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CONTINOUS MEDICAL EDUCATION ABNORMAL UTERINE BLEEDING
The document discusses abnormal uterine bleeding (AUB), with a focus on its prevalence and impact on women's health. It introduces the FIGO classification system for identifying causes of AUB, highlighting categories such as polyps, adenomyosis, and fibroids, along with their associated symptoms and risk factors. Additionally, the document emphasizes the importance of thorough patient assessment and history taking to determine the underlying causes and appropriate management strategies.
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CONTINOUS MEDICAL EDUCATION ABNORMAL UTERINE BLEEDING
- 1. ABNORMAL UTERINE BLEEDINGPRESENTER: DR FARRA SUPERVISOR: DR AMIRAH
- 2. LEARNING OBJECTIVES 1. Introduction 2.Definition 3. Type of AUB 4. FIGO classification
- 3. INTRODUCTION 1. AUB andits sub group, heavy menstrual bleeding (HMB), are common conditions affecting 14–25% of women of reproductive age 2. Have a significant impact on their physical, social, emotional and material quality of life significant costs to both economy and health service. 3. A structured approach for establishing the cause using the Fédération International de Gynécologie et d'Obstétrique (FIGO) PALM-COEIN (Polyp, Adenomyosis, Leiomyoma, Malignancy (and hyperplasia), Coagulopathy, Ovulatory disorders, Endometrial, Iatrogenic and Not otherwise classified) classification system 4. Women most commonly present to gynaecological services with AUB and associated iron-deficiency anaemia.
- 4. DEFINITION 1. Irregularities inthe menstrual cycle involving frequency, regularity, duration, volume of flow outside of pregnancy. 2. A normal menstrual cycle frequency of 24 to 38 days lasts 2 to 7 days 5 to 80 milliliters of blood loss. With regard to volume, however, both the Royal College of Obstetricians and Gynaecologists (RCOG) and American College of Obstetricians and Gynecologists (ACOG) prefer the patient-centred definition of HMB, ‘excessive menstrual blood loss which interferes with a woman's physical, social, emotional and/or material quality of life’, as an indication for investigation and treatment options. Older terms such as oligomenorrhea, menorrhagia, and dysfunctional uterine bleeding should be discarded in favor of using simple terms to describe the nature of abnormal uterine bleeding.
- 6. ABNORMAL UTERINE BLEEDING Acute AUB Excessivebleeding Requires immediate intervention Can occur on its own or superimposed on chronic AUB Chronic AUB Irregularities for most of the previous 6 months
- 7. FIGO CLASSIFICATION OFCAUSE: ‘PALM-COEIN’ 1. Acronym PALM-COEIN 2. Polyp, Adenomyosis, Leiomyoma, Malignancy (and hyperplasia), Coagulopathy, Ovulatory disorders, Endometrial, Iatrogenic and Not otherwise classified ‘PALM’ are assessed visually (imaging and histopathology) and the ‘COEIN’ are non-structural 3. These have been adopted by the European Society for Human Reproduction and Embryology (ESHRE) and used by the European Society for Gynaecological Endoscopy (ESGE).
- 10. OTHER CAUSES OFAUB 1. The PALM-COEIN classification system accepts that women may have more than one underlying aetiology and also that often in the case of structural abnormalities, many women may in fact be asymptomatic.
- 11. POLYPS (AUB-P) 1. Endometrialpolyps are epithelial proliferations arising from the endometrial stroma and glands. 2. The majority are asymptomatic. 3. The contribution of polyps to AUB varies widely ranging from 3.7% to 65% 4. Risk factor: age HRT Tamoxifen therapy Diabetes Hypertension Obesity 5. Visualised on transvaginal ultrasound scanning (TV-USS) may be mistaken for SM fibroids and vice-versa
- 12.
- 13. LEIOMYOMA (AUB-L) 1. Fibroids–leiomyoma “most common tumour of women” 2. Fibroids are associated with Subfertility Miscarriage Preterm labour Obstruction of labour Discomfort Pressure symptoms, typically urinary Compression of the renal tract and pelvic 3. Symptoms: asympromatic in 50% of cases, menstrual, mass, pressure and subfertility
- 15. CONTRIBUTION OF FIBROIDS(LEIOMYOMA) TO AUB 1. The effect of fibroids on endometrial function is now thought to represent a field change within the uterine cavity rather than limited to regions overlying the myoma(s). 2. An increased endometrial surface area and the presence of fragile and engorged vasculature in the perimyoma environment The increase in vascular flow observed along with these enlarged vessels can overcome platelet action 3. Decrease uterine contractility SM fibroids, particularly with those distorting the cavity, were more likely to present with HMB 4. Endometritis in tissue overlaying submucosal fibroid 5. Imbalance of TXA1 and PGI2 6. Expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), heparin-binding epidermal growth factor, platelet-derived growth factor (PDGF), parathyroid hormone-related protein (PTHrP) and prolactin is altered in women with fibroids
- 16. MALIGNANCY (AUB-M) 1. Endometrialcancer is the most common gynaecological malignancy 2. Persistent intermenstrual bleeding, 3. Uterine sarcoma rare but maybe a cause of AUB-M. 4. The risk of development of leiomyosarcoma is reported to increase with age 5. Risk factors for uterine leiomyosarcoma Tamoxifen Previous pelvic radiation therapy Rare inherited disorders such as hereditary leiomyomatosis and renal cell carcinoma (HLRCC)
- 17. COAGULOPATHY (AUB-C) 1. Coagulopathiesare reported to affect 13% of the women 2. The majority of these women suffer from Von Willebrand disease 3. Systemic disorders of haemostasis may be identified in 90% of women 4. Compression caused by a large fibroid uterus may lead to venous thromboembolism (VTE). 5. In the 2018 FIGO system, AUB secondary to anticoagulants was moved from the coagulopathy category to the iatrogenic category.
- 19. OVULATORY (AUB-O) 1. Anovulatorycycles unopposed oestrogen effects on the endometrium causing marked proliferation and thickening observed at the extremes of reproductive age 2. Polycystic ovarian syndrome (PCOS), hyperprolactinaemia, hypothyroidism, obesity, anorexia, weight loss, mental stress and extreme exercise. 3. Typically, women in this group have menstrual cycles that fall out with 38 days or have a variation of >21 days. 4. Drugs that affect dopamine levels, currently fall under this category rather than AUB-I. : TCA PHENOTHIAZINE
- 21. ENDOMETRIAL (AUB-E) 1. AUBthat occurs in the context of a structurally normal uterus with regular menstrual cycles without evidence of coagulopathy is likely to have an underlying endometrial cause. 2. Hypoxia, inflammation, haemostasis and angiogenesis all play crucial roles in the shedding and subsequent scarless repair of the functional upper layer of the endometrium. 3. Perturbation of local glucocorticoid metabolism, aberrant prostaglandin synthesis and excessive plasminogen (resulting in premature clot lysis) have all been implicated in AUB 4. AUB-E may be implicated in many women with AUB, but a lack of clinically available specific tests or biomarkers means that practical testing for such disorders is not yet feasible. 5. As such, diagnosis depends on careful history taking and exclusion of other contributors.
- 22. IATROGENIC (AUB-I) 1. Exogenoustherapy Continuous oestrogen or progestin therapy (systemic or intrauterine delivery routes) or those interventions that act on ovarian steroid release such as gonadotropin-releasing hormone (GnRH) agonists and aromatase inhibitors. 2. Selective oestrogen receptor modulators (SERMs) and more rarely selective progesterone receptor modulators (SPRMs) may cause AUB through direct action on the endometrium. 3. The use of an intrauterine device (IUD) may cause a low-grade endometritis which may also contribute to AUB. 4. Drugs: antiplatelet and anticoagulant therapy
- 23. NOT OTHERWISE CLASSIFIED(AUB-N) 1. Pathologies that are either rare or poorly defined that do not easily fit within the categories described earlier. arteriovenous malformations, endometrial pseudoaneurysms, myometrial hypertrophy and chronic endometritis (not precipitated by an IUD). Pelvic inflammatory disease, chronic liver disease, and cervicitis. 2. The planned regular review of the FIGO PALM-COEIN classification system every 3–5 years through FIGO will allow reassessment, in particular, of this category.
- 24. ASSESSMENT OF THEPATIENT PRESENTING WITH AUB AND FIBROIDS 1. All of the other causes of AUB may co-exist with fibroids. 2. Crucial when a patient with known or suspected fibroids presents with AUB, she is appropriately assessed for the presence of other aetiologies. Structured history, Co-morbidities, Polypharmacy, Body mass index (BMI), Previous surgery Fertility desire Impact of pressure symptoms
- 25.
- 27. 1. An accuratemenstrual history and associated symptoms will identify a likely AUB-O cause. 2. Structured screen for coagulopathies will identify 90% of those women with disorders of systemic haemostasis 3. History will also identify contributors to AUB-I. 4. Combined history and examination will suggest possible AUB-P/-A/-L and should be confirmed with subsequent imaging. TV-USS saline infusion ultrasonography (SIS) hysteroscopy
- 28. ENDOMETRIAL SAMPLING 1. Inthe UK, NICE recommend endometrial sampling in women with persistent inter-menstrual bleeding or aged ≥45 years with treatment failure 2. Clinical judgement for those women aged <40 years with HMB who have risk factors for premalignant change
- 30. REFERENCES 1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970656/?report=printable 2. https://www.ncbi.nlm.nih.gov/books/NBK532913/ 3.https://obgyn.onlinelibrary.wiley.com/doi/10.1016/j.ijgo.2010.11.011 4. https://www.moh.gov.my/moh/attachments/3939.pdf 5. CPG MANAGEMENT OF MENORRHAGIA
- 31.
Editor's Notes
- #3 Significant clinical entity. While there may be relief from HMB during pregnancy and lactation, and an end to the problem at menopause, women affected will tend to suffer the adverse impacts of AUB over what should be the prime years of their lives. Many studies are limited to heavy menstrual bleeding (HMB), but when irregular and intermenstrual bleeding are considered, the prevalence rises to 35% or greater.[1] Many women do not seek treatment for their symptoms, and some components of diagnosis are objective while others are subjective, making exact prevalence difficult to determine.[3] Treatment must remain individualised
- #4 Up to one-third of women will experience abnormal uterine bleeding in their life, with irregularities most commonly occurring at menarche and perimenopause. Variations in any of these 4 parameters constitute abnormal uterine bleeding. Revisions to the terminology were first published in 2007, followed by updates from the International Federation of Obstetrics and Gynecology (FIGO) in 2011 and 2018. The FIGO systems first define abnormal uterine bleeding, then give an acronym for common etiologies. These descriptions apply to chronic, nongestational AUB. In 2018, the committee added intermenstrual bleeding and defined irregular bleeding as outside the 75th percentile
- #6 ACUTE: requires immediate intervention to prevent further blood loss.
- #7 1. Once bleeding is defined as being abnormal, the acronym PALM-COEIN is now being increasingly used for categorising causes:
- #9 Depending on the site, leiomyoma (fibroids) are further subdivided into submucosal (SM) and other (O) and then into nine tertiary categories adapted from the Wamsteker classification [14] (Fig. 2).
- #11 Symptoms: menorhagia, menometrohagia, pmb, imb, prolapse, discharge,
- #12 Typically, adenomyosis is associated with increasing age and may co-exist with fibroids. Furthermore, adenomyosis may be both focal and diffuse and it may be harder to establish diagnosis if fibroids are also present
- #13 20-25% women
- #15 Some of these changes may have an impact on endometrial receptivity and implantation as well as AUB The relationship between AUB and fibroids remains incompletely understood. The obvious paradox is that many women have fibroids but also have entirely normal bleeding patterns. Fibroids are also highly prevalent in women presenting with AUB. This may represent a putative mechanism for some cases of AUB observed in the context of fibroids and may in the future offer a potential therapeutic target. There is increasing knowledge regarding the complex cellular and molecular changes found in association with fibroids, with impact on angiogenesis, alteration in vasoactive substrates and growth factors as well as alteration in coagulation Matrix metalloproteinase (MMP) 2 and 11 levels are increased in fibroids (with MMP 1 and 3 unchanged) but the impact on endometrial bleeding is unclear. VEGF, bFGF, PDGF and PTHrP all have potential angiogenic effects but their specific role within the endometrium in women with fibroids has yet to be determined [17]. Transforming growth factor beta (TGF-β) is produced in excess in the endometrium in women with fibroids and is associated with reduced levels of plasminogen activator inhibitor-1 (PAI-1), thrombomodulin and antithrombin III, both in vivo and in endometrial stromal cells treated in vitro with TGF-β
- #16 Historically, endometrial cancer has rarely occurred in premenopausal women; however, with increasing obesity and rising prevalence of the metabolic syndrome, the endocrine-driven subset of endometrial malignancy has markedly increased in frequency. Race is the only commonality between leiomyosarcoma and leiomyoma with black women having an approximately twofold increased risk Interestingly, the previously held view was that a rapidly enlarging uterus would raise the suspicion for malignancy. This is now no longer held to be true as benign fibroids can grow rapidly and sarcomas grow slowly [35], [36 Both ultrasound scanning (USS) and magnetic resonance imaging (MRI) do not used to accurately predict differentiation between leiomyoma and leiomyosarcoma rarely ovarian cancer may present with AUB. If malignancy or premalignancy is found along with AUB classification, the pathology should be described and staged utilising the appropriate WHO/FIGO systems
- #17 Bleeding previously deemed as AUB-L may be exacerbated by subsequent anticoagulation and presents additional management challenges. The FIGO AUB classification system is a dynamic system with feedback and contemporary debate informing future revisions The position of drug therapies affecting AUB is currently under review with regard to whether anticoagulant/antiplatelet therapies and drugs affecting the HPO axis may be better placed in ‘AUB-I’.
- #18 If 1, 2 or 3 (see Table 2) is ascertained, it indicates positive screen, and further referral for appropriate investigation should be considered.
- #21 1. Endometrial function in the context of menstruation and its disorders is still not fully understood and remains an area of active scientific enquiry, particularly the complexities of the sequence of events triggered by progesterone withdrawal (due to demise of the corpus luteum in the absence of pregnancy). 2. The high prevalence of potential endometrial dysfunction means that it is highly likely that those with AUB-L will often have an element of AUB-E contributing to increased/aberrant menstrual blood loss with its attendant implication for therapy.
- #23 Further areas considered for future sub-classification include AUB-P and AUB-A.
- #24 1, Misdiagnosis will have an impact on treatment options and efficacy, and in the event of undiagnosed coagulopathy, render surgical intervention disproportionately hazardous. must be assessed as these significantly affect treatment approach.
- #27 TV-USS remains the most acceptable and validated first-line investigation. The increasing use of saline infusion ultrasonography (SIS) and selected hysteroscopy will improve sensitivity and specificity for diagnosis of polyps and SM fibroids ∗[37], ∗[44]. Furthermore, women with fibroids may have them confused for focal adenomyosis and vice-versa using conventional imaging [27]. The optimal mode of imaging for suspected adenomyosis has yet to be established The increased use of one-stop clinics with access to outpatient hysteroscopy improves patient satisfaction and facilitates timely investigation and management [46]. MRI plays a role in selected patients with AUB and fibroids, also in the assessment of suitability for uterine artery embolisation (UAE).
- #28 This has been highlighted in the RCOG guidelines with an exception of reducing the age of sampling in the context of treatment failure to 40 [47]. Endometrial sampling challenging if fibroids distort the cavity, outpatient hysteroscopy can facilitate timely exclusion of endometrial pathology.