Background
Menorrhagia is defined as menstruation at regular cycle intervals but with excessive flow and duration and is one of the most common gynecologic complaints in contemporary gynecology. Clinically, menorrhagia is defined as total blood loss exceeding 80 mL per cycle or menses lasting longer than 7 days.[1] The World Health Organization reports that 18 million women aged 30-55 years perceive their menstrual bleeding to be exorbitant.[2] Reports show that only 10% of these women experience blood loss severe enough to cause anemia or be clinically defined as menorrhagia.[1, 3, 4] In practice, measuring menstrual blood loss is difficult. Thus, the diagnosis is usually based upon the patient's history.
A normal menstrual cycle is 21-35 days in duration, with bleeding lasting an average of 7 days and flow measuring 25-80 mL.[5]
Menorrhagia must be distinguished clinically from other common gynecologic diagnoses. These include metrorrhagia (flow at irregular intervals), menometrorrhagia (frequent, excessive flow), polymenorrhea (bleeding at intervals < 21 d), and dysfunctional uterine bleeding (abnormal uterine bleeding without any obvious structural or systemic abnormality).[5]
Nearly 30% of all hysterectomies performed in the United States are performed to alleviate heavy menstrual bleeding.[6] Historically, definitive surgical correction has been the mainstay of treatment for menorrhagia. Modern gynecology has trended toward conservative therapy both for controlling costs and the desire of many women to preserve their uterus.
Heavy menstrual bleeding is a subjective finding, making the exact problem definition difficult. Treatment regimens must address the specific facet of the menstrual cycle the patient perceives to be abnormal, (ie, cycle length, quantity of bleeding). Finally, treatment success is usually evaluated subjectively by each patient, making positive outcome measurement difficult.
Pathophysiology
Knowledge of normal menstrual function is imperative in understanding the etiologies of menorrhagia. Four phases constitute the menstrual cycle, follicular, luteal, implantation, and menstrual.
In response to gonadotropin-releasing hormone (GnRH) from the hypothalamus, the pituitary gland synthesizes follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which induce the ovaries to produce estrogen and progesterone.
During the follicular phase, estrogen stimulation results in an increase in endometrial thickness. This also is known as the proliferative phase.
The luteal phase is intricately involved in the process of ovulation. During this phase, also known as the secretory phase, progesterone causes endometrial maturation.
If fertilization occurs, the implantation phase is maintained. Without fertilization, estrogen and progesterone withdrawal results in menstruation.
Etiologic causes are numerous and often unknown. Factors contributing to menorrhagia can be sorted into several categories, including organic, endocrinologic, anatomic, and iatrogenic.
If the bleeding workup does not provide any clues to the etiology of the menorrhagia, a patient often is given the diagnosis of dysfunctional uterine bleeding (DUB). Most cases of DUB are secondary to anovulation. Without ovulation, the corpus luteum fails to form, resulting in no progesterone secretion. Unopposed estrogen allows the endometrium to proliferate and thicken. The endometrium finally outgrows its blood supply and degenerates. The end result is asynchronous breakdown of the endometrial lining at different levels. This also is why anovulatory bleeding is heavier than normal menstrual flow.
Hemostasis of the endometrium is directly related to the functions of platelets and fibrin. Deficiencies in either of these components results in menorrhagia for patients with von Willebrand disease or thrombocytopenia. Thrombi are seen in the functional layers but are limited to the shedding surface of the tissue. These thrombi are known as "plugs" because blood can only partially flow past them. Fibrinolysis limits the fibrin deposits in the unshed layer. Following thrombin plug formation, vasoconstriction occurs and contributes to hemostasis.
Anatomic defects or growths within the uterus can alter either of the aforementioned pathways (endocrinologic/hemostatic), causing significant uterine bleeding. The clinical presentation is dependent on the location and size of the gynecologic lesion.
Organic diseases also contribute to menorrhagia in the female patient. For example, in patients with renal failure, gonadal resistance to hormones and hypothalamic-pituitary axis disturbances result in menstrual irregularities. Most women in this renal state are amenorrheic, but others also develop menorrhagia. If uremic coagulopathy ensues, it usually is due to platelet dysfunction and abnormal factor VIII function. The resulting prolonged bleeding time causes menorrhagia that can be very tenuous to treat.
Due to the overwhelming factors that can contribute to the dysfunction of either the endocrine or hematological pathways, in-depth knowledge of an existing organic disease is just as imperative as understanding the menstrual cycle itself.
Epidemiology
Frequency
United States
While menorrhagia remains a leading reason for gynecologic office visits, only 10-20% of all menstruating women experience blood loss severe enough to be defined clinically as menorrhagia.[4]
Mortality/Morbidity
Infrequent episodes of menorrhagia usually do not carry severe risks to women's general health.
- Patients who lose more than 80 mL of blood, especially repetitively, are at risk for serious medical sequelae. These women are likely to develop iron-deficiency anemia as a result of their blood loss. Menorrhagia is the most common cause of anemia in premenopausal women. This usually can be remedied by simple ingestion of ferrous sulfate to replace iron stores. If the bleeding is severe enough to cause volume depletion, patients may experience shortness of breath, fatigue, palpitations, and other related symptoms. This level of anemia necessitates hospitalization for intravenous fluids and possible transfusion and/or intravenous estrogen therapy. Patients who do not respond to medical therapy may require surgical intervention to control the menorrhagia.
- Other sequelae associated with menorrhagia usually are related to the etiology. For example, with hypothyroidism, patients may experience symptoms associated with a low-functioning thyroid (eg, cold intolerance, hair loss, dry skin, weight gain) in addition to the effects of significant blood loss.[7]
Sex
Only females are affected by menorrhagia.
Age
Any woman of reproductive age who is menstruating may develop menorrhagia. Most patients with menorrhagia are older than 30 years.[5] This is because the most common cause of heavy menses in the younger population is anovulatory cycles, in which bleeding does not occur at regular intervals.[8]
HALLBERG L, NILSSON L. DETERMINATION OF MENSTRUAL BLOOD LOSS. Scand J Clin Lab Invest. 1964;16:244-8. [Medline].
Goldrath MH. Hysteroscopic endometrial ablation. Obstet Gynecol Clin North Am. Sep 1995;22(3):559-72. [Medline].
Fraser IS, Warner P, Marantos PA. Estimating menstrual blood loss in women with normal and excessive menstrual fluid volume. Obstet Gynecol. Nov 2001;98(5 Pt 1):806-14. [Medline].
Warner PE, Critchley HO, Lumsden MA, Campbell-Brown M, Douglas A, Murray GD. Menorrhagia I: measured blood loss, clinical features, and outcome in women with heavy periods: a survey with follow-up data. Am J Obstet Gynecol. May 2004;190(5):1216-23. [Medline].
Lentz GM. Abnormal Uterine Bleeding. In: Katz VL, Lentz GM, Lobo RA, Gershenson DM. Comprehensive Gynecology. 5th. Philadelphia, PA: Mosby; 2007:915-932.
Wright RC. Hysterectomy: past, present, and future. Obstet Gynecol. Apr 1969;33(4):560-3. [Medline].
Wilansky DL, Greisman B. Early hypothyroidism in patients with menorrhagia. Am J Obstet Gynecol. Mar 1989;160(3):673-7. [Medline].
Noorhasan DJ, Weiss G. Perimenarchal menorrhagia: evaluation and management. J Pediatr. Jan/2010;156 (1):162. [Medline]. [Full Text].
Glasser MH, Zimmerman JD. The HydroThermAblator system for management of menorrhagia in women with submucous myomas: 12- to 20-month follow-up. J Am Assoc Gynecol Laparosc. Nov 2003;10(4):521-7. [Medline].
Collins J, Schlesselman H. Hormone Replacement Therapy and Endometrial Cancer. In: Lobo R. Treatment of the Postmenopausal Woman. Philadelphia, PA: Lippincott, Williams & Wilkins; 1999.
[Guideline] James AH, Kouides PA, Abdul-Kadir R, Edlund M, Federici AB, Halimeh S, 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. May 28 2009;[Medline].
Kadir RA, Economides DL, Sabin CA, et al. Frequency of inherited bleeding disorders in women with menorrhagia. Lancet. Feb 14 1998;351(9101):485-9. [Medline].
Dodson MG. Use of transvaginal ultrasound in diagnosing the etiology of menometrorrhagia. J Reprod Med. May 1994;39(5):362-72. [Medline].
Dijkhuizen FP, Mol BW, Brölmann HA, Heintz AP. The accuracy of endometrial sampling in the diagnosis of patients with endometrial carcinoma and hyperplasia: a meta-analysis. Cancer. Oct 15 2000;89(8):1765-72. [Medline].
Shaw RW. Assessment of medical treatments for menorrhagia. Br J Obstet Gynaecol. Jul 1994;101 Suppl 11:15-8. [Medline].
Jurema M, Zacur H. Menorrhagia. UpToDate. Available at http://bit.ly/fHJVtw. Accessed March 29, 2009.
Fraser IS, McCarron G. Randomized trial of 2 hormonal and 2 prostaglandin-inhibiting agents in women with a complaint of menorrhagia. Aust N Z J Obstet Gynaecol. Feb 1991;31(1):66-70. [Medline].
Jensen JT, Parke S, Mellinger U, Machlitt A, Fraser IS. Effective treatment of heavy menstrual bleeding with estradiol valerate and dienogest: a randomized controlled trial. Obstet Gynecol. Apr 2011;117(4):777-87. [Medline].
Andersson JK, Rybo G. Levonorgestrel-releasing intrauterine device in the treatment of menorrhagia. Br J Obstet Gynaecol. Aug 1990;97(8):690-4. [Medline].
Rauramo I, Elo I, Istre O. Long-term treatment of menorrhagia with levonorgestrel intrauterine system versus endometrial resection. Obstet Gynecol. Dec 2004;104(6):1314-21. [Medline].
FDA Approves Intrauterine Device for Heavy Menstrual Bleeding. Available at http://bit.ly/eKOVjr.
[Best Evidence] Kaunitz AM, Bissonnette F, Monteiro I, Lukkari-Lax E, Muysers C, Jensen JT. Levonorgestrel-releasing intrauterine system or medroxyprogesterone for heavy menstrual bleeding: a randomized controlled trial. Obstet Gynecol. Sep 2010;116(3):625-32. [Medline].
Lukes AS, Moore KA, Muse KN, Gersten JK, Hecht BR, Edlund M, et al. Tranexamic Acid Treatment for Heavy Menstrual Bleeding: A Randomized Controlled Trial. Obstet Gynecol. Oct 2010;116(4):865-875. [Medline].
DeCherney A, Polan ML. Hysteroscopic management of intrauterine lesions and intractable uterine bleeding. Obstet Gynecol. Mar 1983;61(3):392-7. [Medline].
Chullapram T, Song JY, Fraser IS. Medium-term follow-up of women with menorrhagia treated by rollerball endometrial ablation. Obstet Gynecol. Jul 1996;88(1):71-6. [Medline].
Meyer WR, Walsh BW, Grainger DA, et al. Thermal balloon and rollerball ablation to treat menorrhagia: a multicenter comparison. Obstet Gynecol. Jul 1998;92(1):98-103. [Medline].
Garza-Leal J, Pena A, Donovan A, et al. Clinical Evaluation of a Third-Generation Thermal Uterine Balloon Therapy System for Menorrhagia Coupled with Curettage. J Minim Invasive Gynecol. Jan 2010;17(1):82-90. [Medline]. [Full Text].
Goldrath MH. Evaluation of HydroThermAblator and rollerball endometrial ablation for menorrhagia 3 Years after treatment. J Am Assoc Gynecol Laparosc. Nov 2003;10(4):505-11. [Medline].
[Guideline] ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists. Number 81, May 2007. Obstet Gynecol. May 2007;109(5):1233-48. [Medline].
[Best Evidence] Lethaby A, Hickey M, Garry R. Endometrial destruction techniques for heavy menstrual bleeding. Cochrane Database Syst Rev. Oct 19 2005;CD001501. [Medline]. [Full Text].
Lethaby A, Hickey M, Garry R, Penninx J. Endometrial resection / ablation techniques for heavy menstrual bleeding. Cochrane Database Syst Rev. Oct 7 2009;CD001501. [Medline].
Learman LA, Summitt RL Jr, Varner RE, Richter HE, Lin F, Ireland CC. Hysterectomy versus expanded medical treatment for abnormal uterine bleeding: clinical outcomes in the medicine or surgery trial. Obstet Gynecol. May 2004;103(5 Pt 1):824-33. [Medline].
Showstack J, Lin F, Learman LA, Vittinghoff E, Kuppermann M, Varner RE. Randomized trial of medical treatment versus hysterectomy for abnormal uterine bleeding: resource use in the Medicine or Surgery (Ms) trial. Am J Obstet Gynecol. Feb 2006;194(2):332-8. [Medline].
Roberts TE, Tsourapas A, Middleton LJ, et al. Hysterectomy, endometrial ablation, and levonorgestrel releasing intrauterine system (Mirena) for treatment of heavy menstrual bleeding: cost effectiveness analysis. BMJ. Apr 26 2011;342:d2202. [Medline]. [Full Text].

