Heavy menstrual bleeding (HMB), also known as menorrhagia, is a benign yet clinically significant condition for the women who experience it.
Unlike normal menstruation, which produces an average menstrual blood loss of 30 mL to 40 mL per cycle,1 blood loss in HMB is greater than 80 mL per cycle.2
Excessive menstrual blood loss can be correlated to HMB in approximately 30% of women of reproductive age.3
Pathophysiology
During menstruation, blood clotting helps manage the rate of blood flow. Women with HMB have elevated levels of plasminogen activators, which ultimately results in blood clot breakdown that is more rapid than normal.
The result is excessive bleeding during menstruation.3
In nearly half of HMB presentations, no organic pathology can be identified.4 For some women, HMB has been attributed to platelet or hemostatis disorders.5 However, a greater proportion of women without a known cause of HMB may have an undiagnosed bleeding disorder.5,6 HMB may also be related to hormonal imbalance, ovary dysfunction or iatrogenic sources.4
For women in whom an underlying cause is established, uterine fibroids and polyps are among the most common pathologies. Research has identified risk markers for HMB, including age, premenopausal leiomyomata and endometrial polyps.7
Impact of HMB
Approximately 30% of women of reproductive age self-report excessive blood loss during menstruation, resulting in annual indirect costs that approach $12 billion.8 Menstrual problems are among the most common reasons women seek healthcare. More than half of all consultations with primary care physicians for menstrual concerns are related to HMB.9
However, a recent survey conducted by the National Association of Nurse Practitioners in Women's Health found that women in the United States may delay reporting their symptoms because they perceive their excessive menstrual bleeding as normal.10
The effect of HMB on quality of life is what prompts many women to seek treatment. Women who experience HMB often report fatigue, anxiety and social embarrassment. They also report restrictions on social, leisure and physical activities because of the need to change sanitary products frequently.11,12
HMB is a common cause of iron-deficiency anemia in women.8 When severe, anemia can be associated with an increased probability of emergency department visits, blood transfusions and increased overall healthcare costs.13
Diagnosis
HMB is a subjective finding and must be distinguished clinically from other common gynecologic conditions and illnesses, such as endometrial hyperplasia or uterine cancer.
The initial steps in the evaluation of women with suspected bleeding disorders are a thorough medical history and a detailed physical examination.14
Ideally, the history should define the nature of the bleeding, delineate the potential pathology and identify the patient's concerns, expectations and needs.2 Published research and guidelines recommend routine speculum and bimanual examinations for women with excessive bleeding.15-17 Transvaginal ultrasonography may be performed to identify structural abnormalities such as fibroids, polyps or other uterine pathology.2
For women who may have an underlying bleeding condition, tests such as a complete blood count, platelet count and von Willebrand disease assay may be performed to exclude the possibility of anemia or a bleeding disorder.14
It can be difficult to quantify blood loss in women with menstrual irregularities. The patient's perception of excessive bleeding is highly subjective, and objective measurement of blood loss requires specialized techniques that may be impractical for general use.2
In general, measuring menstrual blood loss directly (using the alkaline hematin method) or indirectly (using a pictorial blood loss chart) is not recommended for the diagnosis of HMB.
Practical diagnosis of HMB may be the best approach. This can be defined as excessive blood loss that is not tolerated by the patient 
and negatively affects quality of life.18
Pharmacologic Treatment
Hormonal and nonhormonal pharmacologic agents are considered first-line therapy for HMB.2
These agents can reduce menstrual blood loss and avoid the risks associated with surgery.19
Hormonal therapies such as progestogens, combined oral contraceptives and intrauterine systems are designed to inhibit growth of the endometrium, thereby preventing conception and curtailing heavy bleeding.20
Nonhormonal, noncontraceptive agents may be appropriate for women who cannot or do not want to take hormonal therapies. The administration of nonsteroidal anti-inflammatories (NSAIDs) is thought to reduce prostaglandin levels, which are elevated in women with HMB. However, NSAIDs are contraindicated in women with certain underlying hemostatic disorders because of their inhibitory effect on platelet aggregation.20
Tranexamic acid is an antihemorrhagic drug that decreases fibrinolysis in the uterus by inhibiting the conversion of plasminogen to plasmin.
Oral, immediate-release tranexamic acid has been used for more than 4 decades in applications including the reduction of bleeding in surgery and the treatment of HMB.21 This drug is generally well tolerated; the majority of reported adverse effects are gastrointestinal.9,21
According to prescribing information for tranexamic acid, it should not be prescribed for women who have active thromboembolic disease, a history of thrombosis or thromboembolism, or risk of thrombosis or thromboembolism.22
Surgical Treatment
Endometrial ablation and hysterectomy are the only curative options for HMB. Neither is appropriate for women who want to preserve fertility.2
Surgical interventions are effective in many women; however, they should be considered only after careful review of the risks inherent in surgery.9 Endometrial ablation is an outpatient surgical procedure requiring little, if any, anesthesia.23 Although conception is unlikely after ablation (< 1%), risks are associated with pregnancy in women who have undergone this procedure.24
Historically, hysterectomy has been the definitive treatment for HMB.2 An estimated 33% of patients experience complications after this surgery.25
Approved Treatments
Two medical therapies are approved in the United States for the management of HMB. In 2009, the levonorgestrel-releasing intrauterine system (LNG-IUS; Mirena) was approved for the treatment of HMB in women who wish to use intrauterine contraception for pregnancy prevention. Later in 2009, an oral, nonhormonal, antifinbrinolytic drug, modified-release tranexamic acid (TA; Lysteda), was approved for the treatment of cyclic HMB. LNG-IUS is placed within the endometrial cavity by a healthcare provider and is effective for up to 5 years. TA is self-administered for up to 5 days only during menstrual bleeding.
LNG-IUS releases progestin that suppresses the endometrium, thereby decreasing the proliferative effect of estrogen. This effectively reduces the number of days of menstruation and the volume of menstrual blood loss. The most common adverse effect is intermenstrual bleeding or spotting, which tends to subside after the first three cycles.26 As with other intrauterine devices, perforation or penetration of the uterus may occur during insertion of the LNG-IUS; this incidence is less than 1 in 1,000 insertions.27 The estimated cost for LNG-IUS is approximately $500 to $800.28 The device and the associated services are often covered partially or totally by health insurance.
TA inhibits the breakdown of fibrin clots by competitively blocking the activation of plasminogen to plasmin. TA can produce a reduction in menstrual blood loss approaching 40%.29,30 The most commonly reported adverse effects during administration of TA are headache, menstrual discomfort and back pain.31 A 1-month supply of TA is estimated to cost $175.32 The medication is covered wholly or partially by many health insurance plans.
Management
Strategies for managing HMB should aim to reduce menstrual blood loss and improve the patient's quality of life. Recent treatment guidelines suggest the use of at least one nonsurgical option to manage HMB for at least 3 months before considering a referral for secondary care.2
Determining minimally important changes in HMB is important when evaluating the efficacy of therapies. However, quantitative measurements of menstrual blood loss are not practical in routine care because this method places a burden on the patient to collect and return all sanitary products for laboratory analysis.2 Furthermore, a women's perception of excessive menstrual blood loss does not always correlate to the established clinical definition for HMB (menstrual blood loss greater than 80 mL per cycle).33 Evidence for therapeutic efficacy of a selected treatment should be based on menstrual blood loss changes that are meaningful to the patient.34
Despite the number of instruments available to measure outcomes for patients with menstrual irregularities, few tools appropriately evaluate quality of life in women with HMB.
A review of several quality-of-life instruments suggests a lack of specificity for HMB, unclear responsiveness statistics and unclear scoring issues.24 The Menorrhagia Impact Questionnaire (MIQ) is a validated, patient-reported quality-of-life outcome measure designed to measure the effect of HMB on a woman's self-assessment of menstrual blood loss, limitations in social and leisure activities, physical activities, and the ability to work.24
The MIQ can be useful to track the progress of treatment in women with HMB based on patient-reported changes in quality-of-life aspects that are perceived as beneficial.
It is also important to consider the management of postmenopausal women with vaginal bleeding. As assessed via transvaginal ultrasonograpy, an endometrial lining greater than 4 mm in postmenopausal women with bleeding warrants an investigation to exclude atypia, dysplasia and endometrial cancer.35 Diagnostic tests such as endometrial biopsy, transvaginal ultrasonography, saline infusion sonography and hysteroscopy can be performed to determine the cause of bleeding, but no consensus exists for evaluating women with postmenopausal bleeding.36
Treatment with hormone therapy may prove successful for postmenopausal bleeding. If this strategy is not successful, a referral to a gynecologist may be necessary.37
Comprehensive Care
HMB is a clinically significant condition that affects physical, social, emotional and material quality of life. Management should balance a woman's needs and preferences to improve quality of life while working to reduce menstrual blood loss to an acceptable level with minimal adverse effects. NPs and PAs are in an optimal position to provide comprehensive care for women experiencing HMB.
References
1. Farquhar C, Brown J. Oral contraceptive pill for heavy menstrual bleeding. Cochrane Database Syst Rev. 2009(4):CD000154.
2. National Institute for Health and Clinical Excellence. Heavy menstrual bleeding. Guideline 44. National Collaborating Centre for Women's and Children's Health, editor. London, England; 2007. www.nice.org.uk/nicemedia/pdf/CG44NICEGuideline.pdf
3. El-Hemaidi I, et al. Menorrhagia and bleeding disorders. Curr Opin Obstet Gynecol. 2007;19(6):513-520.
4. Oehler MK, Rees MC. Menorrhagia: an update. Acta Obstet Gynecol Scand. 2003;82(5):405-22.
5. Shankar M, et al. von Willebrand disease in women with menorrhagia: a systematic review. BJOG. 2004;111(7):734-740.
6. Phillipp CS, et al. Platelet functional defects in women with unexplained menorrhagia. J Thromb Haemostas. 2003;1(3):477-484.
7. Apgar BS, et al. Treatment of menorrhagia. Am Fam Physician. 2007;75(12):1813-1819.
8. Liu Z, et al. A systematic review evaluating health-related quality of life, work impairment, and health-care costs and utilization in abnormal uterine bleeding. Value Health. 2007;10(3):183-194.
9. Roy SN, Bhattacharya S. Benefits and risks of pharmacological agents used for the treatment of menorrhagia. Drug Saf. 2004;27(2):75-90.
10. National survey of nurse practitioners reveals serious toll of heavy monthly periods: common condition affects health, lifestyle, and finances but patients delay reporting symptoms [press release] Washington, DC: National Association of Nurse Practitioners in Women's Health; March 21, 2011. http://www.prnewswire.com/news-releases/national-survey-of-nurse-practitioners-reveals-serious-toll-of-heavy-monthly-periods-118356919.html
11. Cote I, et al. Use of health services associated with increased menstrual loss in the United States. Am J Obstet Gynecol. 2003;188(2):343-348.
12. Frick KD, et al. Financial and quality-of-life burden of dysfunctional uterine bleeding among women agreeing to obtain surgical treatment. Womens Health Issues. 2009;19(1):70-78.
13. Morrison J, et al. Assessment of the prevalence and impact of anemia on women hospitalized for gynecologic conditions associated with heavy uterine bleeding. J Reprod Med. 2008;53(5):323-330.
14. American College of Obstetricians & Gynecologists Committee on Adolescent Health Care. ACOG Committee Opinion No. 451: Von Willebrand disease in women. Obstet Gynecol. 2009;114(6):1439-1443.
15. Mohan S, et al. Diagnosis of abnormal uterine bleeding. Best Pract Res Clin Obstet Gynaecol. 2007;21(6):891-903.
16. Siddiqui N, Pitkin J. Menstrual disturbances. Obstet Gynaecol Reprod Med. 2007;17(5):154-162.
17. Woodman J, Piktin J. Menstrual disturbances. Obstet Gynaecol Reprod Med. 2010;20(11):329-334.
18. Bushnell DM, et al. Menorrhagia Impact Questionnaire: assessing the influence of heavy menstrual bleeding on quality of life. Curr Med Res Opin. 2010;26(12):2745-2755.
19. Osei J, Critchley H. Menorrhagia, mechanisms and targeted therapies. Curr Opin Obstet Gynecol. 2005;17(4):411-418.
20. Fraser IS, et al. A benefit-risk review of systemic haemostatic agents: part 2: in excessive or heavy menstrual bleeding. Drug Saf. 2008;31(4):275-282.
21. Wellington K, Wagstaff AJ. Tranexamic acid: a review of its use in the management of menorrhagia. Drugs. 2003;63(13):1417-1433.
22. Lysteda safety information. http://www.lysteda.com/HCP/About_Lysteda/safety_information.aspx
23. Fothergill RE. Endometrial ablation in the office setting. Obstet Gynecol Clin North Am. 2008;35(2):317-330.
24. Hare AA, Olah KS. Pregnancy following endometrial ablation: a review article. J Obstet Gynaecol. 2005;25(2):108-114.
25. Hurskainen R, et al. Diagnosis and treatment of menorrhagia. Acta Obstet Gynecol Scand. 2007;86(6):749-757.
26. Varma R, et al. Non-contraceptive uses of levonorgestrel-releasing hormone system (LNG-IUS)--a systematic enquiry and overview. Eur J Obstet Gynecol Reprod Biol. 2006;125(1):9-28.
27. Faculty of Family Planning and Reproductive Health Care Clinical Efficacy Unit. FFPRHC Guidance. The levonorgestrel-releasing intrauterine system (LNG-IUS) in contraception and reproductive health. J Fam Plann Reprod Health Care. 2004;30(2):99-109.
28. Bayer Healthcare Pharmaceuticals. MIRENA Website - Contraceptive Cost. http://www.mirena-us.com/hcp/ordering_and_reimbursement/contraceptive_cost.jsp
29. Lukes AS, et al. Tranexamic acid treatment for heavy menstrual bleeding: a randomized controlled trial. Obstet Gynecol. 2010;116(4):865-875.
30. Freeman E, et al. A dose-response study of a novel, oral tranexamic formulation for heavy menstrual bleeding. Am J Obstet Gynecol. 2011;205(4):319.
31. Muse K, et al. Long-term evaluation of safety and health-related quality of life in women with heavy menstrual bleeding treated with oral tranexamic acid. Womens Health (Lond Engl). 2011;7(6):699-707.
32. Tranexamic Acid (Lysteda) for Treatment of Menorrhagia. Med Lett Drugs Ther. 2010;52(1342):54-55.
33. Warner PE, et al. Menorrhagia II: is the 80-mL blood loss criterion useful in management of complaint of menorrhagia? Am J Obstet Gynecol. 2004;190(5):1224-1229.
34. Lukes AS, et al. Estimating a meaningful reduction in menstrual blood loss for women with heavy menstrual bleeding. Curr Med Res Opin. 2010;26(11):2673-2678.
35. Brand A, et al. Diagnosis of endometrial cancer in women with abnormal vaginal bleeding. J Soc Obstet Gynaecol Can. 2000;22(1):102-104.
36. van Hanegem N, et al. Diagnostic evaluation of the endometrium in postmenopausal bleeding: an evidence-based approach. Maturitas. 2011;68(2):155-164.
37. Albers JR, et al. Abnormal uterine bleeding. Am Fam Physician. 2004;69(8):1915-1926.
Anne A. Moore is a women's health nurse practitioner who is a professor of nursing at Vanderbilt University in Nashville. She has completed a disclosure statement and reports that editorial assistance for this manuscript was provided by The JB Ashtin Group, Inc. Financial support for manuscript development was provided by Ferring Pharmaceuticals Inc. Moore was not compensated for her work on this manuscript.