Managing Menorrhagia

Learning Objectives

  1. Understand the risk factors for excessive menstrual bleeding
  2. Review the normal menstrual cycle
  3. Describe the causes of excessive menstrual bleeding
  4. Describe the evaluation and management of excessive menstrual bleeding

John E. Lopes JR. and Erin Sherer are assistant professors at the PA program in the School of Rehabilitation and Medical Science, The Herbert H. and Grace A. Dow College of Health Professions, Central Michigan University in Mount Pleasant, Mich. They indicate no relationships to disclose related to the contents of this article.

Menorrhagia is surprisingly common, with data suggesting that approximately 30% of women of reproductive age experience excessive blood loss during menstruation.1,2

While in nearly half of all cases no organic pathology can be found, a number of risk factors may contribute to the development of heavy menstrual blood loss.1

One large survey-based epidemiologic study of more than 2,800 women found that subjects having heavier menstrual flow tend to be younger than 40 and are less likely to be white than their counterparts with normal menstrual flow.2 The study also concluded that women with menorrhagia often have a lower education level and a lower income level than women with normal menstrual flow.

Another study explored possible correlations among menorrhagia and age, parity, body mass index (BMI) and smoking. The study of 182 healthy women did not produce any data suggesting a relationship between menorrhagia and parity, BMI or smoking habits. However, as in similar studies, the researchers concluded that menstrual blood loss increases with age and that the occurrence of menorrhagia is higher in those patients older than 40.3

Differences in ethnicity also may impact the development of heavy menstrual bleeding. Black women report menorrhagia more frequently than do white women. This may reflect differences in frequency of fibroid tumors, or a difference in frequency of subclinical coagulation factor abnormalities such as von Willebrand disease and platelet function disorders, which occur more frequently in black women.4

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The Normal Menstrual Cycle

The human menstrual cycle is the result of the influence of estrogen and progesterone on the endometrium.5,6 The endometrium responds to hormonal stimulation with a series of changes including proliferation, differentiation and necrosis, all leading to menstrual bleeding. The normal menstrual cycle is divided into the follicular, ovulatory and luteal phases.

The follicular phase begins with stimulation of the anterior pituitary by gonadotropin-releasing hormone (GnRH) released by the hypothalamus. The anterior pituitary produces follicle-stimulating hormone (FSH) and luteinizing hormone (LH). FSH and LH act on the ovary to stimulate the development of follicles and the production of estradiol. FSH increases the number of granulosa cells in the ovary, induces the secretion of estrogen via aromatase and enhances the presentation of FSH receptors on the granulosa cells. LH promotes the production of estrogen and androgens by the ovarian theca cells; the androgens are converted to testosterone and estrogen in ovarian and peripheral tissue.

Elevation in circulating estrogen levels exerts a negative feedback effect on the production of FSH and induces the proliferation of the endometrial lining. Elevation in the blood estrogen level is part of a positive feedback loop that increases LH secretion, resulting in the LH surge that causes ovulation. Both the positive and negative feedback cycles must be intact for ovulation to occur. The follicular phase usually lasts about 14 days, with a range of 7 to 21 days. Irregularities in the length of the menstrual cycle typically are related to variability in the follicular phase.

With the LH surge, the mature follicle ruptures and releases an oocyte. The remaining cyst becomes the corpus luteum and starts the luteal phase of the menstrual cycle, which lasts about 14 days and is much less variable than the follicular phase. Production of progesterone by the corpus luteum stabilizes the endometrial lining, promotes the development of glandular tissue and blood vessels and generally prepares the uterus for implantation. If no implantation occurs, the corpus luteum deteriorates, and hormone production decreases. The loss of progesterone support results in ischemic necrosis of the endometrium and menstrual bleeding. The lowering of progesterone and estrogen levels then results in stimulation of FSH and LH production through a negative feedback mechanism.5,6

Average length of bleeding is 3 to 7 days, with an average menstrual blood loss of 30 mL to 40 mL. Bleeding for longer than 10 days or with a loss of more than 80 mL of blood is considered abnormal.6,7

Causes of Menorrhagia

Abnormalities in menstrual flow can be attributed to a number of causes.8,9 The menstrual cycle is most irregular at the extremes of reproductive life. Benign uterine or cervical conditions such as polyps, leiomyomas or ectropion may be associated with bleeding. Endometrial and cervical cancers may present with abnormal bleeding. Systemic causes, such as coagulation and platelet disorders, endocrine abnormalities and hepatic, renal and cardiac disease, also may cause menstrual irregularities, including menorrhagia. Medications such as anticoagulants, estrogen receptor antagonists, hormone replacement therapy, hormonal contraceptives and herbal preparations may be associated with alterations in menstrual bleeding.8,9

Bleeding in adolescence is most often due to the presence of anovulatory cycles.10 As a result of anovulation, the endometrium is exposed to persistent estrogen stimulation with hyperproliferation and eventually oligomenorrhea or breakthrough bleeding, which may be heavy.11 Anovulation and a relative hyperestrogenic state also are responsible for increased bleeding in the perimenopause.12 As the rate of follicle production declines during the menopausal transition, FSH stimulation is not sufficient to cause maturation of the follicle, and the lower estrogen production inhibits the LH surge, leading to endometrial proliferation and heavier bleeding when menstruation occurs.12

Menorrhagia at menarche also may represent the first manifestations of a coagulopathy or platelet function disorder.13 Platelet dysfunction and von Willebrand factor (VWF) deficiency are the two most common disorders of coagulation noted in menorrhagia.13 One of the first stages in the control of menstrual blood loss is platelet plug formation.14 A reduction in platelets, such as with thrombocytopenia, can lead to reduced plug formation and increased bleeding. VWF deficiency is the most common hereditary bleeding disorder. VWF serves as an adhesion factor between platelets and the damaged endothelium; reduced levels of VWF result in poor primary hemostasis in the spiral arteries and increased blood loss.

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Structural abnormalities within the endometrium may contribute to abnormal blood loss with menstruation. Women with menorrhagia menstruate for a longer period and have blood loss up to three times that of normal women.5 Studies of these women indicate that disturbances in the endometrium contribute to heavy bleeding.

Women with menorrhagia have altered proliferation and differentiation of the spiral arterial smooth muscle. Resulting alterations in permeability of the vessels may interfere with paracrine and endocrine factors that help regulate blood loss. In addition, prostaglandin and nitric oxide synthesis are elevated, enhancing prostaglandin production via the cyclooxygenase pathway through a positive feedback mechanism.5

Benign and malignant uterine or cervical disease are associated with menorrhagia during the childbearing years.14 Of these conditions, uterine myomas are more commonly associated with heavy bleeding, and many women with them have a normal endometrium on examination.5 Abnormalities in the endometrial blood vessels overlying the fibroid, possibly due to angiogenic compounds produced by the tumor itself, may be the cause.14

Abnormalities in the development of the endometrial vasculature and synthesis of vasodilatory proteins also may contribute to menorrhagia.10 Vascular smooth muscle cells around the spiral arteries of the endometrium are reduced in women with menorrhagia. Vascular endothelial growth factor (VEGF) production also has been found to be reduced in women with heavy menstrual bleeding. Endothelin expression also is reduced in women with heavy blood loss. The consequence of these abnormalities is that the endometrium is more prone to bleeding because of the inability of the vasculature to constrict normally.10

Evaluation

Focus on identifying the type of abnormal uterine bleeding. Whether the bleeding is anovulatory, ovulatory or anatomic guides the eventual management process.15 Ask the patient about the volume of blood lost at each cycle, whether her cycles are regular or irregular and the presence and timing of any pain.16 The presence of intermenstrual bleeding and pressure sensations in the pelvis may suggest underlying pathology.

It can be difficult to quantify the bleeding in a woman complaining of menstrual irregularities.17 Patient assessment of blood loss is subjective, and estimation is subject to significant variations. Objective measurement of blood loss requires specialized techniques that make it impractical for general use.

Counting pads or tampons or weighing the material is of little value. Menstrual flow consists of cervical and vaginal secretions in addition to blood.18 Measurement of hemoglobin by use of the alkaline hematin method demonstrates that only about 50% of total flow comprises blood.17 Higham and colleagues developed a pictorial chart (Figure 1) that was found to have a sensitivity of 85% and specificity of 89% compared with the alkaline hematin method.17 The chart allows the patient to mark how many napkins or tampons she used and offer a semiquantitative assessment of the amount of blood on each. The napkins and tampons are assigned a score of 1 if lightly stained, 5 for moderate staining and 10 if saturated. However, the product used can make a significant difference in the description of the amount of saturation (Figure 2). The amount of blood that would saturate an entire light absorbency tampon would saturate only about half of a super absorbency tampon. And, the area covered by blood on a regular napkin appears larger than on an overnight napkin. Clots were described by their relationship to a coin size. With a score of 100 as a cutoff, the sensitivity and specificity identified above is achieved.

Physical examination may not be necessary for all patients depending on the history.16 In many cases, physical examination does not add information that would change the treatment decision.

The examination also may be uncomfortable for the woman, particularly for girls with abnormal bleeding within the first 2 years of menarche or who are not sexually active. If the history reveals intermenstrual bleeding, or if the patient is at risk for endometrial hyperplasia, a further evaluation is required.16

Laboratory evaluation should include a complete blood count in all women with menorrhagia to rule out anemia. Other laboratory tests should be ordered only if the history or physical examination suggests a contributory condition such as hypothyroidism.

Ultrasound evaluation is the initial imaging study of choice. Physical findings such as a uterus that is palpable suprapubically or enlarged or irregularly shaped on bimanual examination should prompt referral for ultrasound. Ultrasound also is indicated in a patient who does not respond to medical treatment.

If the patient is at risk for endometrial hyperplasia, an endometrial biopsy should be performed. Biopsy should be considered in women over 35 years of age with intermenstrual bleeding, perimenopausal women with heavy bleeding and women who fail medical treatment.

Management

The management of menorrhagia should take into account the amount of bleeding, any associated pain or discomfort, existing comorbid conditions and potential side effects of treatment.15 If the patient has ovulatory menstrual cycles, treatment might involve hormones. If the patient requires contraception in addition to control of bleeding, combined oral contraceptive tablets are an appropriate measure.

Progestins are the agents of choice for hormonal treatment of menorrhagia. Relatively few contraindications are associated with progestin therapy.18 Even older women who smoke, have risk factors for thrombotic disease or have comorbid conditions that increase the risk for heart attack or stroke can be treated safely with progestin-only therapies.18 These drugs are available in a variety of formulations, so management plans can be individualized.

Patients with bleeding associated with fibroids and who do not wish to undergo surgery can be treated with hormone therapy. Cyclic progestins in the anovulatory patient can help regulate cycles. High-dose continuous regimens can promote amenorrhea in patients with coagulation defects. The use of levonorgestrel-impregnated intrauterine devices can provide delivery of therapeutic concentrations of hormone with minimal systemic effects.15

If the nonsteroidal anti-inflammatory drugs mefenamic acid or naproxen are started at the onset of bleeding and continued for 5 days or until menses stop, bleeding can be reduced by up to 45%. Tranexamic acid, a fibrinolysis inhibitor, can reduce bleeding up to 60% over several cycles.18

Surgical treatment choices include hysterectomy and endometrial ablation.15 Hysterectomy remains the definitive treatment. Endometrial ablation may offer a less invasive and possibly more cost-effective treatment. Endometrial ablation produces complete amenorrhea in up to 50% of cases and an almost 90% patient satisfaction rate.18

References

1. El-Hemaidi I, et al. Menorrhagia and bleeding disorders. Curr Opin Obstet Gynecol. 2007;19(6):513-520.

2. C“t‚ 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.

3. Janssen CA, et al. Menorrhagia-a search for epidemiological risk markers. Maturitas. 1997;28(1):19-25.

4. Miller CH, et al. Population differences in von Willebrand factor levels affect the diagnosis of von Willebrand disease in African-American women. Am J Hematol. 2001;67(2):125-129.

5. Jabbour HN, et al. Endocrine regulation of menstruation. Endocr Rev. 2006;27(1):17-46.

6. Gray SH, et al. Abnormal vaginal bleeding in adolescents. Pediatr Rev. 2007; 28(5):175-182.

7. Hallberg L, et al. Menstrual blood loss-a population study. Variation at different ages and attempts to define normality. Acta Obstet Gynecol Scand. 1966;45(3):320-351.

8. Mohan S, et al. Diagnosis of abnormal uterine bleeding. Best Pract Res Clin Obstet Gynaecol. 2007;21(6):891-903.

9. Albers JR, et al. Abnormal uterine bleeding. Am Fam Physician. 2004;69(8):1915-1926..

10. ESHRE Capri Workshop Group. Endometrial bleeding. Hum Reprod Update. 2007;13(5):421-431.

11. Grover S. Bleeding disorders and heavy menses in adolescents. Curr Opin Obstet Gynecol. 2007;19(5):415-419.

12. Jain A, et al. Endocrine mechanisms and management for abnormal bleeding due to perimenopausal changes. Clin Obstet Gynecol. 2005;48(2):295-311.

13. Kouides PA. Bleeding symptom assessment and hemostasis evaluation of menorrhagia. Curr Opin Hematol. 2008;15(5):465-472.

14. Livingstone M, Fraser IS. Mechanisms of abnormal uterine bleeding. Hum Reprod Update. 2002;8(1):60-67.

15. Telner DE, Jakubovicz D. Approach to diagnosis and management of abnormal uterine bleeding. Can Fam Physician. 2007;53(1):58-64.

16. Lumsden MA, Chard J. Adopt an evidence-based approach to menorrhagia. Practitioner. 2007;251(1692):26-33.

17. Higham JM, et al. Assessment of menstrual blood loss using a pictorial chart. Br J Obstet Gynaecol. 1990;97(8):734-739.

18. Nelson AL, Teal SB. Medical therapies for chronic menorrhagia. Obstet Gynecol Surv. 2007;62(4):272-281.

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