抑制PI3K/Akt信号通路拮抗胰岛素诱导的子宫内膜癌细胞增殖

目的:研究抑制磷脂酰肌醇3激酶(PI3K)/Akt信号通路对胰岛素诱导的子宫内膜癌细胞增殖的拮抗作用。方法:将无血清饥饿的子宫内膜癌Ishikawa3-H-12细胞分为空白对照组、10-6mol/L胰岛素单独刺激组以及不同剂量PI3K抑制剂-LY294002预处理后再用胰岛素刺激组。Western blot检测各组Akt磷酸化(p-Akt)水平,MTT试验观察细胞增殖情况。结果:胰岛素可引起内膜癌细胞Akt活化,刺激15min后p-Akt/Akt比值显著高于空白对照组(68.68%vs 26.21%,P<0.001)。LY294002以浓度依赖方式抑制胰岛素引起的Akt磷酸化。MTT试验显示,在药物处理24h,48h和72h 3个时间点,不同组别570nm吸光度值(OD570nm)均有显著差异(F=156.329,700.973,812.224,均P<0.001)。胰岛素组OD570nm值均高于同时间点的空白对照组(均P<0.001),胰岛素促内膜癌细胞增殖作用于48h时最为显著。LY294002可抑制胰岛素的增殖促进作用,此抑制作用具有浓度依赖性。不同剂量LY294002抑制作用的时间依赖性不同,48h时小剂量(0.1、1、10μmol/L)的抑制作用最为显著,72h时胰岛素重新呈现一定的促增殖作用;而50μmol/L LY294002可以持久抑制胰岛素的促增殖作用。结论:PI3K抑制剂LY294002可以通过抑制Akt磷酸化阻断胰岛素信号传导,拮抗后者促子宫内膜癌细胞增殖的作用。     

A gene signature-based approach identifies thioridazine as an inhibitor of phosphatidylinositol-3'-kinase (PI3K)/AKT pathway in ovarian cancer cells

Objective

Thioridazine, a derivative of phenothiazine, has been reported to have antiproliferative activity on tumor cells. However, the mechanism has not been well defined.

Methods

Using in-silico gene signature based approach, we have demonstrated that thioridazine could inhibit phosphatidylinositol-3′-kinase (PI3K)/Akt pathway, and thus exert cytotoxicity in ovarian cancer cells.

Results

The Connectivity Map indicated that thioridazine induces gene signature similar to that of Akt inhibition. Moreover, preexisting inhibitors of PI3K/Akt pathway were also found to reveal similar signature. In SKOV-3 cells, immunoblot using p85 antibody showed that thioridazine could inhibit PI3K signal. In addition, thioridazine was found to inhibit p-Akt (Ser 473) in a dose-dependent manner. Furthermore, thioridazine was found to decrease cell viability and induce apoptosis. Exposure to thioridazine induced G₀/G₁ arrest and down-regulated the cell cycle regulator, Cyclin D1 and CDK4, and up-regulated p21, p16, and p-CDC25A. Finally, additive cytotoxicity was observed when cisplatin and thioridazine were treated simultaneously.

Conclusions

The current study indicated that in-silico approach, such as Connectivity Map, is a potentially useful method to identify the unknown cellular function among the drugs already in use in clinic. Owing to the property of Akt inhibition and additive cytotoxicity observed with the platinum compound, further research should be focused on this drug.     

Polycystic ovary syndrome and abnormalities in glucose tolerance

Objectives

To compare the prevalence of abnormal glucose tolerance (AGT) among women with polycystic ovary syndrome (PCOS) and controls, and assess risk factors associated with PCOS.

Method

A fasting oral glucose tolerance test after ingestion of 75 g of glucose was administered to 264 women with and 116 without PCOS. Moreover, fasting glucose, insulin, and testosterone levels were measured in the women with PCOS. Body mass index (BMI), waist-to-hip ratio (WHR), and homeostasis model assessment-insulin resistance (HOMA-IR) were calculated for each woman with PCOS.

Results

The AGT prevalence was 14.4% in the PCOS group and 11.2% in the control group (P = 0.17). The women with both PCOS and AGT had significantly higher BMIs, WHRs, testosterone levels, and HOMA-IR values than those with normal glucose tolerance.

Conclusion

While AGT was not associated with PCOS, the women with both PCOS and AGT were significantly more obese, hyperandrogenic, and insulin resistant than those with PCOS and normal glucose tolerance.     

胰岛素增敏剂对多囊卵巢综合征患者卵巢局部胰岛素抵抗的影响

目的探讨多囊卵巢综合征(PCOS)患者卵巢局部胰岛素抵抗状态及胰岛素增敏剂——曲格列酮(troglitazone)对改善卵巢局部胰岛素抵抗的作用。方法收集11例PCOS患者(PCOS组)和排卵功能正常的33例输卵管性不孕患者(对照组)促排卵后卵巢黄素化颗粒细胞(卵巢细胞),进行体外培养,并经不同浓度的胰岛素及胰岛素样生长因子1(IGF-1)作用后,观察卵巢细胞糖原和DNA合成的变化,同时观察卵巢细胞胰岛素受体(IR)、IGT-1受体(IGF-1R)、胰岛素受体底物(IRS)的表达。结果(1)不同浓度IGE-1作用后,PCOS组卵巢细胞的DNA合成增加约为对照组的2倍,曲格列酮可抑制IGF-1的这一作用。(2)胰岛素作用后,PCOS组卵巢细胞的糖原合成量与对照组比较,明显降低;而曲格列酮作用后,两组卵巢细胞中胰岛素促糖原合成作用均增加。(3)与对照组比较,PCOS组卵巢细胞：[RS-1的表达(相对灰度,下同)升高,IRS-2表达降低。曲格列酮可降低IRS-1的表达水平,升高IRS-2的表达水平。结论(1)PCOS患者存在卵巢局部的胰岛素抵抗现象。(2)卵巢局部胰岛素抵抗与PCOS患者卵巢高反应状态相关。(3)曲格列酮可增加卵巢细胞对胰岛素的敏感性。     

Evidence for insulin-mediated control of AQP9 expression in human placenta

The AQP9 gene contains a negative insulin response element, suggesting that it may be modulated by insulin. Previously, we reported AQP9 overexpression in preeclamptic placentas but a lack of functionality of AQP9 in water and mannitol transport. We also observed high serum levels of insulin and TNF-α in preeclamptic women.

Objective

To evaluate whether AQP9 expression is regulated by insulin in the human placenta, and whether the dysregulation of AQP9 observed in preeclamptic placentas may be related to the inability to respond to insulin stimuli.

Methods

Explants from normal and preeclamptic placentas were cultured at different concentrations of insulin. Treatment with TNF-α was used to induce phosphorylation of insulin receptor substrate (IRS), which may desensitize insulin action. AQP9 molecular expression and water uptake was determined.

Results

Insulin decreased the molecular expression of AQP9 exclusively in explants from normal placentas in a concentration-dependent manner. Treatment with TNF-α previous to insulin addition prevented these changes. Moreover, insulin treatment did not modify water uptake neither its sensitivity to HgCl_2.

Conclusion

AQP9 water permeability seems to be independent of its molecular expression, strongly suggesting that AQP9 might not have a key role in water transport in human placenta. We also propose another mechanism of down-regulation of AQP9 molecular expression mediated by insulin in a concentration-dependent manner in human placenta and provide new evidence that in preeclamptic placentas the mechanisms of insulin signaling may be altered, producing an overexpression of AQP9 that does not correlate with an increase in its functionality.     

Phenotypic expression, body mass index and insulin resistance in relation to LH levels in women with polycystic ovary syndrome

Objective

To evaluate LH levels in women with the classic (1990 criteria) and the newer (2003 criteria) PCOS phenotypes, and to examine the impact of BMI and insulin resistance indices on hormone levels.

Study design

In this controlled clinical study 936 women with PCOS, classified as classic (n = 729) and newer (n = 207), and 204 controls were included. All women were divided into normal-weight (BMI < 25 kg/m²) and overweight plus obese (BMI ≥ 25 kg/m²). Serum LH, FSH, anthropometrics, androgens, fasting insulin and glucose, HoMA-IR, number of follicles, and ovarian volume were assessed.

Results

Women with classic PCOS presented significantly higher LH and LH/FSH ratios, and lower glucose/insulin levels than those with the newer phenotype and controls. Overweight plus obese women of all groups had lower LH levels than normal-weight women. Independent positive correlations between LH and androgens and negative correlation between LH and BMI were found.

Conclusions

The higher LH concentrations of the classic phenotypes of PCOS could be attributed to the higher androgen levels, which desensitize the hypothalamus to the negative feedback regulation by progesterone. Moreover, the lower LH levels of overweight plus obese women of all groups could be attributed to the increased peripheral aromatization of androgens to estrogens in adipose tissue leading to suppression of LH secretion.

Condensation

Both normal-weight and overweight women with classic PCOS phenotypes present higher LH levels and LH-to-FSH ratios than women with similar BMI but the newer phenotypes.     

Influence of LH and high-density lipoprotein cholesterol (HDL-C) on metformin response in women with polycystic ovary syndrome

Objective

To search for predictors of metformin response in women with polycystic ovary syndrome (PCOS) through a detailed analysis of clinical and laboratory parameters.

Study design

We designed a prospective study to investigate clinical and laboratory parameters to search for predictors of metformin response in women with PCOS. A total of 53 PCOS patients were given metformin 850 mg twice a day for 6 months, after which patients were classified as responders or non-responders. Parameters analyzed for comparison between the two groups were: plasma fasting insulin glucose/insulin ratio; oral glucose tolerance test (OGTT) with insulin (120 min); HOMA and QUICKI tests; total cholesterol and fractions, triglycerides; LH, FSH, estradiol, progesterone, testosterone, androstenedione, 17-OH progesterone, and DHEAS.

Results

From all patients, 30 (56.6%) were responders and 23 (43.3%) were non-responders. Multinomial analysis showed that the positive response to metformin was associated with higher levels of basal LH (p = 0.038) and lower levels of high-density lipoprotein cholesterol (HDL-C) (p = 0.015).

Conclusion

In weight-matched PCOS subjects, laboratory markers might predict the metformin response. Higher levels of basal LH and lower levels of HDL-C are correlated with a positive response to metformin treatment in PCOS subjects.     

Glucose deprivation activates AMPK and induces cell death through modulation of Akt in ovarian cancer cells

Objectives

Upregulation of glycolysis has been demonstrated in multiple tumor types. Glucose deprivation results in diminished intracellular ATP; this is counteracted by AMPK activation during energy deficiency to restore ATP levels. We sought to determine whether glucose deprivation could induce cytotoxicity in ovarian cancer cells through activation of AMPK, and whether AMPK activators could mimic glucose deprivation induced cytotoxicity.

Methods

Sensitivity to 2DG induced cytotoxicity and glucose deprivation was determined in a panel of ovarian cancer cells. Cellular growth rate, rate of glucose uptake, and response to glucose deprivation were determined. Expression of Glut-1, HIF1-α, AMPK and Akt was determined by immunoblotting.

Results

Incubation of ovarian cancer cells with glucose-free media, 2-DG and AMPK activators resulted in cell death. The glycolytic phenotype of ovarian cancer cells was present in both normoxic and hypoxic conditions, and did not correlate with HIF1-α expression levels. Sensitivity to glucose deprivation was independent of growth rate, rate of glucose uptake, and appeared to be dependent upon constitutive activation of Akt. Glucose deprivation resulted in activation of AMPK and inhibition of Akt phosphorylation. Treatment with AMPK activators resulted in AMPK activation, Akt inhibition, and induced cell death in ovarian cancer cells.

Conclusions

Ovarian cancer cells are glycolytic as compared to normal, untransformed cells, and are sensitive to glucose deprivation. Because ovarian cancer cells are dependent upon glucose for growth and survival, treatment with AMPK activators that mimic glucose deprivation may result in broad clinical benefits to ovarian cancer patients.     

The insulin resistant subphenotype of polycystic ovary syndrome: clinical parameters and pathogenesis

Objective

This study was undertaken to compare clinical and biochemical characteristics of the insulin resistant (IR) and non-IR subphenotypes of polycystic ovary syndrome (PCOS).

Study design

Infertile PCOS women were classified as IR (n = 32) or non-IR (n = 46) on the basis of fasting glucose and insulin levels. The incidence of acanthosis nigricans (AN), hirsutism, and ovulation in response to clomiphene citrate (CC) was compared between the 2 groups, along with serum levels of gonadotropins, and sex steroids. Blood samples from 28 PCOS patients and 8 controls were analyzed by enzymatic immunoassay for autophosphorylated insulin receptor (APIR) and total insulin receptor (TIR) content.

Results

Insulin resistance was associated with obesity (odds ratio [OR] = 3.5, P < .05), AN (OR = 6.0, P < .05), hirsutism (OR = 3.1, P < .05), and resistance to CC (OR = 5.0, P < .05). Mean levels of LH, LH/FSH ratios, and testosterone were lower in women with IR (11.5 ± 6.8 mIU/mL, 2.0 ± 1.0, and 56.6 ± 29.0 ng/dL, respectively) compared with women without IR (15.0 ± 13.4 mIU/mL, 2.4 ± 1.5, and 72.5 ± 29.8 ng/dL, respectively) (P < .05). Mean APIR/TIR ratios in IR women were lower than in non-IR women (P < .05 at 100 nmol/L of insulin) and controls (P < .01 at 1, 10 and 100 nmol/L insulin).

Conclusion

Patients with IR are more likely to be obese and have AN, hirsutism, resistance to CC, and lower LH, LH/FSH ratios, and testosterone levels. Furthermore, IR patients appear to have defective autophosphorylation of the insulin receptor, a key element in insulin action, and a possible mechanism for IR in PCOS.     

The role of family history in clinical symptoms and therapeutic outcomes of women with polycystic ovary syndrome

Objective

To investigate the association between family history and clinical symptoms of polycystic ovary syndrome (PCOS) that were thought to be inherited, by treating women with PCOS with contraceptive pills and metformin, and assessing outcomes.

Methods

Of 164 women with PCOS, 49 with menstrual abnormalities, hyperandrogenism, and abnormal glucose and/or insulin levels underwent a 3-month treatment with contraceptive pills and metformin. Family history was taken, and physical and ultrasound examinations were performed. Serum levels of glucose, insulin, lipoproteins, lipids, and reproductive hormones were measured before and after treatment.

Results

The serum levels of low-density lipoprotein, total cholesterol, apolipoprotein B, and triglycerides were higher in the patients with a family history of the studied symptoms than in those with no such family history. After treatment, changes in testosterone and glucose levels, glucose area under curve, and homeostasis model assessment value differed in the 2 groups.

Conclusion

The patients with a family history of PCOS symptoms thought to be inherited were more sensitive to oral contraceptive and metformin treatment.     

Akt/protein B and estradiol receptor alpha expressions in postmenopausal endometrium

Objective

Estrogen receptor interacts in several types of cells with phosphatidyl-inositol 3-kinase/Akt pathway regulating cell survival and apoptosis. No data are available of the Akt/PKB signaling and its role in the endometrial homeostasis of the postmenopausal uterus. The aim of the present investigation was to study the Akt/protein kinase B signaling in tissue samples retrieved from postmenopausal endometrium of the human uterus with parallel observation of the changes of the expression and phosphorylation of ERalpha.

Study design

Sixty disease-free postmenopausal women were enrolled in the study. Endometrial tissue samples were obtained from diagnostic curettage or direct from the uterus after hysterectomy done for benign uterine lesions other than endometrial disease. For comparison, the studied parameters were also analyzed in endometrial samples of women with regular menstrual cycles (n = 16). In each individual tissue sample the expression and phosphorylation of ERalpha, Akt, and cyclin D1 was analyzed by Western blotting.

Results

The level of Akt protein did not show significant change, however, the activation of Akt proteins and the expression of ERalpha increased parallel with serum estrogen (E2) levels, suggesting the role of E2 in Akt activation and ERalpha expression. The level of pERalpha(Ser167) changed parallel with pAkt(Ser473) levels. Significant correlation was found between the changes of pERalpha and ERalpha (r = 0.650399, p < 0.005), and in that of pERalpha and pAkt (r = 0.639643, p < 0.007), respectively. The expression of cyclin D1 was increased in samples with elevated pAkt levels.

Conclusion

The results are indicating that the postmenopausal endometrium responds to E2 by both genomic and nongenomic mechanism. The interaction between ERalpha and Akt plays crucial role in the regulation of proliferative activity in postmenopausal endometrium.     

Endometrial leukemia inhibitory factor as a predictor of pregnancy after in vitro fertilization

Objective

To determine whether there is an association between endometrial expression of leukemia inhibitory factor (LIF) in the luteal phase of the menstrual cycle preceding in vitro fertilization (IVF) and treatment outcome.

Methods

Biopsy specimens from the endometria of 52 women in the luteal phase were immunostained against LIF. Embryo culture and transfer were done according to standard procedures.

Results

Clinical pregnancy occurred in 39% of the women following IVF, and strong endometrial immunohistochemical staining for LIF was associated with pregnancy (P = 0.01). The women with a strong LIF expression had a 6.4-fold higher chance of becoming pregnant than those with weaker intensities (P = 0.005).

Conclusion

Endometrial expression of LIF during the luteal phase can be used as a predictor of IVF success.     

Knowledge about emergency contraception among family-planning providers in urban Ghana

Objective

To assess the theoretical and practical knowledge about emergency contraception (EC) among family-planning (FP) providers in Ghana and to examine the association between FP providers’ theoretical and practical knowledge.

Methods

Data on 600 FP providers were collected through a census of facilities offering FP services in Kumasi, Ghana, in 2008. Nested linear multivariate regression analysis was used to identify sociodemographic, facility-related, and work-related variables associated with FP providers’ theoretical and practical knowledge about EC.

Results

On average, FP providers gave 4.1 correct answers to the 11 questions assessing theoretical knowledge and 5.6 correct answers to the 8 questions assessing their practical ability to provide EC. The FP providers seemed to learn provision-related aspects through practice without having a particularly good theoretical knowledge on EC as a contraceptive method. The health sector in which FP providers worked, their education and having received EC-specific training, the number of services offered, and the number of women seen during a week were all significant correlates of both theoretical and practical knowledge about EC. The 2 knowledge domains were significantly and positively associated.

Conclusion

There is need to improve knowledge about EC among FP providers in Ghana through in-service training.     

Longitudinal evaluation of cancer-associated biomarkers before and after weight loss in RENEW study participants: implications for cancer risk reduction

Introduction

Obesity is a major risk factor for the development of endometrial cancer (EC). An improved understanding of biologic mechanisms associated with weight loss, including alteration in inflammation, hormonal balance, and cancer antigens expression may lead to the development of effective cancer prevention strategies. The goal of this study was to explore longitudinal biomarker changes in obese women who underwent weight loss intervention, testing the hypothesis biomarker levels can be altered through intentional weight loss.

Methods

Serum samples from 89 participants with Class II and Class III obesity and 43 non morbidly obese comparisons were obtained in Re-Energize with Nutrition, Exercise and Weight Loss (RENEW) study as previously reported. Twenty-one bead-based xMAP immunoassays were utilized, including cancer-associated antigens, cytokines, chemokines, and hormones. One-way repeated measures ANOVA was used to examine the association between changes in biomarker expression levels over time (baseline, 6 months and 12 months). Linear mixed effects models were used to examine longitudinal relationships between biomarker expression levels.

Results

Mean levels of VEGF, soluble E-selectin, GH, adiponectin, IL-6, IL-7, CA-125, and IGFBP-1 significantly differed between time periods. In adjusted mixed linear models, decreasing BMI was significantly associated with lower levels of soluble E-selectin and IL-6 and increases in GH, adiponectin, and IGFBP-1.

Conclusions

This is one of the first efforts to explore changes in cancer-associated biomarkers in a cohort of weight loss research participants at high risk for EC development. Our findings demonstrate that changes in the expression of markers can be achieved with weight loss intervention.     

多囊卵巢综合征患者子宫内膜组织中胰岛素PI3K/Akt信号通路的活化及其意义

目的 通过分析多囊卵巢综合征(PCOS)患者子宫内膜组织中胰岛素的磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)信号通路中Akt的表达及其活化程度,探讨PI3K/Akt信号通路活化在PCOS子宫内膜增生及癌变形成中的作用及意义,并分析影响该信号通路活化程度的因素.方法 选择2007年1月-2008年6月在天津医科大学总医院就诊的PCOS患者52例为PCOS组,非PCOS(输卵管因素不孕或卵巢良性肿瘤)患者32例为对照组;测定所有患者的血清生殖激素水平、空腹血糖及胰岛素水平,并取子宫内膜组织行病理检查;计算体质指数(BMI)、稳态模型评估法计算的胰岛素抵抗指数(HOMA-IR).对PCOS组患者根据病理检查结果分为正常子宫内膜、子宫内膜增生及癌变,根据是否存在胰岛素抵抗分为胰岛素抵抗和非胰岛素抵抗.蛋白印迹法检测子宫内膜组织中Akt、磷酸化Akt(p-Akt)蛋白的表达水平.结果(1)PCOS组患者子宫内膜组织中p-Akt蛋白的表达水平[(46±18)％]高于对照组[(33±9)％],两组比较,差异有统计学意义(P＜0.01).(2)PCOS组子宫内膜增生及癌变患者子宫内膜组织中p-Akt蛋白的表达水平[(56±19)％]高于正常子宫内膜者[(31±12)％],两者比较,差异有统计学意义(P＜0.05);胰岛素抵抗患者子宫内膜组织中p-Akt蛋白的表达水平[(50±19)％]高于非胰岛素抵抗者[(34±10)％],两者比较,差异有统计学意义(P＜0.01).(3)HOMA-IR、BMI与子宫内膜组织中p-Akt蛋白的表达水平呈正相关(r=0.400、0.326,P均＜0.05).结论 PCOS患者子宫内膜存在胰岛素PI3K/Akt信号通路的过度活化,该信号通路过度活化与PCOS子宫内膜增生及癌变有关.胰岛素抵抗、肥胖可能是影响子宫内膜组织中胰岛素PI3K/Akt信号通路过度活化的独立风险因素.     

Relationships between transvaginal colour Doppler findings, infectious parameters and visual analogue scale scores in patients with mild acute pelvic inflammatory disease

Objective

To investigate the relationships between colour Doppler findings, infectious parameters and visual analogue scale (VAS) scores in patients with mild acute pelvic inflammatory disease (PID).

Study design

Twenty-seven patients diagnosed with PID were enrolled in the study. Resistance index (RI) and pulsatility index (PI) of uterine, arcuate and utero-ovarian arteries were measured, as well as VAS score, erythrocyte sedimentation rate, C-reactive protein, white blood cell count and body temperature at hospital admission. After the initial visit, all measurements were repeated and recorded on days 7, 15 and 30.

Results

PI and RI values of uterine arteries showed significant increases between days 1 and 7. However, PI and RI values of uterine arteries, RI values of arcuate arteries and RI values of utero-ovarian arteries showed significant increases between days 1 and 30. Statistically significant decreases in infectious parameters and VAS scores were observed between days 1 and 7, days 1 and 15 and days 1 and 30.

Conclusion

Infectious parameters and VAS scores showed concordant changes with clinical recovery in mild PID. Significant changes were also observed in PI and RI values of uterine arteries, but Doppler measurements of arcuate and utero-ovarian arteries showed a slower and later response to treatment.     

Inequalities in cesarean delivery rates by ethnicity and hospital accessibility in Brazil

Objective

To investigate inequalities in cesarean delivery rates in Brazil according to ethnic group and level of access to hospital delivery.

Methods

Cross-sectional analysis of data for primiparous women with singleton deliveries between 2003 and 2004 from the National Information System of Live-Births (6 064 799 live births). Robust Poisson regression modeling was applied to estimate prevalence ratios of cesarean deliveries for ethnic group and level of access to hospital delivery according to residence.

Results

There were 2 438 180 primiparous deliveries and the cesarean rate was 45.8%. Ethnic inequalities in cesarean delivery rates showed lower rates for all ethnic groups compared with white women, with the lowest rates recorded for indigenous women. The association between ethnicity and cesarean delivery was higher in states with lower access to hospital (P < 0.001). Multiple regression models showed that this association was, in part, explained by older maternal age and higher levels of education and prenatal care.

Conclusions

Overuse of cesarean delivery and strong evidence of ethnic inequalities in cesarean rates exist in Brazil. The inequalities are greater in states with lower access to hospital and were partially explained by socioeconomic factors and prenatal care, suggesting a misuse of medical technology at birth.     

Conservative management as an initial approach for post-operative voiding dysfunction

Objectives

The management of voiding dysfunction after tension-free vaginal tape (TVT) remains controversial. Timing of surgical intervention is debatable and the role of conservative management is not well researched. This study aims to determine whether self catheterisation is an effective first line management option for these patients.

Study design

389 women underwent a TVT operation over a five year period. Twenty-two (5.6%) developed post-operative voiding dysfunction. Twenty women commenced CISC and their progress was monitored by recording voided volumes and residual urine volumes in a voiding diary and uroflowmetry. Residual volumes of less than 100 ml s were considered normal.

Results

Voiding function returned to normal with self catheterisation in 72% of patients and of these, 85% were cured in less than 12 weeks.

Conclusion

CISC is a suitable and effective initial approach to managing the majority of cases of voiding dysfunction and avoids the risks associated with further surgery, including the recurrence of stress incontinence.     

Metabolic and endocrine effects of metformin and metformin plus cyclic medroxyprogesterone acetate in women with polycystic ovary syndrome

Objective

To evaluate the metabolic and endocrine effects of treatment with cyclic medroxyprogesterone acetate (MPA) plus metformin compared with metformin alone in women with PCOS.

Methods

In this prospective randomized study of women with PCOS, 20 women received 850 mg of metformin twice a day, and 20 women received 850 mg of metformin plus 5 mg of MPA twice a day. Body mass index, hormonal and lipid blood profiles, homocysteine blood level, and insulin sensitivities assessed by homeostasis model assessment (HOMA) were recorded at baseline and at 3 months.

Results

Total cholesterol levels decreased in the metformin plus MPA group (P = 0.002) but did not change significantly in the metformin group (P = 0.159). While homocysteine levels remained unchanged in the metformin plus MPA group, they increased significantly in the metformin group (P = 0.002).

Conclusion

There were no adverse effects of short-term cyclic MPA plus metformin treatment on metabolic parameters or insulin resistance in patients with PCOS over a 3-month treatment period.