Effect of ovariectomy, 17-beta estradiol, and progesterone on histology and estrogen receptors of bladder in female partial bladder outlet obstruction rat model.

AIM: The aim of this study was to investigate the effect of bilateral ovariectomy (OVX), 17-beta estradiol (E2), and progesterone (P4) on the histology and estrogen receptor (ER) expression of the bladder using a female partial bladder outlet obstruction (pBOO) rat model. MATERIAL AND METHODS: A total of 60 female Sprague-Dawley rats were evenly assigned into six groups of 10 each. Group A served as the control. Groups B-F underwent induced pBOO. Groups C-F underwent OVX. Groups D-F were given E2 (0.1 mg/kg/day), Group E was given P4 (1 mg/kg/day), and Group F was given P4 and dehydroepiandrosterone (DHEA) (300 µg/kg/day) by an Alzet pump. Four weeks later, serum E2 and P4 levels were evaluated. Each rat was anesthetized and the urinary bladder was removed for weighing and histological study. RESULTS: Expression of ER-ß was not significantly different between the control group and the other study groups. pBOO was shown to increase both bladder weight and detrusor muscle thickness. OVX had an additive effect to BOO on increased blood vessel density in the bladder. E2 was shown to increase blood vessel density, while P4 supplementation decreased blood vessel density. DHEA did not cause any significant effects on blood vessel density. CONCLUSION: Hormone therapy did not change the expression of ER in bladder outlet obstruction. Estradiol stimulated the increased angiogenesis of the bladder detrusor but P4 decreased the angiogenesis of the bladder detrusor. DHEA had no effect on the bladder detrusor.

Anti-proliferative effect of Klimaktoplan® on human breast cancer cells.

OBJECTIVE: With the health concerns of menopausal hormone replacement therapy, alternatives have been sought. Klimaktoplan® is a homeopathic formulation consisting of four main components and has been used for relief of menopausal symptoms for a long time. The study investigated the safety of Klimaktoplan® through its effect on the proliferation of breast cancer (MCF-7) and non-malignant mammary epithelial cells (MCF-10A). METHODS: MCF-7 and MCF-10A cells were cultured in 312.5, 625, and 1,250 µg/ml Klimaktoplan®. 17-Beta estradiol (E2) and medroxyprogesterone 17-acetate (MPA) were used for comparison with Klimaktoplan®. E2 only (0.001, 0.01, and 0.1 µM), and the combination of E2 (0.001, 0.01, and 0.1 µM) and MPA (0.01, 0.1, and 1 µM) were tested. Control cells for Klimaktoplan® and E2 groups were treated with dimethylsulfoxide (DMSO), and DMSO + ethanol was used for the combination group. Cellular proliferation was evaluated by the formation of insoluble formazan after incubation of 4 days. RESULTS: Klimaktoplan® had a concentration-dependent anti-proliferative effect on breast cancer cells at 625 and 1,250 µg/ml, while not affecting proliferation of non-malignant mammary cells at any tested concentration. The effect of lactose was evaluated as lactose (the adjuvant of Klimaktoplan®) affect cell growth. E2 and lactose increased the proliferation of both malignant and non-malignant cells. The effect of E2 + MPA on the proliferation of malignant and non-malignant mammary cells was lower than estradiol only, but was higher than control. CONCLUSIONS: Klimaktoplan® has an anti-proliferative effect on breast cancer cells, but not for non-malignant mammary epithelial cells, unlike E2 and E2 + P. With further research, KP would be a good alternative or additive in women with menopausal symptoms who wish to avoid conventional E or E + P hormone therapy.

The relationship between fat depot-specific preadipocyte differentiation and metabolic syndrome in obese women.

OBJECTIVE: Obesity is strongly associated with metabolic syndrome, but not all obese individuals display a clustering of metabolic risk factors. Recent studies have shown that in vitro subcutaneous (SC)-preadipocyte differentiation is negatively associated with obesity. These results suggest that impaired adipogenesis is an important factor linking obesity to metabolic disorders. We examined whether in vitro preadipocyte differentiation is associated with metabolic syndrome, independent of obesity. DESIGN/PATIENTS/MEASUREMENTS: Paired adipose tissue samples were obtained from the 13 nonobese women and the 65 obese women. The CD34(+)/CD31(-) cells were isolated from the stromal-vascular fraction of both SC and omental (OM) fat depots by immune magnetic separation, and the subset was cultured with a differentiation cocktail. Then, we analysed the relationship between the degree of preadipocyte differentiation and metabolic factors. RESULTS: Obese women without metabolic syndrome (n = 37) had significantly higher SC-preadipocyte differentiation than equally obese women with metabolic syndrome (n = 28); however, OM-preadipocyte differentiation was similar in both groups. SC-preadipocyte differentiation was strongly correlated with triglycerides, HDL cholesterol, homoeostasis model assessment of insulin resistance and OM-adipocyte size. However, OM-preadipocyte differentiation was not correlated with any of these parameters. CONCLUSIONS: This study identified that SC-preadipocyte differentiation is associated with metabolic syndrome independent of obesity, whereas OM-preadipocyte differentiation is not. These findings suggest that, in the setting of obesity, an enhanced adipogenic capacity of SC depots could be protective for metabolic syndrome. Our data underscores an interaction between adipose tissue homoeostasis and metabolic disorder.

Transvaginal single-port natural orifice transluminal endoscopic surgery for benign uterine adnexal pathologies.

Transvaginal natural orifice transluminal endoscopic surgery (NOTES) with pneumoperitoneum has been used in cholecystectomies, appendectomies, and nephrectomies, but transvaginal NOTES using a single port in gynecologic procedures has not been described despite gynecologist familiarity with the vaginal approach. We performed transvaginal single-port NOTES in 10 women with benign uterine adnexal disease: oophorectomy in 3 patients, salpingostomy and salpingectomy in 2 each, and ovarian cystectomy, paratubal cystectomy, and ovarian wedge resection in 1 each. The patients were discharged at 1 or 2 days postoperatively, and were satisfied, with minimal pain, no abdominal scar, and no complications at 2-month follow-up. We conclude that transvaginal single-port NOTES to treat benign uterine adnexal disease is a feasible and attractive option.

Relationship between serum estradiol and follicle-stimulating hormone levels and urodynamic results in women with stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: The purpose of the current study was to determine the relationship between the serum estradiol (E2) and follicle-stimulating hormone (FSH) levels and the urodynamic study results in women with stress urinary incontinence (SUI). METHODS: Eighty women were selected among patients who underwent urodynamic testing for SUI. Basic demographic features were evaluated and laboratory tests were performed. Multiple linear regression analyses were performed among the serum E2 and FSH levels and urodynamic results. RESULTS: E2 had a negative correlation with the Q-tip test in post-menopause. FSH had positive correlations with the post-void residual volume in the uroflowmetry and the voiding and flow times in the pressure-flow study in all of the patients and a negative correlation with the peak flow rate in the pressure-flow study in pre-menopause. CONCLUSIONS: E2 and FSH were associated with urodynamic parameters in female patients with SUI.

Relationship between uric acid and metabolic syndrome according to menopausal status.

OBJECTIVE: Uric acid, the levels of which have been shown to increase after menopause, has been associated with metabolic syndrome. The prevalence of metabolic syndrome has also been determined to increase after menopause. Therefore, we surmised that menopausal status-specific analyses for the characterisation of the relationship between uric acid and the metabolic syndrome were warranted. METHODS: We included 1644 patients: 1018 premenopausal women and 626 postmenopausal women, all of whom participated in annual health examinations at Anam Hospital in Seoul, Korea, from January 2008 through December 2008. RESULTS: On the multivariate logistic regression analysis, uric acid was identified as an independent risk factor for metabolic syndrome in both premenopausal and postmenopausal women. Uric acid levels had different relationships with blood pressure based on menopausal status, however, no such relationships with fasting glucose or age were found. CONCLUSIONS: Increased uric acid levels were associated with increased risk for metabolic syndrome in both premenopausal and postmenopausal women. In studies regarding uric acid and metabolic syndrome in women, the effects of menopausal status should be considered.

Ovarian hyper-response to administration of an GnRH-agonist without gonadotropins.

Several case reports have indicated that a small subgroup of patients may develop ovarian hyperstimulation following the administration of gonadotropin-releasing hormone agonists (GnRHa) without gonadotropins. However, since only few such cases have been published, it is unclear what course to follow in subsequent cycles after ovarian hyperstimulation in the first cycle using only GnRHa. A 33-yr-old woman was referred to in vitro fertilization for oocyte donation. A depot preparation (3.75 mg) of tryptorelin without gonadotropins induced ovarian multifollicular enlargement with high estradiol level, and was followed by human chorionic gonadotropin administration and oocyte retrieval. In a subsequent cycle of the same patient, a low dose of tryptorelin (0.05 mg) did not induce ovarian hyperstimulation, and resulted in clinical pregnancy. This report shows potential management of ovarian hyperstimulation following the administration of GnRHa without gonadotropins.

Age at menarche in a Korean population: secular trends and influencing factors.

This study was designed to identify the secular trend in the age at menarche and to investigate the possible factors that influence the age at menarche using representative Korean data from the 2005 Korean National Health and Nutrition Survey. Three thousand five hundred sixty-two women born between 1920 and 1985 were enrolled to identify secular trends in the age at menarche and 620 girls born between 1986 and 1995 were recruited to evaluate the factors influencing the age at onset of menarche. Mean age at menarche decreased from 16.90 +/- 1.25 years for women born between 1920 and 1925 to 13.79 +/- 1.37 years for those born between 1980 and 1985, indicating a downward trend of 0.68 years per decade (95% CI, 0.64-0.71) in age at menarche. Mean age at menarche of girls born between 1986 and 1995 was 13.10 +/- 0.06 years as estimated by the Kaplan-Meier method. Among girls born between 1986 and 1995, menarcheal girls had a larger waist circumference, a higher body mass index (BMI), and lower maternal menarcheal age and maternal age at birth than premenarcheal girls. The energy and nutrient intake of protein, sugar, fiber, ash, phosphate, natrium, thiamine, riboflavin, and niacin were greater for menarcheal girls than for premenarcheal girls. These data indicate a decreasing secular trend of age at menarche in a Korean population born between 1920 and 1995. Furthermore, maternal menarcheal age, BMI, maternal age at birth, and nutrition are important variables that appear to influence age at menarche in Korean girls.

Years from menopause-to-surgery is a major factor in the post-operative subjective outcome for pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: The purpose of the current study was to determine the main factors associated with post-operative subjective outcome in post-menopausal patients with pelvic organ prolapse. METHODS: Ninety-four women were selected among patients who underwent surgery for grade 3 or 4 prolapse. The outcome was evaluated by the Patient Global Impression of Improvement (PGI-I) scale. Multivariate ordinal regression analysis was performed. RESULTS: The number of patients with improvement (1 or 2 on the PGI-I scale) was 88 (93.7%). Age and years from menopause-to-surgery were negatively (beta = -0.16, P = 0.01) and positively (beta = 0.14, P = 0.01) associated with the PGI-I scale. The aging effect was lost after adjusting for prolapse grade. CONCLUSION: The greater the number of years from menopause-to-pelvic organ prolapse surgery, the less satisfied were the patients. The association between older patients and greater satisfaction appears to be a confounding effect of prolapse grade.

Stemness evaluation of mesenchymal stem cells from placentas according to developmental stage: comparison to those from adult bone marrow.

This study was done to evaluate the stemness of human mesenchymal stem cells (hMSCs) derived from placenta according to the development stage and to compare the results to those from adult bone marrow (BM). Based on the source of hMSCs, three groups were defined: group I included term placentas, group II included first-trimester placentas, and group III included adult BM samples. The stemness was evaluated by the proliferation capacity, immunophenotypic expression, mesoderm differentiation, expression of pluripotency markers including telomerase activity. The cumulative population doubling, indicating the proliferation capacity, was significantly higher in group II (P<0.001, 31.7±5.8 vs. 15.7±6.2 with group I, 9.2±4.9 with group III). The pattern of immunophenotypic expression and mesoderm differentiation into adipocytes and osteocytes were similar in all three groups. The expression of pluripotency markers including ALP, SSEA-4, TRA-1-60, TRA-1-81, Oct-4, and telomerase were strongly positive in group II, but very faint positive in the other groups. In conclusions, hMSCs from placentas have different characteristics according to their developmental stage and express mesenchymal stemness potentials similar to those from adult human BMs.

Prenatally detected congenital perineal mass using 3D ultrasound which was diagnosed as lipoblastoma combined with anorectal malformation: case report.

We report a case of prenatally diagnosed congenital perineal mass which was combined with anorectal malformation. The mass was successfully treated with posterior sagittal anorectoplasty postnatally. On ultrasound examination at a gestational age of 23 weeks the fetal perineal mass were found on the right side. Any other defects were not visible on ultrasonography during whole gestation. Amniocentesis was performed to evaluate the fetal karyotyping and acetylcholinesterase which were also normal. As the fetus grew up, the mass size was slowly increased more and more. At birth, a female neonate had a perineal mass on the right side as expected. During operation, the anal sphincteric displacement was found near the mass and reconstructed through posterior sagittal incision. This is the first reported case of prenatally diagnosed congenital perineal mass, after birth which was diagnosed as lipoblastoma and even combined with anorectal malformation. This case shows that it can be of clinical importance to be aware of this rare fetal perineal mass in prenatal diagnosis and counseling.

Effect of adiponectin and sex steroid hormones on bone mineral density and bone formation markers in postmenopausal women with subclinical hyperthyroidism.

AIM: The relationship between adiponectin and sex hormones with bone mineral density (BMD) and bone formation markers was investigated in postmenopausal women with subclinical hyperthyroidism (SCH). METHODS: Seventy-five postmenopausal women were selected among the patients who participated in a health screening program in 2007. Thirty-seven control women with normal thyroid function were matched to 38 women with SCH by age, body mass index (BMI), and years since menopause (YSM). The associations between adiponectin and sex hormones with lumbar spine BMD and bone turnover markers were investigated. RESULTS: Adiponectin, testosterone (T; total and free forms), and thyroid-stimulating hormone were significantly different between the women with SCH and euthyroid. After adjusting for age, BMI, and YSM, free T (r = 0.351; P = 0.029) and estradiol (E2; r = -0.368; P = 0.024) had significant associations with bone alkaline phosphatase (B-ALP). Total T (r = 0.388; P = 0.021) and E2 (r = -0.376; P = 0.026) had significant associations with osteocalcin. However, there were no significant associations between adiponectin and sex hormones with the BMD levels in the SCH subjects. CONCLUSION: There were correlations between sex hormones with B-ALP and osteocalcin, but no associations between adiponectin and sex hormones with the lumbar spine BMD in postmenopausal SCH patients.

Relationship between the serum CA-125 level and bone mineral density in healthy pre- and post-menopausal women.

BACKGROUND: Osteoporosis and tumour-associated antigen (TAA) levels are associated with inflammatory processes, but little remains known about TAA levels and bone mineral density (BMD). AIMS: We determined whether or not high-normal TAA levels are associated with a lower BMD in healthy women. METHODS: A total of 3769 healthy women were enrolled from the health screening programme over 5 years. Each participant had undergone a basic health examination. Serum carbohydrate antigen (CA)-125, CA-19-9, carcinoembryonic antigen (CEA) and alpha-fetoprotein levels were evaluated as tumour markers. The correlations between serum TAA levels and BMD were analysed. RESULTS: Carbohydrate antigen 125 and CEA levels were positively associated with a higher BMD in the pre-menopause. In the post-menopause, the CA-125 level was positively associated with BMD. In the pre-menopause, CA-125 (r = 0.102; P < 0.001) and CEA levels (r = 0.134; P < 0.001) had a significant correlation with BMD. In the post-menopause, CA-125 was negatively associated with alkaline phosphatase (r = -0.298; P < 0.001). CONCLUSIONS: There was a significant positive association between CA-125 and BMD in healthy women. Additional basic and clinical studies on the relationship between CA-125 and bone are needed.

Current hormone therapy associated with atypical squamous cells of undetermined significance in postmenopausal women.

OBJECTIVE: This study evaluated the relationship between hormone therapy (HT) and squamous cytologic abnormalities of the cervix in postmenopausal Korean women. METHODS: Two hundred sixty-eight cases of atypical squamous cells of undetermined significance (ASCUS), or more severe cervical lesions, and 4728 negative controls were included in this study. Hormone therapy status was analyzed as functions of 2 categories (current user and noncurrent user) and 3 categories (never user, past user, and current user). RESULTS: With HT users categorized as current HT users and noncurrent users, HT use had a significant relationship with abnormal cervical squamous cells (chi2, P = 0.018). When the noncurrent users were more categorized into never users and past users, the relationship did not exist. There was a greater risk of cellular abnormality among current HT users than never users (odds ratio, 1.805; 95% confidence interval, 1.042-3.127; P = 0.035); the risk was no greater among past users than the never users. The risk was limited to ASCUS and not related to more advanced lesions. CONCLUSIONS: In postmenopausal women, current HT use might have an effect on initial abnormal changes of the cervical squamous cells, such as ASCUS; however, the effect is extinguished with respect to more advanced lesions.

Relationship between serum adipocytokine levels and metabolic syndrome in menopausal women.

OBJECTIVE: Adipocytokines are bioactive substances derived from adipose tissues, especially visceral fat, and play a crucial role in the development of metabolic syndrome. The aims of this study were to estimate serum levels of adipocytokines (adiponectin, resistin and TNF-alpha) and to examine the associations between adipocytokine levels and metabolic syndrome in menopausal women. METHODS: We recruited 28 postmenopausal women with features of metabolic syndrome. For the purpose of comparing adipocytokine levels, 30 postmenopausal women without metabolic syndrome were recruited by matching age and body mass index (BMI). Serum levels of adipocytokines (adiponectin, resistin, TNF-alpha) were then determined, and any potential correlations between adipocytokine levels and metabolic syndrome were investigated. RESULTS: There were no significant differences in adiponectin or resistin levels in women with metabolic syndrome when compared with the control group. Conversely, TNF-alpha levels were significantly higher in women with metabolic syndrome. Furthermore, multivariate logistic regression analysis indicated that TNF-alpha was significantly associated with metabolic syndrome. CONCLUSION: Our results suggest that, among the adipocytokines (adiponectin, resistin and TNF-alpha), serum TNF-alpha levels may serve as a useful biomarker for diagnosing metabolic syndrome in menopausal women.

Osteopontin expression correlates with invasiveness in cervical cancer.

AIM: Osteopontin is a secreted, integrin-binding glycophosphoprotein that is overexpressed in many types of cancers and appears to be involved in carcinogenesis and cancer progression. To understand the role of osteopontin in carcinogenesis of cervical cancer, this study was designed to determine whether osteopontin is expressed in cervical cancer and carcinoma in situ (CIS) tissue as well as in normal cervical tissue. METHODS: The expression of osteopontin was immunohistochemically analysed from 68 normal cervix, 55 CIS and 52 invasive cervical cancer tissues using a paraffin-embedded tissue array. Immunostaining was evaluated by intensity and the percentage of stained cells. RESULTS: Osteopontin expression in normal, CIS and cervical cancer tissues was two of 68 (2.9%), 43 of 55 (78.2%) and 46 of 52 (88.4%), respectively (P < 0.01). High intensity (strong positive)/high proportion (more than 50%) staining seen in CIS and cervical cancer tissue samples was 45 of 55 (81.8%)/22 of 55 (40.0%) and 50 of 52 (96.2%)/31 of 52 (59.7%), respectively (P = 0.029 and P = 0.054). There was no significant correlation between the immunostaining score and stage and the immunostaining score and survival. CONCLUSION: Osteopontin may have a potential use as a diagnostic factor for cervical cancer and osteopontin expression is closely correlated with carcinogenesis and invasion of cervical cancer.

Postmenopausal status according to years since menopause as an independent risk factor for the metabolic syndrome.

OBJECTIVE: Features of the metabolic syndrome such as abdominal adiposity, insulin resistance, and dyslipidemia develop with the transition from pre- to postmenopausal status in women. We investigated the effects of postmenopausal status on the prevalence of the metabolic syndrome according to years since menopause. DESIGN: We studied 1,002 women, 618 premenopausal and 384 postmenopausal, who participated in annual health examinations at Anam Hospital in Seoul, Korea. RESULTS: Using multivariate logistic regression analysis, we determined that postmenopausal status was an independent risk factor for the metabolic syndrome. Moreover, after controlling for age and body mass index, postmenopausal women had an increased risk of the metabolic syndrome (odds ratio, 2.93; 95% CI, 1.62-5.33) and the abnormalities of its individual components. The risk for the metabolic syndrome increased up to 14 years since menopause, then decreased. For its individual components, postmenopausal women with 5 to 9 years since menopause had the highest risk of high blood pressure; postmenopausal women with less than 5 years since menopause had an increased risk of abdominal obesity and high glucose. With 10 to 14 years since menopause, postmenopausal women had an increased risk of high triglycerides. CONCLUSIONS: Postmenopausal status is an independent risk factor for the metabolic syndrome and all of its individual components. The risk for the metabolic syndrome increased up to 14 years since menopause. In addition, postmenopausal status has effects during different periods since menopause for each of these components.

BAG-1 expression in normal endometrium, endometrial hyperplasia and endometrial cancer.

BACKGROUND: BAG-1 (Bcl-2-associated athanogene 1) is a BCL-2 binding anti-apoptotic protein that may play a role in carcinogenesis. The purpose of this study is to compare the expression rate of BAG-1 in normal endometrium, endometrial hyperplasia and endometrial cancer, and further to determine a correlation between BAG-1 expression and clinicopathological parameters, and overall survival. METHODS: Tissue samples from 43 patients who were diagnosed with endometrial cancer, tissue samples from 20 patients with endometrial hyperplasia and tissue samples from 20 normal patients were included in the study. Immunohistochemical analyses were performed using a polyclonal anti-BAG-1 antibody from paraffin-embedded blocks. RESULTS: Cytoplasmic BAG-1 expression of the normal endometrium, endometrial hyperplasia and endometrial cancer samples was 4/20 (20%), 3/20 (15%) and 27/43 (62%), respectively. Nuclear BAG-1 expression was 17/20 (85%), 12/20 (60%) and 16/43 (37%), respectively. Cytoplasmic BAG-1 expression correlated with cancer grade (p=0.02). The mean survival of patients with positive/negative cytoplasmic BAG-1 expression and nuclear BAG-1 expression was 49.4/45.4 and 54.0/41.1 months, respectively, but there was no statistical difference for survival (log-rank p=0.31, p=0.55). CONCLUSION: Cytoplasmic BAG-1 is more frequently expressed in endometrial cancer tissues than in normal and endometrial hyperplasia tissues (p=0.0007), and its expression correlates with cancer grade. Nuclear BAG-1 is more frequently expressed in the normal endometrium and hyperplasia tissues than in endometrial cancer tissues (p=0.002). Neither cytoplasmic nor nuclear BAG-1 expression is associated with survival.

Human placenta-derived feeders support prolonged undifferentiated propagation of a human embryonic stem cell line, SNUhES3: comparison with human bone marrow-derived feeders.

Co-culture of human embryonic stem (ES) cells on mouse fibroblast feeders is the commonly used method for in vitro expansion of human ES cells in an undifferentiated state. However, it has potential risks of pathogen transmission from animals; thus, human cell-derived feeders have been employed to minimize this problem. In this study, we compared human placenta-derived feeders with bone marrow to demonstrate its effectiveness as feeders for in vitro long-term culture of human ES cells. We cultured a human ES cell line, SNUhES3, on human placenta-derived mesenchymal stem cell feeders and compared their culture efficiency with human bone marrow-derived feeders and control group (mouse fibroblast feeders, STO). The mean number of human ES cell colonies was 166 +/- 35 in the placenta feeders; this was significantly higher than bone marrow-derived feeders (87 +/- 16, p < 0.05). We could propagate the culture of SNUhES3 on the placenta feeders past the 50th week similar to control group. During the culture, the maintenance of undifferentiated state of SNUhES3 was demonstrated by the expression of SSEA-4, TRA-1-81, TRA-1-60, and Oct-4. However, we failed to propagate the culture of human ES cells on the human bone marrow-derived feeders past the 5th week. The efficiency of embryoid body formation was similar between placenta and control group, indicating the preservation of differentiation ability. Thus, placenta-derived feeders are more efficient for the long-term in vitro culture of human ES cells than bone marrow-derived feeders suggesting the possible role of placenta as a source for human cell-derived feeders.