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Objective: To estimate trends in use and outcomes of progestin therapy for premenopausal patients with endometrial intraepithelial neoplasia., Methods: The MarketScan Database was used to identify patients aged 18-50 years with endometrial intraepithelial neoplasia from 2008 to 2020. Primary treatment was classified as hysterectomy or progestin-based therapy. Within the progestin group, treatment was classified as systemic therapy or progestin-releasing intrauterine device (IUD). The trends in use of progestins and the pattern of progestin use were examined. A multivariable logistic regression model was fit to examine the association between baseline characteristics and the use of progestins. The cumulative incidence of hysterectomy, uterine cancer, and pregnancy since initiation of progestin therapy was analyzed., Results: A total of 3,947 patients were identified. Hysterectomy was performed in 2,149 (54.4%); progestins were used in 1,798 (45.6%). Use of progestins increased from 44.2% in 2008 to 63.4% in 2020 ( P =.002). Among the progestin users, 1,530 (85.1%) were treated with systemic progestin, and 268 (14.9%) were treated with progestin-releasing IUD. Among progestin users, use of IUD increased from 7.7% in 2008 to 35.6% in 2020 ( P <.001). Hysterectomy was ultimately performed in 36.0% (95% CI 32.8-39.3%) of those who received systemic progestins compared with 22.9% (95% CI 16.5-30.0%) of those treated with progestin-releasing IUD ( P <.001). Subsequent uterine cancer was documented in 10.5% (95% CI 7.6-13.8%) of those who received systemic progestins compared with 8.2% (95% CI 3.1-16.6%) of those treated with progestin-releasing IUD ( P =.24). Venous thromboembolic complications occurred in 27 (1.5%) of those treated with progestins; the venous thromboembolism (VTE) rate was similar for oral progestins and progestin-releasing IUD., Conclusion: The rate of conservative treatment with progestins in premenopausal individuals with endometrial intraepithelial neoplasia has increased over time, and among progestin users, progestin-releasing IUD use is increasing. Progestin-releasing IUD use may be associated with a lower rate of hysterectomy and a similar rate of VTE compared with oral progestin therapy., Competing Interests: Financial Disclosure Yukio Suzuki reports receiving payment from The Japan Society for Menopause and Women's Health (JMWH Bayer Grant 2022) and from Honjo (JMSA Scholarship 2022). They received a Honjo-JMSA Scholarship and a JMWH Bayer Grant from the Japan Society for Menopause and Women's Health. Jason D. Wright has received royalties from UpToDate and research support from Merck. The other authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

The objectives of this Clinical Expert Series on endometrial hyperplasia are to review the etiology and risk factors, histologic classification and subtypes, malignant progression risks, prevention options, and to outline both surgical and nonsurgical treatment options. Abnormal uterine and postmenopausal bleeding remain the hallmark of endometrial pathology, and up to 10-20% of postmenopausal bleeding will be either hyperplasia or cancer; thus, immediate evaluation of any abnormal bleeding with either tissue procurement for pathology or imaging should be undertaken. Although anyone with a uterus may develop atypical hyperplasia, also known as endometrial intraepithelial neoplasia (EIN), genetic predispositions (eg, Lynch syndrome), obesity, chronic anovulation, and polycystic ovarian syndrome all markedly increase these risks, whereas use of oral contraceptive pills or progesterone-containing intrauterine devices will decrease the risk. An EIN diagnosis carries a high risk of concomitant endometrial cancer or eventual progression to cancer in the absence of treatment. The definitive and curative treatment for EIN remains hysterectomy; however, the obesity epidemic, the potential desire for fertility-sparing treatments, the recognition of varying rates of malignant transformation, medical comorbidities, and an aging population all may factor into decisions to employ nonsurgical treatment modalities., Competing Interests: Financial Disclosure Susan C. Modesitt reports receiving payment from Elsevier for an editor-in-chief position. The other authors did not report any potential conflicts of interest., (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

A retrospective study from 2015 to 2020 comparing overall survival (OS) outcomes of a cancer unit and centre for presumed early stage endometrial cancers is presented. Cancer centres manage these presumed early endometrial cancer (EC) in situations of complex co-morbidities, surgical challenges as well as their own local unit patients. Our analysis compares 138 patients at KMH (unit) and 282 patients at RDH (centre) on OS, patient demographics, grading histology and final histology. Patients with presumed early stage EC can be reassured regarding no difference in OS between the cancer unit and centre management ( p  = .05). However, rates of minimal access surgery were higher at the cancer centre compared to the unit (93.2% versus 68.1%). The rates of upstaged disease were 4% and 8.8% at the cancer unit and centre respectively ( p  = .096). Sentinel node biopsy and genomic assessment may change future thresholds for centre-level management due to rates of upstaged disease.Impact Statement What is already known on this subject? Presumed lower risk endometrial cancers (endometrioid grades 1 and 2) have a rate of occult nodal involvement of only 1.4%. The BGCS does not recommend lymphadenectomy for low-risk endometrial cancers. These low-risk endometrial cancers should be managed with a hysterectomy and bilateral salpingo-ophrectomy via minimal access surgery. In view of the low rates of occult nodal involvement in low-risk endometrial cancer, surgery can be offered at a cancer unit. What do the results of this study add? Our study demonstrates there is no disadvantage in overall survival in the surgical management of presumed low-risk endometrial cancers at cancer units and centres. However, cancer centres have higher rates of minimal access to surgery despite managing a more elderly population. Our rates of upstaged disease of 4% and 8.8% at the cancer unit and centre indicate a potential benefit of pelvic lymph node assessment. What are the implications of these findings for clinical practice and/or further research? Sentinel lymph node biopsy does not have the surgical morbidity associated with systematic lymph node dissection. Therefore, when applied to presumed early stage endometrial cancer, there are potential changes in the threshold for centre-level management to improve overall survival.

The objective of this study was to assess the endometrial pathology developed (EP) in postmenopausal women with genitourinary syndrome during and after vaginal oestrogen therapy. The 67 patients included were randomly grouped into group I underwent local oestrogen (oestriol) therapy and group II, underwent no therapy. Each patient's medical history was taken and clinical and gynecological examination, with transvaginal ultrasound at the time of inclusion and during the control visits, was done. The study results show no statistically higher risk of EP for vaginal oestrogen therapy of genitourinary syndrome users compared to the non-users in menopause. No one atypical endometrial hyperplasia and endometrial intraepithelial neoplasia case during the study period was found.Impact statement What is already known on this subject? Treatment of genitourinary syndrome with oestrogens in menopausal women is the most commonly used and affordable method. Topical vaginal oestrogens do not have the same stimulating effect on the endometrium as oral ones, and therefore the association between them and endometrial hyperplasia or cancer has not been established categorically. What do the results of this study add? This single-center, randomised study found no statistically higher risk of endometrial pathology for vaginal oestrogen (oestriol) therapy of genitourinary syndrome users compared to the non-users in menopause. No one atypical endometrial hyperplasia and endometrial intraepithelial neoplasia case during the study period was found. What the implications are of these findings for clinical practice and/or further research? This study confirms the safety of local oestrogen (oestriol) therapy of genitourinary syndrome in menopausal women with regards to the development of endometrial pathology and especially atypical endometrial hyperplasia and endometrial intraepithelial neoplasia or well-differentiated carcinoma.

Objective: Type 2 diabetes mellitus (T2DM) is thought to be a risk factor for endometrial hyperplasia, but potential links between the two diseases are unknown. This study aims to evaluate the role of T2DM in the progression of endometrial hyperplasia., Methods: Female Sprague-Dawley rats were randomly divided into normal (N) group, endometrial hyperplasia (NH) group, T2DM (T) group, and endometrial hyperplasia with T2DM (TH) group. Proteomics analysis was performed to determine the protein profile of endometrial tissues. Proliferation, migration, and invasion of cells with/without GLANT2-knockdown were assessed. Immunohistochemical staining and ELISA were used to examine the expression of GALNT2 in endometrial tissues and serum of clinical samples., Results: The highest uterus index and endometrial thickness were observed in TH group, with the expression of proliferation marker PCNA increased significantly, indicating that T2DM facilitates the progress of endometrial hyperplasia. Proteomics analysis showed that there were significant differences in protein profiles among groups and differential proteins were mainly enriched in metabolic pathways. Further verification by molecular biology analysis indicated that GALNT2 is the key target for T2DM facilitating endometrial hyperplasia. The expression of GALNT2 was significantly decreased in high glucose environment. T2DM could synergize the proliferative function of GALNT2 aberration by activating EGFR/AKT/ERK pathway. The decreased expressions of GALNT2 in clinical samples were associated with worse subtypes of endometrial hyperplasia., Conclusion: T2DM promoted the progression of endometrial hyperplasia by regulating the GALNT2-mediated phosphorylation of EGFR and enhancing cell proliferation. GALNT2 has the potential to be a novel biomarker in the treatment of endometrial hyperplasia., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Lynch syndrome (LS) is associated with an increased risk for colorectal, endometrial, and ovarian carcinomas in women. Risk-reducing hysterectomy and bilateral salpingo-oophorectomy (RRHSO) has been shown to be a cost-effective form of management and prevention of gynecological malignancies in patients with LS. Studies of incidental gynecologic malignancies identified in RRHSO are limited. In addition, recommendations on optimal handling of this type of specimen have ranged from submitting for microscopic examination the entire endometrium, fallopian tubes and ovaries to submitting only routine representative sections of these organs. In this study, we present the clinicopathologic findings of 29 cases of LS patients that underwent risk-reducing gynecologic surgery at our institution over a period of 13 yr. Clinical-pathologic information was obtained from the patients' charts and pathology reports. Significant pathologic abnormalities were identified in 17% (5/29) of cases, all showing endometrial hyperplasia. Four of them with atypical and 1 without atypical. All of our cases with endometrial pathology had significant findings on preoperative endometrial sampling. To further study the recommendation of in toto submission of the endometrium, ovaries and fallopian tubes and the utility of preoperative endometrial sampling, we undertook a literature review of all the reported cases of incidental pathologic findings identified in RRHSO. The findings of our cohort and the literature reviewed support in toto submission of endometrium, and adnexal structures in the absence of gross lesions. In addition, our findings show a definite benefit for preoperative endometrial sampling as part of the workup for LS patients undergoing RRHSO.

Study Objective: To evaluate characteristics of young women with endometrial hyperplasia or cancer., Design: Retrospective chart review., Setting: Tertiary care referral center., Participants, Interventions, and Main Outcome Measures: We included 10- to 25-year-old young women seen at a single institution between 2006 and 2017 with International Classification of Diseases 9th and 10th revision codes for endometrial cancer or hyperplasia (cases), or who underwent an endometrial biopsy with other benign pathologic diagnoses (controls). Exclusions included a diagnosis of Lynch syndrome. Comparisons were made using χ 2 , Fisher exact, and nonparametric Wilcoxon rank tests., Results: Sixty-nine patients were identified: 13 cases, 54 controls, and 2 exclusions. Of the 13 cases, 3 had endometrial cancer, 5 had complex atypical hyperplasia (now called endometrioid intraepithelial neoplasia), and 5 had hyperplasia without atypia. A higher proportion of cases had a body mass index (BMI) greater than 30, compared with controls (76.9% vs 40.4%; P < .03). The proportion of patients who had a BMI greater than 30 and were smokers was significantly higher among cases (38.5% vs 9.3%; P < .02). The proportion of patients with a history of polycystic ovary syndrome (PCOS) and smoking was also significantly different between groups (30.8% vs 3.7%; P < .01)., Conclusion: In women aged 25 years and younger with endometrial sampling, a BMI greater than 30 was statistically more common in patients with endometrioid intraepithelial neoplasia or cancer. Although smoking or PCOS alone was not related to endometrial hyperplasia or cancer in this small cohort study, there might be a relationship between endometrial abnormalities and multiple exposures, including smoking and BMI greater than 30 or smoking and a history of PCOS., (Copyright © 2019 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to assess the relation between benign endometrial pathologies (polyp and/or hyperplasia without atypia) and the metabolic status (insulin resistance and metabolic syndrome) of the patients. A total of 168 cases were enrolled in the study. The patients were classified according to the presence of benign endometrial pathologies and their menopausal status. Then, the subjects were evaluated according to the metabolic syndrome criteria and the presence of an insulin resistance. The insulin resistance levels of the cases were analysed by four different methods. Obesity and a waist circumference of greater than 88 cm were observed significantly more in the study group with endometrial pathologies (p = .005 and p < .001, respectively). It was also observed that a fasting blood glucose level of higher than 110 mg/dL increased the risk of developing endometrial polyps and/or hyperplasia without atypia by almost five folds (OR: 5.26, 95% CI: 1.25-22.12). Furthermore, an insulin resistance was found to be significantly high in the study group (p = .002). Based on the observed significant relationship between an insulin resistance and benign endometrial pathologies, it can be concluded that insulin resistance plays an important role in the development of benign endometrial pathologies. Impact Statement What is already known on this subject? Metabolic anomalies such as obesity, type 2 diabetes, hypertension and dyslipidaemia play an important role in abnormal endometrial proliferation. Also, these metabolic anomalies have been known as risk factors for type I endometrial cancer. What the results of this study add? A significant relationship between an insulin resistance and benign endometrial pathologies was observed. What the implications are of these findings for clinical practice and/or further research? Based on this finding, we concluded that an insulin resistance may play an important role in the development of benign endometrial pathologies. The prevention and the treatment of obesity as a key factor of developing an insulin resistance, may reduce not only the incidence of malignant endometrial pathologies, but also the incidence of benign pathologies and of a malignant transformation.

Objectives: The efficacy and safety of 25-μg 17β-estradiol vaginal tablets (Vagifem) were assessed and compared with 1.25-mg conjugated equine estrogen vaginal cream (Premarin Vaginal Cream) for the relief of menopausal-derived atrophic vaginitis, resulting from estrogen deficiency., Design: In a multicenter, open-label, randomized, parallel-group study, 159 menopausal women were treated for 24 weeks with either vaginal tablets or vaginal cream. Efficacy was evaluated by relief of vaginal symptoms and concentrations of serum estradiol and follicle-stimulating hormone. Safety was monitored by the incidence of adverse events, evaluation of endometrial biopsies, and clinical laboratory results. Patients also assessed the acceptability of the study medications., Results: Composite scores of vaginal symptoms (dryness, soreness, and irritation) demonstrated that both treatments provided equivalent relief of the symptoms of atrophic vaginitis. At weeks 2, 12, and 24, increases in serum estradiol concentrations and suppression of follicle-stimulating hormone were observed in significantly more patients who were using the vaginal cream than in those who were using the vaginal tablets (p < 0.001). Fewer patients who were using the vaginal tablets experienced endometrial proliferation or hyperplasia compared with patients who were using the vaginal cream. Significantly more patients who were using the vaginal tablets rated their medication favorably than did patients who were using the vaginal cream (p ≤ 0.001). Patients who were receiving the vaginal tablets also had a lower incidence of patient withdrawal (10% versus 32%)., Conclusions: Treatment regimens with 25-μg 17β-estradiol vaginal tablets and with 1.25-mg conjugated equine estrogen vaginal cream were equivalent in relieving symptoms of atrophic vaginitis. The vaginal tablets demonstrated a localized effect without appreciable systemic estradiol increases or estrogenic side effects. Vaginal tablet therapy resulted in greater patient acceptance and lower withdrawal rates compared with vaginal cream therapy.

Endometrial cancer (EC) has recently become a major gynecological cancer and endometrial hyperplasia increases the risk for developing EC. Previous studies have reported that human high temperature requirement factor A3 (HtrA3), a member of ATP independent serine proteases family, is involved in endometrial carcinogenesis. However, the underlying mechanism of HtrA3 function is unclear in endometrial hyperplasia and cancer. In this study, we investigated that HtrA3 expression was reduced in endometrial hyperplasia as well as EC. The circulating levels of HtrA3 were also significantly reduced in both atypical hyperplasia and EC. Whether hypoxia is involved in the reduction of HtrA3 in EC was further investigated. Immunohistochemistry (IHC) scores of Glut1 and HtrA3 in type 1 and type 2 EC tissues showed the inverse correlation. And hypoxic condition reduced the expression of HtrA3. Furthermore, silencing HtrA3 promoted EC cell migration. Our study demonstrated the reduced levels of HtrA3 in endometrial hyperplasia including atypical hyperplasia which is a premalignant condition; and as the degree of hypoxia increases in EC, HtrA3 eventually loses its expression. Hypoxia is responsible for the reduction of HtrA3 which in turn promotes EC progression. These findings suggested that HtrA3 is an important adaptor in hypoxic regions that drives endometrial cancer development., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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.)

Thirty-eight percent of US adult women are obese, meaning that more children are now born of overweight and obese mothers, leading to an increase in predisposition to several adult onset diseases. To explore this phenomenon, we developed a maternal obesity animal model by feeding mice a diet composed of high fat/ high sugar (HF/HS) and assessed both maternal diet and offspring diet on the development of endometrial cancer (ECa). We show that maternal diet by itself did not lead to ECa initiation in wildtype offspring of the C57Bl/6J mouse strain. While offspring fed a HF/HS post-weaning diet resulted in poor metabolic health and decreased uterine weight (regardless of maternal diet), it did not lead to ECa. We also investigated the effects of the maternal obesogenic diet on ECa development in a Diethylstilbestrol (DES) carcinogenesis mouse model. All mice injected with DES had reproductive tract lesions including decreased number of glands, condensed and hyalinized endometrial stroma, and fibrosis and increased collagen deposition that in some mice extended into the myometrium resulting in extensive disruption and loss of the inner and outer muscular layers. Fifty percent of DES mice that were exposed to maternal HF/HS diet developed several features indicative of the initial stages of carcinogenesis including focal glandular and atypical endometrial hyperplasia versus 0% of their Chow counterparts. There was an increase in phospho-Akt expression in DES mice exposed to maternal HF/HS diet, a regulator of persistent proliferation in the endometrium, and no difference in total Akt, phospho-PTEN and total PTEN expression. In summary, maternal HF/HS diet exposure induces endometrial hyperplasia and other precancerous phenotypes in mice treated with DES. This study suggests that maternal obesity alone is not sufficient for the development of ECa, but has an additive effect in the presence of a secondary insult such as DES., Competing Interests: The authors have declared that no competing interests exist.

Objective: To systematically review the literature on the association between obesity and endometrial hyperplasia or cancer in premenopausal women., Data Sources: We searched the bibliographic databases MEDLINE, EMBASE, PubMed, and CINAHL (inception to May 5, 2015), and checked reference lists of included studies and systematic reviews., Study Eligibility Criteria: Studies of more than 50 women with endometrial pathology diagnosed during premenopause that reported on obesity as a risk factor were eligible., Study Appraisal and Synthesis Methods: Study identification and data extraction were independently performed by 2 authors. Where possible, data were pooled in a generic inverse variance forest plot. Heterogeneity was reported using the I(2) statistic., Results: Nine case-control studies of moderate quality were included. Quantitative analysis of 5 studies showed a dose-response relationship of body mass index and increased risk of endometrial cancer. For studies of women with body mass index of ≥25, the pooled odds ratio was 3.85 (95% confidence interval 2.53-5.84); body mass index of ≥30 was 5.25 (4.00-6.90); and body mass index of ≥40 was 19.79 (11.18-35.03)., Conclusion: Body mass index is a consistent and leading risk factor for endometrial complex hyperplasia or cancer in premenopausal women. Body mass index should be considered when deciding to assess the endometrium in symptomatic premenopausal women., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Endometrial hyperplasia (EH) comprises a spectrum of changes in the endometrium ranging from a slightly disordered pattern that exaggerates the alterations seen in the late proliferative phase of the menstrual cycle to irregular, hyperchromatic lesions that are similar to endometrioid adenocarcinoma. Generally, EH is caused by continuous exposure of estrogen unopposed by progesterone, polycystic ovary syndrome, tamoxifen, or hormone replacement therapy. Since it can progress, or often occur coincidentally with endometrial carcinoma, EH is of clinical importance, and the reversion of hyperplasia to normal endometrium represents the key conservative treatment for prevention of the development of adenocarcinoma. Presently, cyclic progestin or hysterectomy constitutes the major treatment option for EH without or with atypia, respectively. However, clinical trials of hormonal therapies and definitive standard treatments remain to be established for the management of EH. Moreover, therapeutic options for EH patients who wish to preserve fertility are challenging and require nonsurgical management. Therefore, future studies should focus on evaluation of new treatment strategies and novel compounds that could simultaneously target pathways involved in the pathogenesis of estradiol-induced EH. Novel therapeutic agents precisely targeting the inhibition of estrogen receptor, growth factor receptors, and signal transduction pathways are likely to constitute an optimal approach for treatment of EH.

Purpose of Investigation: To investigate the presence of 15-lipoxygenase-1 (15-LOX-1) expression and its potential role in the pathogenesis of endometrial hyperplasia and endometrial adenocarcinomas., Materials and Methods: The authors investigated the presence of 15-LOX-1 expression in samples from patients diagnosed with normal endometrium (n = 12), endometrial hyperplasia (n = 12), and endometrial cancer (n = 12). The immunohistochemical stainings were scored by three independent pathologists. A Western blot of 15- LOX-1 determined the presence of protein expression in normal endometrium. A Kolmogorov-Smirnov test was used to evaluate the data's distribution pattern. For pairwise comparisons of the combined scores between groups, the Mann-Whitney U test was used., Results: Based on the combined scores for 15-LOX-1 expression, strong immunochemistry staining was observed in samples diagnosed with normal endometrium. There was a significant difference in 15-LOX-1 expression between normal endometrium and endometrial adenocarcinoma (p = 0.03). Comparing tissues from normal endometrium and endometrial hyperplasia, there was a decline in the expression from normal endometrium to endometrial hyperplasia. However, the difference was not statistically significant., Conclusion: The present results show that a decrease of 15-LOX-1 expression in the endometrial tumorigenesis process, starting from normal endometrium to hyperplasia and endometrial cancer, might be a trigger. Further studies are required to determine its potential use as a marker in a larger randomized multicenter study.

Background: Definitive management with hysterectomy could be appropriate for some patients with endometrial cancer and its precursor lesions, but poses challenges for those desiring future fertility., Objectives: To review risk factors for endometrial hyperplasia/cancer among premenopausal women and discuss management options for fertility preservation., Search Strategy: A literature search through the PubMed, Ovid, and Cochrane databases was conducted using the terms "endometrial hyperplasia" and "endometrial cancer," cross-referenced with "fertility preservation.", Selection Criteria: All articles published in English between January 1, 2000, and January 1, 2015, were considered if they were readily available online., Data Collection and Analysis: Articles were analyzed and information was synthesized into a comprehensive review., Main Results: Chronic anovulation, obesity, polycystic ovarian syndrome, metabolic syndrome, insulin resistance, and type 2 diabetes mellitus must be appreciated as risk factors for endometrial pathology. Providers must exert vigilance in identifying patients at risk and in initiating pre-emptive strategies. Risk reduction with lifestyle modification, weight loss, and glycemic control can improve regression and overall health. Fertility outcomes for these patients are promising, especially with assisted reproductive technology., Conclusions: Conservative management could be appropriate for carefully selected women with complex atypical endometrial hyperplasia or early-stage endometrial cancer who desire future fertility., (Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

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.

Endometrial hyperplasia (EH) is a condition originating from uterine endometrial glands undergoing disordered proliferation including the risk to progress to endometrial adenocarcinoma. In recent years, a steady increase in EH cases among younger women of reproductive age accentuates the demand of therapeutic alternatives, which emphasizes that an improved disease model for therapeutic agents evaluation is concurrently desired. Here, a new hormone-induced EH mouse model was developed using a subcutaneous estradiol (E2)-sustained releasing pellet, which elevates the serum E2 level in mice, closely mimicking the effect known as estrogen dominance with underlying, pathological E2 levels in patients. The onset and progression of EH generated within this model recapitulate a clinically relevant, pathological transformation, beginning with disordered proliferation developing to simple EH, advancing to atypical EH, and then progressing to precancerous stages, all following a chronologic manner. Although a general increase in nuclear progesterone receptor (PR) expression occurred after E2 expression, a total loss in PR was noted in some endometrial glands as disease advanced to simple EH. Furthermore, estrogen receptor (ER) expression in the nucleus of endometrial cells was reduced in disordered proliferation and increased when EH progressed to atypical EH and precancerous stages. This EH model also resembles other pathological patterns found in human disease such as leukocytic infiltration, genetic aberrations in β-catenin, and joint phosphatase and tensin homolog/paired box gene 2 (PTEN/PAX2) silencing. In summary, this new and comprehensively characterized EH model is cost-effective, easily reproducible, and may serve as a tool for preclinical testing of therapeutic agents and facilitate further investigation of EH., (© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

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.)

Objective: The aim of the present study is to determine the potential risk factors for adenomyosis and to investigate its relationship with accompanying gynecological pathologies and clinical characteristics., Materials and Method: This study is a retrospective analysis of 945 patients who underwent hysterectomy between May 2005 and January 2013 at the Sifa University Medical Faculty Hospital, Clinic of Obstetrics and Gynecology. The study included 327 patients with adenomyosis and 618 patients without adenomyosis by histopathological examination of the uterus., Results: There was a significant positive correlation between development of adenomyosis and presence of leiomyoma (p < 0.0001), history of previous abortion (p < 0.0001), history of previous pregnancy (p = 0.0002), and normal body mass index (p < 0.0001). However, no significant relationship existed between development of adenomyosis and smoking (p > 0.4300), normal delivery (p = 0.9600), cesarean delivery (p = 0.5705), endometrial hyperplasia (p = 0.1721), or ovarian endometriosis (p = 0.8595)., Conclusion: Women who are multiparous have leiomyoma, a previous history of abortion, and a normal body mass index are at increased risk for development of adenomyosis. Adenomyosis might be one cause of unexplained recurrent spontaneous abortion during pregnancy.

Purpose: To evaluate the risk factors for endometrial hyperplasia concomitant endometrial polyps in pre- and post-menopausal women., Materials and Methods: A total of 203 patients undergoing endometrial sampling before hysterectomy were evaluated in this retrospective study. Data recorded were age, gravidity, parity, body mass index (BMI: weight(kg)/height(m)2), endometrial thickness (ET), menopausal status, presence of adenomyosis and diabetes mellitus., Results: Endometrial hyperplasia and polyps were detected in 13 patients. There were statistically significant differences in terms of age, menopausal status, morbid obesity and diabetes mellitus (p<0.005). Logistic regression demonstrated that menopausal status and presence of diabetes mellitus were independent risk factors., Conclusions: According to the current study; menopause and diabetes mellitus are strong risk factors for the presence of concomitant endometrial polyps and endometrial hyperplasia.

Objective: To evaluate the use of a levonorgestrel-releasing intrauterine system (LNG-IUS) for treating endometrial hyperplasia in patients with polycystic ovary syndrome (PCOS)., Methods: LNG-IUSs were inserted in 60 PCOS patients with simple (40 cases), irregular (12 cases), or complex (8 cases) endometrial hyperplasia. Follow-ups were performed at 3, 6, 12, and 24 months after insertion. At each time point, changes in menstruation, hemoglobin level, and endometrial thickness and pathology were recorded. Menstrual changes were assessed with the Pictorial Blood Assessment Chart. Hemoglobin levels were measured by the Blood Routine Test. Endometrial thickness was determined by transvaginal ultrasound. Endometrial pathology was defined as simple, irregular, or complex endometrial hyperplasia by a pathologist after curettage. Outcomes at each time point were compared to baseline (pre-insertion) measurements by Student's t test or ANOVA (for multiple comparisons) with the post hoc Dunnett's test. Differences with a p < 0.05 were considered statistically significant., Results: At all time points after LNG-IUS insertion and in all patients, menstrual blood loss was decreased and hemoglobin level was increased significantly compared to pre-insertion levels. The endometrial thickness was significantly reduced in all groups after 12 months. Most patients showed transformation of the endometrial pathology, with complete disappearance of simple and irregular cases of endometrial hyperplasia and a decreased number of complex endometrial hyperplasia cases., Conclusions: LNG-IUS is an effective, safe, nonsurgical, and atraumatic approach with few side effects for the treatment of endometrial hyperplasia in patients with PCOS., (© 2014 S. Karger AG, Basel.)

Persistence of free fluid in the uterine lumen of bitches with endometrial hyperplasia appears to be diagnostic for mating-induced endometritis and is associated with reduced chances of pregnancy. This study investigated the possibility that reduced fertility might be associated with an effect of uterine fluid on sperm. Uterine lavage fluid was collected pre- and post-insemination from normal bitches without ultrasonographically-detectable luminal fluid (n=4), and previously non-pregnant bitches with endometrial hyperplasia and luminal fluid (n=4). Concentrations of polymorphonuclear neutrophils (PMNs) were measured and the effect of the fluid on the attachment of spermatozoa to the uterine epithelium was studied using medium (M) 199 as a control. To elucidate whether any effect was accounted for by the presence of PMNs, attachment was also measured in M199 with PMNs added at the concentration found in lavage fluid. Pre-insemination lavage fluid from both groups contained low concentrations of PMNs which increased post-insemination; the increase was larger for bitches with uterine fluid. Compared with M199 controls, lavage fluid reduced the attachment of spermatozoa; fluid from bitches with endometrial hyperplasia and uterine fluid had a greater effect than normal bitches, and post-insemination fluid had a greater effect than pre-insemination fluid. Spermatozoal attachment was reduced by a similar magnitude for M199 with added PMNs, although post-insemination fluid from bitches with endometrial hyperplasia reduced attachment more than M199 with added PMNs. Poor fertility in bitches with uterine luminal fluid might be partially associated with impaired attachment of spermatozoa to uterine epithelium, mediated principally, but not solely, by PMN influx into the uterine lumen., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Benign endometroid cystadenofibroma of the ovary is a rare tumour with few reported cases. The association of endometroid cystadenofibroma with endometrial cystic glandular hyperplasia has not been previously reported to authors' knowledge. We are reporting a 75-year-old postmenopausal woman who presented with a large abdominopelvic mass corresponding to 30 weeks size gravid uterus and postmenopausal bleeding. She has a well-oestrogenised vagina. Ultrasound pelvis revealed a large cystic mass extending from pelvis to epigastrium with no solid component and few incomplete septations and no internal echoes. MRI findings showed mainly cystic component with few moderately enhancing, fine, incomplete septa. Endometrial aspiration reported histopathology of cystic glandular hyperplasia without atypia. Serum oestrogen level reported to be high (210 pg/mL). Hysterectomy with bilateral salpingo-oophorectomy was performed. Histopathology of the specimen revealed benign endometroid cystadenofibroma. She remained asymptomatic and disease free during her 6-month follow-up.

Objective: To determine the prevalence of occult uterine pathology in asymptomatic, morbidly obese women before and after bariatric surgery-induced weight loss., Design: Prospective, blinded, non-interventional cohort., Setting: Urban teaching hospital., Population: Morbidly obese women., Methods: Endometrial biopsies were obtained at the time of Roux-en-Y gastric bypass and again 1 year later. Both the patient and the physician were blinded to the results of the initial biopsy until the conclusion of the study. Specimens were independently reviewed by two blinded pathologists., Main Outcome Measure: Effect of bariatric surgery-induced weight loss on the prevalence of endometrial pathology at 1 year., Results: Fifty-nine women underwent an endometrial biopsy during bariatric surgery. The mean (range) age, weight, and body mass index (BMI) were 42 years (22-62 years), 127 kg (87-176 kg), and 46.8 kg/m(2) (36-64.3 kg/m(2) ), respectively. Four women had hyperplasia (three simple and one complex), for an overall prevalence of 6.8%. The prevalence among women not receiving some anti-estrogen therapy was 9.5%. Forty-six women (78%) underwent follow-up biopsy after a mean (range) weight loss of 42 kg (19-67 kg). Simple hyperplasia was identified in 3/46 women at the 1-year follow-up (6.5%). Two women had resolution of hyperplasia, two women had persistent, simple hyperplasia, and one had had a normal initial biopsy. No woman showed progressive pathology or cancer. At the end of the follow-up all but one patient had a documented resolution of endometrial pathology., Conclusions: Asymptomatic morbidly obese women are at relatively high risk of harbouring occult endometrial hyperplasia. Bariatric surgery-associated weight loss reduced but did not eliminate this risk for endometrial pathology., (© 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.)

A 1-year-old, female, previously spayed domestic shorthair cat presented with abnormal behavior characterized by rubbing up against objects, vocalization and abnormal body posture. A diagnostic laparoscopy was performed and a dilated segment of the left uterus and ovary was found in association with ipsilateral renal agenesis. Papillary hyperplasia of the endometrium of the dilated segment was found on histopathology. The occurrence and findings of this condition are reviewed.

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.

Objective: Polycystic ovary syndrome may be associated with an increased risk of endometrial hyperplasia and endometrial cancer, but substantial evidence for this remains to be established. We investigated the prevalence of endometrial hyperplasia and endometrial cancer in a well characterized group of women with polycystic ovary syndrome and/or clinical/biochemical hyperandrogenism., Design: Retrospective observational trans-sectional study., Setting: Out-patient clinic at the Departments of Endocrinology and Gynecology, Odense University Hospital, Denmark., Population: In all, 963 premenopausal women consecutively referred with the diagnoses polycystic ovary syndrome and/or hirsutism during 1997-2008., Methods: All women underwent a standardized evaluation program. In 2011, The Danish Data Bank of Pathology was used to identify women with endometrial histology diagnoses (year range of diagnosis 1982-2011). Main outcome measures. Histology diagnoses, demographic variables., Results: Endometrial hyperplasia was diagnosed in 10 (1.0%) women and endometrial cancer in one (0.1%) woman. The median body mass index of these women was 30.6 kg/m(2) compared with 26.8 kg/m(2) in the total cohort. There were no differences between the cases and total cohort in terms of individual Rotterdam Criteria. In Denmark, 70 cases of endometrial cancer are diagnosed yearly in women 40-55 years, a prevalence of 0.4% in the corresponding period., Conclusion: The results of the present study do not suggest a higher prevalence of endometrial cancer in women with polycystic ovary syndrome and/or clinical/biochemical hyperandrogenism than in the general population., (© 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.)

Endometrial hyperplasia (EH), with or without atypia, is a common gynecologic diagnosis and a known precursor of endometrial carcinoma, the most common gynecologic malignancy. During the reproductive years, the risk of EH is increased by conditions associated with intermittent or absent ovulation, in particular, polycystic ovary syndrome. After menopause when ovulation has ceased, EH is more common in women with conditions that increase levels of circulating estrogen such as obesity or estrogen replacement therapy. Women with EH are at increased risk for both concurrent and subsequent endometrial cancer. The risk of coexisting cancer in women with a diagnosis of EH at endometrial sampling is due to limitations in both endometrial sampling and the diagnostic reproducibility among pathologists. These diagnostic uncertainties add to the complexity of managing EH. This review offers a rational approach to prevention, diagnosis, and treatment of EH, including hormone therapy and conservative surgical methods., (Copyright © 2012 AAGL. Published by Elsevier Inc. All rights reserved.)

Objective: To report for the first time a case of postmenopausal endometrial hyperplasia caused by nonclassic 21-hydroxylase deficiency (NC21OHD). The specific combination of mutations associated with this case has never before been reported., Design: Case report., Setting: Private academic practice., Patient(s): A 67-year-old woman with uterine bleeding due to endometrial hyperplasia was found to have premenopausal gonadotropins with elevated estrogens. Endocrine workup revealed increased 17-hydroxyprogesterone (17-OHP), which led to molecular testing to establish a diagnosis of NC21OHD., Intervention(s): Trial of suppression with low-dose oral dexamethasone., Main Outcome Measure(s): Resolution of postmenopausal bleeding., Result(s): Total estrogens normalized with treatment, and the endometrial stripe became normal., Conclusion(s): This is an unusual case of NC21OHD in which the sole presentation was persistent endometrial hyperplasia, with bleeding past the normal age for menopause. In women with unusual endometrial hyperplasias of this type, we suggest endocrine testing before proceeding to hysterectomy., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

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.

Objectives: to investigate whether body mass index (BMI), hypertension (HTN), diabetes, age, and physical activity can be considered risk factors for endometrial simple hyperplasia in premenopausal women. Furthermore this study was undertaken to determine whether serum concentration of leptin in patients with BMI>or= 30 kg / m2 with endometrial hyperplasia deviate from values in patients with normal endometrium., Materials and Methods: The authors enrolled 167 hyperplasia cases and 282 controls. Demographic characteristics and data on age, diabetes, hypertension, BMI, physical activity, and anthropometric parameters were collected. Leptin concentration in serum was measured with immunoenzymatic test kit from IBL. Univariable and multivariable analysis were performed to verify the association among age, HTN, BMI, physical activity, diabetes, and the presence of uterine hyperplasia. Furthermore the authors evaluated the correlation between BMI and leptin level (with Pearson's linear correlation) in women with simple hyperplasia and in controls., Results: The prevalence of hyperplasia found was 34.4%. The following factors were independently associated with increased risk of endometrial hyperplasia: HTN (odds ratio 3.19, 95% confidence interval 1.20-8.48, p<0.020) and BMI>or=30 Kg/m2 (odds ratio 6.43, 95% confidence interval 3.92-10.53, p<0.000). Mean leptin concentration in serum was higher in patients who had endometrial hyperplasia than in controls (p<0.005) and the leptin levels depended on BMI., Conclusions: The following are risk factors for endometrial hyperplasia in premenopausal women: BMI>or=30 kg/m2 and HTN (blood pressure>or=130/85 or in therapy). Leptin appears to participate in proliferative processes of the endometrium, depending on BMI. Current guidelines may need to be reconsidered.

Background: Many women suffering from menopausal symptoms choose to use dietary supplements made from plants for the relief of their symptoms. These herbal preparations can have phyto-oestrogenic properties. Although probably regarded as 'safe', such preparations can cause adverse drug reactions., Case Description: We describe four patient reports to the Netherlands Pharmacovigilance Centre Lareb. All of these patients suffered from postmenopausal bleeding and used hop- and soy-containing dietary supplements. The reports were all from the same gynaecologist., Conclusion: Postmenopausal bleeding has many possible causes. The use of dietary supplements containing ingredients with phyto-oestrogenic properties, such as hop and soy, may give rise to proliferation of the endometrium. The four reports to Lareb illustrate the association between the use of these supplements and postmenopausal bleeding. Such products are available as over-the-counter preparations and consumers often mistakenly believe that they do not cause adverse drug reactions. During the diagnostic phase, it is important to be aware that the use of a dietary supplement or an herbal drug having phyto-oestrogenic properties may be a possible cause of postmenopausal bleeding.

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.

Background: Supracervical hysterectomy, a surgical technique that involves removal of the uterus while preserving the cervix, places women at an increased risk for future morbidity., Case: The patient presented 7 years after laparoscopic supracervical hysterectomy for benign disease, with pelvic pain, urinary frequency, abdominal bloating, and tenderness. Surgical exploration revealed myometrial implants, along with a larger mass on the mesentery of the sigmoid composed of endometrium with complex atypical hyperplasia in a patient without a prior history of complex atypical hyperplasia. The patient was symptom-free 6 months postoperatively., Conclusion: Histology found during reoperation after laparoscopic supracervical hysterectomy includes endometriosis, residual endometrium, and leiomyomas. In this case, a woman with no prior history of endometrial atypia later developed complex adenomatous endometrial hyperplasia in a peritoneal implant. This finding adds to the list of possible complications after laparoscopic-assisted supracervical hysterectomy and uterine morcellation.

Unlabelled: Factors associated with unopposed estrogenic stimulation such as obesity, exogenous hormone use endometrial hyperplasia are related to the development of the most common form of endometrial carcinoma, that is, the endometroid subtype., Material and Methods: We selected a group of patients diagnosed with endometrial hyperplasia by endometrial biopsy and histopathological examination. The main complaint in all cases was abnormal uterine bleeding. All patients had gynecological examination, vaginal ultrasound, hysteroscopy endometrial biopsy or D&C. 32 patients had also immunohistochemical staining for Ki67, EGF, ER, PGR., Results: Cases with ages between 24-67 years were classified as: 100 simple hyperplasia, 10 complex hyperplasia, 43 atypical simple hyperplasia, 7 atypical complex hyperplasia. PR were 40-60% at all forms of hyperplasia, E2R were 30-40% in simple hyperplasia without atypia and 50-70% in complex hyperplasia without atypia. Correlation between immunohistochemical expression of E2R, PGR, Ki-67, EGF and body mass revealed an high immunohistochemical expression of E2R and Ki-67 in patients with hyperplasia without atypia and a low expression and high reactivity of EGF in cases with high body mass., Conclusions: Vaginal ultrasound and hysteroscopy are efficacious completion for histopathological diagnosis. We recommend an age/risk appropriate screening to detect risk factors and early disease in the asymptomatic patients.

Much of our knowledge of human uterine physiology and pathology has been extrapolated from the study of diverse animal models, as there is no ideal system for studying human uterine biology in vitro. Although it remains debatable whether mouse models are the most suitable system for investigating human uterine function(s), gene-manipulated mice are considered by many the most useful tool for mechanistic analysis, and numerous studies have identified many similarities in female reproduction between the two species. This Review brings together information from studies using animal models, in particular mouse models, that shed light on normal and pathologic aspects of uterine biology and pregnancy complications.

Recently, growing multiple uses of silymarin (SIL) as a complementary and alternative medicine, for alcohol-induced liver disease, acute and chronic viral hepatitis, as well as some other nonhepatic indications have been reported. Therefore, more attention should be paid for the hormonal side effects of SIL. Since the available data on the possible estrogenic effects of SIL is rather rare, this study aimed to further elucidate the different estrogenic effects and antiosteoporotic activity of SIL in ovariectomized (OVX) rats. OVX rats were treated chronically (12 weeks) with ethinylestradiol (EE) or SIL. Uterine and body weight were measured in all animals. Biochemical markers of bone formation (total alkaline phosphatase (ALP), calcium, phosphorus and osteocalcin), endocrinological analysis (estradiol (E2), luteinizing hormone (LH), follicle stimulating hormone (FSH) and parathyroid hormone (PTH)) and serum total cholesterol and total lipids were estimated. Formalin fixed femora and uteri specimens were used for histopathological examination. In addition, the binding property of SIL to the two estrogen receptors (ER) subtypes was tested by molecular docking. EE (strong) and SIL (mild) stimulated uterine weight (increased uterus hyperplastic endometrial glands) but EE only prevented body weight gain following OVX. Treatment of OVX rats with both EE and SIL resulted in protection of trabecula thickness, decreased serum levels of ALP and increased serum levels of both calcium and phosphorus. In contrast to EE, SIL did not decrease OVX induced serum osteocalcin. EE not SIL decreased serum cholesterol, total lipids, LH and FSH and increased serum E2. Both EE and SIL increased serum PTH. The docking study revealed a high affinity of SIL towards ERbeta. In conclusion, findings derived in the present study presented an overview of SIL many estrogenic effects in OVX rats. SIL significantly prevents the bone loss in rats induced by OVX with mild proliferative effects in uterus. The observed effects may be due to additive beneficial effect of SIL on bone either due to direct interaction with ERbeta or increasing bone formation parameters including calcium, phosphorus, osteocalcin and PTH., (Copyright 2009 Elsevier GmbH. All rights reserved.)

Background: Phytoestrogens are widely used by postmenopausal women for the treatment of the climacteric syndrome. The risk of adverse effects of this treatment, however, is unknown., Methods: Using a fixed-effects model, we performed a meta-analysis of side effects comparing phytoestrogen treatment with placebo or no treatment in randomized controlled trials., Results: We identified 174 randomized controlled trials. Side effects were reported in 92/174 randomized controlled trials with 9629 participants. The overall incidence of side effects in the phytoestrogen and control groups was 2019/5502 (36.7%) and 1824/4806 (38.0%), respectively (P=.2; incidence rate ratio [IRR] 1.01; 95% confidence interval [CI], 0.95-1.08). Comparing various side effect categories, we found significantly higher rates of gastrointestinal side effects among phytoestrogen users (P=.003; IRR 1.28; 95% CI, 1.08-1.50). Gynecological (IRR 0.94; 95% CI, 0.74-1.20), musculoskeletal (IRR 1.20; 95% CI, 0.94-1.53), neurological (IRR 0.91; 95% CI, 0.70-1.19), and unspecific side effects (IRR 0.95; 95% CI, 0.88-1.03) were not significantly different between groups. Within side effect categories, we found no significantly higher rates of side effects in women using phytoestrogens. Specifically, the rates of hormone-related side effects such as endometrial hyperplasia, endometrial cancer, and breast cancer were not significantly different between groups., Conclusions: Based on the available evidence, phytoestrogen supplements have a safe side-effect profile with moderately elevated rates of gastrointestinal side effects. Rates of vaginal bleeding, endometrial hyperplasia, endometrial cancer, and breast cancer were not significantly increased among phytoestrogen users in the investigated studies.

Aims: To evaluate the effect of low-dose mifepristone on leiomyoma-related symptoms, uterine and leiomyoma in women with symptomatic leiomyomata., Methods: In a double-blind placebo-controlled trial, 40 patients with symptomatic leiomyoma and normal endometrial histology were randomised to receive 10 mg mifepristone (group 1) or placebo (group 2) daily for three months. Leiomyoma-related symptoms, uterine, leiomyoma and largest leiomyoma volumes were assessed at baseline and every month for three months. Endometrial biopsy was repeated at the end of therapy., Results: Significant change was noticed between the two groups for mean menstrual blood loss (MBL) by first month. Menstrual blood loss declined by 94.8% in group 1 at three months and 84.2% patients attained amenorrhoea in this group. In group 1 complete relief of dysmenorrhoea occurred in significant number of women (80%) but only 33% patients got rid of pelvic pain. There was no change in these symptoms in group 1 Backache, urinary complaints and dyspareunia were not relieved in either group. Uterine, leiomyoma and largest leiomyoma volume declined by 26-32% in group 1 as compared to none in group 2, and this difference was statistically significant only by the end of the third month of therapy. Mean haemoglobin increased from 9.5 to 11.2 g/dL in group 1. In group 1, at the end of therapy, 63.1% of patients had endometrial hyperplasia without atypia., Conclusions: Ten milligrams mifepristone for three months is effective in reducing MBL, increasing haemoglobin and reducing uterine and leiomyoma volume with side-effect of endometrial hyperplasia.

Organ transplantation has become universally accepted treatment of end-stage organ failure. The main problem focuses on preventing the graft from rejection with the use of immunosuppressive agents. High incidence of infection is the most frequent adverse effect of immunosuppressive therapy. Symptoms of inflammation are often reduced in immunosuppressed patients. All invasive diagnostic and therapeutic procedures should be associated with the increase in dose of steroids and prophylactic antibiotics. Ovarian and menstrual function is usually restored in transplanted women. Function of the hypothalamus-pituitary-ovary axis in transplanted women is believed to be normal. Most common abnormal uterine bleeding in graft recipient are: prolonged and profuse menstruation and inter-menstrual bleeding or spotting. Among the underlying diseases are lesions of the uterus (fibroids, endometrial or cervical polyps), infections of sex organs or hormonal disturbances. Higher rate of endometrial hyperplasia (without atypia) is reported in renal graft recipients. Organ transplantation results in the restored fertility thus effective family planning method is necessary in women of reproductive age who do not want to conceive. Vaginal diaphragms are not advised and intrauterine device are contradicted. Observational studies indicate for safety and high rate of acceptance of oral and transdermal hormonal contraception in transplanted women. Over ten-year experiences of HRT administration in graft recipient have proved the benefits of the therapy. Patients after organ transplantation have three to four-fold increased incidence of malignancy compared with general population. All transplant women must undergo regular gynecological screening for premalignant and malignant lesions of sex organs and breast.

A 93-year-old woman was referred to our clinic for abnormal genital bleeding. It was found that she had endometrial hyperplasia and breast cancer. Her uterus was as large as that of a normal adult menstruating woman. She indicated that she had been applying cosmetic cream containing a low concentration of ethynylestradiol to her face and body three times a day for 75 years. It is possible that this long-term use of the ethynylestradiol-containing cream is related to the development of breast cancer and endometrial hyperplasia.

The authors sought to test the hypothesis that characteristics and exposures which influence the balance of estrogen and progesterone bear on the incidence of endometrial hyperplasia (EH), a noninvasive proliferation of the lining of the uterus. Cases included all female members of Group Health (Washington State) who were diagnosed with complex EH or EH with atypia during the period 1985-2003 and whose diagnoses were confirmed in a pathology review (n = 446). Controls were selected randomly from Group Health membership files and were matched to the cases by age and enrollment status at the reference date. An increased risk of EH was associated with increasing body mass index and nulliparity. There was a suggestion of a decreased risk of EH with atypia among current smokers. No association with diabetes or hypertension was found. The risk factors observed to be associated with EH in this study are similar to those associated with endometrial cancer. Whether these risk factors predispose women to cancer simply by increasing EH incidence or continue to augment cancer risk even after EH is present is currently unknown.

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.