Reproductive Life Span and Severe Hypoglycemia Risk in Postmenopausal Women with Type 2 Diabetes Mellitus.

BACKGROUND: Estrogen promotes glucose homeostasis, enhances insulin sensitivity, and maintains counterregulatory responses in recurrent hypoglycemia in women of reproductive age. Postmenopausal women with type 2 diabetes mellitus (T2DM) might be more vulnerable to severe hypoglycemia (SH) events. However, the relationship between reproductive factors and SH occurrence in T2DM remains unelucidated. METHODS: This study included data on 181,263 women with postmenopausal T2DM who participated in a national health screening program from January 1 to December 31, 2009, obtained using the Korean National Health Insurance System database. Outcome data were obtained until December 31, 2018. Associations between reproductive factors and SH incidence were assessed using Cox proportional hazards models. RESULTS: During the mean follow-up of 7.9 years, 11,279 (6.22%) postmenopausal women with T2DM experienced SH episodes. A longer reproductive life span (RLS) (≥40 years) was associated with a lower SH risk compared to a shorter RLS (<30 years) (adjusted hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.69 to 0.80; P for trend <0.001) after multivariable adjustment. SH risk decreased with every 5-year increment of RLS (with <30 years as a reference [adjusted HR, 0.91; 95% CI, 0.86 to 0.95; P=0.0001 for 30-34 years], [adjusted HR, 0.80; 95% CI, 0.76 to 0.84; P<0.001 for 35-39 years], [adjusted HR, 0.74; 95% CI, 0.68 to 0.81; P<0.001 for ≥40 years]). The use of hormone replacement therapy (HRT) was associated with a lower SH risk than HRT nonuse. CONCLUSION: Extended exposure to endogenous ovarian hormone during lifetime may decrease the number of SH events in women with T2DM after menopause.

Association between Serum Uric Acid Levels and Bone Mineral Density in Postmenopausal Women: A Cross-Sectional and Longitudinal Study.

BACKGROUND: Uric acid is one of natural antioxidants in human body. There have been several studies on the correlation between uric acid with oxidative stress and osteoporosis. However, the data are insufficient and results are controversial. In this regard, we determined the association between uric acid levels and bone mineral density (BMD) during the postmenopausal period. METHODS: We analyzed data from 328 postmenopausal women (mean age, 57.3 ± 6.5 years; mean serum uric acid level, 4.6 ± 1.0 mg/dL). The participants were divided into three groups based on tertiles of the serum uric acid level. The participants receiving hormone replacement therapy (HRT), bisphosphonates, or lipid-lowering agents were included. RESULTS: Blood urea nitrogen, serum creatinine, and serum triglyceride levels were significantly higher in the upper tertiles of uric acid levels. No significant difference was found in the mean uric acid levels between medication users and non-users. Each HRT regimen had a different mean serum uric acid level. A cross-sectional analysis showed no significant correlation between the serum uric acid levels and BMD in the spine and femoral neck (spine BMD: 1.050 ± 0.131, 1.060 ± 0.160, 1.084 ± 0.140, p = 0.22; femoral neck BMD: 0.837 ± 0.110, 0.849 ± 0.096, 0.863 ± 0.115, p = 0.28 for each tertile of uric acid). Longitudinal analysis of data from 186 women with follow-up examinations at a mean interval of 14.6 months also revealed no difference in reduction in both spine and femoral neck BMD between tertile groups of serum uric acid (the median BMD reduction for spine: -0.02, 0.01, -0.04, p = 0.95; the median BMD reduction for femoral neck: 0.008, 0.005, -0.003, p = 0.34). CONCLUSIONS: Serum uric acid level is not associated with BMD in postmenopausal women.

Elevated aspartate aminotransferase and alanine aminotransferase in the torsion of ovarian mature cystic teratoma: normalised after operation for torsion.

The aim of the study was to report the elevated liver function test levels in torsion of ovarian mature cystic teratoma (MCT). A retrospective review was performed of 116 patients with MCT who underwent surgery in our hospital between 2010 and 2017. Eleven of 116 patients were with torsion of MCT. Of the 11 torsion of MCT cases, 6 of those showed abnormal elevated levels of aspartate transaminase (AST)/alanine aminotransferase (ALT). After operation, AST/ALT levels recovered to normal ranges. Elevated liver function levels require attention to complications associated with anaesthesia and emergency operation. However, the current report shows that emergency surgery should not be delayed to assess other causes of elevated liver function tests.Impact statementWhat is already known on this subject? Abnormal liver function tests require attention to complications associated with emergency surgery.What do the results of this study add: Our study shows that some patients with torsion of MCT returned to normal levels of AST/ALT after surgery without any medications to improve liver function.What are the implications of these findings for clinical practice and/or further research? This study would offer that in some cases with torsion of MCT, emergency surgery should not be delayed and the assessment of other possible causes of these elevations postponed to postoperative period. Additional studies are required to assess the correlation between elevated AST/ALT levels and torsion of MCT.

Multidisciplinary Approach in Large-sized Submucosal Myoma: Hysteroscopic Myomectomy after Uterine Artery Embolization.

STUDY OBJECTIVE: To evaluate the safety and effectiveness of hysteroscopic myomectomy after uterine artery embolization (UAE) for the treatment of large-sized submucosal myomas with deep intramural invasion that are difficult to treat with 1-step hysteroscopy. DESIGN: A retrospective cohort study (Canadian Task Force classification II-2). SETTING: An academic university hospital. PATIENTS: Eight premenopausal patients with symptomatic submucosal myomas with intramural invasion. INTERVENTIONS: All of the patients after bilateral UAE underwent subsequent hysteroscopic operation 3 to 15 months after UAE. MEASUREMENTS AND MAIN RESULTS: A total of 8 patients who had a large-sized submucosal myoma with deep myometrial invasion were included. The average volume of the submucosal myomas was 87.7±39.9 cm3 as confirmed by magnetic resonance imaging, and the average patient age was 37.6 years. The mean volume reduction of the submucosal myomas was 83.3±16.4% after UAE, and no immediate complications were observed. One-step hysteroscopic myomectomy after UAE was successfully performed in all patients. Leiomyomas with hyaline degeneration were pathologically confirmed. All women showed improved symptoms, and there was no evidence of recurrence 1 year later. One patient conceived naturally and delivered a full-term baby. CONCLUSION: In premenopausal women with large-sized symptomatic submucosal myomas with deep myometrial invasion, hysteroscopic myomectomy after UAE is very effective and safe.

Diagnostic accuracy of inflammatory markers for distinguishing malignant and benign ovarian masses.

Objective: To evaluate the role of inflammatory markers for distinguishing malignant and benign ovarian masses. Methods: Preoperative demographic, clinicopathologic, and laboratory variables were reviewed in patients with an ovarian mass that was subsequently diagnosed as either epithelial ovarian cancer (EOC) or a benign ovarian mass on histologic analysis. The differences between variables of the two groups were further evaluated. Logistic regression analysis was applied to evaluate variables to predict the presence of EOC. Results: According to the analysis of 229 patients with EOC, 120 (52.4%) patients had serous adenocarcinoma. Of the 229 patients, 110 (48.1%) patients had stage I or II disease and 119 (52.0%) had stage III or IV disease. There was a significant difference between EOC and benign ovarian mass in median values of variables such as age, white blood cell (WBC) count, hemoglobin concentration, platelet count, cancer antigen 125 (CA125) levels, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) (all P < 0.001, except for WBC count [P = 0.009]). In addition, there was significant difference in median values of these continuous variables among early-stage EOC, advanced-stage EOC, and benign ovarian mass (P < 0.001 for all variables). On multivariate logistic regression analysis, age (odds ratio [OR] = 4.14, P < 0.001), CA125 levels (OR = 9.87, P < 0.001), NLR (OR = 1.76, P = 0.049), PLR (OR = 2.41, P = 0.004), and LMR (OR = 0.51, P = 0.024) were found to significantly predict the presence of EOC. Conclusion: The three LMR, NLR, and PLR markers were found to be predictors for the presence of EOC. Further prospective studies to assess these markers as screening tools for the presence of EOC are required.

Monocytosis as a prognostic factor for survival in stage IB and IIA cervical cancer.

Objective: To measure hematologic parameters derived from the white blood cell (WBC) count and differential count (DC) as prognostic factors for survival in patients with stage IB and IIA cervical cancer. Methods: We retrospectively examined demographic, clinicopathologic, and laboratory parameters in a cohort of 233 patients with International Federation of Gynecology and Obstetrics stage IB and IIA cervical cancer who underwent surgical resection. We further assessed the effects of the WBC count and DC-derived hematologic parameters on progression-free survival (PFS) and overall survival (OS) after controlling for other parameters. Results: Patients were followed up for a median of 46.6 months (range, 9-142 months). The Kaplan-Meier estimates of PFS and OS at 5 years were 88.5% and 92.3%, respectively. In a multivariate analysis, we identified the absolute monocyte count (AMC) (hazard ratio [HR], 11.78; P <0.001) and tumor size (HR, 5.41; P = 0.003) as the strongest prognostic factors affecting PFS. We also identified AMC (HR, 23.29; P <0.001), tumor size, (HR, 5.27; P = 0.033), and lymph node involvement (HR, 3.90; P = 0.027) as the strongest prognostic factors affecting OS. AMC remained prognostic with respect to PFS or OS in a Cox model that controlled for the neutrophil-lymphocyte ratio or lymphocyte-monocyte ratio, although neither ratio was a significant prognostic factor for survival. Conclusions: Monocytosis and an increased tumor size were found to be independent prognostic factors affecting both PFS and OS in patients with stage IB and IIA cervical cancer.

The Neutrophil-Lymphocyte Ratio Predicts Recurrence of Cervical Intraepithelial Neoplasia.

OBJECTIVE: The purpose of the present study was to determine the prognostic significance of the neutrophil-lymphocyte ratio (NLR) in recurrence of cervical intraepithelial neoplasia (CIN). METHODS: We evaluated the NLR as a prognostic marker in the entire cohort of 230 patients who had undergone surgical resection and were diagnosed with CIN. Subjects were categorized into two different groups based on the NLR (NLR-high and NLR-low) using cutoff values determined by receiver operating characteristic (ROC) analysis. The primary research objective for this study was to validate the impact of the NLR on recurrence-free survival (RFS) in patients with CIN. The secondary objective was to evaluate the impact of other hematologic parameters on RFS in CIN patients. RESULTS: Using the entire cohort, the most appropriate NLR cut-off value for CIN recurrence selected on the ROC curve was 2.1. The NLR-low and NLR-high groups included 167 (72.6%) and 63 patients (27.4%), respectively. According to Kaplan-Meier analysis, RFS rates during the entire follow-up period were considerably lower in the NLR-high group than in the NLR-low group (P = 0.0125). In multivariate survival analysis using Cox proportional hazard model, we identified the NLR, absolute eosinophil count (AEC), hemoglobin concentration, and mean corpuscular volume (MCV) as valuable prognostic factors that impact RFS. CONCLUSIONS: The NLR is an independent prognosticator for RFS following surgical resection in CIN patients. We also found that the AEC, hemoglobin level, and MCV were strongly associated with RFS, as determined by multivariate analysis using a Cox model. These hematological parameters might provide additional prognostic value beyond that offered by standard clinicopathologic parameters.

Is it appropriate for Korean women to adopt the 2009 Institute of Medicine recommendations for gestational weight gain?

BACKGROUND: The 2009 Institute of Medicine (IOM) guidelines for gestational weight gain (GWG) are intended for use among women in the United States. Little data are available on whether the 2009 IOM recommendations can be applied to Asian women. This study aimed to evaluate whether the recommendations are related to adverse pregnancy outcomes in Korean pregnant women. METHODS AND FINDINGS: A retrospective cohort study was conducted for all singleton-pregnant women at a university hospital in Korea. After classifying the enrolled women into four Korean pre-pregnancy body mass index (BMI) categories, the risk of adverse pregnancy outcomes were analyzed for women who gained inadequate or excessive GWG based on 2009 IOM recommendations. Of 7,843 pregnancies, 64.0% of women had normal pre-pregnancy BMI and 42.7% achieved optimal GWG. Across all BMI categories, adverse pregnancies outcomes such as small for gestational age (SGA), large for gestational age (LGA), preterm birth, preeclampsia, and cesarean due to dystocia were significantly associated with GWG (all P ≤ 0.001).Women with normal BMI who gained inadequate weight were more likely to develop SGA and preterm birth and less likely to develop LGA (adjusted odds ratio (aOR) 2.21, 1.33, and 0.54, respectively). Whereas, women with normal BMI who gained excessive weight were more likely to develop LGA, preterm birth, preeclampsia, and cesarean section due to dystocia (aOR 2.10, 1.33, 1.37, and 1.37, respectively) and less likely to develop SGA (aOR 0.60). CONCLUSIONS: It is tolerable for Korean women to follow recommended GWG from the 2009 IOM guidelines to decrease adverse pregnancy outcomes. This will be helpful for antenatal care on GWG not only for Korean pregnant women, but also other Asian women who have lower BMI criteria than Caucasian women.

Effects of menopausal hormone therapy on uterine myoma in menopausal women.

OBJECTIVES: The aim of the present study is to evaluate the long term effects of estrogen-progestogen therapy (EPT) on uterine myomas volume in postmenopausal women. METHODS: We performed a retrospective analysis on postmenopausal women with asymptomatic uterine myoma during the period between April, 2008 and September, 2012. Postmenopause was defined as amenorrhea for longer than a year or serum follicle stimulating hormone levels higher than 40 IU/L. The volume of the myoma was assessed by transvaginal ultrasonography for every 6 months after administration of EPT. RESULTS: Thirty-eight women were included in the study, with 32 in the EPT group and 6 in the control group. Overall, uterine myoma volume (mean ± standard deviation, cm(3)) in the EPT group was 19.5 ± 24.6 at baseline, and those at 6 and 12 months were 24.7 ± 35.1 and 28.5 ± 56.4, respectively. Myoma volume did not change significantly with EPT, and these changes were not significantly different from the control group. Myoma volume changes were not significantly different in the subgroups according to the route of estrogen administrations and the method of progestogen administrations. Clinically significant volume increases during one year of EPT was noted in 28.1% (9/32), however, only one showed transient increases. CONCLUSION: Our results suggest that treating postmenopausal woman with EPT on a long-term basis does not increase the volume of uterine myomas.

The Relationship between Uterine Myoma Growth and the Endocrine Disruptor in Postmenopausal Women.

OBJECTIVES: To investigate the number of leiomyoma patients-exposed to bisphenol A (BPA) and to observe whether the serum concentration of BPA is related to leiomyoma growth. METHODS: A total of 158 patients were recruited for this study. Leiomyoma patients were divided into three groups, mild (n = 48), moderate (n = 32) and severe (n = 28), according to the size of leiomyomas. The control (n = 30) group was defined as having no leiomyomas. Transvaginal ultrasonography was used to identify and measure the leiomyomas. Serum BPA concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: BPA was detected in 87.0% out of a total of 158 samples, and in 86.0% out of 108 leiomyoma patients. In detail, the detection rates of serum BPA were 88.0% in the control group, 77.2% in the mild group, 90.0% in the moderate group and 96.0% in the severe group. The mean BPA concentration in the control group was 0.558 ± 0.097 ng/mL, the leiomyoma groups, the mean BPA concentrations were 0.274 ± 0.063 ng/mL (mild), 0.346 ± 0.064 ng/mL (moderate) and 0.647 ± 0.039 ng/mL (severe) (P = 0.0003). Values represent the mean ± standard error. CONCLUSION: The detection rates of serum BPA in the control and leiomyoma groups were 88.0% and 86.0%, respectively. However, there was no significant difference in the serum BPA concentrations between the control and leiomyoma groups. To verify the effect of BPA on leiomyoma growth, a close and sequential monitoring is recommended for people who are at risk for uterine leiomyoma.

Mullerian inhibiting substance induces apoptosis of human endometrial stromal cells in endometriosis.

CONTEXT: Müllerian inhibiting substance (MIS) is produced in Sertoli cells of fetal testis and causes regression of müllerian ducts in male embryos. MIS also can induce the cell cycle arrest and apoptosis in müllerian duct-derived tumors in vivo and in vitro. OBJECTIVE: Our objective was to investigate the expression of MIS type II receptor (MISR II) and whether MIS can inhibit the proliferation and induce apoptosis in primary cultures of endometrial stromal cells (ESC) of endometriosis. DESIGN AND SETTINGS: In vitro experiments were performed in the university research laboratory. PARTICIPANTS: Tissue samples from 12 patients who had undergone evisceration for ovarian endometrial cysts were included in this study. INTERVENTIONS AND MAIN OUTCOME MEASURES: The expression of MISR II in ESC was investigated by immunohistochemistry. The cell viability and apoptosis in ESC treated with MIS was measured by methylthiazoletetrazolium assay and annexin V analysis. The expression of regulatory proteins in ESC treated with MIS was shown by Western blotting. RESULTS: ESC showed specific immunostaining for the MISR II. ESC treated with MIS exhibited 32% growth inhibition (P = 0.0001). The changes in cell cycle distribution after MIS exposure at 72 h demonstrated that S and G(2)M phases were decreased; G(0)G(1) and sub-G(0)G(1) phases were increased. ESC treated with MIS showed 13.72% annexin V-fluorescein isothiocyanate positivity. In the ESCs, which contain defective p16, MIS increased the expression of pocket proteins p107 and p130 and decreased E2F transcription factor 1. CONCLUSIONS: The results support a central role for MIS in endometriosis. Although the precise mechanism of MIS-mediated inhibition of ESC growth has not been fully defined, these data suggest that MIS has activity against ESC in vitro and may also be an effective targeted therapy for endometriosis.

Rectal endometriosis with invasion into lymph nodes.

Although endometriosis is a common disease in women of reproductive age, rectal endometriosis is rare and lymph node involvement by endometriosis is considered uncommon. We report a 37-year-old woman who had irregular lower abdominal pain and changes in bowel habits. She was operated on with suspected rectal cancer, but the histological diagnosis was rectal endometriosis with lymph node involvement. In women who suffer from digestive complaints, endometriosis should be considered in differential diagnosis. Rectal endometriosis has the ability to invade adjacent tissue as true malignant tumors. Therefore, lymph node involvement should be considered in rectal endometriosis.