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Background: In this study, we aimed to determine the frequency of histopathologic outcomes of solid-organ transplantation in women with abnormal uterine bleeding (AUB) receiving immunosuppressive therapies., Methods: This is a retrospective study including a single-center experience. Data were extracted from hospital records, and solid-organ transplant recipients who were diagnosed with AUB were included., Results: Fifty-five of these patients were renal transplant recipients (79.7%), and 14 were liver transplant recipients (20.3%). Histopathologic examination showed various histopathologic patterns of endometrium in patients with AUB consisting of normal histopathologic findings of endometrium in 31 patients (48.4%); 29 hormonal imbalance during proliferative and secretory phases of menstrual cycle and two atrophic endometrium. Endometrial hyperplasia without atypia was observed in 11 patients (17.2%). Polyp was seen in 22 patients (34.4%); 21 endometrial polyp and one endocervical polyp. There were significant differences in terms of histopathologic findings among the three groups of patients according to different immunosuppressive regimens (P = .029). There was no endometrial hyperplasia in women receiving sirolimus-based immunosuppressive regimens. Moreover, there was no endometrial hyperplasia in the liver transplant recipient group., Conclusions: Sirolimus-based immunosuppressive regimens may be administered to patients who have risk factors for endometrial precancerous lesions, such as endometrial hyperplasia. However, additional well-designed, large-scale studies are warranted to confirm our findings., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The article presents the risk factors of endometrium hyperplastic processes (EHP) in reproduc- tive age women. It is shown that EHP occur in response to hormonal homeostasis violations of the target tissues. It is established that the biologically active substances, which are closely related to immune mechanisms of the reproductive system functioning take place in regulatory mechanisms of cell growth and differentiation of endometrium.

Background: Endometrial pathology risk has been linked to obesity; however, little is known of its prevalence in severely obese women not seeking care for endometrial pathology associated symptoms. This pilot study was designed to explore the frequency and risk factors associated with endometrial pathology in cancer-free, severely obese, bariatric surgery candidates using the Pipelle endometrial sampling technique (SureFlex Preferred Curette, Bioteque America, Inc, New Taipei City, Taiwan)., Methods: Twenty-nine severely obese bariatric surgery candidates with intact uteruses and no history of endometrial cancer or endometrial ablation were included in this subanalysis from a larger cohort of 47. Endometrial samples were obtained using a Pipelle endometrial suction curette at a single time point before surgery. Logistic regression was used to assess the relationship between body mass index and endometrial pathology when adjusting for age and race., Results: Of the 29 successful biopsies, 8 (27.6%) were classified as abnormal endometrium: 1 was classified as complex atypical hyperplasia, 1 was classified as hyperplasia without atypia, 4 samples were identified with endometrial polyps, and 2 samples were identified with metaplasia. None presented with cancer. Increasing body mass index was significantly associated with higher risk of abnormal endometrium (OR = 1.19, 95% CI [1.03-1.36], P = .01)., Conclusions: The findings in this sample suggest that obesity may be associated with increased risk of having undiagnosed endometrial pathology. More thorough examination of relationships between levels of obesity and endometrial pathology are needed to better characterize high cancer risk groups who may benefit from introducing new screening measures., (Copyright © 2015 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

In several species there is a transient uterine inflammatory response after mating that is purported to clear excess and dead spermatozoa, bacteria and other contaminants from the uterus. In particular individuals this inflammatory response is substantial, resulting in an acute mating-induced endometritis, causing infertility. In this study, the influx of polymorphonuclear neutrophils (PMNs) into the uterine lumen of bitches was investigated after artificial insemination with fresh semen. In normal bitches, an influx of PMNs was detected, followed by high pregnancy rates and normal litter size, and may be a physiological inflammatory response. In bitches with endometrial hyperplasia, there was a larger influx of PMNs and pregnancy rates and litter size were reduced, although the effect was partly ameliorated by the post-mating administration of antibiotics. It is postulated that in bitches with endometrial hyperplasia, post-mating endometritis develops with the potential to affect reproduction adversely. In vitro studies demonstrated a reduced ability of spermatozoa to attach to the uterine epithelium of bitches with endometrial hyperplasia. Moreover, PMNs in the co-culture system inhibited spermatozoal attachment to normal and hyperplastic uterine epithelium, especially hyperplastic epithelium. It was concluded that decreased spermatozoal attachment to uterine epithelium mediates a reduction in fertility of bitches with endometrial hyperplasia. This is the first study to detail an apparent physiological uterine inflammatory response to spermatozoa and its perturbation in bitches with endometrial disease, and the first to recognise the clinical significance and potential aetiology of mating-induced endometritis., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: To study the pathologic characteristics of eutopic endometrium in patients with endometriosis., Methods: Pathologic characteristics of eutopic endometrium were studied in 176 patients with endometriosis in Peking Union Medical College Hospital from January 2007 to December 2008 retrospectively., Results: About 72.2% (127/176) of eutopic endometrium were in proliferative phase, 19.9% (35/176) of were observed as endometrial polyp, including 32 cases with simple endometrial polyp and 3 cases with abnormal hyperplasia combined with endometrial polyp. And 4.0% (7/176) showed abnormal hyperplasia. The incidence of pathologic changes in eutopic endometrium was 22.2% (39/176). Among 53 endometriosis patients combined with infertility, the incidence of pathologic changes of eutopic endometrium was 35.9% (19/53), which was significantly higher than 16.3% in non-infertile patients (χ(2) = 8.24, P = 0.004). Among 65 cases with irregular menstruation, the incidence of endometrial polypus and endometrial hyperplasia were 20.0% (13/65) and 10.8% (7/65), which were significantly higher than 17.1% (19/111) and 0 in normal menstruation patients (χ(2) = 13.839, P = 0.003)., Conclusions: The eutopic endometrium of endometriosis were in proliferative phase state. The pathologic changes of eutopic endometrium were more in patients combined with infertility and irregular menstruation.

The aromatase inhibitor anastrazole proved effective in the treatment of endometrial hyperplasia and postmenopausal bleeding in an obese 65-year-old woman with high operative risk. During anastrazole administration for 12 months, the endometrial thickness decreased from 9.8 mm to 2.4 mm and the control endometrial histology showed an atrophic endometrium. Uterine bleeding did not occur in the post-treatment, 3-year follow-up period. The endometrial thicknesses measured yearly by ultrasonography were 2.9, 3.5 and 3.3 mm. The plasma estradiol levels increased from < 73 pmol/l post-treatment to 112, 98 and 103 pmol/l. This case demonstrates that long-term aromatase inhibitor treatment can result in a refractory status of the endometrium and the estradiol produced in the adipose tissue does not exert a proliferative effect.

The assessment of endometrial safety is one of the key requirements for the clinical development of new products for hormone therapy (HT) to treat menopausal symptoms in women who have a uterus. Both the Food and Drug Administration (FDA) in the United States and the European Medicines Agency (EMA) provide detailed guidance on the requirements for the evaluation of biopsies to prove endometrial safety. However, there are some discrepancies between the European and the US requirements, making it difficult to fulfil both guidelines simultaneously. In order to facilitate multinational clinical trials performed within clinical programs to develop novel HT products, we developed an approach considering both guidance documents as far as possible and proposed solutions for issues that are inconsistently described in these guidelines. A table with the required sample sizes is given. Our recommendation for a unified approach for the estimation of the hyperplasia rate for hormone therapies fulfils the intent of the recommendations of both the FDA and the EMA and thus leads to a globally harmonized drug development for hormone therapies.

Objective: To quantify the rate of inconsistency in histopathological reporting between endometrial biopsy specimens (obtained by Pipelle endometrial sampler or curettage) and hysterectomy specimens using the World Health Organization classification criteria., Study Design: A retrospective review of the records of 280 women with a histopathological diagnosis of endometrial hyperplasia treated in Ipswich Hospital NHS Trust, UK from 1 January 1998 to 31 May 2009., Results: Discrepancy was found between the histopathological results of endometrial samples and hysterectomy specimens. The discrepancy was doubled for specimens obtained using a Pipelle endometrial sampler, with false-positive (i.e. overdiagnosis when the hysterectomy specimen showed a better diagnosis) and false-negative (i.e. underdiagnosis when the hysterectomy specimen showed a worse diagnosis) rates of 5.3% and 22.6%, respectively. For curettage specimens, the false-positive and false-negative rates were 1.8% and 13.2%, respectively. All cases of curettage were performed under general or regional anaesthesia, and were preceded by hysteroscopy. Apart from age, no risk factors were associated with a worse diagnosis. The association of age differed between types of endometrial hyperplasia and cancer; the strongest association was seen for cancer and the weakest association was seen for simple hyperplasia., Conclusion: Hysteroscopy and curettage may be considered when simple or complex hyperplasia is diagnosed from a specimen obtained with a Pipelle endometrial sampler. When a diagnosis of atypical hyperplasia is made, irrespective of the method of endometrial sampling, the gynaecologist must be concerned that endometrial carcinoma exists concomitantly within the uterus., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Body mass index is predictive of sonographic endometrial stripe thickness, which in turn is predictive of endometrial hyperplasia in patients with polycystic ovary syndrome. For every 1-mm increase in endometrial stripe, the odds ratio of hyperplasia increased by 1.48 (95% confidence interval, 1.04-2.10)., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: Endometrial hyperplasia is a known risk factor for the development of endometrial cancer, particularly atypical hyperplasia, with a subsequent risk of up to 30%. Of the known risk factors for endometrial hyperplasia, obesity is the most preventable, but there is a paucity of data addressing the association. We tested the hypothesis that patients with endometrial hyperplasia have a higher body mass index (BMI) than patients with abnormal bleeding who are found to have proliferative endometrium., Study Design: This was an Institutional Review Board-approved retrospective study using University Hospital Department of Pathology records. All patients who had endometrial sampling performed between January 1, 2001, and July 30, 2008, were included. The experimental group consisted of patients with endometrial hyperplasia including simple, complex and atypical hyperplasia. The control group consisted of patients who underwent endometrial sampling for abnormal bleeding during the same time period and were diagnosed with proliferative endometrium. BMI was calculated based on documented height and weight within 30 days of endometrial sampling., Results: Forty-two patients with hyperplasia and 103 patients with proliferative endometrium met inclusion criteria, including documented height and weight and nonexposure to hormones. The median BMI in the hyperplasia group was 38 kg/m2 (95% CI 34.8-42.4) and 30 kg/m2 (95% CI 29.9-33.3) in the proliferative group (p < 0.0001)., Conclusion: These data suggest that higher BMI is associated with endometrial hyperplasia as compared to women with lower BMIs and abnormal bleeding.

Objective: Obesity represents the most important risk factor for endometrial pathology. This study aimed to evaluate the prevalence of endometrial injuries, such as polyps, hyperplasia and endometrial cancer in asymptomatic obese women, as well as to recognize the associated risk factors ., Methods: A cross-sectional study was conducted between December 2004 and February 2006. Ninety-four obese (body mass index > or = 30 kg/m2) women were evaluated, divided in two groups of 47 participants each: pre-menopausal and postmenopausal women. Clinical characteristics, physical exams (anthropometric and gynecological), blood count and endometrial assessment by vaginal ultrasonography, biopsy, and hysteroscopy (only for confirmed endometrial pathology), were the variables appraised., Results: In pre-menopausal women, 12.8% of cases had endometrial pathology statistically associated to age, hypertension, hypercholesterolemia and LDL-c increase. In the post-menopausal women, 40.4% of cases had a pathology identified as statistically associated with hypertension, LDL-c and estrone increase. Two cases of endometrial cancer were identified, one in each group., Conclusions: The increased incidence of obesity over recent years has increased risk factors of endometrial cancer. In pre-menopausal women only a small number of cases with endometrial alterations was observed. Therefore, it is suggested that greater attention be given to those over 40 years of age, associated with hypertension and/or higher LDL-c . The menopausal status increases risk of endometrial injury, and when associated with hypertension, LDL-c and/or estrone increase, women become candidates to biopsy aiming for an early diagnosis of cancer, a decisive factor for a favorable prognosis.

Objective: To evaluate the endometrium of menopausal women before and after six months use of total isoflavone., Methods: A non-controlled clinical, type "before and after" trial was carried out with 32 post-menopause women, between 40 and 60 years of age. They received 80 mg/day of total isoflavones obtained from Trifolium pratense (Climadilâ) during six months. They were evaluated at the beginning and end of treatment by transvaginal pelvic ecography, hysteroscopy and endometrial biopsy., Data Analysis: Data collected were registered by means of the Epi info, version 6.04 b software, data analysis was made using the SAS version 8.2 statistics program, considering a significance level (alpha) of 0.05 and a 0.80 power (1-beta). In order to study the average variation of endometrial thickness and variation of the hysteroscopic and hystologic findings the t Student test for paired data was used., Results: Among the 32 participant women, six presented vaginal bleeding and three presented endometrial alteration when compared to the initial exams. Two of the women developed endometrial cell proliferation and one of them endometrial hyperplasia. There were no significant alterations in relation to endometrial thickness., Conclusion: In this study, three women who used isoflavones during the six month period presented endometrial activity.

Polycystic ovarian syndrome (PCOS) is a common endocrinopathy characterized by oligo/anovulatiaon and elevated circulating androgens or evidence of hyperandrogenism after all known potential causes have been excluded. In addition, insulin resistance and accompanying hyperinsulinemia commonly occur in women with PCOS. There is increasing evidence that the endocrinologic and metabolic abnormalities in PCOS may have complex effects on the endometrium, contributing to the infertility and endometrial disorders observed in women with this syndrome. Androgen receptors and steroid receptor co-activators are over-expressed in the endometrium of women with PCOS. Also, biomarkers of endometrial receptivity to embryonic implantation-such as alpha(v)beta3-integrin and glycodelin-are decreased, and epithelial expression of estrogen receptor alpha (ERalpha) abnormally persists in the window of implantation in endometrium in women with PCOS. In addition to being responsive to the steroid hormones estradiol, progesterone, and androgens, the endometrium is also a target for insulin, the receptor for which is cyclically regulated in normo-ovulatory women. In vitro, insulin inhibits the normal process of endometrial stromal differentiation (decidualization). In addition, insulin-like growth factors (IGFs) and their binding proteins are regulated in and act on endometrial cellular constituents, and hyperinsulinemia down-regulates hepatic IGFBP-1, resulting in elevated free IGF-I in the circulation. Thus, elevated estrogen (without the opposing effects of progesterone in the absence of ovulation), hyperinsulinemia, elevated free IGF-I and androgens, and obesity all likely contribute to endometrial dysfunction, infertility, increased miscarriage rate, endometrial hyperplasia, and endometrial cancer common in women with PCOS. The potential mechanisms underlying these disorders, specifically in women with PCOS, are complex and await additional transdisciplinary research for their complete elucidation.

Objectives: We sought to clarify if hypertension has a direct effect on endometrial pathology. Furthermore, we wanted to evaluate the effect of possible differences among the various antihypertensive drugs on the clinico-pathological findings., Patients and Methods: The records of 228 patients who underwent D&C at our tertiary cancer hospital were examined. All other aetiopathogenic factors (DM, tamoxifen, obesity, etc.) for endometrial pathology were excluded, as well as endometrial carcinoma cases. We compared the differences in the clinical symptoms and signs between hypertensive and normotensive women, as well as differences in their histological findings. Furthermore, we carried out a subgroup analysis of the above with respect to the antihypertensive agent(s) the patients used., Results: One hundred and twenty-three patients (54%) were hypertensive and 105 (46%) were normotensive. Vaginal spotting was present in approximately 75% of patients in both groups, but sonographic endometrial thickening was significantly more prevalent among hypertensive women (52.8% versus 34.3%, p=0.004). Hyperplasia was the commonest positive histological finding among hypertensive women (44.7%), compared with polyps for the normotensives. Furthermore, atypia was censored in 4.1% of hypertensive patients only. The subgroup analysis with respect to the various antihypertensives was similar to the above histological distribution, with the exception of the combination b-blocker plus calcium antagonist, which had a significantly more favourable histological profile with over 60% normal endometria., Conclusions: Hypertensive patients tend to require D&C more frequently. Sonographic endometrial thickening is significantly more frequent among them. Hyperplasia with or without atypia occurs in approximately 50% of hypertensive women. No differences in the above were justified depending on the different antihypertensive agents used, with the exception of the b-blocker plus calcium antagonist (+/-ACE inhibitor) combination, which requires further evaluation.

Objective: To assess the role of endometrial thickness on vaginal ultrasound assessment and menstrual history in predicting endometrial hyperplasia in women with polycystic ovary syndrome (PCOS) who presented with infertility due to anovulation., Methods: This was a prospective study in a university referral-based fertility and endocrine clinic. Fifty-six women with PCOS presenting with infertility due to anovulation underwent both vaginal ultrasound assessments and endometrial biopsies. The main outcome measures were the predictive value of sonographic endometrial thickness (primary objective) and the menstrual history with other clinical characteristics (secondary objective) for proliferative endometrium and endometrial hyperplasia in logistic regression analysis. Their predictive value was further examined by receiver operating characteristic curve analysis., Results: Thirty-six PCOS patients (64.3%) had proliferative endometrium and 20 (35.7%) had endometrial hyperplasia. Five of the latter (25%) had cytologic atypia. Endometrial thickness less than 7 mm or intermenstrual interval less than 3 months (corresponding to more than four menstrual periods yearly) was associated with proliferative endometrium only. The endometrial thickness correlated positively with endometrial hyperplasia (P =.018) and, together with the average intermenstrual interval, were significant predictors of endometrial hyperplasia (P <.001)., Conclusion: These findings point to the usefulness of obtaining a detailed menstrual history in women with PCOS by identifying those at increased risk of endometrial hyperplasia and who require an endometrial biopsy. The endometrial thickness corroborates this clinical impression and is particularly useful when the menstrual history is uncertain. Endometrial hyperplasia in this population is effectively excluded when the endometrial thickness is less than 7 mm.

Study Objective: To determine the effectiveness of transcervical endometrial ablation or endomyometrial resection for treating refractory postmenopausal uterine bleeding induced by hormone replacement therapy (HRT)., Design: Prospective observational study., Setting: Community, teaching, and proprietary hospitals., Patients: Twenty-nine postmenopausal women experiencing troublesome uterine bleeding while taking hormones., Interventions: Hormone manipulation, office hysteroscopy or sonohysterography, endometrial curettage, and transcervical endometrial ablation or endomyometrial resection were performed in all 29 patients., Measurements and Main Results: Twenty-seven women (93.1%) who continued HRT became amenorrheic within 2 months of surgery. The two who did not have irregular, intermittent spotting, but neither one required or desired further surgical intervention. Five women discontinued HRT from 3 to 53 months postoperatively (mean 12.5 +/- 8.2 mo) because of apprehension about developing breast cancer and for personal reasons. The 24 (82.8%) who continued HRT were observed for as long as 99 months (mean 36.4 +/- 5.5 mo); 22 (91.6%) of them remained amenorrheic. Pathologic examination of tissue specimens revealed atrophic endometrium in 4 patients, adenomyosis in 7, simple hyperplasia in 4, submucous leiomyomas in 11, endometrial polyps in 4, and proliferative endometrium in 1. There were no perioperative complications., Conclusion: Endometrial ablation or endomyometrial resection was an effective alternative to discontinuing HRT for these postmenopausal women whose uterine bleeding was unrelieved by modification of their sex steroid regimens.

Severe blood loss from dysfunctional uterine bleeding may be refractory to medical therapy and hysterectomy the only option. In two young women with severe bleeding where medical measures were ineffective and hysterectomy was a hazardous option, we performed a transcervical endometrial resection. In both of them the bleeding stopped immediately and no further treatment was required for dysfunctional uterine bleeding. They have had amenorrhea now for over six months. Transcervical endometrial resection is an option when hysterectomy is hazardous and the bleeding is refractory to medical treatment.

The cyclic change of human endometrial cells are controlled by the interaction between hypothalamus, pituitary gland and ovaries, thus making the endometrium proliferate, differentiate, exfoliate and then reproduce. The menstrual cycle is divided into three phases which are called follicle, ovulatory and luteal phase by the morphological change of the ovarium. The endometrial cycle is also classified to proliferative, secretory and menstrual phase. Estradiol (E2) stimulates the proliferation of endometrial cells by the indirect positive mechanism activated by the binding of E2 to E2 receptor. Growth factors (IGF- I, EGF, TGF- alpha etc.) induced by the transcription of the gene promote the proliferation of endometrial cells. Progesterone (P) has antagonistic effects on E2 actions and transform proliferative phase to secretory phase in endometrium. It is suggested that the possible mechanism of carcinogenesis of normal endometrium is the progression of endometrial hyperplasia due to the prolonged and unphysiological exposure to E2. The additional role of oncogenes (fos, fms, myc, myb, erb-B, neu) and growth factors on the mechanism of carcinogenesis of hyperplasia to cancer is very interested.

Of eight mongrel bitches, the antimesometrial side of the nonpregnant left horn of the uterus at the pregnant or nonpregnant luteal phase was scratched with a Kirschner's wire. Cystic endometrial hyperplasia (CEH) was induced in seven of the eight bitches (87.5%). No difference in the incidence of CEH in the left horn was seen between the pregnant and the nonpregnant groups. Histological examinations showed CEH with a dilatation of the basal glands, resembling "Swiss cheese endometrium".

To facilitate our understanding of estrogen participating in the genesis of human endometrial hyperplasia and carcinoma and the influence of the surrounding mesenchyme in their development, we assayed estrogen receptors in the epithelium and stroma of various human endometrial tissues by immunocytochemistry. The receptors were localized in fresh frozen sections using the ER-ICA kits (Abbott Laboratories, North Chicago, Illinois). The receptor content was highest in the proliferative endometrium and decreased gradually throughout the postovulatory phase of the menstrual cycle in both the epithelium and the stroma and this occurred more rapidly in the stroma. Estrogen receptor content was high in both the epithelium and the stroma of hyperplasia and was thus similar to that of the proliferative endometrium, the receptor content was low in the epithelium of endometrial intraepithelial neoplasia (hyperplasia with cytologic atypia) closely resembling that of carcinoma. In carcinomas there was a heterogenous distribution of estrogen receptors both in the epithelium and the stroma, but in general, the receptor content was low as compared with normal proliferative or hyperplastic endometrium; however, in selected cases the content of estrogen receptor in the stroma was high, despite the lack of receptors in the epithelium.