use of desmopressin in mild hemophilia A. Blood Coagul Fibribolysis. 2010;21:615–619.

22. Bolton-Maggs PHB, Chalmers EA, Collins PW, et al. A review of inherited platelet disorders with guidelines for their management on behalf of the UKHCDO. Br J Haematol. 2006;135:603–633.

23. Srámek A, Eikenboom JC, Briët E, Vandenbroucke JP, Rosendaal FR. Usefulness of patient interview in bleeding disorders. Arch Intern Med. 1995;155:1409–1415.

24. Miesbach W, Alesci S, Geisen C, Oldenburg J. Association between phenotype and genotype in carriers of haemophilia A. Haemophilia. 2011;17:246–251. 

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