Urinary bisphenol A in women with polycystic ovary syndrome - a possible suppressive effect on steroidogenesis?

OBJECTIVES: There is a growing evidence indicating an impact of endocrine distrupting chemicals such as bisphenol A (BPA) on human reproduction. Its higher levels in serum or urine have been documented in women with polycystic ovary syndrome (PCOS), however the relationship to ovarian steroidogenesis remains unclear. Aim of the study was to compare urinary BPA (U-BPA) concentrations among PCOS women and control group. Second aim was to assess the relationship of U-BPA to ovarian steroidogenesis in the group with PCOS. METHODS: Eighty six Caucasian women (age 28.5 ± 5.1 years) diagnosed with PCOS and 32 controls of age 24.9 ± 4.4 years were included in the study. Fasting blood samples were analyzed for biochemical parameters and steroid hormones. U-BPA was measured in the morning urine sample using high pressure liquid chromatography. RESULTS: PCOS women had significantly higher U-BPA as compared with control group (p=0.0001). Those with high levels of U-BPA (U-BPA ≥2.14 ug/g creatinine) demonstrated higher serum insulin (p=0.029) and HOMA IR (p=0.037), lower serum estrone (p=0.05), estradiol (p=0.0126), FSH (p=0.0056), and FAI (p=0.0088), as compared with low-BPA group (U- BPA <2.14 ug/g creatinine). In PCOS women, U-BPA positively correlated with age (p=0.0026; R2=0.17), negatively with estradiol (p=0.0001, R2=0.5), testosterone (p=0.0078, R2=0.15), free-testosterone (p=0.0094, R2=0.12) and FAI (p=0.0003, R2=0.32), respectively. CONCLUSIONS: PCOS women have significantly higher U-BPA concentrations than healthy controls. U-BPA positively correlates with age and negatively with ovarian steroid hormones suggesting a possible suppressive effect of bisphenol A on ovarian steroidogenesis.

Urinary vitamin D-binding protein as a marker of ovarian reserve.

BACKGROUND: Ovarian reserve reflects the quality and quantity of available oocytes and has become an indispensable measure for the better understanding of reproductive potential. Proteomic approaches are especially helpful in discerning differential protein expression patterns associated with normal and diseased states and, thus, proteomic analyses are increasingly used to identify clinically useful biomarkers. The aim of this study was to investigate proteins secreted in the urine of patients with different ovarian reserve by proteomic techniques to identify potential markers for assessing ovarian reserve. METHODS: Urine samples were obtained from patients with polycystic ovary syndrome (PCOS) and diminished ovarian reserve (DOR), and from normal control (NC)participants. We used isobaric tags for relative and absolute quantification (iTRAQ) technology combined with mass spectrometry analysis to identify candidate urinary proteins in the three groups. The selected proteins were confirmed using western blot analysis and enzyme-linked immunosorbent assay (ELISA). Diagnostic performance of the selected proteins was assessed using receiver operating characteristic analysis. RESULTS: When Compared with NC samples, 285 differentially expressed proteins (DEPs) were identified in the DOR samples and 372 in the PCOS samples. By analyzing the intersection of the two groups of DEPs, we found 26 proteins with different expression trends in the DOR and PCOS groups. Vitamin D-binding protein (VDBP) was the key protein for the protein-protein interaction network. ELISA quantification of urinary VDBP revealed the highest levels in the PCOS group, followed by the NC group and the lowest levels in the DOR group (115.90 ± 26.02, 81.86 ± 23.92 and 52.84 ± 21.37 ng/ml, respectively; P < 0.05). As a diagnostic marker, VDBP had a sensitivity of 67.4% and a specificity of 91.8% for DOR, and a sensitivity of 93.8% and a specificity of 77.6% for PCOS. CONCLUSIONS: Urinary VDBP is closely associated with ovarian reserve and can be considered as a novel noninvasive biomarker of ovarian reserve. However, studies including large sample sizes are needed to validate these results.

Indicator of early kidney injury in adolescents with polycystic ovary syndrome: Can urine NGAL level be?

INTRODUCTION AND PURPOSE: The Urinary Neutrophil-gelatinase associated lipocalin (NGAL) levels which are a biomarker for early diagnosis of kidney damage that may develop in patients with Polycystic Ovary Syndrome (PCOS) were investigated in the study. MATERIAL AND METHODS: The 30 patients diagnosed with Polycystic Ovarian Syndrome between the ages of 13 and 18 who applied to the Yuzuncu Yil University General Children's Outpatient Clinic were included in the PCOS group and 30 healthy adolescents without any known acute or chronic illness and drug use were included in the control group. FINDINGS: Urine NGAL value was 842.204 ± 21.561 in PCOS group and 775.379 ± 23.98 in control group. NGAL level in PCOS group was statistically significantly higher than control group (p: .045). When we examine the relationship between dyslipidemia and PCOS; While dyslipidemia was positive in 10 (33.7%) patients in the PCOS group, it was negative in 20 (66.7%) patients. While 1 patient had dyslipidemia, 29 patients did not have dyslipidemia in the control group. A significant relationship was found between dyslipidemia and PCOS (p: .005). CONCLUSION: We found that subclinical kidney dysfunction started in early stage patients in PCOS in our study. The urine NGAL level was thought to increase in response to increased oxidative stress in PCOS. We found no relationship between, insulin resistance and urea, BUN, creatinine and NGAL levels. However, we found a negative correlation between NGAL level and LDL. In addition, dyslipidemia, insulin resistance and ALT elevation were detected in the PCOS group.

Can environmental pollutant bisphenol A increase metabolic risk in polycystic ovary syndrome?

BACKGROUND: Bisphenol A (BPA), a widespread industrial substance is recognized as endocrine disrupting chemical and therefore could be associated with polycystic ovary syndrome (PCOS) related metabolic disturbances. PATIENTS: In this study 29 women of reproductive age with diagnosed PCOS were enrolled. METHODS: BPA in urine samples was analyzed by gas chromatography-mass spectrometry. RESULTS: BPA was detected in urines of 48.28% participants. The waist-to-height ratio (WtHR) was statistically significant higher in PCOS BPA+ in comparison to PCOS BPA- women (p = 0.046). PCOS BPA+ women had 6.88 times (95%Cl 1.3481-35.0600, z = 2.319, p = 0.020) higher risk for waist circumference above 80 cm and 4.95 odds (95%Cl 1.0169-24.096, z = 1.981, p = 0.048) to have WtHR over 0.5 when compared to PCOS BPA-. Statistically significant positive association between BPA urine concentrations and insulin serum levels (p = 0.038) was obtained. BPA urine values were associated with elevated HOMA-IR values and reduced HDL levels with moderate significance (p = 0.079 and p = 0.061, respectively). Also, there was 3.75 times (95%Cl 0.7936-17.7203, z = 1.668, p = 0.095) higher risk for PCOS BPA+ women to have testosterone levels above reference values. CONCLUSION: The obtained results suggested that the BPA exposition in PCOS women was followed by increased metabolic risk through promotion of obesity, especially the visceral type, hyperinsulinemia, insulin resistance, dyslipidemia and elevated androgen levels.

Non-invasive urinary metabolomics reveals metabolic profiling of polycystic ovary syndrome and its subtypes.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder, which affects 4-10 % women of reproductive age. Though accumulating scientific evidence, its pathogenesis remains unclear. In the current study, metabolic profiling as well as diagnostic biomarkers for different phenotypes of PCOS was investigated using non-invasive urinary GCMS based metabolomics. A total of 371 subjects were recruited for the study. They constituted the following groups: healthy women, those with hyperandrogenism (HA), women with insulin-resistance (IR) in PCOS. Two cross-comparisons with PCOS were performed to characterize metabolic disturbances. A total of 23 differential metabolites were found. The altered metabolic pathways included glyoxylate and dicarboxylate metabolism, pentose and glucuronate interconversions, and citrate cycle and butanoate metabolism. For differential diagnosis, a panel consisting of 9 biomarkers was found from the comparison of PCOS from healthy subjects. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.8461 in the discovery phase. Predictive value of 89.17 % was found in the validation set. Besides, a panel of 8 biomarkers was discovered from PCOS with HA vs IR. The AUC for 8-biomarker panel was 0.8363, and a panel of clinical markers (homeostasis model assessment-insulin resistance and free androgen index) had 0.8327 in AUC. While these metabolites combined with clinical markers reached 0.9065 in AUC from the discovery phase, and 93.18 % in predictive value from the validation set. The result showed that differences of small-molecule metabolites in urine may reflect underlying pathogenesis of PCOS and serve as biomarkers for complementary diagnosis of the different phenotypes of PCOS.

Dynamic Analysis of the Biochemical Changes in Rats with Polycystic Ovary Syndrome (PCOS) Using Urinary 1H NMR-Based Metabonomics.

Polycystic ovarian syndrome (PCOS) is the most common endocrine disease that causes reproductive abnormalities in fertile women. It is closely related to the persistent anovulatory, insulin resistance, and high androgen. However, the molecular mechanisms underlying the pathological development of PCOS are still unclear. In this study, we aimed to explore the distinctive metabolic patterns in insulin combined with human chorionic gonadotrophin induced PCOS. The dynamic changes of endogenous metabolites in the development of PCOS were studied using untargeted metabolomic approaches based on nuclear magnetic resonance. The results showed that the degree of PCOS disorder metabolites at different periods was not exactly the same. Twelve significantly differential endogenous metabolites from different time points were selected as potential biomarkers relate to pathological process of PCOS. Among them, six metabolites showed a good diagnostic accuracy with PCOS model. The arginine and proline metabolic pathway was considered as one of the most crucial pathways that affects occurrence and development of PCOS. In addition, IRS-1, Akt, PI3K, IκB, and NF-κB (p65) were significantly changed in the ovary tissue of PCOS rats, which revealed that the IRS-1-PI3K/Akt and NF-κB signal pathway may be involved in the development of PCOS. This study demonstrated that metabolomic analysis is a powerful tool for providing novel insight into understanding the pathogenesis of PCOS and provide a basic reference for the diagnosis of PCOS at the onset stage.

Urinary volatile metabolomics as a viable alternative diagnostic tool for polycystic ovary syndrome: An exploratory hypothesis.

Polycystic Ovary Syndrome (PCOS) is a metabolic disorder prevalent globally. Female infertility cases are also on the increase during the recent times which almost matches with the increasing incidence of PCOS. The NIH-USA-defined symptoms for clinical confirmation of PCOS include oligo-ovulation, elevated androgen level and presence of cysts in the ovary. Therapeutic approaches to PCOS require confirmatory diagnostics such as measurement of hormones and ultrasound scan of the ovary, which are in part, invasive. Conversely, the volatile organic compounds (VOCs) that are present in body fluids (urine, feces, saliva, etc.) and exhaled breath are reported to be endogenously altered in diseased state, which may be indicative of diseases including cancer. We hypothesize that the hindered metabolic state in PCOS condition would conditionally alter the VOCs that eventually are excreted in urine, which may offer a template to develop a viable and non-invasive diagnostic tool.

Environmental exposure to triclosan and polycystic ovary syndrome: a cross-sectional study in China.

OBJECTIVES: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy of women at reproductive age. Although the aetiology of PCOS remains unclear, potential effects of environmental endocrine-disrupting compounds on the development of PCOS have drawn increasing attention. The aim of the current study was to examine the association between triclosan (TCS) and PCOS, and explore possible mechanisms on how TCS may contribute to the development of clinical manifestations of PCOS. DESIGN: Cross-sectional study. SETTING: This study was conducted in one tertiary-level hospital located in Zhejiang, China. PARTICIPANTS: A total of 674 infertile women at 18-45 years of age were recruited in 2014-2015. Participants with (n=84) and without (n=212) PCOS with urinary TCS concentration available were included in the analyses. METHODS: Urinary TCS concentration was measured using a high-performance liquid chromatography-electrospray ionisation tandem mass spectrometry. Logistic regression model was used to examine the association between TCS and PCOS. Fractional polynomial regression models were built to fit the potential non-linear relationship between TCS concentrations and luteinising hormone (LH) and LH/follicle stimulate hormone (FSH). RESULTS: The PCOS group had significantly higher level of TCS concentration than the non-PCOS group (the median of TCS (IQR), µg/g creatinine: 1.49 (0.68-3.80) vs 1.06 (0.52-3.02), p=0.0407). Compared with the lowest tertile, the highest tertile of TCS concentration was associated with an increased odd of PCOS (OR 2.12, 95% CI 1.12 to 3.99). After adjusting for potential confounders, the significant association remained (OR 1.99, 95% CI 1.05 to 3.79). Positive relationships were found between TCS levels and LH and LH/FSH ratio in non-PCOS participants. CONCLUSIONS: TCS exposure at a relatively low level is associated with PCOS in Chinese women. Further epidemiological studies are needed to confirm our finding, which may have important public health implications.

Urinary steroid profiling in women hints at a diagnostic signature of the polycystic ovary syndrome: A pilot study considering neglected steroid metabolites.

BACKGROUND: Although the polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women with vast metabolic consequences, its etiology remains unknown and its diagnosis is still made by exclusion. This study aimed at characterizing a large number of urinary steroid hormone metabolites and enzyme activities in women with and without PCOS in order to test their value for diagnosing PCOS. METHODS: Comparative steroid profiling of 24h urine collections using an established in-house gas-chromatography mass spectrometry method. Data were collected mostly prospectively. Patients were recruited in university hospitals in Switzerland. Participants were 41 women diagnosed with PCOS according to the current criteria of the Androgen Excess and PCOS Society Task Force and 66 healthy controls. Steroid profiles of women with PCOS were compared to healthy controls for absolute metabolite excretion and for substrate to product conversion ratios. The AUC for over 1.5 million combinations of metabolites was calculated in order to maximize the diagnostic accuracy in patients with PCOS. Sensitivity, specificity, PPV, and NPV were indicated for the best combinations containing 2, 3 or 4 steroid metabolites. RESULTS: The best single discriminating steroid was androstanediol. The best combination to diagnose PCOS contained four of the forty measured metabolites, namely androstanediol, estriol, cortisol and 20ßDHcortisone with AUC 0.961 (95% CI 0.926 to 0.995), sensitivity 90.2% (95% CI 76.9 to 97.3), specificity 90.8% (95% CI 81.0 to 96.5), PPV 86.0% (95% CI 72.1 to 94.7), and NPV 93.7% (95% CI 84.5 to 98.2). CONCLUSION: PCOS shows a specific 24h urinary steroid profile, if neglected metabolites are included in the analysis and non-conventional data analysis applied. PCOS does not share a profile with hyperandrogenic forms of congenital adrenal hyperplasias due to single steroid enzyme deficiencies. Thus PCOS diagnosis by exclusion may no longer be warranted. Whether these findings also apply to spot urine and serum, remains to be tested as a next step towards routine clinical applicability.

Identification of Potential Biomarkers for Urine Metabolomics of Polycystic Ovary Syndrome Based on Gas Chromatography-Mass Spectrometry.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder, and it's diagnosis is difficult. The aim of this study was to investigate the metabolic profiles of PCOS patients by analyzing urine samples and identify useful biomarkers for diagnosis of PCOS. METHODS: This study was carried out in the Department of Obstetrics and Gynecology of the Maternal and Child Health Hospital of Hunan Province from December 2014 to July 2016. In this study, the urine samples of 21 women with PCOS and 16 healthy controls were assessed through gas chromatography-mass spectrometry to investigate the urine metabolite characteristics of PCOS and identify useful biomarkers for the diagnosis of this disorder. The Student's t-test and rank sum test were applied to validate the statistical significance of the between the two groups. RESULTS: In total, 35 urine metabolites were found to be significantly different between the PCOS patients and the controls. In particular, a significant increase in the levels of lactose (10.01 [0,13.99] mmol/mol creatinine vs. 2.35 [0.16, 3.26] mmol/mol creatinine, P = 0.042), stearic acid (2.35 [1.47, 3.14] mmol/mol creatinine vs. 0.05 [0, 0.14] mmol/mol creatinine, P < 0.001), and palmitic acid (2.13 [1.07, 2.79] mmol/mol creatinine vs. 0 [0, 0] mmol/mol creatinine, P < 0.001) and a decrease in the levels of succinic acid (0 [0, 0] mmol/mol creatinine vs. 38.94 [4.16, 51.30] mmol/mol creatinine, P < 0.001) were found in the PCOS patients compared with the controls. It was possible to cluster the PCOS patients and the healthy controls into two distinct regions based on a principal component analysis model. Of the differentially expressed metabolites, four compounds, including stearic acid, palmitic acid, benzoylglycine, and threonine, were selected as potential biomarkers. CONCLUSIONS: This study offers new insight into the pathogenesis of PCOS, and the discriminating urine metabolites may provide a prospect for the diagnosis of PCOS.

Bisphenol A and Ovarian Reserve among Infertile Women with Polycystic Ovarian Syndrome.

To better understand possible effects of bisphenol A (BPA) exposure on ovarian reserve in women with polycystic ovary syndrome (PCOS), we measured creatinine adjusted urinary BPA (BPA_Cre) concentrations and used regression models to evaluate the association between urinary BPA level and antral follicle count (AFC), antimullerian hormone (AMH), day-3 follicle stimulating hormone levels (FSH) and inhibin B (INHB) in 268 infertile women diagnosed with PCOS. BPA was detected in all women with a median concentration of 2.35 ng/mL (the 25th and 75th percentiles of 1.47 ng/mL and 3.95 ng/mL). A unit increase in BPA_Cre was associated with a significant decrease of 0.34 in AFC (ß = -0.34, 95% CI = -0.60, -0.08; p = 0.01). Likewise, BPA was negatively associated with AMH and day-3 FSH levels, but neither of them reached statistical significance. No association was observed between BPA and INHB. Our results suggest that in women with PCOS, BPA may affect ovarian follicles and, therefore, reduce ovarian reserve.

Cystatin C, a novel cardiometabolic risk marker in women with polycystic ovary syndrome.

OBJECTIVE: To investigate the impact of urinary albumin excretion (UAE) and cystatin C on the metabolic components of polycystic ovary syndrome (PCOS). METHODS: Seventy-five women with PCOS were divided into two groups according to metabolic syndrome as MetS + and MetS-. Clinical, metabolic and renal parameters were compared between the groups. Correlation analyses were performed between cystatin C, microalbuminuria and clinical and metabolic parameters in women with PCOS. RESULTS: Waist/hip ratio (WHR), body mass index, LDL cholesterol, triglyceride, total cholesterol, cystatin C, UAE were significantly higher in the MetS + group compared with the MetS - one. HDL cholesterol was significantly higher in the MetS - group than the MetS + one. The UAE positively correlates with LDL cholesterol, triglyceride and total cholesterol levels. Cystatin C positively correlates with UAE, WHR, LDL cholesterol, triglyceride, total cholesterol levels. CONCLUSIONS: Evaluating UAE and cystatin C may be important for the detection of target subjects at high risk for future metabolic syndrome and cardiovascular disease.

Detection of urine metabolites in polycystic ovary syndrome by UPLC triple-TOF-MS.

BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrine disorder whose pathogenesis remains unclear. There are also no effective biomarkers for this disease. We evaluated the metabolic changes in PCOS patients and to investigate potential metabolic biomarkers for PCOS. METHODS: Twenty-two women with PCOS and 15 healthy controls were studied. Urine samples were assessed through ultra-performance liquid chromatography-mass spectrometry followed by principal component analysis and partial least squares discriminant analysis. RESULTS: Using the presented methods, 59 urine metabolites were found at different concentrations in PCOS patients. Moreover, two novel potential biomarkers, testosterone-glucuronide and 11α-hydroxyprogesterone, and four candidate biomarkers, benzofenap, methionyl-phenylalanine, MG(18:4(6Z,9Z,12Z,15Z)/0:0/0:0) and 2-(14,15-epoxyeicosatrienoyl) glycerol, were found to show significant differences through variance analysis (P<0.01) and were identified as target metabolites. The two potential biomarkers identified in this study highly correlate to the metabolites catalyzed by the ovarian cytochrome P450c17α. CONCLUSIONS: Two novel potential urinary biomarkers, testosterone-glucuronide and 11α-hydroxyprogesterone, and four candidate urinary biomarkers, benzofenap, methionyl-phenylalanine, MG(18:4(6Z,9Z,12Z,15Z)/0:0/0:0), and 2-(14,15-epoxyeicosatrienoyl) glycerol, were identified in PCOS patients by a metabolomic approach. Further study of the biomarkers using larger populations is needed to validate these biomarkers and thereby understand the pathogenesis of PCOS, potentially allowing for its diagnosis.

Association between metabolic syndrome and premicroalbuminuria among Iranian women with Polycystic Ovary Syndrome: a case control study.

OBJECTIVE: The aim of this study was to assess the association between premicroalbuminuria and metabolic syndrome in women with Polycystic Ovary Syndrome (PCOS). METHODS: In this case - control study, we analyzed the medical records of 78 women (mean age ±SD was 27.2± 2.5 years) with PCOS and 63 controls (mean age ±SD was 26.9±2.4 years) from an endocrinology outpatient center of Buali university hospital Qazvin city in Iran during 2008 to 2010. Anthropometric characteristics, Albumin/Creatinine Ratio (ACR), Lipid profile, Liver enzyme concentration and occurrence of metabolic syndrome were compared between the two groups. Premicroalbuminuria was defined as ACR>7mg/g. RESULTS: Premicroalbuminuria was found in 53.8% of PCOS and 33.3% of control group (p value=0.015). Patients with PCOS and premicroalbuminuria had higher serum levels of fasting insulin and glucose, blood pressure and more waist circumference compared to PCOS patients who had ACR<7mg/g. Fifty percent of patients with PCOS and ACR>7mg/g fulfilled criteria of metabolic syndrome; whereas no case of metabolic syndrome was found in PCOS patients without premicroalbuminuria. CONCLUSIONS: Premicroalbuminuria is more prevalent in patients with PCOS compared to normal individuals. Metabolic syndrome is more frequently seen in patients with PCOS and premicroalbuminuria against patients with ACR<7mg/g.

The association of urinary albumin excretion and metabolic complications in polycystic ovary syndrome.

OBJECTIVE: This study was planned to screen polycystic ovary syndrome (PCOS) women for albuminuria and to evaluate the association between urinary albumin excretion (UAE) and metabolic disturbances of PCOS. In addition, this is the first study in the literature evaluating the association between UAE and carotid intima-media thickness (CIMT) in PCOS cases. STUDY DESIGN: The study population consisted of 65 PCOS women. The study was prospectively designed and performed in a university hospital. The diagnosis of PCOS was made according to the Rotterdam criteria: exclusion criteria were hyperprolactinemia, thyroid dysfunction, adrenal dysfunction, diabetes mellitus, hypertension, and pregnancy. Blood samples were collected in the follicular phase of a menstrual cycle and serum samples were analyzed for fasting glucose, insulin, and hormone and lipid profiles. Twenty-four hour urine specimens were collected for the detection of UAE. CIMT was estimated by visual assessment of the distance between the lumen-intima and intima-adventitia interfaces. RESULTS: The mean age and BMI were 23 years and 23 kg/m(2), respectively. The median UAE was 7 mg/day (range: 0.3-154 mg/day). The median UAE as micrograms of albumin per milligram of creatinine (uACR) was 5.6 (0.28-159). Regarding the uACR cutoff value (>6.93 µg/mg), significantly higher levels of triglycerides, 17 OH-progesterone, insulin resistance (HOMA index > 2.1) and increased CIMT were present in these cases. Microalbuminuria (uACR > 25 µg/mg) was present in 6.2%. In the regression analyses serum HDL-C levels were found to be independent predictor for uACR > 2 µg/mg (OR: 0.85) and estradiol levels were the independent predicting factor for uACR > 6.93 µg/mg even after adjustments for age and BMI were performed (OR:1.02). CONCLUSIONS: UAE, expressed as uACR > 6.93 µg/mg, seems to be an associated sign of metabolic problems which might help in discriminating PCOS at risk of future CVD. Further studies are needed before routine use of albuminuria in PCOS cases for the detection of CVD risk.

Predictors of urinary albumin excretion in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate urinary albumin excretion (UAE) in normotensive and nondiabetic women with polycystic ovary syndrome (PCOS) in relation to their clinical, endocrine, and metabolic profiles. DESIGN: Observational study. SETTING: University fertility center. PATIENT(S): Sixty-three women with PCOS were evaluated. INTERVENTION(S): Clinical assessments and urine and blood testing. MAIN OUTCOME MEASURE(S): Urinary albumin excretion, systolic and diastolic blood pressure, serum levels of LH, FSH, PRL, T, 17-hydroxyprogesterone, glucose, insulin, lipids, C-reactive protein, and 24-hour urinary free cortisol. RESULT(S): In univariate and multivariate correlation analysis, UAE correlated with diastolic blood pressure, insulin area under the curve during glucose tolerance test, PRL, and 17-hydroxyprogesterone. Overt microalbuminuria was detected in a significant proportion of subjects. CONCLUSION(S): Urinary albumin excretion in women with PCOS correlates well with other cardiovascular risk factors. Because the relationship between UAE and adverse cardiovascular events is continuous, evaluation of UAE in the presence of PCOS may provide clinically relevant information and may aid in selecting appropriate patients for more aggressive treatment of likely aggravating factors, such as hyperinsulinemia or borderline hypertension.

Metformin does not improve the reproductive or metabolic profile in women with polycystic ovary syndrome (PCOS).

To determine whether metformin, when given to women with polycystic ovary syndrome (PCOS), promotes folliculogenesis by prompting a drop in free sex steroids resulting in a compensatory follicle stimulating hormone (FSH) rise, we conducted a randomized, double-blind, placebo-controlled crossover clinical trial. Eight mid-reproductive age PCOS participants with mean obese body mass index (BMI) and normal glucose tolerance received 8 weeks of metformin, given in a step-up fashion to a maximum dose of 2000 mg daily or placebo with daily urine sampling, 4-6 weeks washout, and crossover to the remaining arm for 8 weeks. To confirm the effects of metformin on glucose and other metabolic markers, a hyperinsulinemic, euglycemic 3-dose clamp (physiologic: 30 mU/m(2) per minute, high: 400 mU/m(2) per minute) followed each treatment. Urinary FSH, luteinizing hormone (LH), or pregnanediol glucuronide (Pdg) did not differ by treatment. Glucose disposal, endogenous glucose production, BMI, ovulation rates, serum sex steroids, free fatty acids, and lipids did not significantly differ by treatment, despite good evidence for compliance with the protocol. During the clamp, high-dose insulin administration was associated with an acute drop in serum LH. We conclude that short-term, high-dose metformin exerts minimal effects on both metabolic markers and reproductive hormones in a small sample of overall morbidly obese women.

Premicroalbuminuria in women with polycystic ovary syndrome: a metabolic risk marker.

OBJECTIVE: To determine the relationship between urinary albumin excretion and features of the metabolic syndrome in women with polycystic ovary syndrome (PCOS). METHODS: We retrospectively analyzed the medical records of 189 premenopausal women (mean age +/- SD, 28.9 +/- 7.7 years) with PCOS and 81 control patients (mean age +/- SD, 37.9 +/- 8.6 years) from a single endocrinology practice. Exclusion criteria were diabetes, heart disease, kidney disease, use of lipid-lowering agents, and use of antihypertensive agents (except spironolactone). The urine albumin-to-creatinine ratio (ACR) was measured in a random single-voided urine sample. Premicroalbuminuria was defined as an ACR >7 mg/g. RESULTS: The prevalence of ACR >7 mg/g was 31.2% in the PCOS group (N = 189) and 35.8% in the control group (N = 81). The metabolic syndrome was noted in 16.3% (27 of 166) of patients with PCOS and in 2.9% (2 of 69) of control subjects. Nine percent of patients with PCOS who had an ACR 7 mg/g had the metabolic syndrome. Patients with PCOS who had an ACR >7 mg/g had significantly higher blood pressure and alanine aminotransferase levels than did those with an ACR 7 mg/g, no significant difference was found in frequency of use of metformin, spironolactone, or oral contraceptives. CONCLUSION: In women with PCOS, an ACR >7 mg/g was strongly associated with the metabolic syndrome, high blood pressure, and elevated alanine aminotransferase levels. It may be useful to consider ACR >7 mg/g as an associated sign of the presence of metabolic syndrome in women with PCOS.