POSTMENOPAUSAL ENDOMETRIUM Dr. Sharda Jain Director: Global Institute of Gynaecoloy at Pushpanjali Crosslay Hospital Secretary general: Delhi Gynaecologist Forum

Learning objectives Menopause Normal Postmenopausal Endometrium Pathophysiology: before & after menopause What warrants investigations Case Studies Endomtrial evaluation Personal Experience Review of Literature

AFTER 12 MONTHS' SPONTANEOUS AMENORRHOEA. FSH >30 Menopause

Postmenopausal Endometrium No more than thin line 2.3 mm ± 1.8 mm (0-10)

PRIOR TO MENOPAUSE: Short cycle (↓ proliferative) ↑ Moderate Elevation of FSH Anovulation – Unapposed oest - DUB - Hyperplastic endo. PATHOPHYSIOLOGY

Once menopause occurs, oestrogen and progesterone are no longer produced by the ovaries; nor are they produced in any appreciable amounts by the liver and fat. The endometrium regresses to some degree, and no further bleeding should occur. If bleeding does resume - endometrium must be evaluated.

AMENORRHEIC + NO HORMONE THERAPY 4.0 SEQUENTIAL HORMONE THERAPY (DAY 5) 4.0 ESTROGEN ALONE/COMBINED ESTROGEN 5.5 WITH PROGESTERONE TIBOLONE 5.5 RALOXIFENE 4.0 TAMOXIFEN 8.0 HYPERTENSIVE ON MEDICATION 6.5 Norms for Endometrial Thickness in Postmenopausal Women (MM)

WHAT WARRANTS INVESTIGATION AND EVALUATION?

Fluid - Anachoic area ↑ Endometrium – Warrants investigation Thick Endometrium NO POST MENOPAUSAL BLEEDING

POST MENOPAUSAL BLEEDING PRECANCEROUS / CANCER of cervix & uterus Benign conditions – eg. Polyp Chronic endometritis- eg. TB Disorders of coagulation/ Blood dyscrasias Systemic Disease- eg. Hypertension Drugs – anticoagulants, Tamoxiphen. Herbal drugs, HRT

Postmenopausal Bleeding Benign conditions are most frequent causes of PMB but endometrial cancer is the most serious potential underlying cause One Should think endo. Ca untill proven otherwise.

75% of women with endometrial cancer are postmenopausal. RISK ASSESSMENT

RISK FACTORS FOR ENDOMETRIAL CANCER are conditions typically associated with chronic elevations of endogenous estrogen levels or increased estrogen action at the level of the endometrium. These include OBESITY. HISTORY OF CHRONIC ANOVULATION. DIABETES MELLITUS. ESTROGEN-SECRETING TUMORS. EXOGENOUS ESTROGEN UNOPPOSED BY PROGESTERONE. TAMOXIFEN USE. A FAMILY HISTORY OF LYNCH TYPE II SYNDROME (HEREDITARY NONPOLYPOSIS COLORECTAL, OVARIAN, OR ENDOMETRIAL CANCER).

Systemic conditions Abnormalities of the hematologic system also must be considered as a possible cause of postmenopausal bleeding. On rare occasions, AUB will be the first sign of leukemia or a blood dyscrasia. Overuse of anticoagulant medications such as aspirin, heparin, and warfarin-which are taken with greater frequency by patients in this age group-may contribute to postmenopausal bleeding.

POSTMENOPAUSAL BLEEDING & HRT The occurrence of uterine bleeding or spotting after the initiation of HRT is not unusual. More than half of HRT users will have some spotting or bleeding at the beginning of therapy. Usually such bleeding is lighter than a menstrual period and lessens with time; after 6 months, it stops completely in most women.

ENDOMETRIAL EVALUATION IS CALLED FOR WHEN : 1.any menopausal woman not taking HRT develops uterine bleeding after more than 1 year of amenorrhea. 2.any postmenopausal woman on HRT for 6 months or more with persistent uterine bleeding. 3. and any previously amenorrheic woman on HRT who begins bleeding without apparent cause.

CASE STUDY years old G 2 P 2 : 16 years postmenopausal Went to physician for pain in abdomen Ultrasound revealed18 mm endometrial strip No discharge/ No Bleeding, 70 kg, BMI - 32 Mild hypert, DM controlled. EB – Well differentiated Adeno Carcinoma Staging laparotmy and pan hysterectomy IA- Disease

68 years Menopausal 20 years 3 episodes of bleeding in last 6 weeks Hypertension/ diabetic/ obese/ BMI-31 TVS – Uterus bulky for age. Endometrial strip is 18 mm. Office E.B. well differentiated adeno-carcinoma 1 A disease CASE STUDY-2

54 years, professor in DU Menopause = 48 years Single episode of spotting on 13/8/2010 TVS – 7-8 mm HPE – Clear all Endo. Ca. CASE STUDY - 3

CASE STUDY year old G2 P2 Had HRT at age 50 for Hot flushes – 6 months Presented with 3 episodes of vaginal bleeding over last 6 weeks (3 years after menopause) TVS show endometrial strip of 12 mm, Uterus- normal in size. E.B. proliferative endometrium Hysteroscopy normal …. Spotting for 3 months Refused Hysterectomy Uterine Balloon Therapy

60 YEARS, UNMARRIED PROFESSOR Menopause – 48 years 52 years – Heavy Bleeding Ultrasound – 3-4 mm Endo. Strip D&C /Hysterectomy – Simple hyperplasia of endometrium - Refused Hysterectomy Uterine Balloon Therapy CASE STUDY - 5

CASE STUDY-6 56 years multi gravida Pain in lower abdomen + ; No Postmenopausal Bleeding Appears well BMI < 25, 60 kg Normotensive General exam unremarkable Speculum: CERVICAL POLYP Ultrasound - Uterus normal, endometrium 12 mm, Both ovaries normal INFLAMMATORY POLYP AND TUBERCULAR ENDOMETRITIS ATT Given - EB & - Hysteroscopy

THE DURATION OR AMOUNT (STAINING VS GROSS) OF BLEEDING DOES NOT MAKE ANY DIFFERENCE. IT GIVES NO CLUE TO DIAG. SAME IS TRUE FOR ENDOMETRIAL THICKNESS. RISK ASSESSMENT

Vaginal ultrasonography. Saline infusion sonography (Hydrosonography) Office Endometrial biopsy. Conventional F/C or D/C Hysteroscopic guided biopsy. DIAGNOSTIC TOOLS

Sensitivity and specificity are often used to summarise the performance of a diagnostic test. Sensitivity is the probability of testing positive if the disease is truly present. Specificity is the probability of testing negative if the disease is truly absent.

VAGINAL ULTRASOUND

Although the test is very specific, it isn't sensitive. Many women without endometrial cancer will have an endometrial thickness of 4 mm or more VAGINAL ULTRASOUND

A CUT-OFF THRESHOLD OF 3 MM OR 5MM ? cut-off point of 3 mm is less likely to miss cancer than cut-offs of 5 mm. But unfortunately a lower cut-off means a greater proportion of women requiring invasive investigation.

THE PATIENT RISK GROUP Low pre-test probability On HRT On tamoxifen therapy High pre-test Probability (high risk) Cut off threshold 5mm Cut off threshold 3mm

Endometrial polyp in hyperechoic thickened endometrium

The introduction of intrauterine fluid (saline-infusion sonography) during transvaginal ultrasound is one of the most significant advances in ultrasonography of the past decade. SALINE – INFUSION SONOGRAPHY

Uterine fibroids and adenomyomas generally are apparent on ultrasound. Uterine polyps may appear as a thickened endometrial stripe, but these and submucous myomas can be clearly identified as filling defects when a SIS is performed SALINE – INFUSION SONOGRAPHY (SIS)

At transvaginal ultrasonography, the finding of a thickened central endometrial complex, with or without cystic changes, is often nonspecific.

The Thickened endometrium may be a polyp With polyps the endometrial-myometrial interface is preserved CYST POLYP well-defined, homogeneous, isoechoic to the endometrium

The Thickened endometrium may be a polyp With polyps the endometrial-myometrial interface is preserved POLYP catheter

Office Endometrial Biopsy

A useful suction endomtrial sampling (Probet) with 3.1 mm in outside diameter and no pump or syringe required.

An endometrial suction sampling with syringe vacuum

SAMPLING OF THE ENDOMETRIUM OFFICE BIOPSY PROCEDURE (Probet Endometrial Curette, Vabra aspirator, Karman cannula) will agree with a D&C under GA ~95% of the time Office biopsy has a 16% false negative rate when the lesion is a polyp or the cancer covering less than 5% of the endometrium –Guido et al. J Reprod Med. 1995;40:553

P reoperative D&C will agree with diagnosis at hysterectomy - 95% of the time The role today of the formal D&C or F/C probably is very limited because the diagnosis usually can be made in the office by endometrial biopsy (95%). DILATATION AND CURETTAGE “Gold STANDARD”

Hysteroscopic visualization has several advantages: immediate office evaluation, visualization of the endometrium and endocervix, the ability to detect minute focal endometrial pathology and to perform directed endometrial biopsies. OFFICE HYSTEROSCOPIC- DIRECTED BIOPSY

ACOG/ CANADIAN (SOGC) WHAT TO DO? CLINICAL PRACTICE GUIDELINES 2000 Endometrium ≥ 4, even if No bleeding Abnormal vaginal bleeding after menopause ↓ Endometrial Cancer must be ruled out

A SYSTEMATIC REVIEW OF 90 STUDIES AND META-ANALYSIS ENDOMETRIAL THICKNESS MEASUREMENT FOR DETECTING ENDOMETRIAL CANCER IN WOMEN WITH POSTMENOPAUSAL BLEEDINg: Opmeer BC, Khan KS et.al (Obstet Gyneol 2010;116:160-7)

Meta analysis 90 Studies of POST MENOPAUSAL BLEEDING OVERESTIMATED THE DIAGNOSTIC ACCURACY OF ENDOMETRIUM THICKNESS CRITICAL THICKNESS – 3 MM TO R/O ENDOMETRIAL CARCINOMA Opmeer & Kan Obsted Gynee 2020

CRITICAL THICKNESS – 3 mm unexplained

No Bleeding TVS Endometrial thickness is > 3mm If low risk office endometrial biopsy and SIS If high risk D/C biopsy OR Hysteroscopy Or both fail to do If Endometrial thickness is < 3mm follow But symptoms persist IN WOMEN WITH CONTINUED BLEEDING AFTER A NEGATIVE INITIAL EVALUATION, FURTHER TESTING WITH HYSTEROSCOPICALLY DIRECTED BIOPSY IS ESSENTIAL,

Unsatisfactory, unable to do Low Risk for Ca High Risk for Ca D&C (D&C + hysteroscopy) ± Hysteroscopy Post Menopausal Bleeding TVS Office Endometrial Biopsy

POST MENOPAUSAL BLEEDING (Our Experience) Etiology% Atrophic Endometrium31 Endo. Hyperplasia (simple complex, atypical) 26 Endometrial Ca.14 Polyp endo/ cervical6 Proliferative Endo (Exogenous Estrogen) 1 Total (Jan 2007 – till date) 78

Post Menopausal Endometrium Endometrium (mm) Number of Patient Details <532 Atrophic-31, Cancer-1 <1016 Cervical Polyp- 3, Endo. Polyp-3, Cancer – 1, Simple Hyperplasia-9, >1030 Carcinoma- = 12 Submucous fibroid-1, Simple hyperplasia - 14 Complex hyperplasia-2 Atypical = 1 Total78

NORMAL ENDOMETRIUM

ENDOMETRIAL POLYP

POLYP AND ATYPICAL HYPERPLASIA

ENDOMETRIAL CANCER: TRANSVAGINAL ULTRASOUND SCREENING < 5 mm Endo strip also showed CA.

ENDOMETRIAL CANCER: TRANSVAGINAL ULTRASOUND SCREENING 6 – 10 mm Endo strip also showed CA.

ENDOMETRIAL CANCER: TRANSVAGINAL ULTRASOUND SCREENING Fluid

Endometrium: Post-menopausal atrophy

ENDOMETRIAL SIMPLE HYPERLASIA

ENDOMETRIAL HYPERLASIA - COMPLEX

ENDOMETRIAL HYPERPLASIA - ATYPICAL

GRADE 1 ENDOMETROID CARCINOMA

GRADE 3 ENDOMETROID CARCINOMA

ENDOMETRIAL CARCINOMA: POOR PROGNOSIS CELL TYPES - PAPILLARY SEROUS

ENDOMETRIAL CARCINOMA - POOR PROGNOSIS CELL TYPES CLEAR CELL