BASIC INFORMATION

Date & Time: October 26, 2023, 11:27 AM (Indian Standard Time)

Lecture Handout Prepared from the Teaching Session by: Dr. R. K. Mishra

SUMMARY

This lecture handout provides a comprehensive, systematic framework for the evaluation and management of Abnormal Uterine Bleeding (AUB). It begins by establishing the foundational diagnostic principles, emphasizing a structured sequence of history, clinical examination, and targeted investigations. The lecture details the critical initial steps, including ruling out pregnancy, classifying bleeding patterns using FIGO nomenclature, and assessing iatrogenic causes. It then transitions to a detailed discussion of diagnostic modalities, establishing transvaginal sonography (TVS) as the primary imaging tool and hysteroscopy with guided biopsy as the gold standard for tissue diagnosis. The management section is bifurcated into strategies for acute and chronic AUB. Acute AUB management focuses on hemodynamic stabilization and rapid hemostasis using hormonal therapies. For chronic AUB, a patient-centered approach is outlined, detailing medical management for non-structural causes (COEIN) and surgical options for structural causes (PALM) or refractory cases. Medical therapies range from non-hormonal agents to various hormonal regimens, including the highly effective levonorgestrel-releasing intrauterine system (LNG-IUS). Surgical options include uterine-sparing procedures like endometrial ablation and definitive treatment with hysterectomy.

KEY KNOWLEDGE POINTS

• The diagnostic process for AUB must follow a systematic sequence: history, clinical examination, and investigations. Ruling out pregnancy is the mandatory first step.

• Iatrogenic causes, including medications (anticoagulants, hormonal agents) and devices (IUDs), must be thoroughly evaluated.

• The FIGO PALM-COEIN classification system guides diagnosis, differentiating structural (PALM) from non-structural (COEIN) causes.

• Transvaginal sonography (TVS) is the first-line imaging modality for AUB, with saline infusion sonography (SIS) and MRI as adjuncts for complex cases.

• Hysteroscopy with guided biopsy is the gold standard for endometrial evaluation, superior to blind sampling methods like D&C.

• Acute AUB is a medical emergency requiring stabilization and hemostasis with high-dose hormonal therapies (e.g., COCs, progestins), which must be tapered gradually.

• Chronic AUB due to non-structural causes (COEIN) is primarily managed medically, with the levonorgestrel-releasing IUS (LNG-IUS) being a highly effective first-line option.

• Surgical management, including endometrial ablation or hysterectomy, is reserved for structural pathologies, failed medical therapy, or based on patient preference after her family is complete.

INTRODUCTION

Abnormal Uterine Bleeding (AUB) is a common and complex clinical presentation in gynecology, encompassing any deviation from the normal menstrual cycle. It accounts for a significant proportion of gynecological consultations and can profoundly impact a patient's quality of life. The underlying etiology can range from benign functional disturbances to life-threatening malignancies. Therefore, a precise and systematic diagnostic evaluation is paramount for effective management. This lecture provides a comprehensive framework for evaluating and managing AUB, integrating a detailed clinical history, physical examination, and targeted investigations guided by the PALM-COEIN classification. It further delineates the management strategies for both acute and chronic AUB, emphasizing an evidence-based, patient-centered approach to care.

LEARNING OBJECTIVES

• To understand and apply the systematic three-step approach to diagnosing AUB: history, clinical examination, and investigation.

• To systematically obtain a relevant clinical history, including bleeding patterns, iatrogenic factors, and screening for coagulopathies.

• To select and interpret appropriate laboratory and radiological investigations, including TVS, SIS, and hysteroscopy.

• To identify the indications for endometrial biopsy and differentiate between sampling techniques.

• To formulate a management plan for acute AUB, including hemodynamic stabilization and hormonal hemostasis.

• To describe the principles of medical and surgical management for chronic AUB based on the PALM-COEIN etiology and patient-specific factors.

CORE CONTENT

1. The Diagnostic Framework for AUB

The management of AUB begins with a structured diagnostic process that must follow a logical sequence to ensure all relevant information is captured and correctly interpreted.

1.1. The Three Pillars of Diagnosis

A clinical diagnosis is reached through three sequential steps:

1. History: A detailed, patient-centered interview forms the foundation of the clinical picture.

2. Clinical Examination: A thorough physical assessment helps corroborate or challenge information gathered during the history.

3. Investigations: Targeted laboratory and imaging studies confirm or refute differential diagnoses.

A definitive diagnosis is the sum total of findings from these three components. Only after a diagnosis is established can a rational treatment plan—medical or surgical—be devised.

2. Key Components of the Patient History

A meticulous history is the most critical step in evaluating AUB.

2.1. Ruling Out Pregnancy

The first and most important step in evaluating any woman of reproductive age with AUB is to rule out pregnancy. Bleeding may be related to complications such as an ectopic pregnancy or miscarriage.

2.2. Bleeding Pattern Analysis

The nature of the bleeding provides crucial diagnostic clues:

• Predictable, Cyclical, Heavy Bleeding: Suggests an underlying structural cause (e.g., Adenomyosis, Leiomyoma) or Coagulopathy (AUB-C), as the hormonal axis is likely intact.

• Predictable, Cyclical Bleeding with Intermenstrual Spotting: Highly suggestive of a focal lesion such as an endometrial or cervical polyp (AUB-P).

• Unpredictable, Acyclical Bleeding: Raises a high index of suspicion for anovulatory dysfunction (AUB-O) or, more critically, malignancy (AUB-M), and warrants urgent evaluation.

2.3. Contraceptive and Medication History (AUB-I)

A thorough review of iatrogenic causes is mandatory:

• Drugs Affecting Coagulation: Anticoagulants (e.g., warfarin) and antiplatelet agents (e.g., aspirin).

• Hormonal Agents: Progestin-only contraceptives, combined oral contraceptives (COCPs), dinogest, and GnRH agonists can cause breakthrough bleeding.

• Intrauterine Devices (IUDs): Copper-IUDs can increase menstrual flow, while the LNG-IUS often causes initial irregular spotting.

2.4. Screening for Coagulopathy (AUB-C)

Evaluation for AUB-C is indicated if a patient has heavy menstrual bleeding since menarche OR any one of the following: history of postpartum hemorrhage, excessive bleeding with surgery, or significant bleeding with dental work.

2.5. Assessing the Impact on Quality of Life (QoL)

It is crucial to inquire about the impact of the bleeding on the patient’s physical, social, professional, and psychological well-being. Any condition that significantly degrades QoL warrants thorough investigation and management.

3. Clinical Examination

A comprehensive examination is performed after obtaining informed consent.

3.1. General Physical Examination

• General Condition & Vitals: Assess for pallor, tachycardia, or hypotension indicating significant blood loss. Check temperature for signs of infection.

• Anthropometry: Calculate BMI, as obesity is a risk factor for AUB-O and endometrial hyperplasia.

• Systemic Signs: Examine for goiter (thyroid dysfunction) or signs of hyperandrogenism (hirsutism, acne), suggesting AUB-O.

3.2. Specific Gynecological Examination

• Per Speculum Examination: Visualize the cervix and vagina to identify local causes of bleeding (e.g., polyps, cervicitis, suspicious lesions).

• Per Vaginal (Bimanual) Examination: Assess uterine size, contour, and mobility.

  • Normal-Sized Uterus: Typically associated with non-structural causes (COEIN).

  • Enlarged Uterus: Suggests a structural cause (PALM), such as adenomyosis, leiomyoma, or malignancy.

4. Investigations: A Targeted Approach

4.1. Laboratory Investigations

• Pregnancy Test: Mandatory for all reproductive-aged women.

• Complete Blood Count (CBC): Essential to assess the degree of anemia. A peripheral film showing microcytic, hypochromic anemia indicates chronic iron deficiency.

• Coagulation Studies (PT, aPTT): Indicated for patients who screen positive for AUB-C.

• Hormonal Profile: TSH and prolactin levels if an ovulatory disorder (AUB-O) is suspected.

4.2. Radiological Investigations

• Transvaginal Sonography (TVS): The first-line imaging modality to evaluate the myometrium, endometrium, and uterine cavity.

  • Endometrium: A trilaminar appearance suggests a proliferative phase; a uniformly hyperechoic appearance suggests a secretory phase. Endometrial thickness >12 mm (premenopausal) or >4 mm (postmenopausal, not on HRT) is abnormal.

• Saline Infusion Sonography (SIS): Involves instilling saline into the uterine cavity during TVS to clearly delineate intracavitary pathologies like polyps and submucosal fibroids.

• Color Doppler Sonography: Differentiates leiomyomas (circumferential vascularity) from adenomyosis (diffuse, vertical vessels).

• Magnetic Resonance Imaging (MRI): Reserved for complex cases, surgical mapping of fibroids, or when ultrasound is inconclusive.

4.3. Tissue Sampling and Direct Visualization

• Indications for Endometrial Biopsy:

  • Age >45 years with AUB.

  • AUB in younger patients with risk factors like obesity, chronic anovulation (PCOS), hypertension, diabetes, or a family history of relevant cancers.

  • Failed medical management.

  • Suspicious ultrasound findings.

• Techniques for Endometrial Sampling:

  1. Dilatation and Curettage (D&C): A blind procedure with a risk of missing focal lesions.

  2. Pipelle Biopsy: An excellent office-based screening tool, but may yield an insufficient sample.

  3. Hysteroscopy-Guided Biopsy: The gold standard, allowing direct visualization and targeted biopsy of pathology, maximizing diagnostic accuracy.

5. Management of Acute Abnormal Uterine Bleeding

Acute AUB is an episode of heavy bleeding requiring immediate intervention.

1. Assess and Stabilize: Achieve hemodynamic stability with IV fluids or blood products as needed.

2. Arrest Hemorrhage (Medical Management):

   • Intravenous Estrogen: Conjugated Equine Estrogen (CEE) 25 mg IV every 4–6 hours.

   • High-Dose Oral Hormonal Therapy:

     • COCs: A formulation with ≥30 mcg ethinyl estradiol, given one tablet TID until bleeding stops, then tapered to BID and then OD over 3 weeks. Contraindicated in patients with VTE risk.

     • Progestins: Preferred for patients with contraindications to estrogen.

       • Norethisterone Acetate: 5 mg TID, then tapered.

       • Medroxyprogesterone Acetate: 10 mg BID, then tapered.

     • Principle of Tapering: Sudden withdrawal will cause rebound bleeding. Hormonal support must be tapered gradually over 20-25 days.

   • Adjunct Therapy: Tranexamic acid (1–3 grams/day) can be used to achieve faster hemostasis.

3. Surgical Management: Reserved for refractory cases. Options include D&C or intrauterine balloon tamponade.

6. Management of Chronic Abnormal Uterine Bleeding

Chronic AUB is abnormal bleeding present for over six months. Management is guided by the PALM-COEIN etiology and patient preferences.

6.1. Medical Management of Non-Structural AUB (COEIN)

This is the cornerstone of therapy for AUB-C, O, E, and N. A trial of at least 3 months is needed to assess efficacy.

• Non-Hormonal Medications:

  • NSAIDs (e.g., Mefenamic acid).

  • Antifibrinolytics: Tranexamic acid (1 g BID or TID).

• Hormonal Medications:

  • Combined Hormonal Contraceptives (OCPs, patch, ring).

  • Progestin-Only Therapy: Oral (Norethisterone, MPA, Dienogest), injectable (DMPA), or intrauterine.

  • Levonorgestrel-releasing Intrauterine System (LNG-IUS): A first-line, long-term, highly effective option, reducing blood loss by up to 80%.

  • GnRH Analogues: Create a temporary hypoestrogenic state.

6.2. Management of Specific COEIN Categories

• AUB-C (Coagulopathy): Manage in collaboration with a hematologist.

• AUB-O (Ovulatory Dysfunction): If fertility is desired, use ovulation induction and antifibrinolytics. If not, standard hormonal therapies apply.

• AUB-I (Iatrogenic): Review drug and dose; if bleeding persists, add tranexamic acid or consider changing the agent.

• AUB-N (Not Otherwise Classified):

  • Arteriovenous Malformation: Uterine artery embolization.

  • Isthmocele (Cesarean Scar Defect): Laparoscopic repair.

6.3. Surgical Management

Indicated for structural causes (PALM), failed medical therapy, or patient choice.

• Uterine-Sparing Procedures (Endometrial Ablation):

  • Involves destruction of the endometrium to induce amenorrhea or hypomenorrhea.

  • Prerequisites: Completed family, malignancy ruled out via biopsy, and counseling on failure risk and need for contraception.

  • Methods: Include hysteroscopic resection (first-generation) and non-resectoscopic techniques like thermal balloon or radiofrequency ablation (second-generation).

• Definitive Procedure (Hysterectomy): Surgical removal of the uterus is the definitive cure for AUB.

SURGICAL PEARLS

• Listen First, Question Later: The most valuable diagnostic clues often emerge when the patient narrates her story uninterrupted. Observation begins the moment she enters the room.

• System Over Speed: Do not jump to investigations. Follow the history-examination-investigation sequence to build a logical clinical picture and avoid unnecessary, costly tests.

• Biopsy Technique Matters: Always prefer hysteroscopy-guided biopsy over blind sampling when focal pathology is suspected. A blind procedure can miss a carcinoma, leading to a dangerous delay in diagnosis.

• Don't Stop Hormones Abruptly: When treating acute AUB, gradual tapering of hormonal therapy is essential to prevent rebound bleeding and treatment failure.

• The Reassuring Pattern: A predictable, cyclical, heavy bleeding pattern is reassuring, as it generally points toward a structural or hematological cause rather than malignancy. In contrast, unpredictable, acyclical bleeding is highly suspicious.

COMPLICATIONS AND THEIR MANAGEMENT

• Intraoperative

  • Severe Nausea/Vomiting: Associated with high-dose intravenous estrogen. Manage proactively with antiemetics.

• Early Postoperative

  • Withdrawal Bleeding: An expected physiological event after a planned course of hormonal therapy.

  • Rebound Heavy Bleeding: Occurs if hormonal therapy is stopped abruptly. Manage by restarting the high-dose regimen and planning a proper taper.

• Late Postoperative

  • Thromboembolic Events: A risk with estrogen-containing therapies. Careful patient selection and risk assessment are crucial.

MEDICOLEGAL AND PATIENT SELECTION CONSIDERATIONS

• Primacy of Ruling Out Pregnancy: Failure to rule out pregnancy in a reproductive-aged woman with AUB is a critical medicolegal pitfall. Document this step meticulously.

• Biopsy in High-Risk Patients: In any patient >45 years with AUB, or younger patients with significant risk factors (obesity, PCOS), an endometrial biopsy is mandatory to rule out malignancy. Document the rationale if a biopsy is deferred.

• Informed Consent: A treatment plan requires a definitive diagnosis. Thoroughly discuss the risks, benefits, and alternatives of all proposed treatments, respecting the patient's choice and desire for uterine preservation.

• Cardiovascular Risk Assessment: Before prescribing COCs, perform a thorough assessment for contraindications, including VTE history, smoking in women over 35, and uncontrolled hypertension.

SUMMARY AND TAKE-HOME MESSAGES

• The diagnosis of AUB requires a systematic progression from history to clinical examination and then to investigations. The absolute first step is to rule out pregnancy.

• Correlate clinical findings with the PALM-COEIN classification: an enlarged uterus suggests a structural (PALM) cause, while a normal-sized uterus often points to a non-structural (COEIN) etiology.

• Hysteroscopy with directed biopsy is the gold standard for endometrial evaluation, offering superior diagnostic accuracy over blind sampling methods.

• Acute AUB is a medical emergency managed by stabilization and high-dose hormonal therapies that must be tapered gradually.

• Chronic AUB management requires a patient-centered approach, tailoring therapy to the established PALM-COEIN diagnosis, with LNG-IUS being an excellent first-line medical option.

MULTIPLE CHOICE QUESTIONS (MCQs)

1. What is the first and most critical step in evaluating a woman of reproductive age presenting with Abnormal Uterine Bleeding (AUB)?

   a) Performing an ultrasound

   b) Taking a detailed menstrual history

   c) Ruling out pregnancy

   d) Conducting a bimanual examination

2. A 46-year-old obese woman with a history of hypertension presents with unpredictable, heavy bleeding. Her uterus is enlarged on examination. According to the PALM-COEIN classification, which etiology is most likely?

   a) Coagulopathy (AUB-C)

   b) Iatrogenic (AUB-I)

   c) Leiomyoma or Malignancy (AUB-L/M)

   d) Ovulatory dysfunction (AUB-O)

3. What is considered the "gold standard" for evaluating and treating focal intrauterine pathology like an endometrial polyp?

   a) Dilatation and Curettage (D&C)

   b) Pipelle office biopsy

   c) Saline Infusion Sonography (SIS)

   d) Hysteroscopy with guided biopsy/resection

4. A patient with acute AUB is started on norethisterone acetate 5 mg TID. The bleeding stops. What is the correct next step in management?

   a) Stop the medication immediately.

   b) Taper the dose to BID for 15-20 days.

   c) Increase the dose to 10 mg TID.

   d) Switch to a combined oral contraceptive.

5. A patient with regular cycles but intermenstrual spotting is most likely to have which condition?

   a) Anovulation

   b) Adenomyosis

   c) Endometrial polyp

   d) Coagulopathy

6. Which of the following is an absolute prerequisite before performing an endometrial ablation procedure?

   a) A uterine cavity length less than 8 cm

   b) Pre-treatment with GnRH agonists for 3 months

   c) An endometrial biopsy ruling out malignancy or hyperplasia

   d) A history of failed medical therapy with LNG-IUS

7. A transvaginal ultrasound in the proliferative phase of the menstrual cycle typically shows what appearance of the endometrium?

   a) A uniformly hyperechoic line

   b) A thin, barely visible line

   c) A classic trilaminar ("triple-line") appearance

   d) A heterogeneous mass with cystic spaces

8. Which medication is a non-hormonal, antifibrinolytic agent used to manage heavy menstrual bleeding?

   a) Mefenamic Acid

   b) Norethisterone Acetate

   c) Tranexamic Acid

   d) Dienogest

9. A 28-year-old patient with AUB-O desires fertility. Which management strategy is most appropriate?

   a) Continuous combined oral contraceptives

   b) Levonorgestrel-releasing IUS (LNG-IUS)

   c) Ovulation induction plus tranexamic acid during menses

   d) Endometrial ablation

10. A bimanual examination of a patient with AUB reveals a normal-sized uterus. Which of the following etiologies is most likely?

    a) Large intramural fibroid

    b) Diffuse adenomyosis

    c) Ovulatory dysfunction (AUB-O)

    d) Uterine sarcoma

11. What is the recommended endometrial thickness cut-off on ultrasound, above which further investigation is warranted in a postmenopausal woman not on hormone therapy?

    a) 2 mm

    b) 4 mm

    c) 8 mm

    d) 12 mm

12. A patient with a known history of deep vein thrombosis presents with acute AUB. Which medical therapy is the most appropriate first-line choice?

    a) High-dose combined oral contraceptives

    b) Intravenous Conjugated Equine Estrogen

    c) High-dose Norethisterone Acetate

    d) Tamoxifen

13. The definitive treatment for a symptomatic isthmocele (cesarean scar defect) causing postmenstrual spotting is:

    a) Uterine artery embolization

    b) Hysterectomy

    c) Laparoscopic repair of the defect

    d) LNG-IUS insertion

14. Which finding on a peripheral blood film is characteristic of chronic AUB?

    a) Macrocytic, normochromic anemia

    b) Microcytic, hypochromic anemia

    c) Normocytic, normochromic anemia

    d) Thrombocytopenia

15. What is the primary mechanism of action of the Levonorgestrel-releasing Intrauterine System (LNG-IUS) in treating AUB?

    a) It creates a systemic hypoestrogenic state.

    b) It induces a potent local progestogenic effect leading to endometrial atrophy.

    c) It mechanically blocks blood flow from the endometrium.

    d) It acts as a systemic antifibrinolytic agent.

16. A 2D TVS shows generalized endometrial thickening, and it is unclear if this is due to a large polyp or diffuse hyperplasia. Which procedure is most effective for definitive differentiation?

    a) Abdominal MRI

    b) Repeat TVS after the next menses

    c) Saline Infusion Sonography (SIS)

    d) A blind D&C

17. The management of any disease is a sequential process that begins with diagnosis and is followed by what?

    a) Patient Counseling

    b) Treatment

    c) Re-evaluation

    d) Investigation

18. A patient has a history of heavy menstrual bleeding since menarche. This is a strong indicator to screen for which condition?

    a) AUB-P (Polyp)

    b) AUB-L (Leiomyoma)

    c) AUB-C (Coagulopathy)

    d) AUB-O (Ovulatory Dysfunction)

19. A definitive diagnosis of AUB is described as the sum total of findings from which three sources?

    a) History, clinical examination, and patient's self-report

    b) Investigations, ultrasound, and hysteroscopy

    c) History, clinical examination, and investigations

    d) Patient's history, family history, and drug history

20. When using combined oral contraceptive pills for acute AUB, what is the minimum recommended dose of ethinyl estradiol for effective endometrial stabilization?

    a) 10 mcg

    b) 20 mcg

    c) 30 mcg

    d) 50 mcg

Answer Key:

1. c, 2. c, 3. d, 4. b, 5. c, 6. c, 7. c, 8. c, 9. c, 10. c, 11. b, 12. c, 13. c, 14. b, 15. b, 16. c, 17. b, 18. c, 19. c, 20. c

MOTIVATIONAL MESSAGE FROM DR. R. K. MISHRA

The mastery of surgery is not a destination, but a continuous journey of refinement. Let every procedure sharpen your skill, every challenge deepen your understanding, and every patient reinforce your commitment to excellence.

My best wishes are with you all as you dedicate yourselves to this demanding and profoundly rewarding profession.