Correlation of abnormal uterine bleeding with sonographic findings and histopathological examination of hysterectomy specimens

Introduction: Abnormal uterine bleeding (AUB) at menopausal transition is alarming and needs thorough evaluation, as it could be the only clinical manifestation of cancer. The aim of the study was to c orrelate abnormal uterine bleeding with sonographic fin dings and histopathological examination of hysterectomy specimens Methodology: This prospective study was do ne to evaluate the gynaecological causes of AUB in menopausal transition in OBG Department, LLRM Medical College, Meerut. These women were evaluated; clinical, ultrasound and histopathological findings were correlated.

In the present study, heavy menstrual bleeding (66.7%) was the commonest type of bleeding pattern. Leiomyoma, DUB and Adenomyosis were the principle causes of AUB. Leiomyoma accounts for the 60.6% of cases, DUB accounts for 15.9%, Adenomyosis accounts for 9.09% and Leiomyoma with Adenomyosis accounts for the 14.39% of cases.

Endometrial biopsy and its interpretation play a pivotal role in the management of AUB cases in menopausal transition. It emphasizes the role of health care professionals t o encourage teaching and implementation of alternative procedures to ensure that women receive the maximum benefits with least morbidity.

AUB (Abnormal uterine bleeding), histopathology, hysterectomy, menopausal transition, ultrasonography

Menopause is t he permanent cessation of menstruation which occurs following loss of ovarian activity. It is derived from Greek word 'mens' - month, 'pausis'- cessation [1]. Perimenopause is a period 3-4 years before menopause and followed by 1 y ear of amenorrhea. It enco mpasses the change from normal ovulatory cycles to cessation of menses, marked by irregularity of menstrual cycles [2]. Perimenopause is the period 2 -8 years preceding menopause and 1 year after the final menses (WHO) [3]. However a better practical definition is the phase preceding the onset of menopause, generally occurring around 40 -50 years of age (beginning at age 47.5, lasting for 4 years) during which the regular cycle of a woman transitions to a pattern of irregular cycles. The Perimenopausal Transition: Age of onset for 95% of women is 39-51 years. Average age of onset is 46 years. Duration for 95% of women is 2 -8years. Average duration is 5 years [1]. While significant awareness has been raised about menopause, less attent ion has been focused on th e perimenopausal or "menopausal transition" period. Many women and their physicians remain unaware of the impact of this transitional phase into menopause [1]. Specifically, heavy and unpredictable perimenopausal bleeding is extremely common [4]. The purpo se of this review is to focus on the hormonal and physiologic changes that are associated with perimenopausal heavy vaginal bleeding, to present the essential evaluation of causes for this heavy flow, and to outline the evidence f or effective medical and s urgical treatments. Advances in the understanding of the normal physiology of perimenopause have led to medical therapies that may lead to fewer surgical procedures and hysterectomies and should be of interest to health care practitioners focusing on women's health [4]. Abnormal uterine bleeding (AUB) refers to a symptom of excessive, prolonged, unexpected or acyclic bleeding regardless of diagnosis or cause. AUB not only affects quality of life such as intimate relationships, day to day living but can have serious adverse consequences as anaemia or malignancy [5]. International Journal of Clinical Obstetrics and Gynaecology http://www.gynaecologyjournal.com ~ 330 ~ The diagnostic goal with perimenopausal bleeding is to exclude carcinoma and to identify the underlying pathology to allow optimal treatment [6]. Ultrasonography may reve al an obvious cavitary lesion or an abnormally thin or thick endometrium. In perimenopausal and postmenopausal women with abnormal bleeding, endometrial biopsy is generally considered unnecessary when the endometrial thickness is less than 4 or 5 mm becaus e the risk of endometrial hyperplasia or cancer is remote. Biopsy is indicated when clinical history suggests long term unopposed estrogen exposure. An endometrial stripe of 5 mm thickness has been shown to be associated with an extremely low risk of endom etrial hyperplasia or car cinoma [2]. Women with endometrial thickness >5 mm warrant additional evaluation with saline infusion sonography or endometrial biopsy [4]. An accurate method of determining whether AUB is functional or structural, one needs a mini mally invasive accurate m ethod. D&C under general anaesthesia was once considered a gold standard investigation in the evaluation of AUB. It can however miss 2-6% of cases of cancer or hyperplasia [6]. Uterine cancer, the most serious cause of uterine bleed ing is diagnosed in fewe r than 10% of endometrial biopsies in women presenting with AUB, indicating that more than 90% of endometrial biopsies revealed benign findings [7]. The older terms perimenopause or climacteric generally refer to the time period in the late reproductive ye ars usually late 40s to early 50s. The more correct terminology for this term is menopausal transition [8]. The present study is designed to evaluate the causes of abnormal uterine bleeding in Menopausal Transition & to correlate t he clinical evaluation wi th ultrasonographic & histopathological examination.

The present study was conducted in the Department of Obstetrics and Gynaecology, LLRM Medical College, Meerut among the women who presented with abnormal uter ine bleeding in menopausal transition age over a period of two years from November 2016 to October 2018. Inclusion criteria A. Patients complaining of abnormal uterine bleeding b. Age 39- 51 years Exclusion criteria A. Post menopausal women Ethical commi ttee approval was take n for the study. Before recruiting the patient into the study, an informed consent was taken. Identification of the patient in relation to name, age, address, religion, socio -economic status, marital status, parity and literacy status was done. Detailed cl inical history including onset and duration of bleeding, drug history, past obstetric medical and surgical history was taken. Thorough clinical examination which included general physical examination, per abdomen, per speculum and per vaginal examination was done. Investigations like complete heamogram, ABO Rh, RBS, Thyroid profile, Urine routine, Renal function test, Liver function test, TVS or TAS and endometrial biopsy was done in all patients, irrespective of the endometrial thick nes. The endometrium was imaged in the longitudinal and cross -sectional plane through the body and the fundus of the uterus. The thickest point of the endometrium was measured from the anterior to posterior myometrial -endometrial junction. Both layers of t he endometrium were mea sured, that is the anterior and posterior layers. Morphological changes like appearance of endometrial strip (homogenous/heterogenous), endometrial thickness (diffuse/focal), margins (regular/irregular) are also noted. Endometrial biopsies were done and th e endometrial samples (endometrial curettage / hysterectomy specimens) sent to pathology laboratory, were analysed. These specimens are fixed in 10%formalin and gross morphology were recorded. Histopathological examination of the endometrial pattern as well as that of hysterectomy specimens were done. These bits were placed in cassettes and kept in fixative and processed in the automatic tissue processor. Paraffin tissue blocks were prepared and 3 -4micrometer thick sectio ns were cut and stained with routine Haematoxylin and Eosin. A detailed histological study was carried out and the findings were noted. Evaluation of ultrasound and histopathological findings of clinically diagnosed AUB cases was done with appropriate Statistical analysis was done.

The study was conducted in the department of obstetrics and Gynaecology, LLRM Medical College, Meerut. Total number of 132 cases were studied, age ranging from 39 -51 years (Mean age=45years). In the present study of 13 2 women in menopausal transition 58.3% belonged to age between 39 -42 years, 23.5% belonged to age between 43-46 years, and rest 18.2% belonged to 47-51 year age group. In the present study 66.7% had Heavy Menstrual Bleeding (HMB), 16.7% had Heavy Bleeding with Intermenstrual Bleeding (HPIB), 9.8% had Intermenstrual Bleeding (IMB), and 6.8% had Frequent Menstrual Bleeding (FMB). Out of 88 patients with Heavy Menstrual Bleeding (HMB), 55 patients had normal menstrual phase of endometrium, 8 patients had diso rdered proliferative endometrium, 15 p atients had atrophic endometrium, 2 patients had endometrial polyp, 6 patients had simple hyperplasia without atypia and 2 patients had chronic endometritis. Out of 22 patients with Heavy with Intermenstrual Bleeding ( HIMB), 17 patients had normal menstrual phase of endometrium, 1 patient had disordered proliferative endometrium, 1 patient had endometrial polyp, 2 patients had simple hyperplasia without atypia and 1 patient had complex hyperplasia without atypia . Out o f 13 patients with Intermenstrual Bleeding (IMB), 9 patients had normal menstrual phase, 1 patient had disordered proliferative phase, 2 patients had endometrial polyp,1 patient had simple hyperplasia without atypia. Out of 9 patients with Frequent Menstru al Bleeding (FMB), 7 patients had norma l menstrual phase endometrium, 1 patient had atrophic endometrium and 1 patient had simple hyperplasia without atypia (Table 1). In the present study, of endometrial biopsy, proliferative endometrium was found in 43. 9% of patients, secretory endometrium in 27.3%, disordered proliferative endometrium in 7.6%, atrophic endometrium in 7.6%, simple hyperplasia without atypia in 7.6%, chronic endometritis in 3%, endometrial polyp in 2.3% and complex hyperplasia without aty pia in 0.8% of patients. Out of 132 pati ents, on clinical examination, 100 patients were diagnosed to be having leiomyomas , finally confirmed by Histopathological examination. 72 cases were to be having leiomyoma, 18 were found to be having leiomyoma and adenomyosis, 6 were found to be having ad enomyosis, 4% found to be having normal morphology of uterus. Out of the 4 patients found to be having adenomyosis, on clinical examination 2 were found to be having adenomyosis and 2 were International Journal of Clinical Obstetrics and Gynaecology http://www.gynaecologyjournal.com ~ 331 ~ found to be having leiomyoma (Table 2). Out of the 28 cases diagnosed to be having DUB, on clinical examination, 6 were diagnosed as leiomyoma, 4 wer e found to be having adenomyosis, One was diagnosed to be having adenomyosis and leiomyoma. 17 cases were correlated with clinical diagnosis since no gross pathology found in the uterus (Table 2). Out of 132 cases, on Ultrasonography 96 patients were diagnosed as leiomyomas. After histopathological examination, out of 96 patients, 74 were diagnosed as leiomyomas, 3 were diagnosed as adenomyosis, 16 were diagnosed as leiomyomas with adenomyosis and 3 patients were diagnosed as Dysfunctional Uterine Bleeding. Out of the 4 patients diagnosed to be having adenomyosis, histopathological examination diagnosed adenomyosis in one case, leiomyoma in one case and dual pathology of leiomy oma and adenomyosis in 2 cases. Out of 4 patients diagnosed as Adenomyosis + Leio myoma, confirmed by histopathological examination. Out of 28 patients who were labelled as Dysfunctional Uterine Bleeding by Ultrasonography, 1 patient was diagnosed to be hav ing leiomyoma, 8 patients were diagnosed to be having adenomyosis, one patient wa s diagnosed to be having adenomyosis with leiomyoma and in the rest of 18 patients no gross pathology was detected on histopathological examination (Table 3). Table 1: Histopathology findings of endometrium in relation to symptoms Final pathology/ Symptoms N (%) Normal menstrual phase N (%) Disordered proliferative phase N (%) Atrophic endometrium N (%) Chronic endometritis N (%) Simple hyperplasia without atypia N (%) Complex hyperplasia without atypia N (%) Endometrial polyp N (%) Total N (%) HMB 55(62.5) 8(80) 15(93.8) 2(100) 6(60) 0 2(40) 88(66.7) HIMB 17(19.3) 1(10) 0 0 2(20) 1(100) 1(20) 22(16.7) IMB 9(10.2) 1(10) 0 0 1(10) 0 2(40) 13(9.8) FMB 7(8) 0 1(6.2) 0 1(10) 0 0 9(6.8) Total 88(100) 10(100) 16(100) 2(100) 10(100) 1(100) 5(100) 132(100) Table 2: Clinical diagnosis and HPE report correlation Clinical Leiomyoma N (%) Adenomyosisn (%) Leiomyoma+ Adenomyosisn (%) DUB N (%) Total N (%) Leiomyoma 72(72) 6(6) 18(18) 4(4) 100(100) Adenomyosis 2(50) 2(50) 0 0 4(100) DUB 6(21.4) 4(14.3) 1(3.6) 17(60.7) 28(100) Total 80(60.6) 12(9.1) 19(14.4) 21(15.9) 132(100) Table 3: USG diagnosis and HPE report correlation Clinical Leiomyoma N (%) Adenomyosisn (%) Leiomyoma+ Adenomyosisn (%) DUB N (%) Total N (%) Leiomyoma 74(77.1) 3(3.1) 16(16.7) 3(3.1) 96(100) Adenomyosis 1(25) 1(25) 2(50) 0 4(100) Leiomyoma+ adenomyosis 4(100) 0 0 0 4(100) DUB 1(3.57) 8(28.5) 1(3.57) 18(64.2) 28(100) Total 80(60.6) 12(9.1) 19(14.4) 21(15.9) 132(100)

Abnormal uterine bleeding is the main reason, women are referred to gynecologists and accounts for two -thirds of all hysterectomies [9]. Evaluation of patients with abnormal uterine bleeding and identifying those with AUB is achieved with combination of the following: his tory, physical examination, ultrasound and histopathological evaluation. AUB in women of menopausal transition age group is associated with endometrial carcinoma in 10% of patients [9], so evaluation of a woman's risk factors for endometrial hyperplasia o r carcinoma is recommended. Though endometrial sampling can be done by endometrial biopsy, endometrial aspiration and hysteroscopy, hysteroscopic guided biopsy is considered gold standard. The

from the study were analyzed and compared with results of other published studies. In the present study, most of the women with AUB belonged to 39-42years age group (58.3%), followed by 23.5% in the age group of 42 -46 years, in the range of age distribution betwee n 39-51 years, which is comparable with the st udy by Archana B et al., at LTMMC hospital, Mumbai [10], 76.1% were in the age group of 40-45 years. In the present study, heavy menstrual bleeding was the commonest type of bleeding pattern (66.7%) followed by heavy and prolonged menstrual bleeding (16.7%), intermenstrual bleeding in 9.8% of patients and frequent menstrual bleeding in 6.8% of patients, i s in concordance with the study done by Gupta et al. [11]. In the present study, endometrial thickness was as sessed using ultrasound, 7.6% had thickness of less than 5mm, 56.8% had ET of 5-8mm, 26.5% of women had ET of 9 -12mm and 9.1% had ET of >12mm. In t he study done by Asma Fared et al . [12], recommended a ET of >6mm single layer endometrium as cut off point f or the further evaluation of AUB in menopausal transition. In the present study, final histopathological examination of endometrium shows normal menstrual phase that is, proliferative and secretory phase (66.7%), which is in concordance with study by Gupta et al . [11] (61%), disordered proliferative phase in 7.6%, atrophic endometrium in 16%, chronic endometritis in 1.5%, simple hyperplasia without atypia in 7.6%, endometrial polyp in 3.8% of patients. No case of malignancy was found in the present study as compared to 3% of cases in Gupta et al. [11] study. Atrophic endometrium was found in 12.1% of cases compared to Gupta et al. [11]. The study by A rchana et al . [10] found proliferative endometrium 66.1% of cases, secretory endometrium in 16.1% of cases, which is also comparable to present study. Finally the clinical, radiological and histopathological findings of hysterectomy specimens were correlat ed. In 75.76% of patients a diagnosis of leiomyoma was made. In 21.2% of patients a diagnosis of DUB and in only 3.03% of patients, provisional diagnosis of adenomyosis was done on clinical International Journal of Clinical Obstetrics and Gynaecology http://www.gynaecologyjournal.com ~ 332 ~ examination. The clinical examination findings were confirmed by u ltrasound which detected leiomyoma in 100% of patients who were suspected to have leiomyoma on clinical exam ination. Out of 4 patients, who were clinically suspected to have adenomyosis, all the 4 were confirmed by USG. The patients who didn’t have any sig nificant finding on clinical examination were labelled as DUB. In the present study DUB was the second most common cause of AUB, accounting for the 21% of cases, which is in concordance with the study by Gupta et al . [11] (28%). In the present study Adenomyosis with Leimyoma is the third common cause of AUB, accounts for the 19% of cases, which is in concordance with the study by Gupta et al. (10%). In the present study Adenomyosis is the least common cause of AUB, in 9,09% of cases, which is in concordance w ith the study by Gupta et al. (6%). The study by Archana et al. [10] found Adenomyosis was the second most common cause of AUB in 29.4% of cases.

AUB is one of the most common problems in women of all age groups affecting 10 -30% of reproductive a ged women and upto 50% of women in menopausal transition. It is a challenging gynaecological problem ca used by various structural abnormalities of the uterus and endometrial pathologies. Endometrium is the mirror image of hormonal status in women of diffe rent age groups. It is important in detecting the cause, clinching the diagnosis and managing the patien ts with AUB. Endometrium can be easily procured in AUB cases by endometrial biopsy which is a simple cost effective and appropriate method that provides accurate diagnostic yield. Endometrial biopsy and its interpretation play a pivotal role in the management of AUB cases in menopausal transition.

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