Postmenopausal bleeding: Incidence, risk factors and diagnosis

Π UNIVERSITY OF KHARTOUM Faculty of Medicine Postgraduate Medical Studies Board Postmenopausal bleeding: Incidence, risk factors and diagnosis By Dr...
Author: Meryl Stafford
8 downloads 0 Views 255KB Size
Π UNIVERSITY OF KHARTOUM Faculty of Medicine Postgraduate Medical Studies Board

Postmenopausal bleeding: Incidence, risk factors and diagnosis

By Dr. Hussien Hassan El Rayah M.B.B.S (University of Alexandria)

A thesis Submitted in partial fulfillment for the requirements of the Degree of Clinical MD in Obstetrics and Gynaecology, October, 2002

Supervisor Prof. A/Salam Gerais FRCOG, Professor of Obstetrics & Gynaecology Department of Obstetrics & Gynaecology Faculty of Medicine, University of Khartoum.

1

‫‪Π‬‬ ‫ﻗﺎﻝ ﺍﷲ ﺗﻌﺎﻟﻰ ‪:‬‬

‫}ﻭﻗﻞ ﺭﺑﻲ ﺯﺩﻧﻲ ﻋﻠﻤﺎ‬

‫{‪.‬‬ ‫ﺻﺪﻕ ﺍﷲ ﺍﻟﻌﻈﻴﻢ‬

‫‪2‬‬

Dedications To: my wife, sons & daughter who surround me with love and patience

3

ACKNOWLEDGEMENT

My

great

thanks

and

sincere

love

to

my

supervisor

Prof. A/Salam Gerais, Department of Obstetrics & Gynaecology, Faculty of Medicine, University of Khartoum, for his continuous support, help and advice, I wish to thank him for his suggestions, invaluable criticism, patience inspite of his extensive business. I would like to thank Dr. Ferial Omar for her support and valuable advice throughout the period of this study. I am in great dept to Dr. Hassan Ahmed Abdalla for his great help and particular grateful to Dr. Mammoun Ibrahin for his unlimited help. I am grateful to all consultants of obstetrics and gyanecology from whom I gained my little experience and whose guidance helped to share my career. My thanks are extended to Mr. Hassan Ali and Miss. Widad Abdel Magsoud for their help in preparing this work.

4

Abbreviations Abbreviation

Meaning

PMB

Postmenopausal bleeding

PMW

Postmenopausal women

GA

General anaesthesia

D&C

Dilatation & curretage

Cx

Cervix

Ca

Cancer

TVS

Transvaginal ultrasound

T.A.H

Total abdominal hysterectomy

B.S.O

Bilateral salpino-oophrectomy

BMI

Body mass index

DM

Diabetes Mellitus

K.T.H

Khartoum Teaching Hospital

EC

Endometrial cancer

KTH

Khartoum Teaching Hospital

UK

United Kingdom

H.R.T

Hormone replacement therapy

PCO

Polycystic ovaries

5

ABSTRACT Objectives to study the incidence, risk factors and diagnosis of Postmenopausal bleeding (PMB). Settings Khartoum Teaching Hospital. Subjects 50 patients of PMB who had been admitted to this hospital from 1st March 2002 to 1st September 2002. Results Incidence of PMB was estimated to be 32.6%, it was calculated from the total number of PMW admitted and the number of PMW attending Gynaecological Clinic and Casualty, 2% of the study group were within 40-49 years, 40% were within the age group of 50 –59 years, 40% within 60 –69 years, 16% within 70-79 years and, only 2% above 80 years. Youngest age 49 years, oldest 85 years. Distribution of endometrial cancer was the same in age groups, 50-59 years, 60-69 years and 70-79 years, unlike that of cervix cancer where five out of six cases were found in the age group 60-69 years. Approximately 2/3 of patients were parous i.e. 62%, only 10% were nulliparous. The distribution of the age of menarche and that of menopause lies within the normal range, 14 and 9 cases give history of hypertension and diabetes mellitus respectively, 3 patients had used an oral contraceptive pills for a duration of less than 5 years, otherwise the drug history of oestrogen, tamoxifen and H.R.T was negative. Personal and family history of Polycystic ovary syndrome (PCO), ovarian, breast cervix and endometrial tumours was found to be negative in all patients. At presentation all patients presented by vaginal bleeding, 20 patients with vaginal discharge, 12 with pelviabdominal masses, 17

6

patients with abdominal pain and few (8 cases) with other symptoms like urinary and G.I.T symptoms. All patients were ambulant, 60% were anaemic, the common finding on Systemic examination (S/E) was bleeding 46%, atrophic vaginitis (42%), while cervical polyp and vaginal metastasis constitute only 4% for each, The uterus was enlarged in 52%, normal in 34% and small in 14% of cases. The commonest investigation done was D & C and biopsy which was carried out in 66% of cases, the result of histopathology showed that, 12 cases were due to benign causes, 11 premalignant and 10 cases to malignant causes, the results of cervical biopsy obtained showed that 6 out of the 6 cases were due to cervical carcinoma. Hysteroscope was not used in all patients. Malignant causes were found in 32% of patients, hyperplasia in 24%, procedentia 10%, fibroids in 8%, atrophic endometritis and vaginitis in 10%, 6% respectively. Proliferative endometrium was found in 4%, cervical polyp in 2%, and endometrial polyp in 4%. The study concluded that there was a higher incidence of genital malignancies, when compared to previous studies. The study also showed no statistical significance relating the triad of obesity, diabetes mellitus and hypertension with PMB and uterine malignancy.

7

‫ﻤﻠﺨﺹ ﺍﻷﻁﺭﻭﺤﺔ‬ ‫ﺘﻤﺕ ﻫﺫﻩ ﺍﻟﺩﺭﺍﺴﺔ ﺍﻟﻤﺴﺘﻘﺒﻠﻴﺔ ﺍﻟﻭﺼﻔﻴﺔ ﻓﻰ ﻤﺴﺘﺸﻔﻰ ﺍﻟﺨﺭﻁﻭﻡ ﺍﻟﺘﻌﻠﻴﻤﻲ ﻓﻰ ﺍﻟﻔﺘﺭﺓ ﻤﻥ‬ ‫‪ 2002/3/1‬ﺇﻟﻰ ‪2002/9/1‬ﻡ ﻭﻗﺩ ﺸﻤﻠﺕ ﻫﺫﻩ ﺍﻟﺩﺭﺍﺴﺔ ‪ 50‬ﺤﺎﻟﺔ ﻨﺯﻑ ﻤﺎ ﺒﻌﺩ ﺴﻥ ﺍﻟﻴﺄﺱ‪.‬‬ ‫ﺃﻏﺭﺍﺽ ﻭﺃﻫﺩﺍﻑ ﺍﻟﺩﺭﺍﺴﺔ‪:‬‬ ‫ ﺘﺤﺩﻴﺩ ﻤﻌﺩل ﺤﺩﻭﺙ ﻫﺫﻩ ﺍﻷﻋﺭﺍﺽ‪.‬‬‫‪-‬‬

‫ﺘﺤﺩﻴﺩ ﺍﻟﻌﻭﺍﻤل ﺍﻟﻤﺅﺩﻴﺔ ﻟﺘﻠﻙ ﺍﻷﻋﺭﺍﺽ‪.‬‬

‫‪-‬‬

‫ﺍﻟﺘﺸﺨﻴﺹ‪.‬‬

‫ﺍﻟﻨﺘﺎﺌﺞ‪ :‬ﻜﺎﻥ ﻤﻌﺩل ﺤﺩﻭﺙ ﻫﺫﻩ ﺍﻷﻋﺭﺍﺽ ﺒﻨﺴﺒﺔ ‪ %32.6‬ﻤﻥ ﺍﻟﻤﺭﻀﻰ ﺍﻟﺫﻴﻥ ﺃﺩﺨﻠﻭﺍ‬ ‫ﺍﻟﻤﺴﺘﺸﻔﻰ ﻭﺍﻟﺫﻴﻥ ﺭﺍﺠﻌﻭﺍ ﻋﻴﺎﺩﺍﺕ ﺍﻟﻘﺎﻴﻨﻲ ﺍﻟﻤﺤﻭﻟﺔ ﻭﺤﻭﺍﺩﺙ ﺍﻟﻘﺎﻴﻨﻲ ﻓﻰ ﻤﺜل ﻫﺫﺍ ﺍﻟﻌﻤـﺭ‪ .‬ﻭﻗـﺩ‬ ‫ﻭﺠﺩ ﺃﻥ ‪ %2‬ﻤﻥ ﺍﻟﺤﺎﻻﺕ ﺍﻟﺘﻰ ﺘﻤﺕ ﺩﺭﺍﺴﺘﻬﺎ ﻜﺎﻨﺕ ﺃﻋﻤﺎﺭﻫﻥ ﻤﺎ ﺒﻴﻥ ‪ 49– 40‬ﺴﻨﺔ‪ %40 ،‬ﻤـﺎ‬ ‫ﺒﻴﻥ ‪ 59-50‬ﺴﻨﺔ‪ %40 ،‬ﻤﺎ ﺒﻴﻥ ‪ 69-60‬ﺴﻨﺔ‪ %16 ،‬ﻤﺎ ﺒﻴﻥ ‪ %79-70‬ﺴﻨﺔ‪ %2 ،‬ﻤـﺎ ﻓـﻭﻕ‬ ‫ﺍﻟﺜﻤﺎﻨﻭﻥ ﺴﻨﺔ‪ .‬ﺃﺼﻐﺭ ﻋﻤﺭ ﻜﺎﻥ ‪ 49‬ﺴﻨﺔ ﻭﺃﻜﺒﺭ ﻋﻤﺭ ‪ 85‬ﺴﻨﺔ‪ .‬ﻤﻌﺩل ﺤﺩﻭﺙ ﺴﺭﻁﺎﻥ ﺘﺠﻭﻴـﻑ‬ ‫ﺍﻟﺭﺤﻡ ﻭﺠﺩﺕ ﺤﺎﻟﺔ ﻭﺍﺤﺩﺓ ﻤﺎ ﺒﻴﻥ ‪ 49-40‬ﺴﻨﺔ‪ ،‬ﺜﻼﺙ ﺤﺎﻻﺕ ﻤﺎ ﺒﻴﻥ ‪ 69-60 ،59-50‬ﻭ ‪-70‬‬ ‫‪ 79‬ﺴﻨﺔ‪ .‬ﺃﻤﺎ ﻤﻌﺩل ﺤﺩﻭﺙ ﺴﺭﻁﺎﻥ ﻋﻨﻕ ﺍﻟﺭﺤﻡ ﻓﻜﺎﻥ ﺤﺎﻟﺔ ﻭﺍﺤﺩﺓ ﻤـﺎ ﺒـﻴﻥ ‪ 59-50‬ﺴـﻨﺔ ﻭ‪5‬‬ ‫ﺤﺎﻻﺕ ﻤﺎ ﺒﻴﻥ ‪ 69-60‬ﺴﻨﺔ‪.‬‬ ‫ﺃﺜﻨﻴﻥ ﻭﺴﺘﻭﻥ ﺒﺎﻟﻤﺎﺌﺔ ﻤﻥ ﺍﻟﺤﺎﻻﺕ ﺍﻟﺘﻰ ﺘﻤﺕ ﺩﺭﺍﺴﺘﻬﺎ ﻤﻥ ﺍﻟﻨﺴﺎﺀ ﺍﻟﻭﻟﻭﺩ ﺒﻴﻨﻤـﺎ ‪%10‬‬ ‫ﻓﻘﻁ ﻤﻥ ﺍﻟﺤﺎﻻﺕ ﺍﻟﺘﻰ ﻟﻡ ﺘﻨﺠﺏ‪.‬‬ ‫ﺘﺎﺭﻴﺦ ﺒﺩﺍﻴﺔ ﺍﻟﺩﻭﺭﺓ ﻭﺍﻨﻘﻁﺎﻉ ﺴﻥ ﺍﻟﻴﺄﺱ ﻜﺎﻥ ﻓﻰ ﺤﺩﻭﺩ ﺍﻟﻤﻌﺩل ﺍﻟﻁﺒﻴﻌﻲ ﻋﻨﺩ ﻤﻌﻅـﻡ‬ ‫ﺍﻟﻨﺴﺎﺀ ﺍﻟﺫﻴﻥ ﺸﻤﻠﺘﻬﻡ ﺍﻟﺩﺭﺍﺴﺔ‪ 14 ،‬ﺤﺎﻟﺔ ﺃﻋﻁﻭﺍ ﺘﺎﺭﻴﺦ ﻤﺭﻀﻲ ﺒﺎﻹﺼﺎﺒﺔ ﺒﺎﺭﺘﻔﺎﻉ ﻀﻐﻁ ﺍﻟﺩﻡ ﻜﻤﺎ‬

‫‪8‬‬

‫ﺃﻥ ‪ 9‬ﺤﺎﻻﺕ ﺃﻋﻁﻭﺍ ﺘﺎﺭﻴﺦ ﺍﻹﺼﺎﺒﺔ ﺒﻤﺭﺽ ﺍﻟﺴﻜﺭﻱ‪ 3 ،‬ﺤﺎﻻﺕ ﺍﺴﺘﻌﻤﻠﻭﺍ ﺤﺒﻭﺏ ﻤﻨـﻊ ﺍﻟﺤﻤـل‬ ‫ﻭﻟﻔﺘﺭﺓ ﺃﻗل ﻤﻥ ‪ 5‬ﺴﻨﻭﺍﺕ‪ .‬ﻟﻡ ﺘﻜﻥ ﻫﻨﺎﻟﻙ ﺃﻱ ﺤﺎﻟﺔ ﻜﺎﻥ ﻟﺩﻴﻬﺎ ﺘﺎﺭﻴﺦ ﻤﺭﻀﻰ ﺃﻭ ﻋﺎﺌﻠﻲ ﺒﺎﻹﺼـﺎﺒﺔ‬ ‫ﺒﻤﺭﺽ ﺴﺭﻁﺎﻥ ﺍﻟﺜﺩﻱ‪ ،‬ﺴﺭﻁﺎﻥ ﺍﻟﻤﺒﻴﺽ ﺃﻭ ﺴﺭﻁﺎﻥ ﻗﻨﺎﺓ ﺍﻟﺭﺤﻡ ﺃﻭ ﺘﺠﻭﻴﻑ ﺍﻟﺭﺤﻡ ﻜﻤﺎ ﻟﻡ ﺘﻜـﻥ‬ ‫ﻫﻨﺎﻙ ﺃﻯ ﺤﺎﻟﺔ ﺘﺴﺘﻌﻤل ﻫﺭﻤﻭﻨﺎﺕ ﺘﺜﺒﻴﻁ ﺍﻟﻤﺒﺎﻴﺽ‪.‬‬ ‫ﻜل ﺍﻟﺤﺎﻻﺕ ﻜﺎﻨﺕ ﺘﻌﺎﻨﻲ ﻤﻥ ﻨﺯﻴﻑ ﺭﺤﻤﻲ‪ 40 ،‬ﺤﺎﻟﺔ ﻜﺎﻨﺕ ﺘﻌﺎﻨﻲ ﻤـﻥ ﺇﻓـﺭﺍﺯﺍﺕ‬ ‫ﺍﻟﻤﻬﺒل‪ 12 ،‬ﺤﺎﻟﺔ ﻭﺭﻡ ﺃﺴﻔل ﺍﻟﺒﻁﻥ‪ 17 ،‬ﺤﺎﻟﺔ ﺃﻟﻡ ﺃﺴﻔل ﺍﻟﺒﻁﻥ‪.‬‬ ‫ﺜﻼﺜﻭﻥ ﺤﺎﻟﺔ ﻜﺎﻨﺕ ﺘﻌﺎﻨﻲ ﻤﻥ ﻓﻘﺭ ﺍﻟﺩﻡ‪ .‬ﻋﻨﺩ ﺍﻟﻜﺸﻑ ﺍﻟﺭﺤﻤﻲ ﻭﺠﺩﺕ ﺁﺜـﺎﺭ ﻨﺯﻴـﻑ‬ ‫ﻤﻬﺒﻠﻲ ﻋﻨﺩ ‪ %46‬ﻤﻥ ﺍﻟﺤﺎﻻﺕ ﻭﻀﻤﻭﺭ ﺍﻟﻤﻬﺒل ﻋﻨﺩ ‪ %42‬ﻤﻥ ﺍﻟﺤﺎﻻﺕ‪ .‬ﺤﺠـﻡ ﺍﻟـﺭﺤﻡ ﻜـﺎﻥ‬ ‫ﻤﺘﻀﺨﻡ ﻓﻰ ‪ %52‬ﻤﻥ ﺍﻟﺤﺎﻻﺕ‪ ،‬ﻁﺒﻴﻌﻲ ﻓﻰ ‪ %34‬ﻭﺼﻐﻴﺭ ﻓﻰ ‪ %14‬ﻤﻥ ﺍﻟﺤﺎﻻﺕ‪.‬‬ ‫ﺃﺩﺍﺓ ﺍﻟﺘﺸﺨﻴﺹ ﺍﻷﻜﺜﺭ ﺸﻴﻭﻋﹰﺎ ﻫﻰ ﻋﻤﻠﻴﺔ ﺍﻟﺘﻭﺴﻴﻊ ﻭﺍﻟﻜﺤﺕ ﻭﺍﺨﺫ ﺍﻟﻌﻴﻨﺔ ﺃﺠﺭﻴﺕ ﻟــ‬ ‫‪ 33‬ﺤﺎﻟﺔ ﻭﻜﺎﻨﺕ ﺍﻟﻨﺘﻴﺠﺔ ﻭﺭﻡ ﺤﻤﻴﺩ ﻋﻨﺩ ‪ 12‬ﺤﺎﻟﺔ‪ ،‬ﺸﺒﻪ ﺨﺒﻴﺙ ‪ 11‬ﻭ ﺨﺒﻴﺙ ﻋﻨﺩ ‪ 10‬ﺤﺎﻻﺕ‪.‬‬ ‫ﺃﺨﺫﺕ ‪ 6‬ﻋﻴﻨﺎﺕ ﻤﻥ ﻋﻨﻕ ﺍﻟﺭﺤﻡ ﻭﻜﺎﻨﺕ ﻨﺘﻴﺠﺘﻬﺎ ﺍﻹﺼﺎﺒﺔ ﺒﺴﺭﻁﺎﻥ ﻋﻨﻕ ﺍﻟﺭﺤﻡ‪.‬‬ ‫ﻟﻡ ﻴﺘﻡ ﻋﻤل ﻤﻨﻅﺎﺭ ﺍﻟﺭﺤﻡ ﻟﻜل ﺍﻟﻤﺭﻀﻰ‪ .‬ﺍﻷﺴﺒﺎﺏ ﺍﻟﺨﺒﻴﺜﺔ ﻭﺠﺩﺕ ﻓـﻰ ‪ %32‬ﻤـﻥ‬ ‫ﺍﻟﺤﺎﻻﺕ‪ ،‬ﻓﺭﻁ ﺍﻟﺘﻨﺴﺞ ﻓﻰ ‪ %24‬ﻤﻥ ﺍﻟﺤﺎﻻﺕ‪ ،‬ﺘﺩﻟﻰ ﺍﻟﺭﺤﻡ ﻓـﻰ ‪ ،%10‬ﻟﺤﻤﻴـﺔ ‪ ،%8‬ﺍﻟﺘﻬـﺎﺏ‬ ‫ﺒﻁﺎﻨﺔ ﺍﻟﺭﺤﻡ ﺍﻟﻀﻤﻭﺭﻱ‪ ،‬ﺍﻟﺘﻬﺎﺏ ﺍﻟﻤﻬﺒل ﺍﻟﻀﻤﻭﺭﻱ ‪ %10‬ﻭ ‪ %6‬ﺒﺎﻟﺘﻭﺍﻟﻰ‪ ،‬ﻓﺭﻁ ﺘﻨﺴﺞ ﺒﻁﺎﻨـﺔ‬ ‫ﺍﻟﺭﺤﻡ ‪ ،%4‬ﺍﻟﻭﺭﻡ ﺍﻟﺤﻠﻴﻤﻲ ﺍﻟﻤﺘﻌﺩﺩ ﻟﺒﻁﺎﻨﺔ ﺍﻟﺭﺤﻡ ‪ ،%4‬ﺍﻟﻭﺭﻡ ﺍﻟﺤﻠﻴﻤﻲ ﺍﻟﻤﺘﻌـﺩﺩ ﻟﻌﻨـﻕ ﺍﻟـﺭﺤﻡ‬ ‫‪.%2‬‬ ‫ﺧﻠﺼﺖ ﺍﻟﺪﺭﺍﺳﺔ ﺇﱃ ﺃﻥ ﻣﻌﺪﻝ ﺃﻣﺮﺍﺽ ﺍﻟﺮﺣﻢ ﺍﳋﺒﻴﺜﺔ ﺃﻛﺜﺮ ﻣﻦ ﻣﺎ ﻫﻮ ﻣﺜﺒﺖ ﰱ ﺍﻷﲝﺎﺙ ﺍﻟﺴﺎﺑﻘﺔ‪ .‬ﱂ ﻳﺜﺒﺖ ﺍﻟﺒﺤﺚ ﻋﻼﻗﺔ ﺇﺣﺼﺎﺋﻴﺔ ﺑﲔ‬ ‫ﺛﻼﺛﻰ ﺍﻟﺴﻤﻨﺔ‪ ،‬ﻣﺮﺽ ﺍﻟﺴﻜﺮﻯ ﻭﺍﺭﺗﻔﺎﻉ ﺿﻐﻂ ﺍﻟﺪﻡ ﻭﺃﻣﺮﺍﺽ ﺍﻟﺮﺣﻢ ﺍﳋﺒﻴﺜﺔ ﻭﺍﻟﱰﻳﻒ ﺑﻌﺪ ﺳﻦ ﺍﻟﻴﺄﺱ‪.‬‬

‫‪9‬‬

CONTENTS Page Dedication ………………………………………………………………...I Acknowledgments………………………………………………………..II Abbreviations……………………………………………………………III English abstract…………………………………………………………..V Arabic abstract………………………………………...………………...VI List of tables…………………………………………………..…...…...VII List of figures ………………………………………...….……………VIII

CHAPTER ONE INTRODUCTION………………………………………………………...1 LITERATURE REVIEW…………………………………………………4 OBJECTIVES…………………………………………………………...25

CHAPTER TWO MATERIALS AND METHODS ………………………...……………...26

CHAPTER THREE RESULTS ……………………………………………………………….28

CHAPTER FOUR DISCUSSION……………………………………………………………57 CONCLUSION ………………………………………………………….63 RECOMMENDATIONS ………………………………………………..65 REFERENCES…………………………………………………………..66 APPENDIX (questionnaire)

10

LIST OF FIGURES Page Fig. 1:

Age distribution of patients

Fig. 2:

Distribution of endometrial cancer and cervical cancer

32

according to age

33

Fig. 3:

Distribution of patients according to residence

34

Fig. 4:

Distribution of patients according to parity

35

Fig. 5:

Distribution of patients according to marital status

36

Fig. 6:

Distribution of patients according to age of menarche

37

Fig. 7:

Distribution of patients according to age of menopause

38

Fig. 8:

Distribution of endometrial cancer and cervical cancer according to the age of menarche

Fig. 9:

39

Distribution of endometrial cancer and cervical cancer according to the age of menopause

40

Fig. 10: Distribution of patients according to the past medical history of hypertension and DM

41

Fig. 11: Distribution of patients according to findings on presentation

42

Fig. 12: Distribution of patients according to uterus size on presentation

43

Fig. 13: Distribution of cases of endometrial cancer according to BMI 44 11

LIST OF TABLES Page Table 1:

Association between medical and gynaecological

history and postmenopausal bleeding

45

Table 2:

Correlation between D & C biopsy and uterus size

46

Table 3:

Correlation between D & C biopsy and uterus surface

47

Table 4:

Correlation between D & C biopsy and uterus mobility

48

Table 5:

Association between drug history and

postmenopausal bleeding Table 6:

Association between family history of disease and

postmenopausal bleeding Table 7:

51

Distribution of patients according to the findings on

vaginal examination Table 9:

50

Distribution of patients according to the findings on

general examination Table 8:

49

52

Distribution of cases of PMB according to the results of

D &C biopsy obtained

53

Table 10: Distribution of cases of PMB according to the results of cervical biopsy obtained

54

Table 11: Distribution of cases of PMB according to U/SS Measurements of endometrial thickness

55

Table 12: Distribution of patients according to the cause of PMB

56

12

INTRODUCTION & LITERATURE REVIEW Postmenopausal bleeding (PMP) is defined as bleeding from the genital tract occurring six months to one year after the onset of menopause. Even without amenorrhoea or irregularity, menstruation continued after the age of 55 years should be investigated.(1) PMB is a symptom not to be underestimated, in 13% of cases the bleeding was caused by neoplastic disease of the genital tract (GT). It should be thoroughly evaluated although screening methods for endometrial cancer are not as effective as those for cervical cancer.(2) Non organic causes were the most common, benign causes were much commoner than malignant causes, bleeding from the uterus was the most common in all cases of PMB. Post menopausal bleeding with an enlarged uterus and women with advanced age has statistically significant correlation with more serious pathology.(3) The commonest cause of bleeding occurring after the menopause is the indiscriminate use of oestrogens; if this be excluded 10% of all cases and 23-50% of those in which the bleeding is continuous or occurs more than once, are accounted for by malignant disease of the cervix or of the body of the uterus. A significant proportion of women with PMB has atrophic endometrium or vagina, other benign causes include endometrial polyps, submucous fibroids, cervical polyps, cervicitis, benign conditions

13

of the vagina, vulva including trauma, infection, foreign bodies and ulcers. Granulosa or theca cell tumours of the ovaries, fallopian tubes tumours as well as tumors of the vagina and vulva are rare causes of PMB.(1) Various risk factors were found to be significantly correlated with malignancy especially a triad of obesity, DM and hypertension, as low parity and late menopause.(4) PMB or discharge calls for immediate investigations, even though there is slight bleeding except when there is a history of oestrogen therapy, E.U.A, D & C and, cervical or endometrial biopsy. This is true even if E.U.A, D & C cervical biopsy are negative, true even if an adequate cause of bleeding such as cervical polyp or senile vaginitis were found, the presence of such lesions does not exclude the presence of carcinoma. When a cause is found treatment is directed to it, where no cause is found origin from another site should be excluded i.e. from the bladder, urethra rectum and anal canal, if no cause is found hystrectomy is advised.(1)

Incidence: PMB is a phenomenon of the western world, it is most common in Caucasian women of high socioeconomic status. The incidence 14

increases with migration from developing to western countries and implicates environmental reasons as the main cause, the disparity is probably due to the increased use of exogenous, the higher degree of obesity, and a higher accessibility to medical services and, therefore, increase in reporting. In Sweden the incidence of PMB varies between 13 per 1000 postmenopausal women at the age of 50 years to 2 per 1000 postmenopausal women at the age of 80 years. In contrast the risk of endometrial carcinoma in women with PMB rises with age from about 1% at the age of 50 years to about 25% at the age of 80 years. The incidence of PMB in the U.K is unknown, however, at Hillingdon Hospital between the years of 1995 and PMB accounted for 4.6% of new gynecologic referrals and 23.6% of new gynecological referral for PMW, the local incidence of PMB has been estimated to be 7 per 1000 PM W. (2) Pathology: Early studies reported the risk of endometrial cancer associated with PMB as 53- 58%, however, more recent reports suggest the incidence to be 1.5 to 28% with an average of 11%, this may reflect increasing awareness of the importance of PMB.

15

A significant proportion of women with PMB have atrophic endometrium, other non-neoplastic causes include cervicitis, cervical polyps, atrophic vaginities.(2) In a group of 163 consecutive cases, malignant cases were found in 27.7% patients, carcinoma of the cervix was the most common 12.9% of the patients, followed by endometrial carcinoma (11%). Important benign causes are cervicitis (12.9%), atrophic vaginity (12.3%), cervical polyps (6.7%), other benign causes include endometrial hyperplasia 3.1%, urethral caruncle (2.5%) oestrogen replacement therapy (1.8%). (5) In Sweden 457 PM women suffering from uterine bleeding were investigated using D & C under G.A. The peak incidence of endometrial carcinoma was found in women between 65 and 69 years of age. Endometrial histopathology showed atrophy (50%), proliferation (4%), secretion (1%), polyps (9%), hyperplasia (10%), adenocarcinoma (8%), 14% not representative; other disorders (3%). Eight women had ovarian tumors. (6) Another study was conducted on 748 patients with PMB, benign causes were most frequent than malignant causes, among the benign causes, the most frequent were cervicits (19.95%), prolapsed uterus with decubitus ulcer (19.41%), dysfunctional hemorrhage (13.29%) and endometrial polyps (12.77%), the cancer of the cervix /cancer of the body ratio was 2 : 1. (7) 16

1198 patients with PMB were evaluated, atrophy was found in 46.3% endometrial polyps in 19.8%, endometrial cancer in 17.5% and hyperplasia in 6.7%. (8) In Taiwan 381 patients with PMB were evaluated for the etiology and incidence of malignancy, the results showed that 55.6% of these women had normal histologic finding, 21.9% had benign pathologic findings, whereas 3.6% had CIN, 11% had endometrial hyperplasia, 5% had cervical cancer, and 2.9% had endometrial cancer. (9) Reported case of PMB secondary to metastatic breast in the endocervix. This is the second reported case of cervical involvement from breast carcinoma.(10) In the records of 50% cases with primary carcinoma of the fallopian tubes the most common symptoms were PMB.(11) Endometrial tuberculosis and sarcoidosis can present with PMB, and should be considered in the differential diagnosis of granulomatous disease of the endometriuml (12,13) History and examination: A thorough history is the most important step in assessing women with PMB, it is an integral part of diagnosis and results of investigations should only be interpreted in conjunction with whole clinical picture. History should make sure if the there is in fact bleeding from genital tract and not from the urological or intestinal region as some women with 17

lesions of the bladder, urethra, rectum and anus may also describe the bleeding as being per vaginum. (2) Drug intake should be recorded, any condition that increases exposure to unopposed oestrogen increases, the risk of endometrial hyperplasia and carcinoma. Break through bleeding is a common problem in PM women taking HRT without progestin and often the single most important factor deferring women from continuing to use HRT. (14) Oestrogen creams used as HRT may cause endometrial stimulation.(1) Tamoxifen used as adjuvant therapy for breast cancer frequently causes episodes of unscheduled uterine bleeding which could be associated with adenomyosis and proliferative changes.(15) Presence of ovarian secretary tumours such as granulosa cell tumours and hyperthecomas are a cause of excessive endogenous oestrogen secretion and PMB.(16) Endometrial carcinoma is more common in women who are older, obese, affluent, white and of low parity and late menopause. Medical triad of obesity, diabetes mellitus and hypertension are associated with high risk of endometrial cancer. Smoking and combined oral contraceptive pills appear to decrease the risk of endometrial cancer.(1) The risk of endometrial cancer increases with

18

age, and the number of risk factors present.(2) History of missed intrauterine device should not be forgotten. In a review of presenting symptoms of 181 endometrial carcinoma patients indicated that 69.6% presented with PMB, 21.0% with irregular bleeding, 3.9% presented with abdominal pain and other 5.5% symptoms less. Those presented with irregular bleeding and other symptoms with abdominal pain had a survival than those presenting with PMB. (17) Although examination may help in the diagnosis, the causes of intrauterine bleeding: vulval, vaginal, cervical or pelvic pathology may easily be diagnosed by means of inspection and further by using speculum. Bimanual examination may exclude cervical carcinoma as a cause of bleeding. An enlarged uterus encountered during examination of PMB women is frequently associated with abnormal endometrial pathology. (18) Adnexa should always be examined, solid cystic masses in the adenxal area can be better identified as suprauterine cause of PMB. (19)

19

Investigations: The aim of investigations is to exclude both endometrial cancer and atypical hyperplasia, previously this has been performed using fractional curettage under general anesthesia, more recently hystroscopy has enabled visualization of the uterine cavity and directed biopsy, however, many women with PMB are overweight, diabetic, or hypertensive, the risk, of GA are substantial in such women, this has led to the development of outpatient investigations such as endometrial sampling, this allows repeat histologic examination of the uterus to determine biologic potential of endometrial hyperplasia and it's progression into endometrial carcinoma.(2) Cupta from Scotland evaluated the optimum methods of investigating women with PMB. In outpatient clinic all women had pipelle endometrial sampling, and transvaginal ultrasound (TVS) to measure the endometrial thickness and to exclude ovarian pathology. In inpatient clinic all women had hysteroscopy and uterine curettage, he recommended the routine use of TVS in all women with PMB. Sampling of the endometrial cavity preferably with outpatient hysteroscopy is mandatory for histological diagnosis, the combination of TVS and outpatient endometrial sampling would spare hospital admission for at least 60% of women with PMB. (20) 20

Methods for excluding endometrial cancer and hyperplasia in women with PMB. (2) Outpatient procedures: - Endometrial sampling. - Hysteroscopy and directed endometrial biopsy. - TVS. - Sonohysteroscopy. Inpatient Procedures: - D & C. - Dilatation and fractional curettage. - Hysteroscopy and curettage. - Hysteroscopy and directed endometrial biopsy. Endometrial sampling: There are now many devices for performing endometrial biopsy in the outpatient clinic, Crimes reported a 20 years experience with vabra aspirator technique, in which the complication rate was lower and the detection rate for endometrial abnormalities was higher, when compared with curettage. However, vabra, aspirator only samples an average of 41.6% of the endometrial surface and less tolerated by the patient. The pipelle is tolerated better than most other forms of office endometrial biopsy devices, but only samples an average of 4.2% of the endometrial surface, it has sensitivity rate between 98% and 68% for 21

detecting endometrial cancer. The incidence of both uterine perforation and infection with the vabra aspirator is 0 - 4/1000. (2) Using the Sherman curette in a dedicated clinic kitchner's group were able to avoid admission for 81% of their patients with PMB, they can be confident in the accuracy of their claim not to have missed any cases of endometrial carcinoma. (21) A comparison of endometrial sampling with the accurate and vabra aspirator and uterine curettage by Goldberg- GL and his group were concluded that, accurate and vabra aspirator has the advantage of being less expensive reliable and, more suitable for routine endometrial sampling.(22) In a multicentre retrospective study using lssacs cell aspirator for 3 years, Polson-DW was concluded that, with an experienced cytologist, lsaacs endometrial aspirator should be used routinely for the primary investigations of PMB. (23) A recent report comparing the pipelle and the Novak curette in a randomized prospective study, in which 149 women underwent pipelle biopsy and 126 a Novak curettage, there was significantly less pain experienced with pipelle biopsy. Of 50 patients who underwent hysterectomy, there was agreement in 96% of patients between pathological results of hysterectomy and those of endometrial samples. The authors concluded that pipelle biopsy appeared to be as effective as 22

Novak curette in obtaining adequate specimen but was associated with less pain. (2) Hysteroscopy: Until recently, hysteroscopy was only available at specialist centers, however, the first successful hysteroscopy on a woman with PMB was reported as long 1869. Hysteroscopy allows a visual inspection of the uterine cavity and can help that foci of abnormal appearing endometrium are sampled for histological analysis, furthermore, the endocervix can be directly visualized, this allows spread of endometrial cancer to be seen, this influencing management. However, hysteroscopy without biopsy is unreliable in differentiating between per-malignant and malignant endometrium.(2) Altaras and his group performed micro-hysteroscopy and endometrial sampling in 39 women with PMB in whom curettage had failed to obtain adequate tissue for analysis, pathology results were obtained in 29(74.3%) of women, three of whom had endometrial cancer.(24) In a further study of 202 patients with PMB in whom curettage had failed, hysteroscopically directed biopsies found 19 cases of endometrial hyperplasia and 7 cases of carcinoma.(2) Liu- Y, Zhou- Y, WenH examined 135 cases women with PMB by hysteroscopy, 39 patients were operated simultaneously, they 23

concluded that hysteroscopy is an effective method for identifying the causes of PMB, which is superior to curettage of the uterus. For some selected cases hysteroscopic operations can be performed at the same time. In another prospective study, hysteroscopy was compared with curettage complemented by Randall polyp forceps, the authors concluded that, curettage alone in P.M. patients is not sufficient for detection and extraction of endometrial polyp. Additional use of Randall forceps improves detection of polyps considerably. However, with both procedures complete extraction of polyps was not achieved in considerable number of patients. Hysteroscopy controlled extraction was superior. (25) Buchholz-F, Bontag-G and Semm-K compared the contact hysteroscopic findings with the histopathological diagnosis of 168 patients who were treated for PMB. The good diagnostic agreement between contact-hysteroscopy and histopathology in mostly benign lesions like atrophic endometrium (94.7%), polyposis (87.5%), mucosal polyps (88%) and myomas (100%) is not achieved in pre-cancerous (77%) and cancerous (75%) lesions. They concluded that contact hysteroscopy is not a substitute for a histopathological diagnosis and, may only provide additional information to D &C. (26)

24

In another group hysteroscopy was performed in 150 patients with PMB, and proved to be an ideal procedure in defining the cause of bleeding through direct vision of the pathologic lesions in the uterine cavity.(27) Ninety-six cases of abnormal uterine bleeding were evaluated by both hysteroscopy and D & C. Hysteroscopy diagnosed endometrial polyps and submucous leiomyoma with 100% accuracy.(3) A total of 149 patients with uterine bleeding were evaluated by means of office hysteroscopy and TVS, it was found that hysteroscopy was 79% sensitive and 93% specific in diagnosing intracavitary pathologic disorders, whereas TVS was only 54% sensitive and 90% specific and it was stated that, office hysteroscopy is a rapid, safe, welltolerated and, highly accurate means of diagnosing the cause of excessive uterine bleeding. It permits patients and physicians to discuss more treatment options before surgery, including outpatient operative procedures, this means savings in time and in drugs, procedure, professional and hospital costs.(28) Townsend-De and his group evaluated 110 women between the age of 40-90 years with persistent PMB, by diagnostic hysteroscopy and managed by operative hysteroscopy, they stated that diagnostic, and operative hysteroscopy was effective in controlling PMB of at least 6 months duration, almost 90% of the patients had either polyps or sub25

mucous fibroids as the primary cause of the bleeding, resection alone and resection with ablation were equally effective in controlling the bleeding.(29) The efficacy of hysteroscopy surgery was assessed in 102 patients with PMB, it was found that major operative complications were rare and included one perforation and, one case of glycine toxicity, 88 patients were satisfied with the results (87%), 6 patients were subsequently treated by hysterectomy, 6 patients complained of recurrent bleeding. They concluded that this modality of treatment appears to be effective over the long term, the operative criteria should take the causes of bleeding and not just the age of the patient into account.(30) The addition of hysteroscopy to endometrial sampling is associated with more possible operative complications, these include water intoxication, pulmonary oedema, air embolism and anaphylaxis, the incidence of perforation has been reported as 13/1000 and other serious complications as 1/1000, these complication rates are significantly lower for diagnostic hysteroscopy alone. Tanizwa reported that the incidence of tumour cells in the pelvic cavity after hysteroscopy in 1115 patients with endometrial cancer was not different than in those patients who had not been hysteroscopied. (2) Ultrasound:

26

Approximately 80% of all curettage procedures performed for PMB result in benign diagnosis, thus if a non- invasive modality such as TVS can be accurately used to determine endometrial thickness, measurements below which pathology id less likely, sampling may be avoided. (31) Measurements of endometrial thickness by TVS may be play a role in screening for uterine malignancy in women with PMB, the best evidence presently available suggests that full double thickness measurements, which include the contents of the cavity should be made using a TVS probe, as normal endometrial thickness varies with different ethnic groups, it is reasonable for Gynecological Ultrasound Units to have their own cut-off levels of normality with 3, 4, 5mm being the most common.(32,33,34.35) Many authors have reported the sensitivity for endometrial carcinoma as 100%, however, the false positive rate is high about 26% for atrophic endometrium and about 55% of women require further investigations, the specificity is even lower in women receiving oestrogen therapy. (2) One author reported a sensitivity for endometrial neoplasia as only 80% using a TVS measurement of endometrial thickness of 5 mm as a cut- off, in that paper 3 of 15 malignant tumours were missed, there were

27

2 cases of stage 1 adencarcinoma with endometrial thickness of 2 mm and 3mm respectively. (36) Interoperator variability of endometrial thickness measurement has not been assessed, the sensitivity of such measurement may be operator dependent. It is therefore possible that a mass of neoplastic endometrium could be missed by inexperienced monographers, this is more likely with retroverted uterus.(37) An advantage of U/S for investigating PMB is the opportunity for examining the whole pelvis. Gredmark, et al., found that 8 of 547 women who presented with PMB had ovarian tumours, as many ovarian cancers can not be palpated in Bimanual examination. (38) A largest study known as Nordic trial found that for a cut- off value of ( 4 mm (96%) sensitivity, (68%) specificity was achieved, the risk of finding pathologic endometrium at curettage below this value is 5.5% and it would seem justified to refrain from it.(39) Grigoriou, et al., evaluated the endometrial thickness by TVS in 250 women with PMB before undergoing D & C, they believe that it is reasonable to have cut-off limit for normal post menopausal uterus at 5mm TVS is a valuable diagnostic instrument, as sensitive as D & C, for detecting pathological conditions in the uterine mucosa.(40) Giusea-Chifer-MG; et al., studied the importance of endometrial biopsy, TVS, hysteroscopy and D & C in 80 patients with PMB, they 28

found that the sensitivity in detecting endometrial malignancy was 94.4% for endometrial biopsy and 100% for TVS, when the endometrial thickness was more than 8 mm, they concluded that when the thickness of endometrial echo is less than 3 mm, there is no need for anatomopathologic investigations, where the limit was 4 mm or more active endometria were detected requiring further histopathologic investigations by hystroscopy and directed biopsies, above 8 mm malignancy may be found. (41) One study of a total number of 289 women with PMB, concluded that endometrial thickness of ( 4 mm may serve as a cut- off point for predicting pathology negative cases with an accuracy of 100%, then as the endometrial thickness increases, the probability of finding endometrial pathology in curettage increases linearly with a positive predictive value of 74.6%. (42) Another study evaluated the role of TVS in the investigations of PMB in 50 women and, 25 asymptomatic controls, their result showed endometrial thickness in all asymptomatic controls was less than 5 mm and endometrial thickness greater than 5 mm to be 100% sensitive and, 64% specific in identifying endometrial pathology. TVS follow-up without curettage may be considered for PMB patients with uniform endomtrium less than 5 mm thick.(43)

29

In one study 930 patients with PMB were selected in the absence of hormonal therapy for at least 6 months, TVS was performed 3 days before histological evaluation using Bi-endometrial thickness in a longitudinal plane, they have shown that an endometrial thickness of

Suggest Documents