Correlation of Body Mass Index with Endometrial Pathology in Perimenopausal Women with AUB: A Prospective Study

Abnormal uterine bleeding (AUB) refers to a wide range of anomalies in the menstrual cycle, including variations in flow volume, length, and frequency that do not occur during pregnancy. Up to one-third of women will suffer AUB at some point in their lives, the perimenopausal and menstrual cycles are when these abnormalities most frequently occur. A typical menstrual cycle has a frequency of 24–38 days, lasts 2–7, and results in blood loss of 5–80 mL. Any variations in these four factors qualify as irregular uterine hemorrhage.[ 1 ] AUB is more common in some groups than others, according to earlier studies, with an overall frequency that varies between 10% and 30%.[ 2 3 ] AUB is said to be existent with a prevalence of 17.9% in India.[ 4 ] The Menstrual Disorders Working Group of the International Federation of Gynecology and Obstetrics proposed the “PALM-COEIN” classification of AUB, which has the support of the American College of Obstetricians and Gynecologists. This classification system takes into account the multifactorial etiology of abnormal menstrual bleeding.[ 5 6 ] The etiologies of AUB are divided into two categories using this system: “related to uterine structural abnormalities” and “unrelated to uterine structural abnormalities” [ Table 1 ]. Federation of gynecology and obstetrics system - polyp, adenomyosis, leiomyoma, malignancy classification[ 7 ] AUB: Abnormal uterine bleeding Body mass index (BMI) rises in correlation with endometrial cancer incidence as obesity rates among women have risen in recent years. Despite abundant data showing a connection between endometrial cancer and obesity, few people are aware of it.[ 7 ] From menarche until menopause, it affects quality of life and places a financial burden on 9%–14% of women.[ 8 ] According to recent data, 35% of adults (20 and older) worldwide are overweight (BMI 25 kg/m 2 ) and 12% are obese (BMI 30 kg/m 2 ). It has been noyed that the prevalance of elevated BMI is increasing in several Asian and African countries as well.[ 9 ] Over the past 20 years, the increased incidence of obesity has been noted on a global level.[ 10 ] In this study, we sought to evaluate the relationship between BMI and the perimenopausal ladies’ aberrant and normal endometrial pathology. We also evaluated the correlation of transvaginal ultrasonography findings with histopathological findings.

The distribution of study participants on the basis of histopathological findings was done. Out of 72 patients, 22 patients had histopathological findings of adenocarcinoma (3, 13.6%) and EH (19, 86.4%) and rest 50 patients had normal proliferative (13, 26%) or secretory (9, 18%) endometrium or had adenomyosis (13, 26%), leiomyoma (12, 24%), or Polyp (3, 6%), as shown in Figure 1 . Distribution of study participants on the basis of histopathological findings On the basis of BMI, 51.5% (32/72) were overweight, 31.9% (23/72) were of normal BMI, 11.1% (15/72) were obese, and 5.5% (2/72) were underweight [ Figure 2 ]. Distribution of study participants on the basis of body mass index. BMI: Body mass index The mean age of study participants in Groups A and B was 52.37 ± 2.68 and 48.74 ± 7.98, respectively ( P = 0.003). Only 22.7% (5) and 16% (8) patients were nulliparous in Group A and B, respectively, with most of them of parity 1–2 in both groups (50% in A and 58% in B) followed by ≥3 in 27.3% and 26%, respectively ( P = 0.944). The distribution of patients across both groups on the basis of BMI ≥30 and <30 kg/m 2 was highly significant ( P = 0.0001). The mean BMI in Groups A and B was 32.68 ± 3.56 and 26.18 ± 5.38, respectively ( P = 0.012). The mean waist circumference and mean endometrial thickness (ET) were also significant across both groups ( P = 0.026 and 0.001, respectively) [ Table 2 ]. Baseline characteristics of study participants in both groups *Multiple response. BMI: Body mass index, AUB: Abnormal uterine bleeding, DM: Diabetes mellitus, TVS: Transvaginal ultrasonography Among Group A ( n = 22), 100% (3) patients of adenocarcinoma, 80% (4) patients of complex hyperplasia with atypia, 66.7% (2) of complex hyperplasia, and 54.4% (6) of simple hyperplasia without atypia were obese ( P = 0.33) [ Table 3 ]. Correlation of histopathological findings of carcinoma or en dometrial hyperplasia with body mass index The correlation of transvaginal ultrasound (TVS) findings with that of histopathology was statistically significant ( P = 0.002). Adenomyosis and polyp had 100% correlation percentage on TVS and histopathology. Whereas findings of the bulky uterus on TVS had varied diagnosis on basis of histopathological findings [ Table 4 ]. Correlation of transvaginal ultrasonography and histopathological findings AD: Adenomyosis, CHWA: Complex hyperplasia with atypia, CH: Complex hyperplasia without atypia, PP: Proliferative endometrium, SE: Secretory endometrium, SH: Simple hyperplasia without atypia, TVS: Transvaginal ultrasonography

According to the results of our study, there is a direct link between a high BMI and AUB due to EH. The importance of weight loss as a preventative intervention for AUB and as a component of conservative therapy must thus be emphasized. Primary cancer prevention and determining the priorities for research and public health action will benefit greatly from counseling and educating the affected women as well as the general population about the importance of physical activity as a preventative factor against AUB, endometrial cancer, and hyperplasia. TVS is a superior diagnostic technique for the assessment of AUB as an initial procedure since it is noninvasive, easily tolerable by women, and without any consequences. Another benefit of TVS is that it allows us to see the ovaries, endomyometrial junction adnexa, and myometrium. There are no conflicts of interest.

The most frequent presenting symptom in the gynecology outpatient department is AUB, which can range from a benign discovery to endometrial cancer. Numerous diseases of the reproductive system, as well as nongynecological factors, are among the causes of AUB.[ 13 ] Based on the patient’s age and the existence of endometrial cancer risk factors, such as anovulatory cycles, obesity, nulliparity, and age older than 35, further investigation of irregular uterine bleeding is dependent.[ 11 ] Obesity is a key contributing factor to the development of gynecological cancer.[ 14 ] The current study emphasizes that compared to the general population, women with excessive BMI and weight are predicted to have an increased incidence of AUB caused by EH. Despite the study’s potential sample size limitations, it shows that roughly 68.1% of patients had abnormal BMIs, with 51.5% of them being overweight and 11.1% being obese. The average BMI was 26.34 kg/m 2 + 7.98 kg/m 2 . In addition, the study indicates that AUB patients with BMIs >30 experience their symptoms for a longer period. In our study, there was a significant association between BMI and EH and cancer ( P = 0.033). Numerous research have produced outcomes that are similar. AUB patients have a significant incidence of obesity, according to several Indian research.[ 15 16 ] In the study by Varner et al . on 1557 cases, in patient with BMI >30 which was 45%, the duration of symptoms was shorter as compared to 12 years of duration of symptoms in those with BMI >25.[ 17 ] The longer history of AUB among the obese people may be a reflection of their propensity to put off seeking treatment, or it may be the result of their doctor delaying an elective hysterectomy because of the increased morbidity rates that are expected in this population. Similar findings were seen in our study, where the majority of the women with BMIs >30 kg/m 2 reported symptoms that persisted for longer than 2 years. Obese women are more likely than nonobese women to suffer irregular menstrual cycles, according to a number of studies.[ 12 14 16 ] These investigations have revealed the need for achieving a healthy body weight as part of the treatment for AUB, in addition to restoring the predictability of bleeding, managing anemia, and managing numerous related medical disorders.[ 15 ] Women with a BMI >40 had a 6.25 relative risk of dying from endometrial cancer, according to a prospective American research. Women with a BMI >35 had an increased risk of dying from ovarian or cervical cancer.[ 18 ] Another Dutch case-cohort research revealed a significant link between obesity and endometrial cancer.[ 19 ] Although the inclusion of other metabolic syndrome components increases the risk even more, obesity appears to be the essential aspect of metabolic syndrome in endometrial carcinogenesis.[ 11 ] The quantity of circulating estrogens in postmenopausal women is directly influenced by the level of adiposity because the conversion of androgens to estrogens takes place in adipose tissue. Women continue to gain belly fat after menopause as estrogen levels fall.[ 20 ] Patients with endometrial carcinoma and hyperplasia showed substantially larger mean waist circumferences than those with noncancerous pathology of AUB ( P = 0.026). As a result, the measurement of waist circumference may be a significant indicator of endometrial cancer during menopause. A study found that compared to women with EH and cancer, those with endometrial cancer had a greater frequency of the overall metabolic syndrome.[ 11 ] For many years, dilatation and curettage were the most frequently utilized methods for obtaining an endometrial biopsy in cases of perimenopausal and postmenopausal hemorrhage. The false-negative rate for the dilatation and curettage method of detecting endometrial cancer and hyperplasia has been found to be between 2% and 6%. The primary cause is a sampling mistake related to curettage, and a single curettage will not entirely remove the endometrium’s surface from the uterine canal.[ 21 ] We also evaluated the correlation between transvaginal ultrasonography (TVS) findings with histopathology findings, which was statistically significant. The findings on TVS showed a significant correlation with histopathology findings. The mean ET in those with EH and adenocarcinoma was 14.79 ± 2.15 mm, which was significantly higher than the noncancerous pathology group with AUB ( P = 0.001). In research by Hunter and McClure, TVS sensitivity with biopsy was 75%, and specificity was 90%.[ 22 ] Aslam et al . claimed that[ 23 ] ET was abnormal if TVS detected 8 mm. It had a 67.7% specificity and a 71.4% sensitivity. TVS showed a sensitivity of 92.3% and a specificity of 68.96%, according to Shobhitha et al ., with an ET cutoff of 8 mm for EH.[ 21 ] EH was reported in 85 (70.83%) instances by Shokouhi on TVS. Eighty-five (70.83%) instances had EH detected by pathology, comprising 82 cases of simple cystic hyperplasia, one case of atypical simple hyperplasia, and two cases of complicated hyperplasia. Pathology found evidence of EH in 81 of these 85 patients. In premenopausal and postmenopausal women, TVS accuracy was 88.25% and 100%, respectively.[ 24 ] TVS, however, also has certain challenges. The technique’s unpredictability has prevented readings from being standardized. Since TVS is an operator-dependent modality, the accuracy and quality of the signal depend largely on the skill of the operator. Finally, TVS is a diagnostic tool that may reveal an anomaly in the endometrium or uterine cavity; pathologic analysis is necessary for a precise diagnosis.[ 24 25 ]

This was prospective observational study. The duration of the study was 12 months (June 2022–May 2023). Women aged 40–55 years with AUB according to PALM-COEIN criteria attending a tertiary care center of Northern India for treatment. Women aged 40–55 years with AUB according to PALM-COEIN criteria. Those who had existing cervical, uterine, and ovarian cancer, pelvic inflammatory disease or premenopausal women with coagulation disorders or were pregnant, or women with liver disorders, or chronic kidney disease were excluded from the study. For sample size estimation, the study used is Özdemir et al .[ 11 ] The sample size formula used is: Zα/2 - critical value of the normal distribution at α/2 (for a confidence level of 95%, α = 0.05 and the critical value is 1.96) p - Proportion of females with BMI >30 kg/m 2 and abnormal endometrial pathology (value is 78.2%) d - Estimated margin of error (value is 0.1). Zα/2 - critical value of the normal distribution at α/2 (for a confidence level of 95%, α = 0.05 and the critical value is 1.96) p - Proportion of females with BMI >30 kg/m 2 and abnormal endometrial pathology (value is 78.2%) d - Estimated margin of error (value is 0.1). To detect the difference in the proportion of overweight or normal females with abnormal endometrial pathology, significant with a 95% confidence interval and power of 80%, the required minimum sample size was 66 patients. With 10% dropouts, the final sample size calculated was 72 patients. Endometrial hyperplasia (EH) was reclassified by the WHO in 2014[ 10 ] into two categories: Benign and atypical EH, also known as endometrial intraepithelial neoplasia (EIN) and well-differentiated cancer. In difficult instances, additional immune-histochemical markers and molecular abnormalities may be used to assist the differential diagnosis between benign uterine lesions and atypical hyperplasia/EIN.[ 10 ] All the females who were diagnosed with AUB according to PALM-COEIN criteria were enrolled in the study after informed written consent. In the outpatient department, each woman underwent a thorough clinical evaluation that included a detailed history, physical examination, and baseline tests such as full hemogram, LFT, RFT, coagulation profile, and transvaginal ultrasound. These results were entered in a predesigned pro forma. All the ladies underwent height and weight measurements followed by BMI calculations at the time of enrollment.[ 10 ] BMI is a straightforward measure of weight in relation to height that is frequently used to categorize individuals as being underweight, overweight, or obese. A BMI <18.5 was considered underweight, BMI 18.5–24.9 as normal weight, BMI ≥25.0 as overweight, and BMI ≥30.0 as obesity. Its formula is kg/m 2 or weight in kilograms divided by height in meters squared.[ 12 ] Each subject’s height was measured by having them stand straight, barefooted, on the base of the conventional stadiometer, with a plate fastened to the vertical, two-meter wooden scale. The patients were instructed to stand unaided with their arms by their sides and their heads in a stable position. With the aid of a horizontal, thin plate, the height was measured at the vertex of the head in centimeters, to the nearest millimeter. Weight was determined using a weighing machine that ranges from 0 to 125 kg and height was determined using a stadiometer.[ 13 ] After a complete history and a physical examination were done, the patients were prepared for endometrial biopsies. For endometrial aspiration, the endometrial cavity was curetted using the cannula with the inner piston. Following a successful attempt, the specimen was placed in formalin and sent for histopathological examination. The endometrial sections were examined by two different pathologists who were blinded with respect to the clinical status of the patients in the two clinics. Patients were divided into two groups according to endometrial biopsy findings; women in Group A were diagnosed with EH or carcinoma ( n = 22), whereas women in Group B had normal endometrium ( n = 50). Secretory and proliferative endometrium, atrophy, endometrial polyps, and endometrial epithelial fragments with mucoid material were considered normal endometrium, which were considered in Group A. As mild hyperplasia, with reversible proliferations may have different etiology and pathogenesis than carcinomas, we analyzed the data separately for endometrial cancer and hyperplasia, which was considered Group B. Baseline characteristics were compared between the two groups. Transvaginal ultrasonography (TVS) findings and histopathological findings were compared to see whether the findings of TVS and histopathology were similar and if similar then to what extent. Correlation of histopathological findings of carcinoma or Endometrial Hyperplasia with the classification of BMI was also observed. Every enrolled patient was given a unique identification number (UIN) hence the name was confidential throughout the study. The investigations such as transvaginal ultrasonography and histopathology were sent as per the UIN maintaining anonymity. The results of the investigations were properly explained to the patient by the principal investigator in a detailed form. Written informed consent was properly documented and maintained. Collected data were entered into an Excel sheet and were analyzed on completion. The data were analyzed using SPSS version 24.0. Descriptive summary using frequencies, percentages, graphs, mean, and standard deviation was used to present the study results. Probability ( p ) was calculated to test statistical significance at the 5% level of significance. The categorical variable was analyzed using the Chi-square test. Continuous variable was calculated using independent t -test.