POSTMENOPAUSAL ENDOMETRIUM

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

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

3. Menopause • AFTER 12 MONTHS' SPONTANEOUS AMENORRHOEA. • FSH >30

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

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

6. 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.

7. Norms for Endometrial Thickness inPostmenopausal Women (MM) 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

8. WHAT WARRANTS INVESTIGATION AND EVALUATION?

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

10. 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

11. 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.

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

13. 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).

14. 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.

15. 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.

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

17. CASE STUDY - 1 64 years old G2 P2 : 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

18. CASE STUDY-2 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

19. CASE STUDY - 3 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.

20. CASE STUDY - 4 • 54 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

21. CASE STUDY - 5 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

22. 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

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

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

25. 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.

26. VAGINAL ULTRASOUND

27. 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

28. 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 womenrequiring invasive investigation.

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

30. Endometrial polyp in hyperechoic thickened endometrium

31. saline-infusion sonography

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

33. SALINE – INFUSION SONOGRAPHY (SIS) 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

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

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

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

37. Endometrial biopsy • Office Endometrial Biopsy

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

39. An endometrial suction sampling with syringe vacuum

40. 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

41. DILATATION AND CURETTAGE “Gold STANDARD” Preoperative 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%).

42. OFFICE HYSTEROSCOPIC-DIRECTED BIOPSY 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.

43. ACOG/ CANADIAN (SOGC) WHAT TO DO?CLINICAL PRACTICE GUIDELINES2000 • Endometrium ≥ 4, even if No bleeding • Abnormal vaginal bleeding after menopause ↓ • Endometrial Cancer must be ruled out

44. 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)

45. 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

46. unexplained CRITICAL THICKNESS – 3 mm

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

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

49. POST MENOPAUSAL BLEEDING(Our Experience)

50. Post Menopausal Endometrium