CHAPTER 2 Cynthia Farquhar and Julie Brown Department of Obstetrics and Gynecology, University of Auckland, Auckland, New Zealand The International Federation of Gynecology and Obstetrics (FIGO) defines chronic abnormal uterine bleeding (AUB) as “bleeding from the uterine corpus that is abnormal in duration, volume, and/or frequency and has been present for the majority of the last 6 months” [1, 2]. The prevalence of AUB in the general population is predicted to range between 11% and 13% rising to 24% for those women aged 36–45 years [3]. The extent of the menstrual bleeding has been linked to the likelihood of anemia [4, 5]. Heavy menstrual bleeding (HMB) without underlying pathology (also known as menorrhagia or dysfunctional uterine bleeding) can be a major health problem for many women, frequently resulting in referral for hysterectomy (National Health Committee, 1998) [6]. The National Institute for Health and Clinical Excellence defines HMB as “as excessive menstrual blood loss which interferes with the woman’s physical, emotional, social, and material quality of life, and which can occur alone or in combination with other symptoms.” (p8) [7]. Table 2.1 indicates that menstrual blood loss per month in excess of 80 ml is considered to be “heavy” [8]. Unfortunately, measurement of the volume of monthly menstrual blood loss is not possible outside the research setting, and clinicians are dependent on self‐report by women about the heaviness of their menstrual loss. Table 2.1 Suggested “normal” limits for menstrual parameters in the mid‐reproductive years Source: Fraser et al. 2007 [8]. HMB may occur at any time between puberty and the menopause and is typically described as either ovulatory or anovulatory. A history of HMB with regular menstrual cycles is usually associated with ovulation whereas an anovulatory pattern of bleeding with erratic intervals between menstrual periods, is common in puberty and as women near the menopause. Anovulatory menorrhagia may also be present in women with polycystic ovaries who often have irregular and heavy menses. This “dysfunctional uterine bleeding” is defined in the NICE guidelines as “Abnormal vaginal bleeding that occurs during a menstrual cycle that produced no egg (ovulation did not take place). The occurrence of irregular or excessive uterine bleeding in the absence of pregnancy, infection, trauma, new growth or hormone treatment” (p. xiii) [7]. Vannella et al. (2008) reported iron deficiency anemia (serum ferritin <30 μg dl−1) in two‐thirds (67%) of women (aged 20–56 years) who had a diagnosis of menorrhagia [9]. As HMB is the most common presentation of abnormal menstrual bleeding this chapter will focus on HMB. Differential diagnoses of HMB that should be considered include uterine pathology such as fibroids and hyperplastic endometrium, complications of early pregnancy such as miscarriage, carcinoma of the cervix and endometrium (rarely), and exogenous hormones taken for menopausal symptoms. Fibroids are present in about 40% of women with menorrhagia [7] although they are probably only responsible for menorrhagia when they result in an enlargement of the endometrial cavity or when they are submucous fibroids. Rarely, disorders of coagulation may be present. Approximately 5% of women with menorrhagia have endometrial hyperplasia, a premalignant condition of the endometrium, which is more likely to occur in women who weigh 90 kg or more and women who are 45 years old. In the majority of women no obvious cause is found for their HMB [6, 7]. Scope: This chapter is limited to women with HMB without pathology and does not cover the management of women with known pathology such as endometrial hyperplasia and uterine fibroids. The following search strategy was used to identify potential studies to answer the clinical questions. The databases that were searched included MEDLINE, Embase, and the Cochrane Database of Systematic Reviews from inception until January 2012. The following search terms were used: uterine hemorrhage/or menorrhagia/or metrorrhagia, dysfunctional uterine bleeding, AUB, metrorrhagia, menometrorrhagia, HMB, hypermenorrhagia, and systematic review and meta‐analysis. The clinical symptoms that women with HMB experience is variable with some women only presenting after severe anemia has been diagnosed and others presenting with no derangement in their hematology results. The NICE guidelines for HMB recommend that history taking should cover the nature of the bleeding (frequency, heaviness, and length) and seek to identify any potential pathology (pain or pressure symptoms) and also to identify the woman’s concerns and expectations [7]. Although it is possible to objectively measure menstrual blood, the tests involve the collection of menstrual pads and tampons and are rarely undertaken except in the research setting. Subjective measures such as pictorial bleeding charts are reported to have highly variable sensitivity and sensitivity and are not recommended. [7] (p35). There is no simple and reliable way of identifying women who have severe HMB and the question of whether menstrual blood loss is a problem can only truly be determined by the woman herself [7] (p35). Women with anemia have been found to be more likely to have excessive menstrual blood loss and therefore anemia can be used as an indicator of the severity of HMB providing other factors such as diet are taken into account. Ferritin levels have been reported to be the most sensitive test for diagnosing Fe deficiency anemia [10]. A full history should be obtained including the nature of bleeding and symptomology that may indicate structural or histological abnormalities. A physical examination (observation, abdominal palpation, visualization of the cervix, and bi‐manual examination) is recommended prior to investigations for structural or histological abnormalities, and prior to levonorgestrel intrauterine system (LNG‐IUS) fitting [7]. The preceding paragraph has described that anemia is common and testing is recommended. There are other conditions that may be present such as hormonal, thyroid, and coagulation disorders. Studies have reported on the association between hormonal conditions and HMB and no link has been reported [11, 12]. There is only one case‐control study that considered thyroid disorders and there was no evidence of a link between thyroid disorders and menstrual disorders [13]. With regard to coagulation disorders such as von Willebrand disease, two systematic reviews suggested a prevalence between 5% and 20% [14, 15]. No case‐control studies were available to establish the prevalence in the general population. The NICE guidelines 2007 made the following recommendations for laboratory testing for women with HMB: The question of which women should be further investigated for pathology such as fibroids and endometrial pathology is an important one as some serious underlying conditions may be present (for example, endometrial hyperplasia) and some conditions are not amenable to medical treatments (e.g. use of tranexamic acid in women with HMB in association with uterine bleeding has been shown not be effective). Therefore, women at risk of endometrial hyperplasia and carcinoma should have an assessment of their endometrium by either ultrasound or by endometrial biopsy. For women in the premenopausal age group the threshold for endometrial biopsy is ≥12 mm [6, 16]. Risk factors for endometrial pathology include high body mass indices (≥90 kg), age > 45 years, persistent intermenstrual bleeding and treatment failure [3, 6, 16–18]. Women with a clinical examination that suggests a structural or histological abnormality further investigations such as pelvic ultrasound is recommended [3, 7]. If there is uncertainty about the location of a centrally located fibroid, then saline infusion sonography is a useful second line investigation. There is no role for magnetic resonance imaging in the investigation of AUB as a first line test [6, 16]. The NICE guideline 2007 notes the common association between anemia and women with HMB with iron deficiency anemia emerging as a clinical problem with a menstrual blood loss of 60–80 ml [7]. Serum ferritin is the most accurate test for iron deficiency anemia (likelihood ratio (LR) 51.85 at a level of <15 ng ml−1) [7]
Abnormal menstrual bleeding
Background
Clinical dimensions of menstruation and menstrual cycle
Descriptive term
Normal limits (5th–95th centile)
Volume of monthly blood loss (ml)
Heavy
Normal
Light
>80
5–80
<5
Clinical questions
Search strategy
Critical appraisal of literature for each clinical question
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