Abnormal Uterine Bleeding PDF

26 Abnormal Uterine Bleeding Etiology and Management of Acute and Chronic Excessive Bleeding Timothy Ryntz, Roger A. Lobo KEY POINTS The mean amount of menstrual blood loss in one cycle is acute bleeding most...

26 Abnormal Uterine Bleeding Etiology and Management of Acute and Chronic Excessive Bleeding Timothy Ryntz, Roger A. Lobo KEY POINTS The mean amount of menstrual blood loss in one cycle is acute bleeding most rapidly and has particular efficacy for more approximately 35 mL but may be as much as 60 mL, with an chronic use in women with abnormal bleeding who ovulate. average loss of 13 mg of iron. Heavy menstrual bleeding Patients who are being treated for abnormal uterine bleeding occurs in 9% to 14% of healthy women. as a result of endometrial causes (and who are ovulatory) may Diagnostic tests in women with menorrhagia include measure- be given oral contraceptives, nonsteroidal antiinflammatory ment of hemoglobin, serum iron, serum ferritin, beta human drugs (antiprostaglandins), TXA or a prolonged course of chorionic gonadotropin, thyroid-stimulating hormone, and progestogens, or levonorgestrel released locally from an intra- prolactin levels; endometrial biopsy and hysteroscopy; sonohys- uterine system (LNG-IUS). Those treated with the LNG-IUS terography; and hysterosalpingography. Magnetic resonance have similar outcomes at 1 year to those treated by surgery, and imaging may be helpful in the diagnosis of adenomyosis or the LNG-IUS is preferred in women with inherited bleeding surgical planning for leiomyoma but is not part of the initial disorders. evaluation. Various endometrial ablation techniques achieve a 22% to High doses of oral or intravenous estrogen usually stops acute 55% amenorrhea success rate at 1 year but an 86% to 99% bleeding episodes in most cases of abnormal bleeding. An alter- satisfaction rate with regard to normalizing menstruation. native regimen is high-dose oral progestogen for a week, with Within 4 years after endometrial ablation, approximately 25% tapering of the dosage thereafter. Tranexamic acid (TXA) stops of women treated will have a hysterectomy. Abnormal uterine bleeding (AUB) can present in many ways, greater is defined as heavy menstrual bleeding, which occurs in from infrequent episodes, to excessive flow or prolonged 9% to 14% of women (Shapley, 2004). duration of menses and intermenstrual bleeding. Alterations in Although mortality and serious complications of AUB are the pattern or volume of blood flow of menses are among the uncommon, their effect on health-related quality of life is most common health concerns of women. Infrequent uterine significant. Direct costs are calculated at more than $1 billion bleeding is called oligomenorrhea if the intervals between annually in the United States, and indirect costs as a result of lost bleeding episodes vary from 35 days to 6 months, and amenor- work, social function, and vitality have been estimated at more rhea is defined by no menses for at least 6 months. These are than $12 billion annually (Liu, 2007). discussed in Chapter 38. Excessive or prolonged bleeding is discussed in this chapter, and an overview of several therapeu- tic modalities being used to treat excessive uterine bleeding is CAUSES OF ABNORMAL UTERINE BLEEDING also provided. The causes of AUB can be described by a universally accepted To define excessive AUB, it is necessary to define normal men- systematic nomenclature. This system was reported by the Inter- strual flow. The mean interval between menses is 28 days national Federation of Gynecology and Obstetrics (FIGO) in (!7 days). Thus if bleeding occurs at intervals of 21 days or less 2011. It subdivides causes of AUB into nine main categories, or 35 days or more, it is abnormal. The mean duration of men- which are arranged according to the acronym PALM-COEIN: strual flow is 4 days. Few women with normal menses bleed more polyp, adenomyosis, leiomyoma, malignancy and hyperplasia, than 7 days, so bleeding for longer than 7 days is considered to coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, be abnormally prolonged. It is useful to document the duration and not yet classified. The causes that constitute the first group and frequency of menstrual flow with the use of menstrual diary (PALM) are structural or histologic and are diagnosed through cards; however, it is difficult to determine the amount of imaging or biopsy. Those that compose the second group menstrual blood loss (MBL) by subjective means. Several studies (COEIN) are nonstructural (Fig. 26.1). The term dysfunctional have shown that there is poor correlation between subjective uterine bleeding (DUB) is no longer favored and should be dis- judgment and objective measurement of MBL (Chimbira, 1980). carded. In the past this term represented causes of abnormal Although subjective methods are used in predicting blood bleeding when structural causes and other specific defects, such loss, and some investigators have used a pictorial bleeding assess- as coagulation defects, had been excluded. Cases that previously ment chart, a more accurate system is the alkaline hematic would have been described as DUB are now referred to as AUB method, which measures hematin. Average MBL is 35 mL. Total as a result of ovulatory dysfunction or endometrial causes. volume, however, is twice this amount, being made up of endo- According to FIGO, this classification system should be metrial tissue exudate. In the absence of disease, the amount of notated in a consistent and systematic manner. The acronym MBL increases with parity but not age. An MBL of 80 mL or AUB is followed by the letters PALM-COEIN and a subscript 594  CHAPTER 26 Abnormal Uterine Bleeding 595 Polyp Coagulopathy polyps in up to 12% of women undergoing routine gynecologic Adenomyosis Ovulatory dysfunction examination; small endometrial polyps smaller than 1 cm appear 26 Submucosal to regress spontaneously (Hamani, 2013). Endometrial polyps Leiomyoma Endometrial Other were discovered in 32% of 1000 patients on office hysteroscopy Malignancy and Iatrogenic about to undergo in vitro fertilization, suggesting a possible hyperplasia Not yet classified association between endometrial polyps and infertility (Hinckley, 2004). Women with symptomatic polyps can be treated safely and effectively with operative hysteroscopy. Adenomyosis Adenomyosis (AUB-A) is defined by the presence of endometrial glands and stroma in the uterine myometrium. The presence of Fig. 26.1 PALM-COEIN Classification System for Abnormal Uterine ectopic endometrial tissue leads to hypertrophy of the surround- Bleeding. The basic system comprises four categories that are defined ing myometrium. Adenomyosis can occur as focal (adenomyoma) by visually objective structural criteria (PALM), four that are unrelated to or diffuse, with a peak incidence in the fifth decade of life. structural anomalies (COEI), and one reserved for entities that are not Multiparity is considered the most significant risk factor for yet classified (N). The leiomyoma category is subdivided into patients developing adenomyosis, but any process that allows for penetra- with at least one submucosal myoma (LSM) and those with myomas tion of endometrial glands and stroma past the basalis layer (e.g., that do not affect the endometrial cavity (L0). PALM-COEIN, polyp, dilation and curettage, cesarean delivery, spontaneous abortion) is adenomyosis, leiomyoma, malignancy and hyperplasia, coagulopathy, thought to contribute. There also appears to be a positive correla- ovulatory dysfunction, endometrial, iatrogenic, and not yet classified. tion between overexpression of immunoproteins interleukin-6, (From Munro MG, Critchley HOD, Broder MS, Fraser IS. FIGO interleukin-18, and cyclooxygenase-2 and the presence of classification system [PALM-COEIN] for causes of abnormal uterine ectopic endometrial tissue, though these may not be causative bleeding in nongravid women of reproductive age. Int J Gynecol (Leyendecker, 2004; Huang, 2010). Adenomyosis is a histologic Obstet. 2011;113(1):3-13.) diagnosis, but findings of an enlarged, asymmetric uterus on ultrasound and magnetic resonance imaging (MRI) are indicative. Anechoic avascular cysts scattered throughout the myometrium on sonography are considered pathognomonic for adenomyosis 0 or 1 associated with each letter to indicate the absence or on ultrasound. MRI, which is both more sensitive and more presence, respectively, of the abnormality. For example, a specific than ultrasound, will demonstrate thickening of the junc- patient with abnormal bleeding caused by a polyp would be tional zone, the area between the endometrium and the myome- described as AUB-P1A0L0M0-C0O0E0I0N0. Because patients trium, equal to or greater than 12 mm (Figs. 26.2 and 26.3) may have abnormal bleeding as a result of more than one con- (Dueholm, 2007). Abnormal bleeding caused by adenomyosis is dition, this notation allows for description of simultaneous thought to be a result of altered uterine contractility and is com- factors. For example, a patient with abnormal bleeding that is monly associated with profound dysmenorrhea. both irregular and heavy may have endometrial hyperplasia as a result of anovulation. As such, this patient’s bleeding would be described as AUB-P0A0L0M1-C0O1E0I0N0. Leiomyoma What follows is an introduction to each of the pathologic Leiomyoma (AUB-L), or fibroids, are benign tumors of the uterine conditions described by the PALM-COEIN system. After this myometrium with a complex and heterogeneous clinical presenta- discussion, a diagnostic approach for women with AUB will be tion as varied as their biologic origins. Various genetic mutations outlined. Treatments for acute and chronic bleeding as a result of these conditions conclude this chapter. Endometrial Polyps Endometrial polyps (AUB-P) are localized overgrowths of endometrial tissue, containing glands, stroma, and blood vessels, covered with epithelium (Peterson, 1956). Endometrial polyps are most commonly found in reproductive-age women, and estrogen stimulation is thought to play a key role in their devel- opment. As such, polyps are rarely found before menarche. Molecular mechanisms involving overexpression of endometrial aromatase and gene mutations in HMGIC and HMGI[Y] have also been proposed (Maia, 2006; Tallini, 2000). The majority of endometrial polyps are benign. A systematic review of the oncogenic potential of endometrial polyps demon- strated that symptomatic vaginal bleeding and postmenopausal status are associated with an increased risk of malignancy. Among symptomatic postmenopausal women with endometrial polyps, 4.5% had a malignant polyp compared with 1.5% in asymptomatic women (Lee, 2010). A strong correlation exists for both tamoxifen use and obesity and the development of malignancy in endometrial Fig. 26.2 Transvaginal sonography of uterus with adenomyosis: polyps. Diabetes mellitus and hypertension have not been reliably heterogeneous and hypoechogenic, area in the fundal myometrium shown to increase the risk for malignancy in an endometrial polyp. with characteristic anechoic lacunae, and ill-defined borders, sagittal The importance of small and asymptomatic endometrial pol- view (A) and coronal and axial views (B). (Courtesy Dr. J. Lerner, yps is less clear. Transvaginal ultrasound detected asymptomatic Columbia University Medical Center, New York.) 596 PART III General Gynecology cancers can cause abnormal bleeding, there are only approxi- mately 3000 new cases reported annually in the United States. Bleeding from cervical malignancy classically presents as coital bleeding or intermenstrual bleeding; thus a thorough cervical evaluation is an important part of the workup of any woman with these symptoms. In a series of 73 women with coital bleeding referred for evaluation, squamous cell carcinoma of the cervix was present in 1.4% of patients, and 15% had cervical intraepi- thelial neoplasia. AUB is the most common presenting symptom of endometrial cancer. Although endometrial cancer presents most often in the seventh decade, 15% of cases are diagnosed in premenopausal women, and 3% to 5% present in women younger than age 40 (Haidopoulos, 2010). Conditions that lead to increased circulating levels of estrogen are risk factors, for example, obesity is associated with increased estrone levels as a result of peripheral conversion by aromatase in adipose tissue, but the primary source of estrogen in premenopausal women remains the ovary. Impaired ovulation and the absence of progesterone withdrawal can result in sus- tained exposure of the endometrium to estrogen. This hyperes- trogenic state can lead to the pathologic progression from normal endometrium to hyperplasia and ultimately to adenocarcinoma. Lynch syndrome, or hereditary nonpolyposis colorectal can- cer, is an autosomal dominant disease caused by a disruption in the mismatch repair (MMR) genes. Lynch syndrome also carries a 40% to 50% lifetime risk of endometrial cancer, with a signifi- cant proportion of endometrial cancers occurring before age 45. In addition, estrogen-producing ovarian tumors may manifest in AUB. Granulosa theca cell tumors are the most common tumors Fig. 26.3 Magnetic resonance image of asymmetric adenomyosis, to have this presentation, although many ovarian tumors can as indicated by arrows. (From Tamai K, Koyama T, Umeoka S, produce estrogen. et al. Spectrum of MR features in adenomyosis. Best Pract Res Clin Obstet Gynaecol. 2006;20(4):583-602.) Coagulopathy Systemic diseases, particularly disorders of blood coagulation are described in leiomyoma, but the pathogenesis is thought to (AUB-C) such as von Willebrand disease and prothrombin defi- initiate from myometrial injury leading to cellular proliferation, ciency, may initially present as AUB (Minjarez, 2008). Routine decreased apoptosis, and increased production of extracellular ma- screening for coagulation defects is mainly indicated for adoles- trix. Critical in this pathway is the overexpression of transforming cents with prolonged heavy menses beginning at menarche. In growth factor beta that leads to fibrosis of these tumors (Laughlin, adults, screening for these disorders is of little value unless oth- 2011). Transforming growth factor beta also contributes to implan- erwise indicated by clinical signs such as bleeding gums, epistaxis, tation failure in women with fibroids who are subfertile. or ecchymosis. Research has indicated that 20% of adolescent Although the prevalence of fibroids among women is approxi- girls who require hospitalization for AUB have coagulation mately 70%, as many as 50% of these will be symptomatic disorders (Claessens, 1981). Coagulation defects are present in (Gupta, 2008). Mechanisms by which fibroids cause abnormal approximately 25% of those whose hemoglobin levels fall to less bleeding are varied and depend on size, location, and number. than 10 g/100 mL, in one-third of those who require transfu- Subclassification of leiomyomas describes their location through- sions, and in 50% of those whose severe menorrhagia occurred at out the myometrium (Fig. 26.4). Intracavitary fibroids (type 0) and the time of the first menstrual period. Others report that a co- submucosal fibroids, where more than 50% are intracavitary (type 1) agulation disorder is found in only 5% of adolescents hospital- or less than 50% are intracavitary (type 2), as well as intramural ized for heavy bleeding (Falcone, 1994). fibroids, which are large, may increase the overall surface area of Both studies indicated that the likelihood of a blood disorder the endometrial cavity or alter uterine contractility. These effects in adolescents with heavy menses is sufficiently high that all ado- in turn lead to abnormal and excessive uterine bleeding. Whereas lescents should be evaluated to determine whether a coagulopathy hysterectomy for fibroids remains among the leading indications is present. for the procedure in the United States, treatments are diverse Disorders of platelets are most often quantitative, but defects and include hormonal or surgical ablation of the endometrium, in platelet membrane or storage granules can result in normal uterine artery embolization, radiofrequency ablation, and myo- circulating levels with altered function. Hemophilias A and B mectomy through a variety of surgical approaches. are X-linked recessive deficiencies of factor VIII and factor IX, According to the FIGO system, leiomyomas can be notated in respectively. Women who are carriers for these disorders can the PALM-COEIN system with a subscript 0 in their absence or have reduced levels of factors VIII and IX, some less than 30% of by the number 1 when present. Additionally, the letters SM can normal and enough to be considered to have mild hemophilia. be inserted to indicate a fibroid’s location as submucosal. Rare inherited coagulopathies of the other clotting factors (V, VII, X, XI, XIII) include menorrhagia as a potential symptom. Other disorders that produce platelet deficiency, such as leuke- Malignancy mia, severe sepsis, idiopathic thrombocytopenic purpura, and Malignancies (AUB-M) associated with the female reproductive hypersplenism, can also cause excessive bleeding. tract include vulvar, vaginal, cervical, endometrial, uterine, and Chronic anticoagulation as a result of heparin, low-molecular- adnexal (ovarian or fallopian tube) cancers. Although vaginal weight heparin, direct thrombin inhibitors, and direct factor Xa  CHAPTER 26 Abnormal Uterine Bleeding 597 Polyp Coagulopathy Adenomyosis Submucosal Ovulatory dysfunction 26 Leiomyoma Other Endometrial Malignancy and hyperplasia Iatrogenic Not yet classified Leiomyoma SM - 0 Pedunculated intracavitary subclassification Submucosal system 1