This document summarizes a study on abnormal uterine bleeding in pre-menopausal women. The study examined 3006 endometrial samples from women aged 30 to 50 who presented with abnormal uterine bleeding. It found that the rate of atypical hyperplasia and carcinoma increased with each successive 5-year age group, with the highest rates occurring in women aged 45-50. Specifically, atypical hyperplasia was 3.85 times more likely and carcinoma was 4.03 times more likely in women aged 45-50 compared to those under 40. While abnormal growths can occur under age 40, the study supports guidelines recommending endometrial sampling for women over 45 presenting with abnormal uterine bleeding.

1. Abnormal Uterine Bleeding in Pre-menopausal Women:
When Should We Investigate the Endometrium?
Samina Iram, Specialty Trainee in Obstetrics and Gynaecology, Ayman Ewies, Consultant Gynaecologist
The Ipswich Hospital NHS Trust, Heath Road, Ipswich, Suffolk, UK
Poster set out and produced by Medical Illustration at The Ipswich Hospital NHS Trust DMI ref: 1111-09.indd © The Ipswich Hospital NHS Trust, 2009. All rights reserved. Not to be reproduced in whole, or in part, without the permission of the copyright owner.
Background
• Endometrial carcinoma accounts for over 50% of primary
female genital invasive cancers and approximately 9.5% of
primary cancers of all types1
.
• The risk of developing endometrial carcinoma increases
with age and it is classically considered as a disease of post-
menopausal women. However, up to 20% of cases occur
before the menopause between 40 – 50 years of age, and
3 – 5% occur below age of 402
.
• There is lack of consensus amongst different regulatory bodies
as regards the cut-off age for sampling the endometrium
in those presenting with abnormal uterine bleeding (AUB).
It ranges from age of 35 years (American College of
Obstetricians and Gynaecologists)3
to 45 years (National
Institute of Clinical Excellence – NICE, UK4
and Royal College
of Obstetricians and Gynaecologists of Australia and New
Zealand)5
.
Objectives
To quantify the rate of endometrial hyperplasia and carcinoma in
different age categories in pre-menopausal women presenting
with AUB to find out whether the age is a risk factor for
developing these diseases.
Setting
The Ipswich Hospital NHS Trust, Suffolk, UK.
Methods
• A retrospective review of histopathology reports of
endometrial samples taken from 3006 women aged ≥ 30 to
≤ 50 years who presented with AUB between 1st January
1998 and 31st December 2007.
• Women were divided into three subgroups according to age;
group 1: 30 – ≤ 40 (n = 862), group 2: 40 – ≤ 45 (n = 1035) and
group 3: 45 – ≤ 50 (n = 1109).
Results
• Atypical hyperplasia was diagnosed in 2 (0.1%), 7 (0.2%),
and 20 (0.7%) women in groups 1, 2 and 3, respectively.
Endometrial carcinoma was diagnosed in 4 (0.1%), 2 (0.1%),
14 (0.5%) women in groups 1, 2 and 3, respectively.
• The results from the logistic regression revealed that the rate
of atypical hyperplasia (OR: 3.85; 95% CI: 1.75, 8.49; p=0.01)
and carcinoma (OR: 4.03; 95% CI: 1.54, 10.5; p=0.04) was
significantly higher in women in group 3 when compared to
younger women.
• The percentage of cases of atypical endometrial hyperplasia
and carcinoma was directly related to the age (chi-square test
= 29.6 with 8 degrees of freedom, p-value <0.0001).
• There was no statistically significant difference as regards
simple and complex hyperplasia in different age categories.
Table 1: The percentage of endometrial samples with either no
disease or benign histolology in different age categories
Age group 30 - <40
Group 1
40 - <45
Group 2
45 - 50
Group 3
Total Number of Cases 862 1035 1109
No Hyperplasia / carcinoma 841 (97.6%) 1001 (96.7%) 1043 (94.0%)
Normal histopatholgy 770 (89.3%) 894 (86.4%) 909 (82%)
Benign pathology 46 (5.3%) 81 (7.8%) 84 (7.6%)
Insufficient sample 25 (2.9%) 26 (2.5%) 50 (4.5%)
*Begin histology includes benign endometrial polyps and inflammation
Table 2: The percentage of endometrial hyperplasia and
carcinoma in different age categories.
Histopathological finding expressed as number (%)
Age group
Total
3006 (100%)
No Disease
2885 (96%)
Simple
Hyperplasia
56 (1.9%)
Complex
Hyperplasia
16 (0.5%)
Atypical
Hyperplasia
29 (1.0%)
Carcinoma
20 (0.7%)
30-<40 862 (29) 841 (28) 10 (0.3) 5 (0.2) 2 (0.1) 4 (0.1)
40-<45 1035 (34) 1001 (33) 22 (0.7) 3 (0.1) 7 (0.2) 2 (0.1)
45-50 1109 (37) 1043 (35) 24 (0.8) 8 (0.3) 20 (0.7) 14 (0.5)*
Table 3: The results from the logistic regression with odds ratios
(95% confidence interval) of endometrial hyperplasia and
carcinoma in different age categories.
Age group
Simple
Hyperplasia
Complex
Hyperplasia
Atypical
Hyperplasia
Carcinoma
30-<40
1
p=-
1
p=-
1
p=-
1
p=-
40-<45
1.85 (0.87,3.93)
p=0.11
0.50 (0.12, 2.09)
p=0.34
2.93 (0.61, 14.1)
p=0.18
0.42 (0.08, 2.27)
p=0.32
40-45
1.88 (0.90, 3.96)
p=0.10
1.25 (0.41, 3.82)
p=0.70
7.90 (1.84, 33.9)
p=0.005
2.74 (0.90, 8.36)
p=0.07
30-<45
1
p=-
1
p=-
1
p=-
1
p=-
45-50
1.28 (0.76, 2.20)
p=0.35
1.72 (0.64, 4.58)
p=0.28
3.85 (1.75, 8.49)
p=0.01
4.03 (1.54, 10.5)
p=0.04
Discussion
• Although the rate of hyperplasia and carcinoma is significantly
higher in women aged 45-50 yrs; nonetheless, they do occur
in younger age groups.
• Our data supports NICE recommendations that endometrial
sampling should be considered in all women over 45 years of
age with AUB.
• However, in younger age groups, investigations should be
individualized, and sampling may be reserved to women with
irregular menstrual bleeding, in those with heavy cyclical
menstrual loss and failed treatment for 3 months, or in case
of associated risk factors for endometrial hyperplasia or
carcinoma.
References
1 Crissman, J D R S Azoury, et al (1981) Endometrial carcinoma in women 40 years of age or younger. Obstet Gynecol 57(6): 699-704.
2 Clark, T J, C H Mann, et al (2002). Accuracy of outpatient endometrial biopsy in the diagnosis of endometrial cancer: a systematic quantitative review.
Bjog 109(3): 313-21.
3 Oriel, K A and S Schrager (1999). Abnormal uterine bleeding. Am Fam Physician 60(5): 1371-80; discussion 1381-2.
4 National-Institute-for-Health-and-Clinical-Excellence Heavy Menstrual Bleeding. NICE Clinical Guidelines 44, London, RCOG, 2007. Retrieved 4th October 2008 from:
http://www.nice.org.uk/nicemedia/pdf/CG44NICEGuideline.pdf.
5 New Zealand-National-Health-Committee Guidelines for the management of heavy menstrual bleeding, 1998. Retrieved 4th October 2008 from:
http://www.nzgg.org.nz/guidelines/0032/HMB_fulltext.pdf.
Number of endometrial samples with no
serious pathology
0
200
400
600
800
1000
1200
1 2 3
Histological Finding
Number
Insufficient Sample
Benign Pathology
Normal Histology
Figure 1: