Unit II ABNORMAL UTERINE BLEEDING Dr. Sony Singh, MD, FRCSC Director of Minimally Invasive...

Unit II

ABNORMAL UTERINEBLEEDING

Dr. Sony Singh, MD, FRCSC Director of Minimally Invasive Gynecology

The Ottawa Hospital

Dr. Mina Wesa, MD, FRCSC Fellow in Minimally Invasive Gynecology

The Ottawa Hospital

Dr. Shahid Islam, MD, PhD, FRCPCAssociate Professor and Program Director , Lab Medicine-Anatomical Pathology, University of Ottawa Staff Physician, Ottawa Hospital

Disclosure

Unit II – AUB – Dr. Sony Singh

You may only access and use this PowerPoint presentation for educational purposes. You may not post this presentation online or distribute it without the permission of the author.

Describe menorrhagia, metrorrhagia, menometrorrhagia, oligomenorrhea

Classify abnormal uterine bleeding in ovulatory and anovulatory bleeding

Categorize abnormal uterine bleeding into anatomical, medical/pharmacological and biochemical hormonal causes – using PALM-COEIN nomenclature!

Elaborate a clinical approach to abnormal uterine bleeding inpremenarchal, reproductive, peri and post-menopausal women

Unit II – AUB – Dr. Sony Singh

Objectives

Elaborate a clinical approach to abnormal uterine bleeding and briefly discuss available treatment options

Compare the normal menstrual cycle with anovulatory conditionssuch as PCOS, POF and menopause

Formulate a differential diagnosis of vaginal bleeding with respect topre-menarchal, pre-menopausal and post-menopausal causes

Describe pharmacological and surgical management of menorrhagia

Describe the etiology and presenting signs and symptoms of anovulatory vaginal bleeding (including menopause, PCOS and ovarian tumors)

Unit II – AUB – Dr. Sony Singh

Objectives

(Live speaker)

Unit II – AUB – Dr. Sony Singh

Case Presentation

Abnormal Uterine Bleeding (AUB)

Refers to menstrual bleeding of abnormal quantity, duration, or schedule

Common gynecologic complaint, accounting for over 30% of outpatient gynecologic visits

Wide differential Structural uterine pathology (fibroids, polyps, adenomyosis) Anovulation Disorders of hemostasis Neoplasia

ALWAYS RULE OUT PREGNANCY!!!

INTRODUCTION

TERMINOLOGY - Traditional

• Amenorrhea: absence of menstruation for at least three usual cyclic lengths

• Oligomenorrhea: cyclic length> 35 days

• Polymenorrhea: Cyclic length <24 days

TERMINOLOGY - Traditional

• Menorrhagia: regular, normal intervals with excessive volume and durations of flow

• Metrorrhagia: irregular intervals with normal or reduced volume and duration of flow

• Menometrorrhagia: Irregular intervals and excessive volume and duration of flow

Malcolm G. Munro MD, FRCS(c), FACOG

Professor, Department of Obstetrics & Gynecology

David Geffen School of Medicine at UCLA

Director of Gynecologic Services

Kaiser Permanente Los Angeles Medical Center

Ian S. Fraser MD, FRCOG, FRANZCOGProfessor in Reproductive Medicine Department of

Obstetrics & Gynaecology

Queen Elizabeth II Research Institute for Mothers and Infants

University of Sydney

Hilary O. D. Critchley MD, FRCOG, FRANZCOGProfessor of Reproductive Medicine Section of Obstetrics &

Gynaecology

Head, Division of Reproductive and Developmental Sciences

University of Edinburgh

TERMINOLOGY - Revised

FIGO Classification System for

Abnormal Uterine Bleedingin the Reproductive Years

For the “Menstrual Agreement Process”:

FIGO Classification System for Causes of Abnormal Uterine Bleeding in the Reproductive Years

Structural abnormality No structural abnormality

Polyp

Adenomyosis

LeiomyomaMalignancy & Hyperplasia

Coagulopathy

Ovulatory Dysfunction

Endometrial

Iatrogenic

Not Yet Classified

Up to 30% of women in Canada will seek medical assistance for this problem during their reproductive years

Significant health care burden for women, their families, and society

Major impact on women’s quality of life, productivity, utilization of healthcare services

PREVALENCE

Perimenarche Perimenopause Postmenopause

Menarche Menopause

10 - 14

Reproductive

14 - 45 40 - 60

Early

50 - 65

Late

60 - DeathBirth - 10

Premenarche

The Cultural Context of Menstruation

The Affected Populations

The Cultural Context of MenstruationImpact of Heavy Menstrual Bleeding

Quality of Life

Regulation of Normal Menstruation

Characteristics of Normal Menstruation

NORMAL ABNORMAL

Duration of flow 4 – 6 days <2 days or >7 days

Volume of flow 30 mL >80 mL

Length of cycle 24 – 35 days

ETIOLOGY OF AUB

Neonatal period

Prepubertal period

Adolescence Reproductive years Peri- menopause

Post- menopause

Estrogen withdrawal

Foreign body

Infection

Blood dyscrasia

Hypothalamic

Anovulation (central, intermed, gonadal)

Carcinoma (uterus, cervix)

Atrophic vaginitis

Sarcoma immaturity Functional (blood dyscrasia, hypothyroid,

Climacteric Carcinoma (uterus,

botryoides

Ovarian tumor

Inadequate luteal function

luteal dysfunction)

Iatrogenic (contraception,

Polyps ovarian)

EstrogenTrauma Psychogenic

(including anorexia, bulemia)

anticoagulation,hemodialysis)

Pregnancy (abortion, ectopic, RPOC, GTD)

replacement

Uterine

ETIOLOGY OF AUB – Reproductive years

Neonatal period

Prepubertal period

Adolescence Reproductive years

Peri- menopause

Post- menopause

Estrogenwithdrawal

Foreign body

Infection

Sarcoma botryoides

Ovarian tumor

Trauma

Blood dyscrasia

Hypothalamic immaturity

Inadequate luteal function

Psychogenic (including anorexia, bulemia)

Anovulation (central,intermed, gonadal)Functional (blood dyscrasia, hypothyroid, luteal dysfunction)

Iatrogenic (contraception, anticoagulation, hemodialysis)

Pregnancy (abortion, ectopic, RPOC, GTD)

Uterine

Carcinoma(uterus, cervix)

Climacteric

Polyps

Atrophicvaginitis

Carcinoma (uterus, ovarian)

Estrogenreplacement

FIGO Classification System for Causes of Abnormal Uterine Bleeding in the Reproductive Years

Structural abnormality No structural abnormality

Polyp

Adenomyosis

LeiomyomaMalignancy & Hyperplasia

Coagulopathy

Ovulatory Dysfunction

Endometrial

Iatrogenic

Not Yet Classified

FIGO Classification System for Causes of AUB in the Reproductive Years

Structural abnormality No structural abnormality

Polyp

Adenomyosis

LeiomyomaMalignancy & Hyperplasia

Coagulopathy

Ovulatory Dysfunction

Endometrial

Iatrogenic

Not Yet Classified

Common cause of abnormal genital bleeding in pre- and postmenopausal women

Hyperplastic overgrowths of endometrial glands and stroma around a vascular core, sessile or pedunclulated

Single, multiple, variable size and location, may beasymptomatic

Prevalence rises with increasing age, premenopausal > postmenopausal

Risk factors: Tamoxifen, obesity, HRT

95% benign

POLYPS: AUB-P

Malignancy Risk Factors:Size > 1.5 cm Tamoxifen use Postmenopausal

All symptomatic polyps should be removed

Asymptomatic polyps:

Premenopausal women – remove if:o Polyp > 1.5 cm diametero Multiple polypso Polyp prolapsed through cervixo Infertilityo Risk factors for endometrial cancer

Postmenopausal women – remove all endometrial polyps

TREATMENT - Polyps

Hysteroscopic Polypectomy - Scissors

Hysteroscopic Polypectomy – Electrosurgical Loop Resectoscope

FIGO Classification System for Causes of AUB in the Reproductive Years

Structural abnormality No structural abnormality

Polyp

Adenomyosis

LeiomyomaMalignancy & Hyperplasia

Coagulopathy

Ovulatory Dysfunction

Endometrial

Iatrogenic

Not Yet Classified

Ectopic endometrial glands and stroma within the uterine musculature

Hypertrophy and hyperplasia of surrounding myometrium, diffusely enlarged uterus “globular”

True incidence unknown as definitive diagnosis based on histopathology (following hysterectomy)

Pathogenesis – endometrial invagination versus mullerian rests.

Pathology: Uniformly enlarged, boggy uterus Thickened myometrium

ADENOMYOSIS: AUB-A

PATHOGNOMONIC on microscopy: Presence of endometrial tissue within the myometrium

Clinical Manifestations: Heavy menstrual bleeding Painful menstruation Chronic pelvic pain Enlarged, globular uterus on exam, may be tender

Symptoms typically noted in women 40-50 years old, given traditional diagnosis by hysterectomy.

Newer MRI criteria for diagnosis suggest disease may cause dysmenorrhea and chronic pelvic pain in adolescents and younger reproductive-age women as well.

Often the diagnosis of “pure” adenomyosis may be obscured by other pathology McElin TW, Adenomyosis of the uterus, Obstet Gynecol Annu. 1974;3(0):425.

Kunz G et al., Adenomyosis in endometriosis – prevalence and impact on fertility. Evidence from magnetic resonance imaging, Hum Reprod. 2005;20(8):2309.

ADENOMYOSIS: AUB-A Clinical Manifestations

Definitive diagnosis only by histopathology (hysterectomy)

Preoperative diagnosis by characteristic clinical manifestations (menorrhagia,

dysmenorrhea, enlarged uterus)

MRI is best imaging technique Increased signal in areas of adenomyosis Exclude malignancy Distinguish adenomyosis from fibroids

Transvaginal ultrasound up to 83% sensitive and 85% specific (Meredith SM, 2009)

ADENOMYOSIS: AUB-A Diagnosis

Hysterectomy – definitive treatment

Hormonal options Progestins (Levonorgestrel IUD) Gondaotropin releasing hormone (GnRH) analogs Aromatase inhibitors ? Combined hormonal contraception

Conservative surgery Endometrial ablation or resection Laparoscopic myometrial electrocoagulation Excision of adenomyosis – no plane, “woody” tissue consistency

Uterine artery embolization (UAE) – some success Kim MD et al., Long-term results of uterine artery embolization for symptomatic

adenomyosis, AJR Am J Roentgenol. 2007;188(1):176.

ADENOMYOSIS: AUB-A Treatment

Recurrent symptoms within 6 months after cessation of hormonal therapy

FIGO Classification System for Causes of AUB in the Reproductive Years

Structural abnormality No structural abnormality

Polyp

Adenomyosis

LeiomyomaMalignancy & Hyperplasia

Coagulopathy

Ovulatory Dysfunction

Endometrial

Iatrogenic

Not Yet Classified

Most common pelvic tumor in women

Benign, originate from myometrial smooth muscle

Women of reproductive age

Symptoms: AUB Pelvic pain or pressure Infertility or adverse pregnancy outcomes

Clinically apparent in 12-25% women, noted on pathological exam in approx. 80% of uteri

LEIOMYOMA (Fibroids or Myomas): AUB-L

LEIOMYOMA: AUB-L Terminology

European Society of Hysteroscopy Classification System for

Submucosal Fibroids

LEIOMYOMA: AUB-L

INCREASED RISK•Incidence is 2 to 3 fold greater in black women than in white womenBaird DD et al., Am J Obstet Gynecol. 2003;188(1):100

•Early menarche (< 10 yrs old)

•Red meats

•Alcohol (beer)

•Other – hypertension, family history

DECREASED RISK•Higher parity

•Green vegetables, fruits

•Dietary vitamin A

•Smoking

Risk Factors

Abnormal uterine bleeding

Pelvic pressure and pain

Reproductive dysfunction

LEIOMYOMA: AUB-L Clinical Manifestations

Abnormal uterine bleeding

Pelvic pressure and pain

Reproductive dysfunction

LEIOMYOMA: AUB-L Clinical Manifestations

Abnormal uterine bleeding

Pelvic pressure and pain

Reproductive dysfunction

LEIOMYOMA: AUB-L Clinical Manifestations

Abnormal uterine bleeding

Pelvic pressure and pain

Reproductive dysfunction

LEIOMYOMA: AUB-L Clinical Manifestations

PHYSICAL EXAMINATION:Bimanual pelvic examination – enlarged uterusSpeculum examination – prolapsed submucous fibroid, cervical contour

LEIOMYOMA: AUB-L Diagnosis

IMAGING:Transvaginal Ultrasound (TVS)

95-100% sensitive Most widely used modality – accessible, cost-effective

Saline Infusion Sonography (Sonohysterography) Improved assessment of intracavitary fibroids

LEIOMYOMA: AUB-L Diagnosis

Fibroid in 53 yo womanwho presented with PMBJoizzo, JR et al., AJR Am J Roentgenol 2001

TVS SIS

Diagnostic HysteroscopyCan be performed in officeSaline or CO2 distension media? accuracy compared to ultrasound

LEIOMYOMA: AUB-L Diagnosis

LEIOMYOMA: AUB-LDiagnostic Hysteroscopy

Magnetic Resonance Imaging To distinguish among leiomyomas, adenomyosis, and adenomyomas Expensive Reserved for complex surgical planning Also to distinguish fibroids from leiomyosarcomas, before uterine artery embolization

(UAE)

LEIOMYOMA: AUB-L Diagnosis

Post UAE

No role for prophylactic treatment – Exceptions: planning pregnancy, hydronephrosis

Treatment choice based on: Type, severity of symptoms Size Location Patient age Reproductive plans

Options: Expectant Medical management Surgical management

LEIOMYOMA: AUB-L Treatment

Hormonal therapiesEstrogen–progestin contraceptives

Levonorgestrel–releasing intrauterine system (“Mirena IUD”)

Progestin injections (Depot Medroxy Progesterone Acetate – DMPA)

Progestin pills

Gonadotropin-releasing hormone (GnRH) agonists, antagonists

Selective progesterone receptor modulators (“SPRMs” – Ulipristal acetate)

Antifibrinolytics (?)

Danazol - ++ side effects

LEIOMYOMA: AUB-L Medical Management

LEIOMYOMA: AUB-L Surgical Management

UAE

Hysteroscopy

Myomectomy

Laparoscopy/Laparotomy

AUB-L

Hysterectomy

Vaginal

Laparoscopic

Abdominal

LEIOMYOMA: AUB-L Hysteroscopic Myomectomy

LEIOMYOMA: AUB-L Laparoscopic Myomectomy

FIGO Classification System for Causes of AUB in the Reproductive Years

Structural abnormality No structural abnormality

Polyp

Adenomyosis

LeiomyomaMalignancy & Hyperplasia

Coagulopathy

Ovulatory Dysfunction

Endometrial

Iatrogenic

Not Yet Classified

Endometrial hyperplasia Proliferation of endometrial glands that may progress to or coexist with endometrial

cancer Result of chronic UNOPPOSED estrogen stimulation without balancing effects of

progesterone Women present with abnormal uterine bleeding Histologic diagnosis – ENDOMETRIAL BIOPSY

MALIGNANCY / HYPERPLASIA: AUB-M

MALIGNANCY / HYPERPLASIA: AUB-M

Normal endometrium

HISTOLOGY % RISK OF COEXISTING CA

Simple hyperplasia without atypia 1

Complex hyperplasia without atypia 3

Simple hyperplasia with atypia 8

Complex hyperplasia with atypia 29

Normal proliferative endometrium

MALIGNANCY / HYPERPLASIA: AUB-M Treatment

Atypicalhyperplasia

(often complex)

Pre-menopausal

Fertility desired High dose Progestintherapy

Childbaringcompleted Total

Hysterctomy

Post-menopausalTotal

Hysterectomy Bilateral salpingo-

oophorectomy

FIGO Classification System for Causes of AUB in the Reproductive Years

Structural abnormality No structural abnormality

Polyp

Adenomyosis

LeiomyomaMalignancy & Hyperplasia

Coagulopathy

Ovulatory Dysfunction

Endometrial

Iatrogenic

Not Yet Classified

Initial screening for an underlying disorder of hemostasis in patients with excessive menstrual bleeding should be structured by medical history.Positive screen comprises any of the following:

COAGULOPATHY: AUB-C

Von Willebrand disease identified in 13% of women with HMB.

Screening for bledding disorders in women with HMB

Heavy menstrual bleeding (HMB) since menarche

One of the following:Postpartum hemorrhageSurgery-related bleedingBleeding associated with dental work

Tow or more of the following symptoms:Bruising one to two times per monthEpistaxis one to two times per monthFrequent gum bleedingFamily history of bleeding symptoms

CONSULT HEMATOLOGY!!

Options:No desire for pregnancy:Combined oral contraceptivesLevonorgestrel-releasing IUSEndometrial ablation

If pregnancy desired:AntifibrinolyticsFactor replacement therapydDAVP at the onset of menses

COAGULOPATHY: AUB-C Treatment

FIGO Classification System for Causes of AUB in the Reproductive Years

Structural abnormality No structural abnormality

Polyp

Adenomyosis

LeiomyomaMalignancy & Hyperplasia

Coagulopathy

Ovulatory Dysfunction

Endometrial

Iatrogenic

Not Yet Classified

Unpredictable bleeding pattern Variable amount of flow Absence of cyclic production of

progesterone

OVULATORY DYSFUNCTION: AUB-O

FIGO Classification System for Causes of AUB in the Reproductive Years

Polyp

Adenomyosis

LeiomyomaMalignancy & Hyperplasia

Coagulopathy

Ovulatory Dysfunction

Endometrial

Iatrogenic

Not Yet Classified

Predictable cyclic menses, normal ovulation No other causes of AUB identified

Possible mechanism (s): Disorder of endometrial hemostasis – deficient vasoconstrictos (PGF2α, endothelin-1),

accelerated fibrinolysis Endometrial inflammation, infection Abnormal local inflammatory response Abnormal vasculogenesis

DIAGNOSIS OF EXCLUSION!

ENDOMETRIAL: AUB-E

FIGO Classification System for Causes of AUB in the Reproductive Years

Polyp

Adenomyosis

LeiomyomaMalignancy & Hyperplasia

Coagulopathy

Ovulatory Dysfunction

Endometrial

Iatrogenic

Not Yet Classified

IATROGENIC: AUB-I

FIGO Classification System for Causes of AUB in the Reproductive Years

Polyp

Adenomyosis

LeiomyomaMalignancy & Hyperplasia

Coagulopathy

Ovulatory Dysfunction

Endometrial

Iatrogenic

Not Yet Classified

Rare entities

Arteriovenous malformations (AVMs)

Myometrial hypertrophy

Other disorders not yet identified

NOT YET CLASSIFIED: AUB-N

(To be added)

Lets run through a case to consolidate all this

Evaluation of AUB in Premenopausal Women

Unit II – AUB – Dr. Sony Singh

Evaluation of AUB in Perimenopausal Women

Unit II – AUB – Dr. Sony Singh

Evaluation of AUB in Postmenopausal Women

Unit II – AUB – Dr. Sony Singh

AUB – Normal Cavity, No Malignancy

Endometrial Ablation

Non-hysteroscopic

Hysteroscopic

Hysterectomy

Vaginal

Abdominal

Laparoscopic