Type 2 diabetes mellitus facilitates endometrial hyperplasia progression by activating the proliferative function of mucin O-glycosylating enzyme GALNT2.

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.

Endometritis in the bitch: Immunohistochemical localization of cyclooxygenase 2.

Background: In several mammals, subfertility or infertility associated with endometritis was reported. Although there have been studies about endometritis in bitches, the pathophysiological mechanisms are not completely known. Aim: This study aimed to evaluate the immunohistochemical expression of Cyclooxygenase 2 (COX2) in clinically healthy bitches with normal uterine tissue and bitches with endometritis. Methods: Forty-eight mixed breed bitches in diestrus were used. Uterine biopsies were collected for diagnosis [normal endometrium (n = 15; NE), cystic endometrial hyperplasia (n = 1), atrophy (n= 2), acute endometritis (n = 9; AE), subacute endometritis (n = 7; SE), and chronic endometritis (n = 14; CE)]. Immunostaining and quantification of positively stained cells was performed on full-thickness uterine biopsies. Data were analyzed by the GLIMMIX procedure of SAS. Results: COX2 immunostaining was scattered and restricted to cells in the stroma in bitches with NE. However, in bitches with endometritis, strong staining was observed in the luminal epithelium, glandular epithelium, and stromal cells. Staining was also observed in inflammatory cells localized in the stroma as well as inside of the glands. The percentage of COX2 positive stromal cells in bitches with AE, SE, and CE was significantly higher compared with NE (p < 0.005). In addition, the percentage of COX2 positive stromal cells in bitches with SE, and CE was significantly lower compared with AE (p < 0.003). Conclusion: COX2 could be involved in the pathophysiological mechanisms producing endometritis without the presence of cystic endometrial hyperplasia in bitches. However, further researches on this topic are required.

Evaluation of Cystic Endometrial Hyperplasia and the Normal Estrous Cycle in Longitudinal Sections of Uterus from Female Harlan Sprague-Dawley Rats.

The National Toxicology Program (NTP) has recently introduced the practice of examining longitudinal histological sections of the female rodent uterus to improve the identification of non-neoplastic lesions, preneoplastic lesions, and uterine tumors. This practice has created a need for reference material that includes normal histology, spontaneous lesions, and inducible lesions in longitudinal as well as transverse sections of the body of the uterus, uterine horns, cervix and vagina. Using 3 archived NTP reproductive and developmental toxicity studies, the authors reviewed longitudinal and transverse sections of uteri from female Hsd:Sprague Dawley SD® (Hsd:SD) rats for cystic endometrial hyperplasia (CEH). The purposes of this review were to (1) evaluate if existing criteria for CEH in transverse uterine sections could be applied to longitudinal sections to develop diagnostic features of CEH in longitudinal uterine sections of rat uterus and (2) create an atlas of the normal estrous cycle phases in longitudinal sections of young and mature adult Hsd:SD rat uteri. The information provided in this original article should help facilitate the examination of longitudinal sections of the uterus in future commercial and governmental rodent studies.

Fertility outcome after medically treated pyometra in dogs.

Cystic endometrial hyperplasia-pyometra complex (CEH/P) is a challenge in canine reproduction. Present study aimed to assess fertility after medical treatment. One-hundred-seventy-four bitches affected by CEH/P received aglepristone on days 1, 2, 8, then every 7 days until blood progesterone < 1.2 ng/mL; cloprostenol was administered on days 3 to 5. Records were grouped according to bodyweight (BW): small (< 10 kg, n = 33), medium (10 ≥ BW < 25 kg, n = 44), large (25 ≥ BW < 40 kg, n = 52), and giant bitches (BW ≥ 40 kg, n = 45). Age; success rate; aglepristone treatments number; relapse, pregnancy rates; diagnosis-relapse, -first, -last litter intervals; litters number after treatment, and LS were analyzed by ANOVA. Overall age was 5.14 ± 1.75 years, without difference among groups. Treatment was 100% successful, without difference in treatments number (4.75 ± 1.18), relapse (15/174, 8.62%) and pregnancy (129/140 litters, 92.14%) rates, intervals diagnosis-relapse (409.63 ± 254.9 days) or -last litter (418.62 ± 129.03 days). The interval diagnosis-first litter was significantly shorter (163.52 ± 51.47 days) and longer (225.17 ± 90.97 days) in small and giant bitches, respectively. Overall, 1.47 ± 0.65 litters were born after treatment. Expected LS was achieved in each group, as shown by ΔLS (actual-expected LS by breed, overall -0.40 ± 1.62) without differences among groups. Concluding, CEH/P affects younger dogs than previously described. Relapses were rarer than previously reported. Medical treatment with aglepristone+cloprostenol is effective and safe, preserving subsequent fertility, as demonstrated by negligible changes in LS.

Is there any difference between endometrial hyperplasia and endometrial carcinoma in terms of expression of TRPM2 and TRPM7 ion channels?

Background/aim: This study compared TRPM2 and TRPM7 ion channel gene expression and immunohistochemical staining in endometrial hyperplasia and endometrium adenocarcinoma. Materials and methods: Sections were taken from paraffin blocks of 120 patients who were divided into 6 groups as follows: G1 (n = 20), proliferative endometrium (PE); G2 (n = 20), EH without atypia; G3 (n = 20), EH with atypia; G4 (n = 20), stage 1A, grade 1 EC; G5 (n = 20), stage 1A, grade 2 EC; and G6 (n = 20), stage 1A, grade 3 EC. TRPM2 and TRPM7 genes were analyzed with qRT-PCR in paraffin-embedded tissue samples. Under light microscopy, TRPM2 and TRPM7 immunostaining scores of the samples taken from polylysine slides were evaluated. Results: Compared to G1, TRPM2 mRNA gene expression was significantly downregulated in G3 and G5. TRPM2 immunoreactivity scores were similar in all groups. TRPM7 mRNA gene expression was significantly downregulated in G2, G3, and G6 when compared to G1. TRPM7 immunoreactivity scores were similar in G1, G2, and G3, but significantly decreased in G4, G5, and G6 Conclusion: Reduction in TRPM7 ion channel activity may be a progression marker for endometrial hyperplasia regardless of the atypical criteria.

Neural precursor cell-expressed developmentally down-regulated 4-like: a new biomarker in the pathophysiology of endometrial cancer.

Objectives Endometrial cancer is the most frequent tumor of the female genital tract. Ubiquitin is a small protein (8.5 kDa) found in all eukaryotic cells, binds to substrate proteins via a three-phase enzymatic pathway referred to as ubiquitination and plays an important role in cellular stability. Neural precursor cell-expressed developmentally down-regulated 4-like (NEDD4L) functions in the last phase of this enzymatic process. In this study, we investigated NEDD4L protein expression in endometrial cancer. Methods The study participants were divided into patients with benign endometrial pathologies (Group 1, n = 23), patients with endometrial hyperplasia (Group 2, n = 21) and patients with endometrial cancer (Group 3, n = 20). NEDD4L expression was detected by immunohistochemical staining and H scores were calculated to standardize staining intensity. Statistical analysis was performed using SPSS 16.0. Results NEDD4L expression levels according to H scores were significantly lower in patients diagnosed with endometrial cancer compared with those with benign endometrial pathologies. Conclusion NEDD4L is involved in maintaining cell stability, and reduced NEDD4L expression as a result of gene mutation may disrupt this balance in favor of tumorigenesis.

Insulin resistance and overweight prolonged fertility-sparing treatment duration in endometrial atypical hyperplasia patients.

OBJECTIVE: Our previous study showed that insulin resistance (IR) was related to endometrial hyperplasia as well as endometrial cancer. But the exact impact of IR on fertility-sparing treatment in endometrial hyperplasic disease is unclear. This study investigated how IR affects fertility-sparing treatment in endometrial atypical hyperplasia (EAH) patients. METHODS: The 151 EAH patients received fertility-sparing treatment were retrospectively investigated. All patients received high-dose progestin combined with hysteroscopy. Therapeutic effects were evaluated by hysteroscopy every 3 months during the treatment. RESULTS: The median age was 33.0 years old (range, 21-54 years old). Sixty-one patients (40.4%) were insulin resistant. Three patients were excluded from the analysis because they chose hysterectomy within 3 months after initiation of progestin treatment. The 141 out of 148 (95.3%) patients achieved complete response (CR). No difference was found in cumulative CR rate between those with or without IR (90.2% vs. 95.6%, p=0.320). IR significantly affected therapeutic duration to achieve CR (8.1±0.5 months with IR vs. 6.1±0.4 months without IR, p=0.004). Overweight (body mass index [BMI]≥25 kg/m²) was associated with higher risk of treatment failure (odds ratio=5.61; 95% confidence interval=1.11-28.35; p=0.040) and longer therapeutic duration to achieve CR (7.6±0.5 months vs. 6.3±0.4 months, p=0.019). EAH patients with both IR and overweight (IR+BMI+) had the longest therapeutic time compared with other patients (8.8±0.6 months vs. 5.6±0.7, 6.3±0.4, and 6.4±0.8 months for IR-BMI+, IR-BMI-, and IR+BMI-, respectively, p=0.006). CONCLUSION: IR and overweight were associated with longer therapeutic duration in EAH patients receiving progestin-based fertility-sparing treatment.

Complex non atypical hyperplasia and the subsequent risk of carcinoma, atypia and hysterectomy during the following 9-14 years.

INTRODUCTION: The aim of this study was to evaluate the long-term risk of developing atypical hyperplasia/endometrial cancer or having a hysterectomy after being diagnosed with complex non-atypical hyperplasia (CH). MATERIAL AND METHOD: A historic cohort study of 114 women diagnosed with CH between January 1st 2000 and December 31st 2005. All patient records and pathologic reports were reviewed with complete follow up on all patients in the national pathologic database until September 1st 2014. Kaplan-Meier analysis was used to determine (1) no hysterectomy and (2) no diagnosis of endometrial cancer or atypia after the CH diagnosis. RESULTS: 15% (n = 17) were diagnosed with endometrial cancer and 7% (n = 8) with atypia, most during the first year (10 cancer, 7 atypia). 9% (8/85) of the remaining women at risk developed cancer or atypia in the follow-up period after one year. By Kaplan-Meier the five-year risk for cancer or atypia was 20% (CI; 14-21). The risk of having undergone hysterectomy within five years was 30% (CI; 22-39). CONCLUSION: The long-term risk of being diagnosed with atypia or cancer after a CH diagnose is not insignificant, when disregarding patients having undergone hysterectomy. More than half the women with atypia or cancer are diagnosed or operated during the first year. This could indicate the presence of concomitant but unidentified cancer or atypia at the time of initial sampling. This study reinforces the importance of follow up or treatment of women with CH - especially, but not only during the first year. KEY MESSAGE: The risk of having a hysterectomy or diagnosed with atypical hyperplasia/cancer endometrie is high after a diagnosis of complex hyperplasia without atypia.

The regulation of Hh/Gli1 signaling cascade involves Gsk3ß- mediated mechanism in estrogen-derived endometrial hyperplasia.

The present study was undertaken to explore the functional involvement of Hh signaling and its regulatory mechanism in endometrial hyperplasia. Differential expression of Hh signaling molecules i.e., Ihh, Shh, Gli1 or Gsk3ß was observed in endometrial hyperplasial (EH) cells as compared to normal endometrial cells. Estradiol induced the expression of Hh signaling molecules and attenuated the expression of Gsk3ß whereas anti-estrogen (K1) or progestin (MPA) suppressed these effects in EH cells. Cyclopamine treatment or Gli1 siRNA knockdown suppressed the growth of EH cells and reduced the expression of proliferative markers. Estradiol also induced the nuclear translocation of Gli1 which was suppressed by both MPA and K1 in EH cells. While exploring non-canonical mechanism, LY-294002 (Gsk3ß activator) caused a decrease in Gli1 expression indicating the involvement of Gsk3ß in Gli1 regulation. Further, Gsk3ß silencing promoted the expression and nuclear translocation of Gli1 demonstrating that Gsk3ß serves as a negative kinase regulator of Gli1 in EH cells. Similar attenuation of Hh signaling molecules was observed in rats with uterine hyperplasia undergoing anti-estrogen treatment. The study suggested that Hh/Gli1 cascade (canonical pathway) as well as Gsk3ß-Gli1 crosstalk (non-canonical pathway) play crucial role in estrogen-dependent cell proliferation in endometrial hyperplasia.

Polycystic ovary syndrome and endometrial hyperplasia: an overview of the role of bariatric surgery in female fertility.

One of the most effective methods to tackle obesity and its related comorbidities is bariatric surgery. Polycystic ovary syndrome (PCOS) and endometrial hyperplasia (EH), which are associated with increased risk of endometrial carcinoma, have been identified as potentially new indications for bariatric surgery. PCOS is the most common endocrine disorder in women in the reproductive age and is associated with several components of the metabolic syndrome such as obesity, insulin resistance and hypertension. EH is a pre-cancerous condition which arises in the presence of chronic exposure to estrogen unopposed by progesterone such as both in PCOS and obesity. The main bariatric procedures are Roux-en-Y gastric bypass, laparoscopic sleeve gastrectomy and laparoscopic adjustable gastric banding. These procedures are well established and when correctly selected and performed by experienced bariatric surgeons, they can achieve significant weight loss and remission of obesity related co-morbidities. Studies have shown that bariatric surgery can play an important role in the management of patients with PCOS and improve fertility. Similarly, bariatric surgery has a positive effect on endometrial hyperplasia, making surgically induced weight loss a potentially attractive option for endometrial cancer prevention and treatment. Obesity has an adverse impact on spontaneous pregnancy, assisted reproduction methods and feto-maternal outcomes. After bariatric surgery obese women with subfertility can achieve spontaneous pregnancy. However, while bariatric surgery reduces the risk of pre-eclampsia and gestational diabetes, there is an increased risk of small for gestational age and possible increased risk of stillborn or neonatal death. In this article we will review the evidence regarding the use of bariatric surgery as a treatment modality in patients with PCOS and EH. We also provide an overview of the common bariatric procedures.

Efficacy of the Levonorgestrel-Releasing Intrauterine System on IVF-ET Outcomes in PCOS With Simple Endometrial Hyperplasia.

OBJECTIVE: This study investigated the in vitro fertilization (IVF) outcome of levonorgestrel-releasing intrauterine system (LNG-IUS) pretreatment for simple endometrial hyperplasia (EH) in patients with polycystic ovary syndrome (PCOS) undergoing IVF embryo transfer (IVF-ET). METHODS: One hundred ninety patients with PCOS and simple EH without cytologic atypia were allocated randomly to 2 independent arms, that is, the LNG-IUS group (90 patients) and the non-LNG-IUS group (100 patients). Four hundred fourteen patients with PCOS without endometrial disease comprised the control group. Each patient was reevaluated by transvaginal ultrasonography (TVS) and endometrial biopsy after 6 months. For each patient, IVF outcome measures, such as number of recombinant follicle-stimulating hormone, endometrial thickness on human chorionic gonadotropin (HCG) day, hormone levels (progesterone, luetinizing hormone, and serum estradiol) on HCG day, number of oocytes, fertilization rate, clinical pregnancy rate, and miscarriage rate were compared among the 3 groups. RESULTS: In general, the 3 groups did not differ with respect to the main clinical and biochemical data. After 6 months, patients in LNG-IUS group had an EH resolution rate of 87.77%. In the non-LNG-IUS group, the resolution rate was 15.00%, and 3% of these patients showed progression of EH. The clinical pregnancy rates in the non-LNG-IUS group were significantly lower (28.04%) than that in the LNG-IUS group (46.06%) and the control group (44.65%). The miscarriage rate was highest in the non-LNG-IUS group, but no significant difference in miscarriage rate existed among the 3 groups. CONCLUSION: The study illustrates that the LNG-IUS can be safely used for 6 months as a treatment for patients with PCOS and simple EH. Additionally, use of the LNG-IUS can increase the clinical pregnancy rates and implantation rates of patients with PCOS and simple EH who undergo gonadotropin-releasing hormone agonist IVF-ET protocols.

Uterine fluid from bitches with mating-induced endometritis reduces the attachment of spermatozoa to the uterine epithelium.

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.

Evaluación morfológica endometrial histeroscópica / Hysteroscopic evaluation of endometrial morphology

Objetivo. Evaluar la prevalencia de hiperplasia endometrial y adenocarcinoma en varios grupos de endometrios definidos por histeroscopia por las características morfológicas. Material y métodos. Estudio prospectivo de 830 histeroscopias efectuadas entre el 1 de junio del 2004 y el 31 de diciembre del 2005 en la consulta externa de patología cervical e histeroscopia del Hospital Donostia de San Sebastián. El endometrio se clasifica como atrófico, hipotrófico, activo, hipertrófico, sospecha de adenocarcinoma y adenocarcinoma según una serie de características morfológicas definidas por histeroscopia y se correlacionan con el diagnóstico histológico de la biopsia de endometrio obtenida tras la histeroscopia. Resultados. La sensibilidad, la especificidad y el valor predictivo negativo (VPN) de la morfología endometrial histeroscópica en el diagnóstico de patología premaligna y maligna son muy altos: S 87,5% (IC del 95%, 0,753-0,941), E 94,8% (IC del 95% 0,925-0,965) y VPN 98,7% (IC del 95%, 0,971-0,994). El diagnóstico morfológico de adenocarcinoma tiene una altísima especificidad (E: 99,9%, S: 74,3%, LH(+) 625,486), juntando los grupos morfológicos de sospecha de adenocarcinoma y de adenocarcinoma la sensibilidad llega al 100% (S: 100% y E: 96,3%). Conclusiones. La prevalencia de enfermedad premaligna es muy baja en los grupos histeroscópicos con morfología de atrofia, hipotrofia y endometrio activo, ligeramente superior en el endometrio hipertrófico y significativamente mayor en los casos de diagnóstico morfológico histeroscópico de sospecha de adenocarcinoma y de adenocarcinoma, donde también encontramos una prevalencia muy alta de adenocarcinoma. El diagnóstico morfológico histeroscópico exclusivamente, sin toma de biopsia, es una herramienta válida para excluir y confirmar patología endometrial(AU)

Objective. To determine the prevalence of endometrial hyperplasia and adenocarcinoma in distinct groups of endometrial morphology defined by hysteroscopy, and to study the validity of hysteroscopic diagnosis in identifying endometrial tumors. Materials and methods. We performed a prospective study of 830 hysteroscopies carried out between June 1, 2004 and December 31, 2005 in the Gynecology Outpatient Clinic of Hospital Donostia in San Sebastian, northern Spain. Hysteroscopy was used to classify endometria into atrophic, hypotrophic, active, hypertrophic, suspicious for adenocarcinoma and adenocarcinoma, according to a series of morphological criteria. The findings were later correlated with the histopathological diagnoses obtained through endometrial biopsy. Results. The sensitivity, specificity and negative predictive value (NPV) of hysteroscopic evaluation of endometrial morphology in diagnosing malignant and premalignant disease were extremely high. Sensitivity was 87.5% (95% CI 0.753-0.941), specificity was 94.8% (95% CI 0.925-0.965) and NPV was 98.7% (95% CI 0.971-0.994). The specificity of morphological diagnosis of adenocarcinoma was 99.9%, sensitivity was 74.3%, and the likelihood ratio for a positive result was 625,486. When the groups of adenocarcinoma and suspicious for adenocarcinoma were combined, sensitivity was 100% and specificity was 96.3%. Conclusions. The prevalence of premalignant disease is very low in the hysteroscopic morphological groups of atrophic, hypotrophic and active endometria. Premalignant disease is slightly more prevalent in hypertrophic endometria and is significantly more prevalent in cases in which the hysteroscopic diagnosis is of suspicious adenocarcinoma and adenocarcinoma. In these cases, the prevalence of adenocarcinoma is very high. Hysteroscopic evaluation of endometrial morphology alone, without biopsy, is a valid tool to exclude or confirm endometrial disease in some groups(AU)

Efficacy of the levonorgestrel intrauterine system (LNG-IUS) in the prevention of the atypical endometrial hyperplasia and endometrial cancer: retrospective data from selected obese menopausal symptomatic women.

The aim of this retrospective study was to evaluate the efficacy of levonorgestrel intrauterine system-releasing (LNG-IUS) insertion in preventing atypical endometrial hyperplasia (AH) and endometrial cancer (EC) in symptomatic postmenopausal overweight/obese women. A total of 34 overweight/obese postmenopausal women, presenting abnormal uterine bleeding (AUB) and endometrial hyperplasia (EH), and who were submitted to LNG-IUS insertion, were identified from registry data. Endometrial histology at LNG-IUS insertion showed simple EH in 20 cases (58.8%), complex EH in 14 cases (41.2%). At 36 months, 91% of patients showed no recurrence of AUB and a significant reduction in the mean endometrial thickness (from 8.2 ± 2.2 to 3.2 ± 1.5 mm, p < 0.05) was observed. Histologic regression of EH was observed in 27 (79.4%) and 33 (97.5%) cases at 12 and 36 months, respectively. None of the women in which EH persisted, reported cellular atypia or cancer progression at 12 and 36 months of follow-up. LNG-IUS represents an effective treatment option to manage postmenopausal obese women affected by AUB and EH. The device seems to be able to prevent the onset of AH and EC in women at high risk. Further prospective controlled studies in a well selected group of women are needed.

Bariatric surgery and endometrial pathology in asymptomatic morbidly obese women: a prospective, pilot study.

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.

Fertility-sparing treatment of endometrial cancer precursors among young women: a reproductive point of view.

BACKGROUND: Early-stage endometrial cancer and complex atypical hyperplasia are treated with hysterectomy and bilateral salpingo-oophorectomy. An emerging issue among younger women affected is the possibility of a fertility-sparing treatment with progestative therapy and close follow-up. AIM: To assess the possibility of conceiving after a diagnosis of atypical endometrial hyperplasia among women younger than 40 years old, in term of delaying definitive treatment and achieving pregnancy. MATERIALS AND METHODS: 15 women younger than 40 years old with complex CAH or early carcinoma of the endometrium and a wish to preserve fertility. Progestins were administered orally for at least a 12 weeks period. Endometrial biopsies were used at follow-up. RESULTS: In 11 women, a complete pathological remission of the disease was observed. 4 pregnancies were attained in 4 women. 3 showed progression and underwent definitive surgery at 18 months. 1 showed no response at 24 months and 3 cycles and was counseled to receive a hysterectomy. CONCLUSIONS: A conservative approach in patients younger than 40 years appears a valid option, and a progestative therapy trial should be attempted whether a valid consensus is attained. Considering the risk to find AEH at biopsies and eventually a carcinoma at hysterectomy (25% of cases) a careful management is strictly required.

The role of hypertension, body mass index, and serum leptin levels in patients with endometrial hyperplasia during premenopausal period.

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.

Delayed uterine fluid clearance and reduced uterine perfusion in bitches with endometrial hyperplasia and clinical management with postmating antibiotic.

In many species a transient uterine inflammatory response follows mating and is proposed to remove excess spermatozoa, bacteria, and other contaminants from the uterus. Similar events have been documented in the bitch involving increased uterine contractions, polymorphonuclear neutrophil influx and uterine artery vasodilation. Some healthy bitches with endometrial hyperplasia have increased numbers of uterine luminal polymorphonuclear neutrophils after mating and reduced fertility; it is purported that this represents a presumed postmating endometritis. This study used B-mode and Doppler ultrasonography at the time of mating to measure uterine contractions, clearance of ejaculated fluid, and uterine artery velocity in normal bitches and those with endometrial hyperplasia. Mating resulted in an increase in the number of uterine contractions, although fewer mating-induced contractions were noted in bitches with endometrial hyperplasia. Interestingly, uterine fluid cleared significantly more slowly after mating from the bitches with endometrial hyperplasia than the normal bitches (P = 0.01). In a further study, Doppler ultrasonography showed that in normal bitches there was a significant increase in uterine artery blood velocity (P = 0.04) and a decrease in the resistance index after mating (P = 0.04), indicating vasodilation. In bitches with endometrial hyperplasia the baseline resistance index was significantly higher than normal bitches (P = 0.05), and furthermore, although there was a significant decrease in resistance index after mating, in the bitches with endometrial hyperplasia this was of a smaller magnitude that in normal bitches. These findings indicate lower baseline uterine perfusion, and a blunted vasodilation response to mating in bitches with endometrial hyperplasia. Short-duration postmating administration of systemic antibiotic increased pregnancy rates in bitches with endometrial hyperplasia (P < 0.01). Litter sizes in bitches with endometrial hyperplasia were lower than those of normal bitches both before and after treatment with postmating antibiotic (P = 0.04 and < 0.01, respectively). Mating-induced endometritis in bitches with endometrial hyperplasia appears to affect fertility by reducing the uterine vasodilatory response to mating and delaying clearance of uterine fluid as a result of decreased uterine contractions but the effect can be ameliorated in part by the postmating administration of antibiotic.

Perturbed sperm-epithelial interaction in bitches with mating-induced endometritis.

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.