Can dysglycemia in OGTT be predicted by baseline parameters in patients with PCOS?

Background: Polycystic ovary syndrome (PCOS) is considered a risk factor for the development of type 2 diabetes mellitus (T2DM). However, which is the most appropriate way to evaluate dysglycemia in women with PCOS and who are at increased risk are as yet unclear. Aim of the study: To determine the prevalence of T2DM, impaired glucose tolerance (IGT), and impaired fasting glucose (IFG) in PCOS women and potential factors to identify those at risk. Subjects and methods: The oral glucose tolerance test (OGTT), biochemical/hormonal profile, and ovarian ultrasound data from 1614 Caucasian women with PCOS and 362 controls were analyzed in this cross-sectional multicenter study. The data were categorized according to age and BMI. Results: Dysglycemia (T2DM, IGT, and IFG according to World Health Organization criteria) was more frequent in the PCOS group compared to controls: 2.2% vs 0.8%, P = 0.04; 9.5% vs 7.4%, P = 0.038; 14.2% vs 9.1%, P = 0.002, respectively. OGTT was essential for T2DM diagnosis, since in 88% of them basal glucose values were inconclusive for diagnosis. The presence of either T2DM or IFG was irrespective of age (P = 0.54) and BMI (P = 0.32), although the latter was associated with IGT (P = 0.021). There was no impact of age and BMI status on the prevalence of T2DM or IFG. Regression analysis revealed a role for age, BMI, fat deposition, androgens, and insulin resistance for dysglycemia. However, none of the factors prevailed as a useful marker employed in clinical practice. Conclusions: One-third of our cohort of PCOS women with either T2DM or IGT displayed normal fasting glucose values but without confirming any specific predictor for dysglycemic condition. Hence, the evaluation of glycemic status using OGTT in all women with PCOS is strongly supported.

Publisher Correction: Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Oral contraceptives increase platelet microparticle levels in normal-weight women with polycystic ovary syndrome.

PURPOSE: Platelet microparticles (PMPs), which are microvesicles shed from platelets, participate in inflammation, vascular homeostasis, and thrombosis. PMPs are increased in obese women with polycystic ovary syndrome (PCOS). Agents that modulate hormonal aspects of PCOS could affect the levels of PMPs. The aim of the present study was to evaluate the effects of oral contraceptives (OCPs), antiandrogen, and metformin use for 6 and 12 months on PMPs in normal-weight women with PCOS. METHODS: Forty-five women with PCOS and 13 healthy women were recruited. Biochemical, hormonal, and clinical parameters were recorded. Women with PCOS received treatment with OCPs, OCPs+antiandrogens, or metformin, depending on their main complaint or clinical/biochemical findings. PMPs were measured at baseline and after 6 and 12 months. RESULTS: At baseline, patients with PCOS had higher levels of PMPs than controls (p = 0.017), which increased after 6-month treatment with OCPs (p = 0.006). Subsequently, they decreased after 12-month treatment (p = 0.046). Metformin had no effect on PMP levels. CONCLUSION: In conclusion, PMP levels are increased in PCOS and further increase with OCP use. This effect could possibly contribute to the increased risk of venous thromboembolism associated with OCP use. However, further studies are needed to elucidate the exact role of PMPs in PCOS.

Lipid accumulation product is associated with metabolic syndrome in women with polycystic ovary syndrome.

OBJECTIVE: There is a need for a simple and accurate method for the assessment of cardiovascular risk in polycystic ovary syndrome (PCOS). Lipid accumulation product (LAP) is based on the assessment of waist circumference and serum triglycerides that yield an estimation of lipid overaccumulation. We aimed to determine whether LAP is associated with metabolic syndrome (MetS) in Caucasian women with PCOS. DESIGN: We studied 222 women with PCOS who were diagnosed using the Rotterdam criteria. In all the subjects and controls, LAP was determined and the MetS was assessed using three different international criteria, NCEP-ATP III, IDF, and JIS. ROC curve and logistic regression analyses were performed to determine and analyze associations with the MetS. RESULTS: In the study population the prevalence of MetS was 16.2-19.4%. The cut-off value of 25.9 determined that LAP has the strongest association with MetS whichever international criteria are used, followed by HDL (NCEP-ATP III and JIS) and glucose (IDF). CONCLUSIONS: LAP is used as an independent clinical indicator for MetS in our PCOS women of Caucasian origin. The high diagnostic accuracy of LAP is superseding the need for the use of multiple clinical indicators for the assessment of lipid accumulation as a prerequisite for diagnosis of metabolic and cardiovascular diseases in PCOS women.

Association of Calpain (CAPN) 10 (UCSNP-43, rs3792267) gene polymorphism with elevated serum androgens in young women with the most severe phenotype of polycystic ovary syndrome (PCOS).

OBJECTIVES: To highlight a possible association of Calpain (CAPN 10) gene UCSNP-43 polymorphism with hormonal and metabolic traits of young women with different phenotypes of polycystic ovary syndrome (PCOS). DESIGN: PCOS women were genotyped for the CAPN 10 gene UCSNP-43 polymorphism. A comparison of clinical and biochemical features of women with PCOS stratified on the basis of the CAPN 10 gene UCSNP-43 variants was assessed. METHODS: Anthropometric, hormonal and biochemical measurements were carried out in 668 PCOS women and 200 healthy controls. Subjects were also genotyped for the CAPN 10 gene UCSNP-43 polymorphism. The genotype frequency distributions between groups and controls were compared using the chi-square test. The association of the polymorphism with the clinical and biochemical features of the study cohort was estimated as well. RESULTS: No association of the frequency of CAPN 10 gene UCSNP-43 polymorphism with PCOS was detected. No association of the polymorphism with the anthropometric, biochemical and hormonal features was detected both in PCOS and control women. The polymorphism was associated with serum Δ4 androstenedione (p = 0.018), as well as with 17-OH progesterone (17-hydroxyprogesterone) among women with PCOS phenotype A (p = 0.012). CONCLUSIONS: CAPN 10 gene polymorphism UCSNP-43 is deprived of a metabolic contribution to cardiovascular disease (CVD). However, due to its association with androgen excess in phenotype A, CAPN 10 gene polymorphism UCSNP-43 could be used as a genetic marker for CVD in young PCOS women.

Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations.

Polycystic ovary syndrome (PCOS) is a common, highly heritable complex disorder of unknown aetiology characterized by hyperandrogenism, chronic anovulation and defects in glucose homeostasis. Increased luteinizing hormone relative to follicle-stimulating hormone secretion, insulin resistance and developmental exposure to androgens are hypothesized to play a causal role in PCOS. Here we map common genetic susceptibility loci in European ancestry women for the National Institutes of Health PCOS phenotype, which confers the highest risk for metabolic morbidities, as well as reproductive hormone levels. Three loci reach genome-wide significance in the case-control meta-analysis, two novel loci mapping to chr 8p23.1 [Corrected] and chr 11p14.1, and a chr 9q22.32 locus previously found in Chinese PCOS. The same chr 11p14.1 SNP, rs11031006, in the region of the follicle-stimulating hormone B polypeptide (FSHB) gene strongly associates with PCOS diagnosis and luteinizing hormone levels. These findings implicate neuroendocrine changes in disease pathogenesis.

Associations of menstrual cycle irregularities with age, obesity and phenotype in patients with polycystic ovary syndrome.

OBJECTIVE: Limited data suggest that menstrual cycle abnormalities are more pronounced in younger and more obese patients with polycystic ovary syndrome (PCOS). We aimed to evaluate the association between menstrual cycle pattern and age, obesity and PCOS phenotype in a large population of women with PCOS. DESIGN: We studied 1,297 women with PCOS and divided them according to: a) age in ≤ 20, 21-30 and > 30 years old, b) body mass index in normal weight, overweight and obese and c) PCOS phenotype in phenotype 1 (anovulation, hyperandrogenemia and polycystic ovaries), 2 (anovulation and hyperandrogenemia without polycystic ovaries), 3 (hyperandrogenemia and polycystic ovaries without anovulation) and 4 (anovulation and polycystic ovaries without hyperandrogenemia). RESULTS: The proportion of women with regular menstrual cycles progressively increased in the older age groups, being 8.1, 10.5 and 12.7% in women ≤ 20, 21-30 and > 30 years old, respectively (p = 0.037). The proportion of women with regular menstrual cycles did not differ between normal weight and obese women but was higher in overweight women (9.3, 9.4 and 13%, respectively; p = 0.020). The proportion of women with regular cycles alternating with irregular cycles was highest in women with phenotype 4, intermediate in women with phenotype 2 and lowest in women with phenotype 1 (74.3, 69.4 and 61.7%, respectively; p = 0.027). CONCLUSIONS: Menstrual cycle pattern is more irregular in women with the "classic" PCOS phenotypes than in phenotype 4 but appears to normalize with ageing. On the other hand, obesity does not appear to have an important effect on menstrual cycle pattern in PCOS.

Excess Metabolic and Cardiovascular Risk is not Manifested in all Phenotypes of Polycystic Ovary Syndrome: Implications for Diagnosis and Treatment.

AIM: To assess the potential differences in the metabolic and cardiovascular disease (CVD) risk between the distinct phenotypes of the Polycystic Ovary Syndrome (PCOS) according to the Rotterdam definition regardless of body mass index (BMI). PATIENTS-METHODS: The study included 300 women; 240 women with PCOS, according to the Rotterdam criteria and 60 controls without PCOS. All women were further subdivided, according to their BMI, into normal-weight and overweight/obese and PCOS women were furthermore subdivided to the 4 phenotypes of the syndrome. A complete hormonal and metabolic profile as well as the levels of high sensitivity C reactive protein (hsCRP) and lipoprotein-associated phospholipase A2 (Lp-PLA2) were measured. OUTCOMES: Levels of surrogate markers of subclinical atherosclerosis (hsCRP and Lp-PLA2), levels of evaluated CVD risk score using risk engines, and several correlations of CVD risk factors. RESULTS: hsCRP levels were higher but not significantly so in PCOS women compared with controls. In lean PCOS patients, Lp-PLA2 levels were significantly higher, compared with lean controls, mainly in the 2 classic phenotypes. Overweight/obese patients in all 4 phenotypes had significantly higher Lp-PLA2 levels compared with overweight/obese controls. Evaluated CVD risk according to 4 risk engines was not different among phenotypes and between PCOS patients and controls. There were several correlations of risk factors with metabolic syndrome and non-alcoholic fatty liver disease requiring appropriate treatment. CONCLUSION: Only 2 of 4 Rotterdam phenotypes, identical with those of the classic PCOS definition, have excess cardiometabolic risk. These need to be treated to prevent CVD events.

Effect of hyperglycemia and hyperinsulinemia on glutathione peroxidase activity in non-obese women with polycystic ovary syndrome.

OBJECTIVE: In order to gain deeper insight into molecular mechanisms underlying oxidative stress (OS) and its relation to insulin resistance and hyperandrogenemia, plasma markers of OS and antioxidant glutathione-peroxidase (GPX) activity were studied in non-obese polycystic ovary syndrome (PCOS) women via the oral glucose tolerance test (OGTT) and hyperinsulinemic euglycemic clamp. DESIGN: In 36 PCOS women, plasma nitrotyrosine, thiol groups, uric acid (UA) and GPX activity were studied during OGTT and clamp. Insulin resistance was assessed by the homeostasis model (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), Matsuda insulin sensitivity index (ISI) and M/I ratio. RESULTS: In PCOS patients, significant positive correlations were obtained for UA with testosterone (r=0.385, p=0.039) as well as indices of insulin resistance. Acute hyperglycemia during OGTT induced alteration in both OS markers and GPX. The change in nitrotyrosine and GPX during OGTT correlated with testosterone (r=0.543, p=0.036 and r=-0.457, p=0.025, respectively). The most significant association was found between OS markers and ISI. CONCLUSIONS: Our results indicate that non-obese PCOS women are prone to oxidative stress induced by hyperglycemia, but this seems not to be related to the direct effect of hyperinsulinemia during clamp. Oxidative stress markers correlated with indices of insulin resistance and circulating testosterone.

The influence of combined oral contraceptives containing drospirenone on hypothalamic-pituitary-adrenocortical axis activity and glucocorticoid receptor expression and function in women with polycystic ovary syndrome.

OBJECTIVE: Most women with PCOS have increased adrenal androgen production, enhanced peripheral metabolism of cortisol and elevation in urinary excretion of its metabolites. Increased cortisol clearance in PCOS is followed by a compensatory overdrive of the hypothalamic-pituitary-adrenocortical (HPA) axis. We hypothesized that oral contraceptives containing ethinylestradiol and drospirenone (EE-DRSP) could modulate glucocorticoid receptor (GR) expression and function and thus affect HPA axis activity in PCOS patients. DESIGN: We analyzed 12 women with PCOS (age 24.17±4.88 years; body mass index 22.05±3.97 kg/m²) treated for 12 months with EE-DRSP and 20 BMI matched controls. In all subjects testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), cortisol (basal and after dexamethasone), concentrations of GR protein, phospo-GR211 protein, number of GR per cell (B(max) and its equilibrium dissociation constant (K(D)) were measured. RESULTS: Before treatment, increased concentrations of testosterone and DHEAS (p<0.001, respectively), unaltered basal cortisol and an increased sensitivity (p<0.05) of the HPA axis to dexamethasone were observed in PCOS women in comparison to controls. After treatment, testosterone (p<0.01), DHEAS (p<0.05) and cortisol suppression after dexamethasone (p<0.01) were decreased in PCOS women. There were no changes in GR protein concentration, GR phosphorylation nor in the receptor functional parameters B(max) and K(D) in women with PCOS before and after the therapy, and in comparison to controls. CONCLUSIONS: Prolonged treatment with EE-DRSP in PCOS women decreased serum androgens and increased cortisol in the presence of decreased sensitivity of the HPA axis and did not exert changes in GR expression and function.

Effect of 5-HT7 receptor blockade on liver regeneration after 60-70% partial hepatectomy.

BACKGROUND: Serotonin exhibits a vast repertoire of actions including cell proliferation and differentiation. The effect of serotonin, as an incomplete mitogen, on liver regeneration has recently been unveiled and is mediated through 5-HT2 receptor. The aim of the present study was to investigate the effect of 5-HT7 receptor blockade on liver regeneration after partial hepatectomy. METHODS: Male Wistar rats were subjected to 60-70% partial hepatectomy. 5-HT7 receptor blockade was applied by intraperitoneal administration of SB-269970 hydrochloride two hours prior to and sixteen hours after partial hepatectomy and by intraperitoneal administration of SB-258719 sixteen hours after partial hepatectomy. Animals were sacrificed at different time points until 72 h after partial hepatectomy. Liver regeneration was evaluated by [(3)H]-thymidine incorporation into hepatic DNA, the mitotic index in hematoxylin-eosin (HE) sections and by immunochemical detection of Ki67 nuclear antigen. Reversion of 5-HT7 blockade was performed by intraperitoneal administration of AS-19. Serum and liver tissue lipids were also quantified. RESULTS: Liver regeneration peaked at 24 h ([(3)H]-thymidine incorporation into hepatic DNA and mitotic index by immunochemical detection of Ki67) and at 32 h (mitotic index in HE sections) in the control group of rats. 5-HT7 receptor blockade had no effect on liver regeneration when applied 2 h prior to partial hepatectomy. Liver regeneration was greatly attenuated when blockade of 5-HT7 receptor was applied (by SB-258719 and SB-269970) at 16 h after partial hepatectomy and peaked at 32 h ([(3)H]-thymidine incorporation into hepatic DNA and mitotic index by immunochemical detection of Ki67) and 40 h (mitotic index in HE sections) after partial hepatectomy. AS-19 administration totally reversed the observed attenuation of liver regeneration. CONCLUSIONS: In conclusion, 5-HT7 receptor is a novel type of serotonin receptor implicated in hepatocyte proliferation.

Non-alcoholic fatty liver disease in women with polycystic ovary syndrome: assessment of non-invasive indices predicting hepatic steatosis and fibrosis.

OBJECTIVE: Insulin resistance contributes to the pathogenesis of both polycystic ovary syndrome (PCOS) and non-alcoholic fatty liver disease (NAFLD). The main aim of the present study was the evaluation of non-invasive indices of hepatic steatosis and fibrosis in PCOS women with or without metabolic syndrome (MetS). DESIGN: In this cross-sectional study, three non-invasive indices for hepatic steatosis [NAFLD liver fat score, lipid accumulation product (LAP) and hepatic steatosis index (HIS)] and four for fibrosis [FIB-4, aspartate aminotransferase (AST)-to-Platelet Ratio Index (APRI), body mass index (BMI)-Age-Alanine aminotransferase (ALT)-Triglycerides (BAAT) and BMI AST/ALT Ratio Diabetes (BARD)] were calculated in 314 PCOS women (77 with, 237 without MetS) and 78 controls. RESULTS: All steatosis indices were significantly higher in the PCOS than the control group (NAFLD liver fat score: -0.139 ± 0.117 vs. -0.976 ± 0.159, p<0.001; LAP: 43.3 ± 1.9 vs. 34.7 ± 3.1, p=0.036; HIS: 44.6 ± 0.5 vs. 42.1 ± 0.8, p=0.016). FIB-4 and BAAT [fibrosis stage (F)2-4] were higher in the PCOS group (0.480 ± 0.020 vs. 0.400 ± 0.013, p<0.001; and 15.6% vs. 5.1%, respectively), whereas APRI and BARD were not. All steatosis indices were significantly higher in PCOS women with than without MetS (NAFLD liver fat score: 1.874 ± 0.258 vs. -0.793 ± 0.099, p<0.001; LAP: 76.8 ± 4.9 vs. 33.4 ± 1.4, p<0.001; and HIS: 49.8 ± 1 vs. 43 ± 0.5, p<0.001). Of the fibrosis indices, only BAAT (F2-4: 50.6% vs. 4.2%) was higher in PCOS women with MetS. CONCLUSIONS: Non-invasive indices of hepatic steatosis were significantly higher in PCOS, especially in the presence of MetS, whereas indices of hepatic fibrosis yielded controversial results. Further studies are warranted to evaluate the long-term outcomes of hepatic steatosis and fibrosis indices in PCOS women.

Diverse impacts of aging on insulin resistance in lean and obese women with polycystic ovary syndrome: evidence from 1345 women with the syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) represents a moving spectrum of hormonal to metabolic abnormalities, as women with the syndrome are aging. Hormonal abnormalities, anovulation, and hyperandrogenic signs were predominant during the early years of PCOS and fade away with the years. Metabolic abnormalities and insulin resistance (IR) remain throughout the PCOS life cycle; however, it is unclear as to how they change, as women with the syndrome are aging. OBJECTIVE: To evaluate the changes in IR and its associations with clinical, biochemical, hormonal, and ultrasound findings in a large cohort of women with PCOS and controls, as they are aging. DESIGN: A cross-sectional study was carried out to evaluate the diverse impacts of aging on IR. SETTING: An outpatient clinic was chosen for the study. PARTICIPANTS: A total of 1345 women with PCOS (Rotterdam criteria) and 302 controls of Caucasian origin and Greek ethnicity comprised the study group. MAIN OUTCOME AND MEASURES: The impact of age on IR, as calculated using homeostasis model assessment of IR (HOMA-IR) index, and several PCOS characteristics were evaluated. RESULTS: In PCOS, age (-0.045±0.008) was negatively, and BMI positively (0.18±0.007) associated with HOMA-IR (R(2)=0.36). When data were stratified with regard to the BMI status, a negative association of age with HOMA-IR was found in lean, normal, and overweight patients (r: -0.266, -0.233, -0.192, P<0.001), which was neutralized in obese patients (r: -0.009, P: NS). Free androgen index and BMI were positively associated with HOMA-IR in all age quartiles. When mean HOMA-IR values were plotted according to BMI subgroups at different age quartiles, a significant gradual decrease in HOMA-IR was observed in normal (P<0.001) and overweight (P: 0.004), but not obese, women (P: 0.202) across age quartiles. CONCLUSIONS: Aging increases IR in obese but not in lean and overweight women with PCOS. As BMI and androgens are positively associated with HOMA-IR and androgens decline through time, it appears that if women with PCOS do not become obese they may exhibit a better metabolic profile during their reproductive years.

Elevated serum androstenedione is associated with a more severe phenotype in women with polycystic ovary syndrome (PCOS).

OBJECTIVE: To evaluate the impact of elevated serum Δ4A levels on the hormonal and metabolic features of the different phenotypes of PCOS. DESIGN: 1276 women with PCOS according to the Rotterdam criteria were included, in whom serum hormonal levels were determined. RESULTS: In PCOS women as a whole, as well as in patients presenting clinical and/or biochemical hyperandrogenemia (phenotypes I and II), Δ4A levels >3.8 ng/ml were positively related to LH, LH/FSH ratio, T, DHEAS, 17 OH progesterone and FAI and negatively related to T/Δ4A ratio. In the milder phenotype III, a positive correlation between Δ4A levels >3.8 ng/ml and T, DHEAS, 17 OH progesterone and FAI and a negative one between increased Δ4A and T/Δ4A ratio were reported. In the whole PCOS group with androstenedione >3.8 ng/ml, an increased ovarian volume was observed, while a greater mean follicular number was found only in phenotypes I and II. CONCLUSIONS: Increased serum Δ4A levels, which are associated with more severe PCOS phenotypes, possibly contribute to the worsening of PCOS features and therefore could be a valuable marker of biochemical hyperandrogenemia.

Prevalence and impact of hyperandrogenemia in 1,218 women with polycystic ovary syndrome.

Hyperandrogenemia modifies phenotypic characteristics of women with polycystic ovary syndrome (PCOS). The aim of the present study is to evaluate (a) the prevalence of hyperandrogenemia in PCOS women (Rotterdam criteria) and (b) the impact of either the degree or the type of hyperandrogenemia on phenotype. Anthropometric, clinical, hormonal, metabolic and ultrasound characteristics of 1,218 women with PCOS were analyzed in this cross-sectional study. The prevalence of hyperandrogenemia was 58.8 %. Women with hyperandrogenemia had higher luteinizing hormone (LH), follicle-stimulating hormone (FSH), free androgen index, lower sex-hormone-binding globulin (SHBG) and fasting glucose levels compared to women with normal androgens (p < 0.001 for all comparisons; p = 0.001 for fasting glucose). Regarding the presence of isolated hyperandrogenemia, the group with only elevated testosterone levels was termed GT and an analogous categorization was made for dehydroepiandrosterone sulfate (GD) and androstenedione (Δ4) (GΔ4), respectively. GT, GD and GΔ4 comprised the 17.2, 7.6 and 4.1 % of total cohort, respectively. These groups differed significantly between them in LH, LH/FSH ratio, and SHBG (p < 0.001). Hyperandrogenemia is found in almost 60 % of women with PCOS (Rotterdam criteria), and it affects hormonal characteristics of these women such as LH and SHBG values. Regarding the impact of isolated hyperandrogenemia on PCOS characteristics, it appears that Δ4 and testosterone elevations are associated with increased LH levels.

The benefit-to-risk ratio of common treatments in PCOS: effect of oral contraceptives versus metformin on atherogenic markers.

OBJECTIVE: To compare the effects of oral contraceptives (OCPs) and metformin on atherogenic markers, including serum levels of advanced glycated end products (AGEs) and C-reactive protein (CRP), in lean women (Body Mass Index below 25 kg/m(2)) with polycystic ovary syndrome (PCOS), defined by NIH criteria. DESIGN: Prospective open-label study. RESULTS: One hundred and twenty women with PCOS were treated for 6 months with one of the following treatments: ethinylestradiol plus cyproterone acetate (OCP 1, n=40) or ethinylestradiol plus drospirenone (OCP2, n=40) or metformin (MET, n=40). The three groups were age and BMI-matched (mean age: 22 ± 0.56 yrs in group OCP1; 23.24 ± 0.64 yrs in group OCP2; 21.50 ± 0.53 yrs in group MET; mean BMI 21.80 ± 0.35 kg/m(2) in group OCP1; 22.37 ± 0.48 kg/m(2) in group OCP2; 23.03 ± 0.67 kg/m(2) in group MET). At 6 months serum AGEs were decreased in group OCP1 (P=0.005) and group MET (P=0.001), whereas these were marginally decreased in group OCP2 (P=0.069). Treatment with metformin was associated with a greater percent decrease of AGEs. CRP was decreased with metformin (P<0.001), but was increased with OCPs (P<0.001). CONCLUSIONS: This study evaluates common therapeutic options in women with PCOS by reconsidering and prioritizing the goals of treatment. OCPs and metformin appear to have differential effects on atherogenic molecules in lean PCOS patients, but metformin was superior in reducing serum AGEs and CRP. Clinicians should individualize the benefit-to-risk ratio of pharmaceutical intervention in women with PCOS in order to choose the formulation with the greatest overall efficacy as well as safety in terms of cardiovascular risk.

The role of orlistat combined with lifestyle changes in the management of overweight and obese patients with polycystic ovary syndrome.

OBJECTIVE: Obesity is frequently present in women with the polycystic ovary syndrome (PCOS) and aggravates insulin resistance (IR) and hyperandrogenemia. We aimed to assess the effects of orlistat combined with lifestyle changes in overweight and obese women with PCOS and body mass index (BMI)-matched controls. DESIGN: Prospective study. PATIENTS: We studied 101 women with PCOS (age 26·1 ± 6·4 years, BMI 34·5 ± 5·9 kg/m(2) ) and 29 BMI-matched women with normal ovulating cycles. All women were instructed to follow a low-calorie diet to exercise and were treated with orlistat 120 mg tid for 6 months. MEASUREMENTS: Metabolic and endocrine characteristics of PCOS, blood pressure (BP) and lipid profile. RESULTS: A significant and comparable reduction in BMI was observed in women with PCOS and controls. Systolic and diastolic BP decreased only in women with PCOS. Serum low-density lipoprotein cholesterol levels decreased in both women with PCOS and controls; however, this reduction was greater in controls. In contrast, serum high-density lipoprotein cholesterol levels did not change in women with PCOS and decreased in controls. Serum triglyceride levels decreased significantly and to a comparable degree in the two groups. Similarly, markers of IR improved significantly and to a comparable degree in women with PCOS and controls. Serum testosterone levels and the free androgen index decreased significantly in women with PCOS and did not change in controls. CONCLUSIONS: Orlistat combined with lifestyle changes induces substantial weight loss in women with PCOS, resulting in improvements in IR, hyperandrogenemia and cardiovascular risk factors.

Uterine volume and endometrial thickness in the early follicular phase in patients with polycystic ovary syndrome.

OBJECTIVE: We aimed to evaluate uterine volume and endometrial thickness during the early follicular phase in patients with polycystic ovary syndrome (PCOS) and healthy controls. METHODS: We studied 1,016 PCOS patients and 182 healthy controls. The anthropometric, endocrine, and metabolic characteristics of PCOS were determined. Uterine volume and endometrial thickness were also recorded. RESULTS: Uterine volume progressively increased with age both in PCOS patients and controls. Patients with PCOS and body mass index (BMI) ≥25 kg/m2 had greater uterine volumes than PCOS patients with BMI <25 kg/m2 (P<.001). Patients with the classic PCOS phenotypes (i.e., with oligo-ovulation and/or anovulation [ANOV] and hyperandrogenemia [HA] with or without polycystic ovaries [PCO]) had smaller uterine volume than PCOS patients with the additional phenotypes introduced by the Rotterdam criteria (i.e., with PCO and either ANOV or HA; P = .033) and controls (P = .045). CONCLUSION: Uterine volume increases progressively with age and obesity in PCOS patients. The smaller uterine volumes and endometrial thicknesses in the classic PCOS phenotypes might be attributed to the more severe HA of these patients.