Histopathological correlation of endometrial samples in pre and postmenopausal women with abnormal uterine bleeding

Introduction: Abnormal Uterine Bleeding (AUB) is the most common clinical presentations in pre and postmenopausal women and is caused by various etiological factors ranging from inflammatory, benign to malignant lesions. The microscopical examination of the endometrium carries an important role in diagnosing various etiopathological factors in cases of AUB. Objectives: 1. To know the spectrum of lesions of the endometrium with respect to age. 2. To determine histopathological correlation of endometrial samples in pre and postmenopausal women. Materials and Methods: A cross sectional study was conducted from October 2009 to September 2011,involving 250 female patients, 40 years and above presenting with AUB. The patient’s endometrial samples were collected by biopsy, D & C or hysterectomy. Results: The maximum incidence of AUB in premenopausal women were seen in 40-42 years age group (38.42%), while in postmenopausal women, highest incidence of AUB cases were seen in the age group of 50-52(43.3%). years In the present study there was a high association between histopathological spectrum of endometrial lesions and age. Proliferative pattern was the commonest endometrial profile in the age group of 50-54 years (30.31%), where as secretory pattern (30.29%) was common in the age group of 45-49 years, atrophic Endometrium (100%) is seen in the age group of 65-69 years, polyps (24.9%) in the age group of 60-64 years, endometritis (9.0%) in age group of 45-49 years, irregular shedding (21.6%) in the age group of 40-44 years, simple hyperplasia (19.6%) in the age group of 45-49 years, whereas endometrial adenocarcinoma was more frequent in the age group of 55-59 years (11.7%). In premenopausal women, the most common endometrial pattern was secretory (26.8%), while in postmenopausal women majority of the endometrial profiles were atrophic (41.7%). Conclusion: This study showed that other than normal physiological changes in both pre and postmenopausal women, various benign and malignant conditions also occurred with increasing frequency. There was high association between the various bleeding presentations and spectrum of endometrium lesions found. Hence, the symptom “abnormal uterine bleeding”, requires prompt attention with respect to the etiology whether physiological or pathological and cannot be ignored. Therefore, microscopic analysis of the endometrium must be considered in all elder women presenting with AUB.


Introduction
Abnormalities in menstruation are a common cause of general practice consultations inthe primary or tertiary care centre 1 .Endometrium is the mirror of hormonal status in a female. 2 Menstrual dysfunction continues to be a huge burden on the healthcare system with varying etiology and considerable social implications.
Abnormal uterine bleeding (AUB) has been defined as change in frequency of menses, duration of flow, or amount of blood loss In adolescents, vaginal bleeding 3 which occurs before menarche is abnormal, while in women of child bearing and premenopausal age, any change in menstrual period, frequency, duration or amount of flow, as well as bleeding between cycles, are considered as abnormal.
In post menopausal women, AUB is described as vaginal bleeding for 12 months or more, after the cessation of menses or unpredictable bleeding in those who have been receiving hormonal therapy for 12 months or more. 4 Abnormal uterine bleeding can be a harbinger of sinister pelvic pathology or denote a relatively minor problem, therefore a thorough investigation into the problem is called for in every patient presenting with this complaint. 5 The gold standard is hysteroscopy and endometrial biopsy, the latter which is usually the first step in the diagnosis of AUB, along with diagnostic endometrial curettage which is mandatory without delay in all cases of perimenopausal and postmenopausal bleeding to rule out malignancy. The microscopical examination of the endometrium plays an important role in diagnosing various etiopathological factors in cases of AUB. 6 This study is therefore conducted to know the various endometrial lesions among pre and postmenopausal women with abnormal uterine bleeding in Navodaya Medical College Hospital and Research Centre, Raichur.
Aims and Objectives 1. To know the spectrum of lesions of the endometrium with respect to age. 2. To determine histopathological correlation of endometrial samples in pre and postmenopausal women.

Materials and Methods
Source of data:All female patients in the premenopausal group (45 + 5 years) and postmenopausal group (50 years and above) presenting with abnormal uterine bleeding, admitted in the inpatient ward of tertiary care hospital and from other peripheral referral centers, are the subjects of this study. A cross sectional study for a period of two years has been done.

Methods of collection of data:
Samples of the endometrial tissue were obtained by: D and C Endometrial Biopsy Hysterectomy. Detailed Requisition forms with clinical data of the study subjects were received along with samples of the endometrial tissue in 10% formalin bottles. The tissue samples were fixed in 10% formalin solution for 12 hours and prepared for microscopic examination by a series of Histopathology processes. Inclusion criteria: All patients in the premenopausal group (45 + 5 years) and post menopausal group (50years and above) presenting with abnormal uterine bleeding.

Methods of Study
A prospective study of 250 AUB cases was conducted and the results were analyzed according to age and histopathological spectrum of endometrial lesions.
Descriptive statistics were applied according to variable (i.e), frequency and percentage were calculated for bleeding patterns and histopathological spectrum of endometrial lesions in 250 AUB cases. Maximum and minimum age of the study group was described and mean age was calculated. The data was expressed in proportion of Chi -square test(or Fisher's Exact test in case of a small sample) which was used to examine association between age, and histopathological spectrum of endometrial lesions. Avalue < 0.05 was considered as significant and 0.01 as highly significant.

Age incidence of AUB cases in pre and menopausal women
A total number of 250 cases were enrolled in the study over a period of 2 years, out of which, 160 cases (64%) were premenopausal women and90 cases (36%) were postmenopausal women.
The Age incidence of the premenopausal women varied from 40 to 49 years with a mean(Standard deviation) age of 43.6 (+3) years. Highest number of patients wereseen between 40 to 42 years, whereas minimum were seen in 48 years and above age group and the same is shown below in the table.    In the present study there was also a high association between histopathological spectrum of endometrial lesions and the age (p<0.0001).

Discussion
Total number of 250 patients presented with abnormal uterine bleeding were included in the study.

Age incidence of AUB cases
The age incidence of the patients with abnormal uterine bleeding, varied from 40 to67 years and maximum presentation was seen in the age group of 40 to 49 years (64%) in the present study, which correlated with studies conducted by Shekhar P 7 and Tariq Sarfraz 8 In this study, premenopausal women with AUB accounted to 64%, whilepostmenopausal women accounted to 36%, the findings of which varied with similar studies by Baral R 9 .who reported AUB in 46.6% of premenopausal and 4.6% postmenopausal women.
Proliferative endometrial pattern (23.2%) which is the predominant endometrialprofile in this study, correlated with the observations of Veena et al, 6 in their similar study who also reported high incidence (30.8%), whereas the incidence of the same in separate studies conducted by Muzaffir et al 10 (25.8%) and Dangal G 11 (17.8%) were low, when compared to our study.
Irregular shedding in our study accounted to 16.4% of cases, where as the findings of Baral et al 9 reported a high incidence (26.6%) in their study and lower incidences were documented by authors like Veena M et al 6 (7.7%) and Muzaffar et al 10 (0.8%).In the present study, the incidence of simple hyperplasia was 12% which was similar to the findings of Veena M et al 6 (14.5%), Baral R et al 9 (12.3%) and Dangal G 11 (10%), whereas the studies of Muzaffar et al 10 (23.5%), showed comparatively higher incidence. Among the endometrial profiles in this study, endometritis (4.8%) was comparatively less common, the findings of which were consistent with that of Dangal G 11 in which they recorded 6%, but varied with the study conducted by Muzaffaret al 10 which showed 13%. The incidence of endometrial adenocarcinoma in the present study was very low(1.2%) and similar findings was noted in the studies conducted by VeenaM et a 6 (2.9%) and Baral R 9 et al (1%). But, contradictory to our study Dangal G 11 reported ahigher incidence (9.5%) of this lesion.

Age incidence of histopathological spectrum of endometrial lesions
There was high association between age and histopathological spectrum of endometrial lesions in our study subjects (p<0.0001). Proliferative pattern was the most common endometrial profile occurring in the age group of 45-54 years (23.5%) in the present study, the findings of which were supportive in the study conducted by Archana Bhosle, 12 who reported 66.1% in the above mentioned age group, whereas Muzaffar et al 10 in their study documented that, secretory profile (41.3%) was more common in the age group of 45-54 years.
In our study atrophic endometrium (41.7%) was seen commonly in the age group of50 years and above, which was similarly observed by Ali Hassan et al 13 (42%) and Narula 14 (41.7%) in their studies, who reported a high incidence in the same age group.
Cases of irregular shedding of the endometrium (17.4%) in our study were seen occurring with increasing frequency in the age group of 40-49 years and was similar to the findings of Baral R et al 9 (32%) in their study, who reported an increasedincidence in the above age group.
In the present study, polyps (14.8%) were the next common among the endometrial lesions in the age group of 55 years and above, which corroborated with the study of Ali Hasan et al 13 (17.9%), whereas, inflammatory conditions like endometritis (7.3%) was mostly seen in age group of 40-49 years, the supportive findings of which were seen in the studies conducted by BaralR 9 (3%) and Muzaffar (11.1%) et al. 10 Endometrial hyperplasia occurred more in the age group of 40-49 years (15.7%) in this study and this finding  The peak incidence of endometrial adenocarcinoma in the present study was seen inthe age group of 55-59 years (11.7%) which almost correlated with the studyconducted by Dangal G 11 (17.7%) and Ali Hassan 13 (7.5%), whereas in the study of Baral R et al 9 there was a correlation with the age, but a higher incidence of thislesion was observed (21%).
The profile of irregular shedding in our study was 17.4%, which was higher than the findings of Baral R et al 9 (6%) and Muzaffir et al 10 (0.4%).
In the present study, cases of endometritis accounted to 6.3%, which was consistentwith the studies of Muzaffiret al 10 (6.8%), but a lower incidence was seen in the studies of Baral R 9 (3%).
Polyps, in our study accounted to 5.3%, on the contrary to Muzaffiret et al 10 whoreported a low incidence of 0.4%. In the present study, the incidence of endometrial hyperplasia was 15.9%, which was similar to the findings of Muzaffiret et al 10 (20%) and Dangal G 11 (23%) whereas, the studies of Baral R et al 9 (29%), showed comparatively higher incidences.

Postmenopausal Women
In postmenopausal women, majority of the endometrial profiles were atrophic (41.7%). This finding corroborated with the observations of Ali Hassan et al 13 , and Dangal G 11 the former who reported a high incidence of 42%, while the latter reported an incidence of 64.4%.The profile of irregular shedding in our study was 13.3%, which was similar to the findings of Baral R 9 (14%). Polyps in our study accounted to 8.3% of cases, whereas a slightly higher incidence (13.3%) was reported by Ali Hassan et al. 13 Endometrial hyperplasia were less common (3.4%) in this study, the findings of which comparatively varied with the findings of Baral R et al 9 and Ali Hassan et al 13 who reported higher incidences of 21% and 13.2% respectively. A low incidence was seen in TB endometritis (1.7%) which corroborated with the observations of Nasira S et al 15 (0.6%), while stromal sarcomas (1.7%) in the present study also occurred in low incidence, but varied with the study of Ashraf et al 16 (16%) who reported a high incidence.
In the present study, all of the cases of endometrial adenocarcinoma (5%) presented in postmenopausal women, which was consistent with the studies of Ali Hassan et al 13 (7.7%), but a higher incidence was seen in the studies of Baral R et al 9 (21%) and Dangal G 11 (17.7%).

Conclusion
The present study was undertaken firstly, to know the spectrum of lesions of the endometrium with respect to age and secondly, to determine various histological patterns of the endometrium in pre and postmenopausal women. This study showed that other than normal physiological changes in both pre and postmenopausal women, various benign and malignant conditions also occurred with increasing frequency. There was also high association between the various bleeding presentations and spectrum of endometrium lesions found. Hence, the symptom "abnormal uterine bleeding", requires prompt attention with respect to the etiology whether physiological or pathological and cannot be ignored. Therefore, microscopic analysis of the endometrium must be considered in all women over 40 years of age presenting with AUB. The categorization of the endometrial causes of AUB among pre and postmenopausal women has been hampered by applying inconsistent nomenclature, making it difficult to compare studies performed by different researchers, on homogenous populations of patients experiencing AUB.
Thus, for the development of a more extensive 'living' document that includes nomenclature of bleeding patterns, endometrial profiles and classifications of Abnormal Uterine Bleeding, these recommendations should be the starting point for further debate and research.

Conflict of Interest:
None.