Risk Of Endometrial Hyperplasia Research Articles

Endometrial Thickness as a Predictor of Endometrial Hyperplasia in Infertile Patients with Polycystic Ovary Syndrome

Background: Women with polycystic ovary syndrome (PCOS) are at higher risk of developing endometrial hyperplasia (EH). This study determined the prevalence of EH among women with infertility due to PCOS and assessed the predictive value of endometrial thickness (ET) measurement by trans-vaginal scan (TVS). Study Type & Population: This was a prospective study on infertile women with and without PCOS in which clinical data, hormonal profile, ET and endometrial biopsy (EB) for histopathological examination were collected. Methods: Thirty-seven women with PCOS and 23 women without PCOS presenting with infertility and/or abnormal uterine bleeding underwent TVS, hysteroscopy, laparoscopy and EB. Results: The overall prevalence of EH was 23.3 % while in PCOS group: 18.3 %. The mean ET (14.8 mm) was significantly higher in patients with EH (t = -2.74, P value = 0.009). The lower value of ET among women with EH was 10 mm. A cut-off point of 9.5 mm was set. An ET of >9.5 mm had 92.9% sensitivity and 51.85% specificity for the presence of EH. Women with ET ≥ 9.5 mm were 1.28 times more at risk of EH than women with ET 9.5 mm. Women with oligomenorrhea and irregular cycles were 5.5 and 13.7 times more at risk of EH compared to those with regular cycles, respectively. ET was positively correlated with insulin resistance (r = 0.439, P = 0.007). Conclusion: ET ≥ 9.5 mm predicts EH in infertile women with PCOS, with a high degree of sensitivity and a moderate degree of specificity. In PCOS patients with oligomenorrhea or irregular cycles, the risk of EH is higher than women with regular cycles.

Evaluation of <i>Epimedium brevicornum</i> Maxim extract for anti-osteoporosis activity in rats

Purpose: To evaluate the therapeutic effect of Epimedium brevicornum Maxim. extract (EBME) on ovariectomy-induced osteoporosis in rats. Methods: The rats were divided into six experimental groups, viz, control (group 1) and five ovariectomy-induced (OVX) groups. The OVX groups include OVX-inducing agent only group (group 2), OVX with 17s-estradiol (E 2 , 25 μg/kg/day, group 3), OVX with 60 mg EBME/kg body weight/day (group 4), OVX with 120 mg EBME/kg body weight/day (group 5) and OVX with 240 mg EBME/kg body weight/day (group 6). The treatment started for the OVX groups with a single weekly dose of OVX inducing agent for 4 weeks, followed by oral daily dose of E 2 (group 3) or EBME (groups 4, 5 and 6) for another 16 weeks. Bone mineral density (BMD) of the 4th lumber vertebrae (4LV) and right femur of each rat was estimated. BMD determination was preceded by the measurement of the length of the femur and identification of diaphysis (center). Trabecular microarchitecture was assessed via three representative 4LV. The other parameters measured in this study were serum alkaline phosphatase (ALP), urinary calcium (U-Ca), urinary phosphorus (U-P), urinary creatinine (U-SCr) and osteocalcin (OC) levels. Result: The results showed that the BMD decrease induced by OVX in 4LV and femur was significantly mitigated by high dose of EBME. EBME also protected the trabecular microarchitecture against OVXassociated deterioration, evidenced by decreased bone turnover marker levels in 4LV at high EBME dose. Trabecular number (Tb-N, 3.7 ± 0.2), trabecular thickness (Tb-Th, 0.082 ± 0.011), and trabecular spacing (Tb-Sp, 0.17 ± 0.01) of the highest dose EBME-treated OVX rats ’4LV were significantly ( p < 0.05) different from the corresponding values of EBME-free OVX rats. Conclusion: The results reveal that administration of high doses of EBME lasting for 16 weeks not only protected against OVX-induced osteoporosis in rats but was also without the risk of endometrial hyperplasia. Thus, the extract may be a better alternative to other agents in current use for the treatment of postmenopausal osteoporosis in elderly women. However, its efficacy and safety require further investigations. Keywords: Epimedium brevicornum Maxim., Postmenopausal osteoporosis, Ovariectomy, Bone mineral density

Advances in the Diagnosis and Treatment of PCOS.

While the Rotterdam criteria look simple and easy to follow, in clinical practice diagnosis of PCOS may be problematic because of the use of inaccurate commercial androgen assays. Progresses in ovarian ultrasound and in AMH measurement have modified the way to make the diagnosis of PCOS and an update of Rotterdam criteria may be necessary. In classic severe form of PCOS, ovarian follicle count is a very reliable diagnostic criterion but AMH measurement may also present high diagnostic specificity and sensitivity. This finding is particularly important when no clinical signs of androgen excess are present and only commercial assays for androgen measurement are available. At the contrary, in mild PCOS phenotypes, sensitivity of AMH measurement is too low whileFNPO count maintains a high diagnostic sensitivity. However, at least in ovulatory hyperandrogenic PCOS phenotype, increased AMH values in association with enlarged ovarian size permit the diagnosis of ovulatory PCOS in 85% of these patients. Treatment of PCOS women has to be directed to get fertility or in patients not seeking fertility to solve or attenuate the psychological implications of androgen excess and of irregular menses and the risk of endometrial hyperplasia. The therapeutic protocols that are used in our department are presented.

Body mass index trumps age in decision for endometrial biopsy: cohort study of symptomatic premenopausal women

Clinical guidelines recommend that women with abnormal uterine bleeding with risk factors have an endometrial biopsy toexclude hyperplasia or cancer. Given the majority of endometrial cancer occurs in postmenopausal women, it has not been widely recognized thatobesity is a significant risk factor for endometrial hyperplasia and cancer in young, symptomatic, premenopausal women. We sought to evaluate the effect of body mass index on risk of endometrial hyperplasia or cancer in premenopausal women with abnormal uterine bleeding. This was a retrospective cohort study in a single largeurban secondary women's health service. Participants were 916 premenopausal women referred for abnormal uterine bleeding of any cause and had an endometrial biopsy from 2008 through 2014. The primary outcome was complex endometrial hyperplasia (with or without atypia) or endometrial cancer. Almost 5% of participants had complex endometrial hyperplasia or cancer. After adjusting for clinical and demographic factors, women with a measured body mass index ≥30 kg/m2 were 4 times more likely to develop complex hyperplasia or cancer (95% confidence interval, 1.36-11.74). Other risk factors were nulliparity (adjusted odds ratio, 3.08; 95% confidence interval, 1.43-6.64) and anemia (adjusted odds ratio, 2.23; 95% confidence interval, 1.14-4.35). Age, diabetes, and menstrual history were not significant. Obesity is an important risk factor for complex endometrial hyperplasia or cancer in premenopausal women with abnormal uterine bleeding who had an endometrial biopsy in a secondary gynecology service. As over half of women with the outcome in this study were age <45 years, deciding to biopsy primarily based on age, as currently recommended in national guidelines, potentially misses many cases or delays diagnosis. Body mass index should be the first stratification in the decision to perform endometrial biopsy and/or to refer secondary gynecology services.

Risk Factors (Excluding Hormone Replacement Therapy) for Endometrial Hyperplasia: a Systematic Review

Objective: To conduct a systematic review of risk factors associated with the development of Endometrial Hyperplasia (EH). Data sources: Ovid MEDLINE, EMBASE and Web of Science databases were searched from inception to 30 June 2015. Study eligibility: Fifteen observational studies that reported on EH risk in relation to lifestyle factors (n=14), medical history (n=11), reproductive and menstrual history (n=9) and measures of socio-economic status (n=2) were identified. Pooled relative risk estimates and corresponding 95% confidence intervals (CI) were able to be derived for EH and Body Mass Index (BMI), smoking, diabetes and hypertension, using random effects models comparing high versus low categories. Results: The pooled relative risk for EH when comparing women with the highest versus lowest BMI was 1.82 (95% CI 1.22–2.71; n=7 studies, I2=90.4%). No significant associations were observed for EH risk for smokers compared with non-smokers (RR 0.88, 95% CI 0.66-1.17; n=3, I2=0.0%), hypertensive versus normotensive women (RR 1.51, 95% CI 0.72–3.15; n=5 studies, I2=79.1%), or diabetic versus non-diabetic women (RR 1.77, 95% CI 0.79–3.96; n=5 studies, I2=31.8%) respectively although the number of included studies was limited. There were mixed reports on the relationship between age and risk of EH. Too few studies reported on other factors to reach any conclusions in relation to EH risk. Conclusions: A high BMI was associated with an increased risk of EH, providing additional rationale for women to maintain a normal body weight. No significant associations were detected for other factors and EH risk, however relatively few studies have been conducted and few of the available studies adequately adjusted for relevant confounders. Therefore, further aetiological studies of endometrial hyperplasia are warranted.

Topical Vaginal Estrogen Use and Risk of Endometrial Hyperplasia or Cancer [24

Topical Vaginal Estrogen Use and Risk of Endometrial Hyperplasia or Cancer [24

Эффективность использования низких доз дроспиренона и 17b-эстрадиола у женщин в постменопаузе (обзор литературы)

Vasomotor symptoms, including hot flushes (HF), are the most common symptoms of menopause, requiring treatment with estrogen and/or progestogen. Recent international guidelines recognize the need to use the lowest effective dose of hormone replacement therapy. Drospirenone (DR) in combination with 17-estradiol (E) is used as hormone therapy (HT) for relief the symptoms and prevention of postmenopausal osteoporosis.The aim of this review is a meta-analysis of studies examining the efficacy and safety of low-dose DR and E for the treatment of vasomotor symptoms inpostmenopausal women.The review presents data of 2 large randomized controlled studies that evaluated the lowest effective dose combination DR/E, the safety of this dose for endometrium, identified features of its pharmacodynamics and pharmacokinetics, depending on various factors.In the first, a study of the lowest effective doses of DR/E for the treatment of HF in postmenopausal women was made. It led to the conclusion that the com-bination of DR 0,25 mg/E of 0,5 mg is the minimum effective dose. Efficacy of low doses of DR/E correlated with exposure DR and E in serum, while smoking had a negative impact on the Efficacy of treatment.Another study assessed the risk of endometrial hyperplasia and bleeding pattern in patients receiving 0,25 mg DR/E of 0,5 mg for 12 months. At the end of the study no evaluable women in the DR/E2 group had an endometrial biopsy result of hyperplasia or worse, which endometrial confirmed the safety of receiving DR 0,25 mg/E of 0,5 mg.Thus, the minimum effective dose for the relief of HF without causing any significant impact on the endometrium is DR of 0,25 mg/E of 0,5 mg. According to the results of the pharmacokinetic study a correlation between effectiveness of low dose DR/E with DR and E exposure levels was showed, and smoking reduces the effectiveness of hormonal therapy. This drug not only copes with moderate to severe hot flashes, but also reduces the incidence of symptoms of vulvovaginal atrophy, improving quality of life.

Supervised clustering of immunohistochemical markers to distinguish atypical and non-atypical endometrial hyperplasia

The risk of endometrial hyperplasia (EH) progressing into endometrioid endometrial cancer ranges from 1% for simple EH without atypia (EHWA) to 46.2% for atypical EH (AEH). Differentiation between both entities is crucial to determine optimal management. As preoperative diagnosis of AEH can be difficult, we aimed to establish clusters of immunohistochemical markers to distinguish EHWA from AEH. We studied 13 immunohistochemical markers (steroid receptors, pro/anti-apoptotic proteins, metalloproteinases (MMP), tissue inhibitor of metalloproteinase (TIMP), CD44 isoforms) known for their role in endometrial pathology. Using supervised clustering, we determined clusters of co-expressed proteins which contributed the most in differentiating EHWA from AEH. From 39 tissue samples (17 EHWA and 22 AEH), we found three clusters of co-expressed proteins: Cluster 1 included two proteins (over-expression of estrogen receptor (ER) and under-expression of progesterone receptor (PR) B in AEH compared to EHWA); Cluster 2: an ER, PR A, MMP-2 and TIMP-1 over-expression and a PR B and TIMP-2 under-expression; Cluster 3: over-expression of ER and MMP-7 and under-expression of PR B and TIMP-2. AEH can be accurately distinguished from EHWA using a supervised clustering of immunohistochemical markers. This promising approach could be useful to improve the preoperative diagnosis of EH.

Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a commonly encountered endocrine disorder that is characterized by a combination of hyperandrogenism, menstrual disturbances (predominantly oligomenorrhea), and a classic sonographic polycystic ovarian morphology. Additional sequelae associated with PCOS include infertility and enhanced risk of developing type 2 diabetes mellitus and cardiovascular disease. The prevalence of depressive disorders and obstructive sleep apnea is disproportionately higher in women with PCOS, and this population is at increased risk for endometrial hyperplasia and endometrial cancer. This chapter reviews the definition, epidemiology, etiology and genetics, pathophysiology, diagnosis (including history, physical examination, and laboratory tests), differential diagnosis, and management of PCOS. Syndromes and diseases associated with PCOS are discussed. Tables describe the three approaches to PCOS, conditions mimicking PCOS, diagnosis of the metabolic syndrome in women using the National Cholesterol Education Program criteria, workup for PCOS, comprehensive care for PCOS patients, and the multistep approach to treatment of PCOS-related anovulatory infertility. Figures include transvaginal ultrasound images of a normal ovary and a multifollicular ovary in a woman with PCOS, the Ferriman-Gallwey scoring system for quantifying hirsutism, acanthosis nigrans on the neck of a woman with PCOS and insulin resistance, the relationship between body mass index and basal luteinizing hormone levels, oral glucose challenge results in nonobese women with PCOS, and an algorithm for treatment decision making. This review contains 6 highly rendered figures, 6 tables, and 120 references.

Перспективы использования мио-инозитола в предгравидарной подготовке женщин с поликистозом яичников и инсулинорезистентностью

Polycystic Ovarian Syndrome (PCOS) is the main infertility cause due to metabolic and hormonal dysfunctions of the ovaries. This syndrome is comorbid with insulin resistance and substantially increases the risk of endometrial hyperplasia, obesity, breast cancer, myocardial infarction and stroke. Women with PCOS have an increased risk of anovulatory cycles, infertility and miscarriage.One of the promising nutricial directions in the complex treatment of PCOS is the use of myo-inositol. A systematic analysis presented in this paper, showed that oral administration of myo-inositol at a dose of 2-4 g/day helps to reduce insulin resistance, excessive androgen secretion, the risk of hirsutism and acne, normalization of lipid profile and blood pressure. Its reception improves functioning of the reproductive axis in patients with PCOS, normalizes ovulation and formation of mature oocytes. Inclusion of myo-inositol in the process of preparing for the procedure of in vitro fertilization (IVF) can significantly improve the results in patients with PCOS and other disorders associated with infertility.

Continuous use of oral contraceptives: an overview of effects and side‐effects

To describe the effects and side-effects of the continuous use of oral contraceptives. A review of articles concerning oral contraceptives taken continuously or in cycles with hormones taken for more than 21 days per cycle. We searched publications in PubMed and Embase. Randomized controlled trials were selected if possible, otherwise case-control studies or cohort studies with controls were chosen. A level of evidence as described by the Centre for Evidence Based Medicine (Oxford University, Oxford, UK) was assigned to all selected studies. Clinical and paraclinical effects and side-effects of oral contraceptives administered continuously. The studies suggest that the endometrium is inactive during continuous use of oral contraceptives and the risk of endometrial hyperplasia is not increased. Numbers of bleeding days are halved with continuous use; however, spotting and irregular bleeding are more often seen in the beginning of use, decreasing with time. Hemostatic parameters and serum lipid and carbohydrate profiles in continuous and conventional users do not differ. Menstrual cycle-related symptoms are relieved better by continuous treatment. After surgery for endometriosis, the effect of continuously used oral contraceptives on the risk of recurrence of pain has been found to be less than that of gonadotropin-releasing hormone (GnRH) analogues, but better than the rate seen during conventional cyclic use. Oral contraceptives taken continuously or in long cycles seem to offer benefits with regard to menstrual symptoms and the recurrence of symptoms related to endometriosis. Long-term studies, comprising large groups of women, are lacking.

Diagnosis and Management of Endometrial Hyperplasia

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.

Does Transvaginal Ultrasonography Have Good Diagnostic Value in Endometrial Pathology?

Introduction: Endometrial biopsy is usually considered unnecessary in post-menopausal uterine bleeding when the endometrial thickness (ET) is less than 5 mm because the risk of endometrial hyperplasia or cancer is low. However, there is still much controversy from this as some believe that the diagnostic value of ET in diagnosis of endometrial pathology (EP) in postmenopausal bleeding is necessary. In this study, the diagnostic value of ET for diagnosis of EP in post-menopausal bleeding was evaluated. Materials and methods: Sixty post-menopausal women with uterine bleeding were evaluated. Transvaginal ultrasonography (TVS) was used for measurement of ET followed by dilatation and curettage in a one-day interval. According to the EP, patients were divided in two groups, normal and abnormal. Endometrial atrophy was considered as normal and hyperplasia, polyps and carcinoma was considered as abnormal. Results: Twenty nine cases had ET more than 6 mm, among them, 25 cases had abnormal pathology (hyperplasia, polyp, cancer) and 4 cases were normal (atrophy). Thirty-one patients had ET equal or less than 6mm, among them, 26 cases were normal (atrophy) and 5 cases had abnormal pathology. The sensitivity, specifi ty, positive and negative predictive values of TVS in the diagnosis of uterine pathology were 83.3%, 86.7%, 86.2%, 83.9% respectively. Conclusion: We suggest that an ET of less than 6 mm in TVS is unlikely to indicate EP in post-menopausal women with uterine bleeding.

Aberrant Expression of the Von Hippel-Lindau Gene in Human Endometrial Hyperplasia and Endometrial Carcinoma

The purpose of this study was to determine whether aberrant expression of the von Hippel-Lindau (VHL) gene in human hyperplastic and malignant endometrial tissues was involved in endometrial carcinogenesis. Fresh tissue samples of endometrial hyperplasia consisting of simple (n = 26), complex (n = 23), and atypical hyperplasia (n = 20); endometrial carcinoma (n = 17); and normal endometrium (n = 40) were measured using Western blotting and real-time reverse transcription polymerase chain reaction. Paraffin-embedded sections of endometrial hyperplasia (n = 90), endometrial carcinoma (n = 30), and normal endometrium (n = 60) were detected by immunohistochemical method. Von Hippel-Lindau staining was present in the cytoplasm of epithelial cells and stroma. A decreased expression of VHL mRNA in endometrial hyperplasia from simple, complex, to atypical hyperplasia was observed. There were statistical differences on VHL messenger RNA (mRNA) levels among simple, complex, and atypical hyperplasia (P < 0.01). The VHL mRNA levels in endometrial carcinoma were significantly lower than those in normal endometrium, simple hyperplasia, or complex hyperplasia (P < 0.01) but similar to those in atypical hyperplasia (P > 0.05). Von Hippel-Lindau protein levels by Western blotting and staining intensity by immunohistochemistry were coincident with the VHL mRNA levels. Aberrant expression of the VHL gene is associated with the risk of endometrial hyperplasia progressing to endometrial carcinoma, and its expression levels are useful as a predictive indicator for endometrial carcinoma.

Lasofoxifene in Postmenopausal Women With Osteoporosis

Previous studies have demonstrated that lasofoxifene, a nonsteroidal selective estrogen-receptor modulator, decreases bone resorption, bone loss, and low-density lipoprotein cholesterol in postmenopausal women. Its effects of the risk of fractures, breast cancer, and cardiovascular disease are unclear. The postmenopausal evaluation and risk-reduction with lasofoxifene trial was an international, randomized, placebo-controlled trial that investigated the effects of lasofoxifene on the risk of fractures, estrogen receptor (ER)-positive breast cancer, and cardiovascular disease in a population of postmenopausal women with osteoporosis. The study subjects were a population of women between the ages of 59 and 80 years who had a bone mineral density T score of -2.5 or less at the femoral neck or spine. Participants were randomized to receive once-daily lasofoxifene at a dose of either 0.25 mg (low-dose, n = 2852) or 0.5 mg (high-dose, n = 2852) or placebo (n = 2852, control group) for 5 years. The trial was conducted at 113 sites in 32 countries. Vertebral and nonvertebral fractures and ER-positive breast cancer were the primary study end points. Major coronary heart disease events and stroke were the secondary endpoints. Compared with placebo, treatment with the high-dose lasofoxifene was associated with a reduction in the risk of vertebral fractures (13.1 cases vs. 22.4 cases per 1000 person-years; hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.47-0.70), nonvertebral fractures (18.7 vs. 24.5 cases per 1000 person-years; HR, 0.76; 95% CI, 0.64-0.91), ER-positive breast cancer (0.3 vs. 1.7 cases per 1000 person-years; HR, 0.19; 95% CI, 0.07-0.56), major coronary heart disease events (5.1 vs. 7.5 cases per 1000 person-years; HR, 0.68; 95% CI, 0.50―0.93), and stroke (2.5 vs. 3.9 cases per 1000 person-years; HR, 0.64; 95% CI, 0.41-0.99). At 5 years compared to the placebo group, postmenopausal women receiving low-dose lasofoxifene showed reduced rates of vertebral fractures (16.0 vs. 22.4 per 1000 person-years; HR, 0.69; 95% CI, 0.57-0.83) and stroke (2.4 vs. 3.9 cases per 1000 person-years; HR, 0.61; 95% CI, 0.39-0.96). Both drug doses were associated with increased risk of a venous thromboembolic event: Compared to the placebo which had 1.4 venous thromboembolic events per 1000 person-years, the low-dose group had 3.8 events per 1000 person-years (HR, 2.67; 95% CI, 1.55-4.58) and the high-dose group had 2.9 events per 1000 person-years (HR, 2.06; 95% CI, 1.17- 3.61). No increased risk of endometrial hyperplasia or endometrial cancer was observed at 5 years with either dose. Deaths per 1000 person-years were 7.0 and 5.7 for low dose and high dose, respectively, compared to 5.1 for the placebo (P = ns for both comparisons). These findings show that treatment of postmenopausal women with osteoporosis using a daily dose of lasofoxifene of 0.5 mg is associated with reduced risks of vertebral and nonvertebral fractures, ER-positive breast cancer, major coronary heart disease, and stroke, and an increased risk of thromboembolic events.

Abstract A13: Overexpression of adipokine receptors and dysregulation of AMPK signaling in normal and hyperplastic endometrium from obese women

Abstract Background: Excess adipose tissue in the obese woman produces inflammatory cytokines, called adipokines, that are thought to regulate proliferation in peripheral tissues such as the endometrium to promote the development of cancer. Epidemiological studies indicate that the adipokines IL-6, leptin, TNFα and adiponectin are dysregulated in the obese woman and in women with endometrial cancer (EC). Activation of the IGF-IR/PI3K/mTOR pathway is an important contributor to the development of endometrial complex atypical hyperplasia (CAH), the precursor to endometrioid-type endometrial cancer. Adipokines act through their receptors to activate pathways that exhibit signal transduction crosstalk with the IGF-IR/PI3K/mTOR pathway that is thought to either promote activation (IL-6, leptin) or inhibit this pathway (TNFα, adiponectin). The goal of these studies was to assess the corresponding adipokine receptors (IL-6Rα, IL6-Rβ, Ob-Rb, AdipoR1, AdipoR2, TNFαR1 and TNFαR2) expression and activation of AMPK and IGF-IR/PI3K/mTOR signaling pathways in normal endometrium from lean and obese women and in endometrial hyperplasia from obese women. Methods: We quantitated adipokine receptor transcript levels of the receptors by qRT-PCR in timed endometrial biopsies obtained from lean women (BMI &amp;lt; 25 kg/m2) and obese women (BMI &amp;gt; 30 kg/m2) that were histologically confirmed to have normal proliferative phase endometrium. These biopsies were compared to biopsies from obese women with endometrial CAH. We assessed functional activation of AMPK and mTOR pathways by immunohistochemistry. Results: There was a significant stepwise increase in the expression of AdipoR1, TNFαR1 and TNFαR2 in normal lean endometrium, normal obese endometrium and obese endometrial CAH. In addition, IL-6Rβ transcripts were significantly increased in obese endometrial CAH as compared to both lean and obese normal endometrium. Phosphorylation of AMPK was increased in obese normal endometrium compared to lean normal endometrium. Surprisingly, in endometrial CAH mTOR signaling was activated and activation of AMPK was lost compared to lean and obese normal endometrium. Conclusions: The stepwise increase in the expression of AdipoR1, TNFαR1 and TNFαR2 in the obese endometrium and endometrial CAH as compared to normal lean endometrium suggests that dysregulation of adipokine receptor expression is an early event and may be predictive of women at risk of developing endometrial CAH and EC. The overexpression of AdipoR1 in obese endometrium may contribute to activation of AMPK. The overexpression of AdipoR1 and activation of AMPK in obese endometrium may be a compensatory mechanism to dampen growth factor signaling through the IGF-IR/PI3K/mTOR pathway. In endometrial CAH there is upregulation of IL-6Rβ which may contribute to activation of mTOR by activating PI3K upstream. Activation of mTOR and loss of AMPK activation may contribute to the abnormal proliferation seen in endometrial CAH. These studies suggest that overexpression of adipokine receptor expression may be an important contributor to the risk of endometrial hyperplasia and cancer in obese women. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A13.

Heirarchical Clustering and Beyond in PCOS Endometrium: Brave New World

Heirarchical Clustering and Beyond in PCOS Endometrium: Brave New World

Endometrial Hyperplasia Risk in Relation to Recent Use of Oral Contraceptives and Hormone Therapy

We sought to examine the relationship between recent use of oral contraceptives and hormone therapy and endometrial hyperplasia (EH) risk. Cases comprised women diagnosed with complex EH (n = 289) or atypical EH (n = 173) between 1985 and 2003. One age-matched control was selected for each case; excluded were women with a prior hysterectomy or diagnosis of EH or endometrial cancer. Hormone use in the 6 months prior to the date of the case's first symptoms was ascertained using a pharmacy database and medical records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. Three (1.1%) cases had used oral contraceptives, compared to 16 (6.0%) controls (OR = 0.2, 95% CI: 0.0-0.6). Fifty-one (16.8%) cases had taken estrogen-only hormone therapy, in contrast to two (0.7%) controls (OR = 37.6, 95% CI: 8.8-160.0). The risk of EH among estrogen plus progestin hormone users did not differ from that of non-users (OR = 0.7, 95% CI: 0.4-1.1). This study suggests that previous findings of the association of estrogen-only hormone therapy with increased risk of EH and the lack of an association between estrogen plus progestin hormone therapy and EH risk are likely to apply to both complex EH and atypical EH. Further examination of the association between oral contraceptives and EH, with greater numbers of OC users, is warranted.

ENDOMETRIUM AND HORMONAL REPLACEMENT THERAPY

BACKGROUND Estrogen induces endometrial stimulation and increases the risk for endometrial hyperplasia and endometrial cancer. Added progestin diminishes endometrial stimulation.The risk for endometrial hyperplasia with hormonal replacement therapy (HRT) dependsof the type of formulation. Unopposed estrogen increases the risk of abnormal uterinebleeding, endometrial hyperplasia and carcinoma in a dose and time dependent manner.When progestin was added for 10 or more days, no endometrial hyperplasia has beenseen with sequential HRT. No increased risk for endometrial hyperplasia has been foundwith continuous combined regimens. During the first year of HRT irregular bleeding andspotting was more likely in continuous combined therapy than in sequential therapy.Howerever, during the second year of the therapy it was more likely under sequentialregimens. CONCLUSIONS Only women after hysterectomy can use unopposed estrogen

Risk of complex and atypical endometrial hyperplasia in relation to anthropometric measures and reproductive history.

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.