Alterations in Toll-Like Receptor 7 and -9 mRNA Levels in Lungs after Ovariohysterectomy in a Pyometra Mouse Model.

BACKGROUND: Pyometra (P) leads to sepsis and multiple organ dysfunction syndrome. Toll-like receptors (TLRs) recognize pathogens which can cause P. The aim of this study was to investigate TLR-7 and -9 via the MYD88 pathway and the nuclear factor kappa B (NFκB) response in the uterus of a P mouse model before and after ovariohysterectomy (RP) as well as potential lung injury. MATERIALS AND METHODS: 200 female C57BL/6J mice were randomly divided into groups (N = 10/subgroup; sham 1, 2, 3, 7; P1, 2, 3, 7; 1RP1, 2, 3, 7; 2RP1, 2, 3, 7; 3RP1, 2, 3, 7) according to the day of euthanasia. Pathogens were administrated in the groups P and RP in order to induce P. RESULTS: Alterations in blood chemistry, histopathology, and RT-qPCT analysis before (P) and after RP were observed. Significant correlations were also found between MYD88, NFκB, and TLR9 in P and RP groups in the lungs and in RP groups in the uterus, suggesting that the immune system responded via the TLR9-MYD88 pathway. CONCLUSIONS: This is the first report of immunohistochemical TLR-7 and -9 localization and of TLR-7, -9, MYD88, and NFκB mRNA expression in the uterus causing lung injury in a P mouse model.

Single nucleotide polymorphisms of Toll-like receptor-4 and of autophagy-related gene 16 like-1 gene for predisposition of premature delivery: A prospective study.

To investigate the impact of carriage of single nucleotide polymorphisms (SNPs) of the Toll-like receptor-4 (TLR4) and of autophagy-related gene 16-like-1 (ATG16L1) in preterm delivery (PTD).A prospective cohort of 145 pregnant women was studied. Women were prospectively followed-up until delivery. Genotyping for rs4986790 (Asp299Gly transition) and rs4986791 (Thr399Ile transition) of TLR4 and for rs2241880 of ATG16L1 was done by PCR-restriction fragment length polymorphism. The primary study endpoint was the impact of carriage of minor alleles of TLR4 on early PTD before gestational week 32. Associations with human chorionic gonadotrophin (hCG) were also analyzed. Peripheral blood mononuclear cells were isolated from 15 healthy women and stimulated for cytokine production.No difference in clinical characteristics was observed between women delivering full term and preterm. The frequency of early PTD was 25% among women carrying minor alleles of TLR4 and 6.8% among women carrying major alleles (P: .032). Odds ratios for PTD were 3.85 among women carrying the GG genotype of rs2241880 and major alleles of TLR4 and 0.26 among carriers of GG genotype and minor alleles of TLR4 (P: .030). The co-presence of GG genotype of rs2241880 and hCG above 70 U/L was an independent variable for PTD. Stimulated production of interleukin-6 was greater among women with GG genotypes of rs2241880.Minor alleles of SNPs of TLR4 predispose to early PTD. The GG genotype of rs2241880 of ATG16L1 is associated with PTD when hCG is supra-elevated.

Early changes of the heat-shock protein 60 to 70 ratio as prediction of miscarriage in pregnancy.

PROBLEM: To study the balance of circulating heat shock protein (HSP)60 and HSP70 in pre-term delivery. METHOD OF STUDY: A two-stage approach was used. At first stage, we run retrospective analysis of prospective collected clinical data, and at a second stage, we studied an animal model of pre-term delivery (PTD). Blood samples were collected for prenatal screening in 3629 women. Samples from 23 women with miscarriage before gestational week 21 and 53 well-matched comparators for age, body mass index, parity, and previous miscarriage with full-term pregnancy were depicted. Women with risk factors were excluded. HSP60 and HSP70 were measured by an enzyme immunosorbent assay. PTD was induced after injection of low dose of bacterial lipopolysaccharide; mice were killed for the measurement of HSP60 and HSP70 in blood and tissues. The study endpoint was the association of the HSP60 to HSP70 ratio to miscarriage. RESULTS: A ratio >6 could distinguish between women who will miscarry from women with term pregnancies with sensitivity 60%, specificity 81.8%, positive predictive value 81.8%, and negative predictive value 60% (OR: 6.750, P = 0.025). Mice of the LPS-group PTD had this ratio significantly increased in maternal serum, placentas, and embryos compared to the sham-operation group. Gene expression of hsp60/70 remained in tissues unaltered. CONCLUSION: A HSP60/HSP70 ratio equal to or more than 6 until gestational week 12 is accompanied with great likelihood for miscarriage. A similar ratio applies in an animal model of PTD induced by low-dose LPS.

The influence of thyroid disorders on bone density and biochemical markers of bone metabolism.

Background Thyroid dysfunction, predominantly hyperthyroidism, has been previously linked to impaired bone mass density (BMD) and increased risk of fractures. On the other hand, data in the field of hypothyroidism (HT) are missing. The purpose of the present study was to investigate the impact of thyroid disorders on bone density serum and urine calcium (Ca) and phosphate (P) as well as serum osteocalcin and alkaline phosphatase and urine hydroxyproline in a series of post-menopausal women. Materials and methods The study was conducted in the Reproductive Endocrinology Outpatient Clinic of our hospital. A consecutive series of post-menopausal women was included, after excluding patients under hormone treatment (including levothyroxine supplementation) and those who received raloxifene, tamoxifen or tibolone during the study period as well as those who received treatment during the previous 12 months were excluded from the present study. Results Overall, 188 women were included in the present study. Among them, 143 women had normal thyroid function, 32 women had hyperthyroidism and 13 women had HT. Correlation of thyroid function indices with osteoporosis indices revealed statistically significant correlations between thyroxine (T4) and free triiodothyronine (T3) with T-, Z-scores and BMD. Logistic regression analysis concerning the impact of HT and hyperthyroidism on T-score, Z-score and bone mass density revealed that both pathological entities negatively affect bone health (p < 0.05). Conclusion The findings of our study suggest that not only hyperthyroidism, but also HT negatively affects BMD. Future studies should investigate this association and corroborate our findings.

Platelet to lymphocyte and neutrophil to lymphocyte ratio as predictive indices of endometrial carcinoma: Findings from a retrospective series of patients and meta-analysis.

BACKGROUND: The purpose of the present study is to present new data concerning the diagnostic efficacy of neutrophil to lymphocyte (NLR) and platelet to lymphocyte (PLR) ratios in detecting endometrial carcinoma and to summarize the existing knowledge by accumulating all the available data in the existing literature. MATERIALS AND METHODS: We retrospectively identified patients with evidence of endometrial pathology (vaginal bleeding or increased endometrial thickness) that undergone dilatation and curettage. For the meta-analysis we used the Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar databases to identify relevant articles in the field. RESULTS: In our retrospective series we identified 106 women with endometrioid endometrial carcinoma and 72 controls. PLR and NLR values were comparable among the two groups (p>.05). Eleven studies were included in the present systematic review with a total of 4168 patients. The meta-analysis included 1013 patients. PLR values were not significantly different among the two groups. On the other hand, NLR was significantly raised among patients with endometrial carcinoma (MD 0.73, 95% CI 0.01, 1.45). CONCLUSION: The findings of our meta-analysis support that NLR values are significantly elevated in patients with endometrial cancer compared to controls. Moreover, there seem to be evidence to support that both PLR and NLR values increase in patients with advanced stage disease, including positive lymph nodes, lymphovascular space involvement and distant metastases. Future studies are needed in this field to reach firm conclusions and these should specifically target patients with advanced stage disease.

Correlation of platelet to lymphocyte and neutrophil to lymphocyte ratio with hormonal and metabolic parameters in women with PCOS.

Background The purpose of our study is to evaluate the association of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) with hormonal and metabolic parameters in patients with polycystic ovarian syndrome (PCOS) in order to assess whether these ratios may become useful tools during the evaluation of the severity of low grade inflammation. Methods The present study is based in secondary outcomes from a prospectively collected patient database. A total of 266 women with PCOS participated in this study and blood a complete blood count examination (CBC) that was used for the calculation of PLR and NLR was available in 182 patients. Results Association statistics revealed that PLR had a significant correlation to 17-OH progesterone (r = -0.177, p = 0.024) and Matsuda index values (r = 0.234, p = 0.009), whereas NLR was correlated with follicle stimulating hormone (FSH) (r = -0.204, p = 0.007), free testosterone (r = 320, p < 0.001), Δ4-androstendione (r = 0.234, p = 0.003), sex hormone binding globulin (SHBG) (r = -0.350, p < 0.002) and high-density lipoprotein (HDL) (r = -0.171, p = 0.039). Conclusion According to the findings of our study, both PLR and NLR seem to be correlated with some hormonal and metabolic indices. This association is clearer in the case of NLR and serum androgens as it seems to be positively affected by their levels. PLR and NLR were not affected by the presence of obesity.

The impact of mild hypercholesterolemia on glycemic and hormonal profiles, menstrual characteristics and the ovarian morphology of women with polycystic ovarian syndrome.

Background The severity of polycystic ovarian syndrome (PCOS) has been clearly associated with insulin resistance, obesity and metabolic syndrome. The purpose of the present cross-sectional study is to investigate whether mild hypercholesterolemia alters the biochemical and clinical profile of PCOS patients. Methods Our study is based on a prospectively collected population of women of reproductive age who were diagnosed with PCOS according to the definition of the Rotterdam European Society of Human Reproduction and Embryology/American Society for Reproductive Medicine (ASRM/ESHRE) criteria. For the correlation analysis we used the non-parametric Spearman's rank correlation coefficient. Partial correlation was also performed to control for potential confounders observed in the univariate analysis. Results Overall, 235 patients were included. Their mean age ranged between 14 and 45 years old and the body mass index (BMI) between 17 and 54. Women with mild hypercholesterolemia had a higher BMI and their fasting insulin was increased as well as indices of insulin resistance [Homeostatic model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI), Matsuda index] compared to women with PCOS with normal cholesterol levels. Correlation statistics suggested that the effect of serum lipids on the hormonal profile of patients was weak. Both low-density lipoprotein (LDL) and high-density lipoprotein (HDL) exerted a significant mild negative correlation to glucose and insulin. However, after controlling the results for BMI and age (the two variables that were found significantly different in the univariate analysis) we observed that this effect was non-significant. Conclusion Mild hypercholesterolemia does not affect the hormonal profile of patients with PCOS; hence, to date, there is no evidence to suggest its treatment for the correction of menstrual and hormonal abnormalities in PCOS women.

The impact of the metabolic syndrome on bone mass density: a prospective case control study.

Background Obesity and metabolic syndrome (MetS) during the perimenopausal period and in menopause have been linked to altered bone mass density (BMD) in various experimental studies. However, current clinical studies provide conflicting results in this field. The purpose of the present study was to evaluate this association. Materials and methods We conducted a prospective case control study that was based on a consecutive series of menopausal women who attended the Reproductive Endocrinology Outpatient Clinic of our hospital between January 2013 and December 2016. Results One hundred and forty post-menopausal women were included in the present study. After stratifying the women in two groups according to the presence of MetS we observed that bone turnover markers remained unaffected by the presence of MetS (p > 0.05). On the other hand, both the T- and Z-scores of women with MetS were significantly higher compared to healthly postmenopausal women [T-score: 0.4 (-0.7 to 1.3) vs. -1 (-1.62 to -0.1), p < 0.001] [Z-score: 0.55 (-0.3 to 1.7) vs. -0.4 (-1.1 to 0.4), p = 0.003]. Conclusions According to the findings of our study the presence of MetS during the perimenopausal years seems to have a mild benefit on bone mass density. The pathophysiology that underlies this effect remains unclear as bone turnover markers seem to be unaffected by MetS.

Dehydroepiandrosterone-Sulfate, Insulin Resistance and Ovarian Volume Estimation in Patients With Polycystic Ovarian Syndrome.

Objective: To investigate the potential association of DHEA-S with metabolic and hormonal alterations and with disorders of ovarian morphology. Materials and methods: The present study was based on women with PCOS that attended the Gynaecological Endocrinology - Paediatric and Adolescence Endocrinology Department of our clinic. Overall, 321 patients who met the Rotterdam ESHRE/ ASRM - Sponsored criteria for the definition of PCOS were included. Women's personal medical history was recorded, anthropometric parameters were assessed and blood was drawn for analysis of metabolic and hormonal parameters. A gynaecological ultrasound was also performed to evaluate ovarian morphology. Results: Correlation analysis revealed a significant negative correlation of DHEA-S with the mean volume of the right and left ovary and with the maximum volume of the largest ovary. This finding remained significant after adjusting for age and BMI (ß ± SE = -0.39 ± 0.17, p = 0.023 in the case of mean ovarian volume and ß ± SE = -0.36 ± 0.17, p = 0.032 in the case of the maximum volume of the maximum ovarian volume). Conclusion: The findings of our study reveal a clear negative association of DHEA-S with ovarian volume. To date, however, current evidence in this field are restricted to experimental animal models. Future clinical studies are needed in this field to corroborate our findings.

Giving Birth After Fertility Sparing Treatment for a Yolk Sac Tumour: Case Report.

Yolk Sac Tumours (YSTs) of the ovary, also called Endodermal Sinus Tumours (ESTs), are the second most common Malignant Ovarian Germ Cell Tumours (MOGCTs), after dysgerminomas. YSTs occur primarily in children and young women. We present a case report of a 20-year-old woman who had been diagnosed with YST (tumour diameter of 29 cm). The patient underwent fertility sparing surgery and was subsequently treated with adjuvant chemotherapy (four cycles of bleomycin, etoposide and cisplatin). Two years after the diagnosis of YST, she successfully gave birth to a healthy girl (birth weight 3,500 g, Apgar score of 9-10 and a spontaneous vaginal delivery). During pregnancy, she had microscopic hematuria and bilateral nephrolithiasis, was ultrasonographically diagnosed. The conception after fertility sparing treatment of YST is possible and the birth of a healthy child is feasible. There are no current guidelines for surveillance of such patients during pregnancy; however, structured pregnancy surveillance in such survivors seems necessary.

Evaluation Analysis of miRNAs Overexpression in Liquid-Based Cytology Endometrial Samples.

Background: miRNAs have an important role as their deregulation is linked to endometrial cancer. Methods: A custom miScript® miRNA PCR Array was used to investigate for the first time the expression of eight miRNAs in forty-nine histologically confirmed Liquid Based cytology endometrial samples. The expression profile of the same miRNAs was also examined in sixty formalin-fixed tissue samples. Results: Expression of seven miRNAs was significantly higher in malignant samples with three of them (mir-182, mir-141 and mir-205) performing optimally. Conclusion: These results suggest the potential use of this non-invasive method of sampling for miRNA expression studies. Furthermore miRNA overexpression could serve as an ancillary or reflex test for optimal identification of malignant samples especially in morphologically inadequate samples.

Synchronous Endometrial and Ovarian Carcinoma: A Case Series.

Synchronous ovarian and endometrial cancer (SEOC) is a rare instance but it accounts for 50-70% of all synchronous female genital tract tumors. We report three cases of women who were diagnosed with SEOC and underwent surgical staging. All cases were of the endometrioid subtype, grade 1, both in the ovarian and endometrial component. Two of them were stage Ia/Ia, and the third was stage Ib/Ib. More than 2 years after the diagnosis, all patients were alive and recurrence-free. The present report critically discusses the main characteristics, risk factors, and management of patients with SEOCs.

Quantitative Measurement of L1 Human Papillomavirus Type 16 Methylation for the Prediction of Preinvasive and Invasive Cervical Disease.

Background: Methylation of the human papillomavirus (HPV) DNA has been proposed as a novel biomarker. Here, we correlated the mean methylation level of 12 CpG sites within the L1 gene, to the histological grade of cervical precancer and cancer. We assessed whether HPV L1 gene methylation can predict the presence of high-grade disease at histology in women testing positive for HPV16 genotype. Methods: Pyrosequencing was used for DNA methylation quantification and 145 women were recruited. Results: We found that the L1 HPV16 mean methylation (±SD) significantly increased with disease severity (cervical intraepithelial neoplasia [CIN] 3, 17.9% [±7.2] vs CIN2, 11.6% [±6.5], P < .001 or vs CIN1, 9.0% [±3.5], P < .001). Mean methylation was a good predictor of CIN3+ cases; the area under the curve was higher for sites 5611 in the prediction of CIN2+ and higher for position 7145 for CIN3+. The evaluation of different methylation thresholds for the prediction of CIN3+ showed that the optimal balance of sensitivity and specificity (75.7% and 77.5%, respectively) and positive and negative predictive values (74.7% and 78.5%, respectively) was achieved for a methylation of 14.0% with overall accuracy of 76.7%. Conclusions: Elevated methylation level is associated with increased disease severity and has good ability to discriminate HPV16-positive women that have high-grade disease or worse.

Endocervical Carcinogenesis and HPV Vaccination: An Occasional Circumstance or a Gap in the Chain?

As a result of the Human Papillomavirus (HPV) vaccination program, the prevalence of precancerous dysplasia and invasive cervical cancer has substantially decreased. In this brief report, we present a case of a young patient who was diagnosed with in situ adenocarcinoma of the cervix. This 30-year-old female had completed the HPV vaccination after she became sexually active and has been undergoing annual gynecological assessments, including clinical examination and Pap test, all of which had been negative. This year, her Pap test revealed a low grade squamous intraepithelial lesion (LGSIL) and additionally a colposcopy was performed. Given the extent of the lesion and since the colposcopy was inadequate, the patient underwent a type 3 large loop excision of the transformation zone and a curettage of the endocervix under local anesthesia. The pathological diagnosis from cervical biopsy revealed an in situ adenocarcinoma of the endocervix with negative limits. The HPV subtypes 16 and 83 were detected with PCR. After proper consultation she decided to preserve her fertility and to undergo a regular follow-up, postponing hysterectomy after the completion of her family planning. In conclusion, this case report highlights the need for diagnostic surveillance regarding HPV-related cervical cancer even after vaccination.

An ovarian mass after breast cancer: Metachronous carcinoma or metastasis? A case report.

INTRODUCTION: Differentiating between primary and secondary ovarian cancer can be a difficult task. In hereditary conditions breast malignancies and primary ovarian cancer often coexist. PRESENTATION OF CASE: We present a 45-year-old patient with an ovarian mass two years after the diagnosis of a lobular, triple negative breast carcinoma. There was concern whether the lesion represented a metachronous ovarian cancer or a metastasis of the lobular carcinoma. The final histological examination showed a metastatic lesion, deriving from the lobular breast carcinoma, as evidenced by the immunohistochemical profile; nevertheless, there were changes in hormonal receptor expression in the metastatic lesion compared to the primary, triple negative tumor. The patient underwent genetic testing for BRCA1 and BRCA2 mutations and was negative. In the adjuvant setting the patient received 6 cycles of chemotherapy with carboplatin and paclitaxel; eighteen months later, the patient remains without disease recurrence. DISCUSSION AND CONCLUSION: This case report highlights the role of imaging, histology and predominantly immunohistochemistry as valuable tools in the assessment of ambiguous ovarian lesions after breast cancer.

Hyperandrogenemia in women with polycystic ovary syndrome: prevalence, characteristics and association with body mass index.

BACKGROUND: Hyperandrogenemia is one of the major diagnostic features for the diagnosis of polycystic ovary syndrome (PCOS). The aim of this study was to estimate the prevalence and the characteristics of hyperandrogenemia in women with PCOS and to investigate the association of clinical and biochemical characteristics with body mass index (BMI) according to the presence of hyperandrogenemia. MATERIALS AND METHODS: We studied 266 women diagnosed with PCOS. Hyperandrogenemia was defined by testosterone (T) and/or free testosterone (FT) and/or ∆4 androstenedione (Δ4-A) higher than 75% of the upper limits of each hormone. Patients were stratified in two groups according to a BMI threshold of 25 kg/m2. RESULTS: Hyperandrogenemia was present in 78.2% of the patients. Elevated levels of T were found in 58.4%, while elevated levels of FT and Δ4-A were found in 42.5% and 34.1% of patients. In normal weight women (BMI≤25 kg/m2) with hyperandrogenemia lower values of hip circumference and HOMA-IR and increased levels of T, FT, Δ4-A, 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone sulfate (DHEAS), white blood cells (WBC) and neutrophils were observed compared to women without hyperandrogenemia. Also, in overweight women higher levels of T, FT, Δ4-A, 17-OHP, DHEAS and cortisol were measured, while lower thyroid-stimulating hormone (TSH) levels were comparable to women without hyperandrogenemia. CONCLUSION: This study showed high prevalence of hyperandrogenemia in PCOS women. Women with BMI≤25 kg/m2 have significant differences in androgens, WBC, neutrophils and HOMA-IR and women with BMI≥25 kg/m2 in androgens, TSH and cortisol according to the presence or not of hyperandrogenemia.

Serum inhibin and leptin: Risk factors for pre-eclampsia?

BACKGROUND: Pre-eclampsia and eclampsia are parts of the broader spectrum of hypertensive disorders complicating pregnancy. This study aims to examine the association between serum inhibin and leptin levels and pre-eclampsia. METHODS: This study included 98 consecutive cases of pregnant women with pre-eclampsia, together with their 98 pregnant controls, matched for age, gestational week and time period of delivery. Maternal venous blood samples were obtained within 24h before delivery. In addition to serum inhibin and leptin, birth order, multiple pregnancy, maternal age, maternal overweight/obesity, maternal education, maternal smoking and family history of diabetes/hypertension, were examined as risk factors. Multivariate logistic regression analysis was performed. RESULTS: At the univariate analysis, serum inhibin and leptin levels were significantly higher in cases vs. CONTROLS: Pre-eclampsia occurred more frequently in primiparous women, whereas overweight and obesity were also associated with pre-eclampsia. At the multivariate analysis, higher serum inhibin levels were associated with pre-eclampsia (multivariate OR=1.09, 95%CI: 1.03-1.17, p=0.004, increase per 0.1ng/mL). On the other hand, leptin was not independently associated with the occurrence of pre-eclampsia (multivariate OR=1.02, 95%CI: 0.95-1.09, p=0.631, increase per 10ng/mL). CONCLUSIONS: Elevated serum inhibin levels seem to be associated with pre-eclampsia, reflecting placental dysfunction. Increased serum leptin levels may merely reflect an elevated maternal body mass index, which is a well-known risk factor for pre-eclampsia.

A reporting system for endometrial cytology: Cytomorphologic criteria-Implied risk of malignancy.

BACKGROUND: There have been various attempts to assess endometrial lesions on cytological material obtained via direct endometrial sampling. The majority of efforts focus on the description of cytological criteria that lead to classification systems resembling histological reporting formats. These systems have low reproducibility, especially in cases of atypical hyperplasia and well differentiated carcinomas. Moreover, they are not linked to the implied risk of malignancy. METHODS: The material was collected from women examined at the outpatient department of four participating hospitals. We analyzed 866 consecutive, histologically confirmed cases. The sample collection was performed using the EndoGyn device, and processed via Liquid Based Cytology, namely ThinPrep technique. The diagnostic categories and criteria were established by two cytopathologists experienced in endometrial cytology; performance of the proposed reporting format was assessed on the basis of histological outcome; moreover, the implied risk of malignancy was calculated. RESULTS: The proposed six diagnostic categories are as follows: (i) nondiagnostic or unsatisfactory; (ii) without evidence of hyperplasia or malignancy; (iii) atypical cells of endometrium of undetermined significance; (iv) atypical cells of endometrium of low probability for malignancy; (v) atypical cells of endometrium of high probability for malignancy; and (vi) malignant. The risk of malignancy was 1.42% ± 0.98%, 44.44% ± 32.46% (nine cases), 4.30% ± 4.12%, 89.80% ± 8.47%, and 97.81% ± 2.45%, respectively. CONCLUSION: We propose a clinically oriented classification scheme consisting of diagnostic categories with well determined criteria. Each diagnostic category is linked with an implied risk of malignancy; thus, clinicians may decide on patient management and eventually reduce unnecessary interventional diagnostic procedures. Diagn. Cytopathol. 2016;44:888-901. © 2016 Wiley Periodicals, Inc.

Office Endometrial Cytological Sampling: Examining Predictors of Strenuousness.

BACKGROUND/AIM: Endometrial cytology is an alternative perspective for the diagnosis of endometrial cancer. The present study examined the potential risk factors for strenuousness in endometrial cytology sampling. PATIENTS AND METHODS: One hundred and eighty-one women who underwent endometrial cytological sampling with the Endogyn curette participated in the study. Strenuousness in obtaining the sample was graded into a five-level scale-score. Various parameters were assessed in association with the strenuousness score. Multivariate ordinal logistic regression analysis was performed. RESULTS: Postmenopausal status (adjusted OR=2.63, 95%CI=1.52-4.56, p=0.001) and previous invasive/surgical procedures in the cervix (adjusted OR=2.15, 95%CI=1.10-4.24, p=0.026) were associated with higher strenuousness score. Participants' age at sampling, phase of menstrual cycle, endometrial thickness, obesity, current hormonal use and reproductive history of women were not significantly associated with the strenuousness of the procedure. CONCLUSION: Increased difficulty during endometrial sampling is noted in postmenopausal women, and in patients with previous surgical procedures in the cervix.