Endocrine and metabolic characteristics of polycystic ovary syndrome in Chinese women with different phenotypes

Objective The aim of this study was to describe the endocrine and metabolic characteristics of Chinese women with polycystic ovarian syndrome (PCOS) according to different phenotypes, including menstrual cycle pattern and body mass index (BMI). Design Retrospective study. Patient(s) A total of 3539 patients with PCOS and 590 controls were recruited from the Centre for Reproductive Medicine. Patients with PCOS were divided into three groups according to the characteristics of the menstrual cycle (amenorrhoea, oligomenorrhea and eumenorrhea) and the BMI (<25 kg/m²; 25 ≤ and ≤ 30 kg/m²; and BMI > 30 kg/m²). Measurements Waist circumference, hip circumference, weight, height, Ferriman–Gallwey score, and endocrine and metabolic variables were measured. Results The serum testosterone, luteinizing hormone (LH) and oral glucose tolerance test 2 h‐glucose levels were increased in the amenorrhoea group (P < 0·05). The triglycerides (TG) and low‐density lipoprotein‐cholesterol (LDL) levels were the highest in the amenorrhoea group (P < 0·05). The same trend existed in total cholesterol and non‐ high‐density lipoprotein‐cholesterol (HDL) levels, although there was no statistical significance (P > 0·05). Subjects with a BMI<25 kg/m² had higher values of follicle stimulating hormone (FSH), LH, LH/FSH and prolactin (P < 0·001) than the other two groups. The levels of TG, LDL and non‐HDL and the indices of glucose and insulin metabolism increased with the change in BMI (P < 0·001). Conclusions The amenorrhoea group had severe endocrine and metabolic abnormalities, which appeared to be related to latent long‐term complications and higher morbidity. The degree of dysbolism was positively associated with the change in BMI.     

Retinol-binding protein in nonobese women with polycystic ovary syndrome

Objective Although polycystic ovary syndrome (PCOS) is frequently associated with insulin resistance, cardiovascular disease and various metabolic diseases, the mechanisms linking PCOS to metabolic changes are not fully understood. Retinol‐binding protein (RBP) was recently reported as an adipocytokine that may link insulin resistance and lipid metabolism. The aim of this study was to investigate the potential role of RBP in women with PCOS. Research design and methods Fifty women with PCOS and 40 healthy women, all of whom were age‐ and weight‐matched, were studied. Blood was obtained to determine RBP levels as well as metabolic and hormonal parameters, and the homeostasis model assessment of insulin resistance (HOMA‐IR) was calculated for each subject. Results The RBP levels were higher (P < 0·01) in women with PCOS after adjusting for age, body mass index (BMI), mean blood pressure, triglyceride (TG), high density lipoprotein (HDL)‐cholesterol, low density lipoprotein (LDL)‐cholesterol, fasting glucose, fasting insulin, estimated glomerular filtration rate (GFR), LH/FSH, total testosterone and SHBG levels. PCOS status was the strongest predictor of elevated RBP levels. In both the PCOS and control groups, RBP levels were significantly correlated with HOMA‐IR (P = 0·03 in the PCOS group; P = 0·01 in controls). In addition, RBP levels were significantly correlated with total cholesterol, LDL‐cholesterol and TG levels in PCOS (P < 0·01, P < 0·01 and P = 0·01, respectively). Conclusions Higher RBP levels in the PCOS group, when compared to the non‐PCOS group, were observed, and this difference may play a role in the pathophysiology found in women with PCOS. Further studies are needed to clarify the role of RBP in these women.     

Increased arterial stiffness in nonobese women with polycystic ovary syndrome (PCOS) without comorbidities: one more characteristic inherent to the syndrome?

Background Polycystic ovary syndrome (PCOS) is associated with adverse metabolic effects. Some cardiovascular disease (CVD) risk markers are increased in women with PCOS. However, early markers of atherosclerosis are also associated with obesity and insulin resistance, which are related to PCOS. These markers may result either directly from PCOS or indirectly as a consequence of the comorbidities associated with the syndrome. Context To assess the presence of early CVD markers in young, nonobese women with PCOS. Patients Forty women with PCOS and 50 healthy women with regular menstrual cycles, matched for age and body mass index (BMI). Measurements The following CVD markers were assessed by ultrasonography: common carotid artery (CCA) stiffness index (β), distensibility and intima–media thickness (IMT), and brachial artery flow‐mediated dilatation (FMD). Inflammatory markers, including interleukin (IL)‐6, tumour necrosis factor (TNF)‐α, homocysteine, C‐reactive protein (CRP), glycaemia, lipid profile and insulin, were also assessed. Results CCA β was higher in PCOS than in control women (3·72 ± 0·96 vs. 3·36 ± 0·96, P = 0·04) and CCA distensibility was lower (0·31 ± 0·08 vs. 0·35 ± 0·09 mmHg^?1, P = 0·02). Waist circumference, total testosterone and the Free Androgen Index (FAI) were higher in PCOS patients than in controls (78·2 ± 10·0 vs. 71·5 ± 7·2 cm, P = 0·001; 88·1 ± 32·4 vs. 57·1 ± 21·2 ng/dl, P < 0·01; 12·7 ± 15·7%vs. 4·7 ± 2·3%, P < 0·01, respectively), while SHBG was reduced (37·9 ± 19·1 vs. 47·8 ± 18·3 nmol/l, P = 0·01). The remaining variables did not differ between the groups. Conclusions Young women with PCOS exhibit changes in vascular elasticity even in the absence of classical risk factors for CVD, such as hypertension and obesity.     

Serum lipoprotein lipid profile in women with the polycystic ovary syndrome: relation to anthropometric, endocrine and metabolic variables

OBJECTIVE Although often associated with insulin resistance and glucose intolerance, various lipoprotein abnormalities have been found in polycystic ovary syndrome (PCOS) but not Invariably so when the degree of obesity is taken into account. We have therefore Investigated the serum lipid profile in a group of women with polycystic ovary syndrome with and without obesity. DESIGN Cross-sectional study of serum lipoprotein lipids and plasma free fatty acids in relation to anthropometric, metabolic and hormonal variables in women with PCOS and weight-matched controls. PATIENTS Twenty-four obese (Pob, mean BMI ± SD 30·6±3·3kg/m²) and 25 non-obese (Pnob, 22·2 ±2·3kg/m²) women with PCOS. Twenty obese (Cob, 30·2 ± 3·5 kg/m²) and 20 non-obese (Cnob, 21·4 ± 1·5 kg/m²) controls. MEASUREMENTS Fasting concentrations of plasma free fatty acids, serum cholesterol and triglycerides in high density lipoproteins (HDL), low density lipoproteins (LDL) and very low density lipoproteins (VLDL) In relation to insulin sensitivity index (M/I; assessed with the euglycaemic insulin clamp), glucose tolerance (k-value; intravenous glucose tolerance test), basal serum hormone concentrations, and body fat distribution (skinfolds and waist hip ratio). RESULTS Plasma concentrations of free fatty acids were markedly higher in Pob than in the other groups (all P < 0 001). The lipoprotein lipids did not differ between Pob and Cob, or between the non-obese groups, whereas both obese groups had higher serum concentrations of triglycerides, totally and in VLDL, and lower HDL-cholesterol than their non-obese counterparts. Pob also had higher serum levels of total and LDL-cholesterol than Pnob. Pob had a more pronounced subcutaneous truncal-abdominal adiposity, higher fasting insulin levels and lower M/I than the other groups, and a lower k-value than Cob. Cob had higher levels of fasting insulin than Cnob. Free fatty acid levels correlated with the k-value (inversely) in both women with PCOS and controls, and with M/I (inversely), age and testosterone levels in PCOS. Step-wise regression analysis for the total population, comparing endocrine, anthropometric and metabolic explanatory variables, showed that the serum levels of HDL-cholesterol and triglycerides were mainly correlated with body fat distribution (both) and fasting insulin levels (triglycerides), and levels of total and LDL-cholesterol with BMI and age. CONCLUSIONS Plasma free fatty acid correlations were markedly increased In obese women with PCOS, closely associated with the lower insulin sensitivity and lower glucose tolerance in these women. In spite of these profound metabolic aberrations, the lipoprotein lipid profile was not significantly more abnormal in obese women with PCOS than in their weight-matched controls.     

Adult‐type hypolactasia and calcium intake in polycystic ovary syndrome

Objective Adult‐type hypolactasia (ATH) is related to lower calcium and milk intake, which might be associated with obesity and metabolic disturbances. Women with polycystic ovary syndrome (PCOS) frequently suffer from metabolic disturbances including central obesity. We aimed to examine the association of ATH and calcium intake with anthropometric, metabolic and endocrine parameters in a cohort of PCOS and control women. Design Metabolic, endocrine and anthropometric measurements and oral glucose tolerance tests were performed in 504 PCOS and 366 control women. Genotyping of ATH, defined by the ‐13910 variant of the MCM6 gene, was performed. Calcium intake was assessed by questionnaires. Results Adult‐type hypolactasia was more prevalent in PCOS women (29·8%) than in controls (23·5%) (P = 0·040). PCOS women with ATH had higher waist‐to‐hip ratio (WHR) (0·80 [0·75–0·88] vs 0·78 [0·73–0·85], P = 0·046), glucose 2 h (5·28 [4·57–6·33] mmol/l vs 5·67 [4·68–6·78] mmol/l, P = 0·037), HbA1c (5·2 [5·0–5·4]%vs 5·1 [5·0–5·3]%, P = 0·009), parathyroid hormone (3·72(2·91–4·86] pmol/l vs 3·61 [2·94–4·63] pmol/l, P = 0·030) and Ferriman‐Gallwey‐Scores (FG Scores) (7 [3–12] vs 4 [1–9], P = 0·002) and lower 25(OH)D levels (54·4 [35·2–80·6] nmol/l vs 68·4 [49·7–89·4] nmol/l, P < 0·001) than PCOS women without ATH. The association of 25(OH)D and FG‐Scores with ATH remained significant in age‐, BMI‐ and WHR‐adjusted analyses. PCOS women within the highest quartile of calcium intake had significantly lower testosterone (P = 0·023) and androstenedione (P = 0·032) and significantly higher high‐density lipoprotein (HDL) levels (P = 0·035) than PCOS women with lower calcium intake. Conclusion Our results indicate an association of ATH with PCOS susceptibility. Moreover, ATH might influence WHR, HbA1c and FG‐Scores as well as 25(OH)D levels. Higher calcium intake was associated with lower androgens and higher HDL levels.     

Adiponectin levels in adolescent girls with polycystic ovary syndrome (PCOS)

Objective To determine serum adiponectin concentrations in adolescent girls with and without polycystic ovary syndrome (PCOS) and to assess possible correlations of adiponectin levels with insulin and androgen levels. Design Prospective case–control study. Setting Endocrine clinics in the community. Patients Forty‐four adolescent girls were grouped as follows: 14 were overweight [body mass index (BMI) standard deviation score >1·645] with PCOS; 16 were lean (BMI SDS <1·036) with PCOS; and 14 were lean (BMI SDS <1·036) without PCOS. Intervention Blood samples were collected from all girls between 8 and 11 am , after an overnight fast. Main outcome measures Serum levels of adiponectin, leptin, insulin, Müllerian‐inhibiting substance, luteinizing hormone, follicle‐stimulating hormone, testosterone, 17‐alpha‐hydroxyprogesterone, androstendione, dehydroepiandrosterone sulphate (DHEAS) and 17β‐oestradiol. Results Adiponectin concentrations were significantly decreased in obese adolescents with PCOS (10·5 ± 5·5 μg/ml) compared with that in lean girls with or without PCOS (16·9 ± 8·64 and 18·0 ± 7·4 μg/ml respectively). Leptin levels were significantly elevated in obese adolescents with PCOS compared with the levels in normal weight adolescents with PCOS, and compared with that in normal weight controls. Insulin levels were markedly higher in obese adolescents with PCOS compared with that in normal weight adolescents (12·3 ± 12·2 vs. 4·5 ± 2·9, P < 0·05), and compared with that in normal weight PCOS adolescents (7·4 ± 4·9); however, this difference was not statistically significant. Insulin levels did not differ between normal weight adolescents with PCOS and normal controls. Adiponectin concentrations correlated inversely with BMI, leptin and insulin. Conclusions Hypoadiponectinaemia is evident only in obese adolescents with PCOS and therefore does not seem to be involved in the pathogenesis of PCOS in this age group.     

Circulating leptin concentrations in polycystic ovary syndrome: relation to anthropometric and metabolic parameters

OBJECTIVE To determine the relation between metabolic and anthropometric parameters and circulating leptin concentrations in women with polycystic ovary syndrome (PCOS). DESIGN AND PATIENTS Correlation of fasting serum leptin concentrations with anthropometric measures and multiple metabolic parameters including insulin and glucose responses to a 2-hour 75-g oral glucose tolerance test (OGTT) in 85 women with PCOS (17–36 years, body mass index (BMI) 29.9 ± 0.9 kg/m², mean ± SD) and 18 control women (25–47 years, BMI 25 ± 1.7 kg/m²). Diagnostic criteria for PCOS: characteristic ovarian morphology on ultrasound plus at least two of (1) elevated serum testosterone; (2) elevated serum androstenedione; and (3) reduced serum SHBG concentrations. MEASUREMENTS Concentrations of androgens, lipids, PRL, gonadotrophins, and leptin were measured in the baseline fasting blood sample from an OGTT. Insulin and glucose were measured throughout OGTT. Serum leptin concentrations were measured by radioimmunoassay. RESULTS Log leptin levels in the PCOS group correlated significantly with BMI (r = 0.85, P < 0.0001) and with 8 other parameters including waist/hip ratio (r = 0.51, P = 0.0005). By stepwise regression analysis, only BMI (P < 0.0001) and plasma high density lipoprotein concentration (P = 0.02) were independently correlated with log leptin levels, both positively. There was no effect of fat distribution, as measured by waist/hip ratio, on leptin concentrations. Comparison of control subjects to a BMI-matched subgroup of 55 PCOS subjects revealed significantly higher circulating concentrations of LH, testosterone, DHEAS, progesterone and androstenedione, and higher glucose and insulin responses to OGTT in the PCOS group. Leptin levels were not different between the PCOS subgroup and control group (14.8 ± 1.3 vs 12.1 ± 2.3 μg/l, mean ± SE, P = 0.26) and the relation of BMI to leptin levels determined by linear regression analysis also did not differ between the two groups. CONCLUSIONS Our results indicate that circulating leptin concentrations in women with PCOS, a condition characterized by hyperandrogenaemia, increased LH concentrations and insulin resistance, are strongly related to BMI and not independently affected by circulating levels of insulin, gonadotrophins or sex hormones.     

Elevated fasting insulin is associated with cardiovascular and metabolic risk in women with polycystic ovary syndrome

AimsPCOS is associated with various immediate and long term health complications. The aim of this study was to investigate the association of serum fasting insulin concentration with cardiovascular and metabolic risk factors in women with polycystic ovary syndrome.MethodsA total of 349 women, 249 women with polycystic ovary syndrome and 100 age-matched healthy controls, were recruited in this case-control study. Fasting insulin and various other biochemical, hormonal and clinical parameters were measured in all participants. The correlation of insulin with cardiometabolic risk factors was evaluated in PCOS women with normal and high serum insulin concentration.ResultsFasting Insulin, BMI, WHR, FAI, LH: FSH, HOMA, QUICKI were significantly higher in PCOS women compared with healthy controls (p < 0.01). Fasting insulin showed a positive correlation with more cardiovascular and metabolic risk factors in PCOS compared to controls. The BMI, BAI, LAP, HOMA IR, QUICKI and FAI were significantly higher (all p < 0.05) in PCOS patients with higher insulin levels than with PCOS women with normal levels.ConclusionFasting insulin is an important determinant in the pathogenesis of obesity and hyperandrogenism in PCOS. It is associated with an increased risk of cardiovascular and metabolic disorders in women with PCOS.     

Evidence for visfatin as an independent predictor of endothelial dysfunction in polycystic ovary syndrome

Objective Emerging evidence links adipocyte‐secreted hormones, in particular adiponectin and visfatin, to cardiovascular pathology. Although adipocytokines dysregulation is common in polycystic ovary syndrome (PCOS) within the context of obesity and insulin resistance, their participation in the process of vascular injury remains elusive. Design and Methods This prospective, case–control study enrolled 102 young women (69 patients with PCOS and 33 eumenorrheic age‐matched controls); serum adiponectin, resistin and visfatin, testosterone, SHBG, lipids, glucose, insulin, the homeostasis model assessment of insulin resistance (HOMA‐IR) and high‐sensitivity C‐reactive protein (hs‐CRP) were simultaneously measured in all participants. Body composition analysis was performed using dual X‐ray absorptiometry. Endothelium impairment was assessed by carotid artery intimae‐media thickness (CIMT) and brachial artery flow‐mediated vasodilatation (FMD), respectively. Results In PCOS, both univariate and multivariate analyses evidenced that circulating visfatin was significantly related to free testosterone (P = 0·024) and brachial artery FMD (P = 0·008; P < 0·01 in multivariate analyses). By every visfatin tertile, a stepwise decrease in FMD was observed in all and PCOS only (P = 0·036), not confounded by age, body mass index, total body fat mass, testosterone, SHBG or HOMA‐IR. Multiple regression analysis retained visfatin and free testosterone as independent predictors of FMD, explaining about 20% of FMD variability. Adiponectin correlated with CIMT and hs‐CRP, but the association was driven by age, body mass and body fat. No relationship between resistin and endothelial markers was found. Conclusion Visfatin may be a candidate to play a role in the pathogenesis of endothelial dysfunction in PCOS, independently of additional risk factors.     

Alteration of ghrelin-neuropeptide Y network in obese patients with polycystic ovary syndrome: role of hyperinsulinism

Objective Insulin, ghrelin, neuropeptide Y (NPY) and leptin interact in the regulation of energy homeostasis. Most of these signals are altered in polycystic ovary syndrome (PCOS), which is characterized by a high prevalence of obesity. The present study was conducted to evaluate ghrelin–NPY and ghrelin–leptin interplays in relation to insulin secretion in obese PCOS subjects. Design Pilot prospective study. Patients Seven obese PCOS women and seven age–weight matched controls. Measurements Hormonal measurements, oral glucose tolerance test (OGTT) and a ghrelin test (1 µg/kg i.v. bolus). PCOS patients repeated the clinical work‐up after 4 months of metformin treatment (1500 mg/day orally). Results At baseline, PCOS women showed a significantly higher insulinaemic response to the OGTT compared to controls (P < 0·05). In basal conditions, PCOS women exhibited lower NPY levels than controls (P < 0·01). Ghrelin injection markedly increased NPY in controls (P < 0·01), whereas PCOS women showed a deeply blunted NPY response to the stimulus (area under the curve – AUC–NPY: P < 0·01 vs. controls.). Metformin treatment induced a significant decrease in insulin levels (P < 0·01) and the concomitant recovery of NPY secretory capacity in response to ghrelin (AUC–NPY: P < 0·05 vs. baseline) in PCOS women. Leptin levels, which were similar in the two groups, were not modified by ghrelin injection; metformin did not affect this pattern. Conclusion Hyperinsulinaemia seems to play a pivotal role in the alteration of NPY response to ghrelin in obese PCOS women. This derangement could be implicated in the physiopatology of obesity in these patients.     

Dissociation of endothelial function and arterial stiffness in nonobese women with polycystic ovary syndrome (PCOS)

Objective Polycystic ovary syndrome (PCOS) is associated with cardiovascular risk but it is not clear if this is independent of obesity and insulin resistance. This study therefore investigates endothelial function and arterial stiffness in nonobese, noninsulin resistant women with PCOS. Design This is cross‐sectional case–control study. Patients A total of 19 young women with PCOS, with body mass index (BMI) <30 kg/m², and 19 healthy controls matched for age and BMI were included in the study. Measurements Endothelial function was assessed with flow mediated dilatation (FMD) of the brachial artery, while arterial stiffness was assessed with pulse wave velocity (PWV) and augmentation index (AI). Results There were no significant differences between PCOS and control subjects when assessing the following clinical and biochemical variables: blood pressure, homeostasis model assessment insulin‐resistance index, lipids and oestradiol. Women with PCOS had higher free androgen index scores (5·14 ± 3·47 vs. 3·25 ± 1·42, P = 0·036). The PCOS subjects had significantly lower FMD of the brachial artery compared with the controls (6·5 ± 2·9%vs. 10·5 ± 4·0%, P < 0·01). There were no significant differences in markers of arterial stiffness (PWV 5·8 ± 1·1 vs. 6·0 ± 1·0, P = 0·58, AI 16·5 ± 10·2 vs. 20·3 ± 10·2, P = 0·25). Conclusions Women with polycystic ovary syndrome who are young, nonobese, and have no biochemical evidence of insulin resistance, have abnormal vascular function, but normal arterial stiffness, when compared with age and weight matched control subjects. Whether this leads to a greater risk of cardiovascular disease requires further investigation.     

Receiver operating characteristic analysis of the performance of basal serum hormone profiles for the diagnosis of polycystic ovary syndrome in epidemiological studies.

OBJECTIVE: We have used receiver operating characteristic (ROC) analysis to determine the diagnostic performance of several serum parameters, in order to evaluate their potential usefulness in establishing the diagnosis of polycystic ovary syndrome (PCOS) in epidemiological studies. DESIGN: Prospective study. METHODS: One hundred and fourteen women reporting spontaneously for blood donation were included in the study. Menopausal and oral contraceptive-treated women were excluded. Serum samples were obtained at the moment of donation, independently of fasting, time of day or day of menstrual cycle. Measurements included total testosterone, sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), LH, FSH and estradiol. The free testosterone (FT) concentration and the free androgen index (FAI) were calculated from testosterone and SHBG levels. ROC curves were calculated for all these serum determinations. RESULTS: Eight patients were diagnosed with PCOS, according to the presence of oligomenorrhea, hirsutism, acne and/or hyperandrogenemia, and exclusion of non-classic congenital adrenal hyperplasia, hypothyroidism and hyperprolactinemia. Of the parameters studied SHBG, FAI, FT and DHEAS were considered adequate measures for the diagnosis of PCOS. For example, serum SHBG levels showed an area under the ROC curve of 0.875+/-(S.E.(w))0.045 (95% confidence interval 0.800-0.929). A SHBG decision threshold <37 nmol/l had a sensitivity of 87.5%, a specificity of 86.8%, a positive likelihood ratio of 6.63, and a negative likelihood ratio of 0.14, for the diagnosis of PCOS. CONCLUSIONS: Our present results strongly suggest that decreased SHBG levels, and increased FAI, free testosterone concentration and DHEAS concentrations, are highly effective as single analytical procedures in epidemiological studies for the detection of PCOS in women of reproductive age.     

Adiponectin is independently associated with insulin sensitivity in women with polycystic ovary syndrome

OBJECTIVE: The polycystic ovary syndrome (PCOS) is associated with obesity and insulin resistance predisposing to diabetes mellitus type 2 and atherosclerosis. Adiponectin is a recently discovered adipocytokine with insulin-sensitizing and putative antiatherosclerotic properties. The aim of the study was to elucidate determinants of circulating adiponectin levels and to investigate the potential role of adiponectin in insulin resistance in PCOS women. PATIENTS AND MEASUREMENTS: Plasma adiponectin and parameters of obesity, insulin resistance and hyperandrogenism were measured In 62 women with PCOS and in 35 healthy female controls. RESULTS: Both in PCOS and controls, adiponectin levels were lower in overweight or obese women than in normal-weight women, without any difference between PCOS and controls after adjustment for body mass index (BMI). In PCOS and in controls there was a significant correlation of adiponectin with BMI (r = -0.516, P < 0.001), fasting insulin (r = -0.404, P < 0.001), homeostasis model sensitivity (HOMA %S) (r = -0.424, P < 0.001) and testosterone (r = -0.279, P < 0.01), but no correlation with androstenedione (r = -0.112, P = 0.325), 17-OH-progesterone (r =-0.031, P = 0.784) or the LH/FSH ratio (r =-0.033, P = 0.753). Multiple linear regression analysis revealed that BMI and HOMA %S but not testosterone were independently associated with adiponectin plasma levels, explaining 16% (BMI) and 13% (HOMA %S) of the variability of adiponectin, respectively. In PCOS patients insulin sensitivity, as indicated by continuous infusion of glucose with model assessment (CIGMA %S) was significantly correlated with adiponectin (r = 0.55; P < 0.001), BMI (r =-0.575; P < 0.001), waist-to-hip ratio (WHR) (r =-0.48; P = 0.001), body fat mass assessed by dual-energy X-ray-absorptiometry (DEXA) [Dexa-fat (total) (r = -0.61; P < 0.001) and Dexa-fat (trunk) (r = -0.59; P < 0.001)] and with testosterone (r = -0.42; P = 0.001). Multiple linear regression analysis demonstrated that markers of obesity such as BMI, total or truncal fat mass, age and adiponectin were independently associated with CIGMA %S, and that circulating adiponectin accounted for about 18% of the degree of insulin resistance in PCOS. By contrast, testosterone was not a significant factor, suggesting that PCOS per se did not affect insulin sensitivity independent from obesity, age and adiponectin. Metformin treatment for 6 months in insulin-resistant PCOS women (n = 9) had no effect on plasma adiponectin (P = 0.59) despite significant loss of weight and fat mass and improvement in hyperandrogenaemia. CONCLUSIONS: PCOS per se is not associated with decreased levels of plasma adiponectin. However, circulating adiponectin is independently associated with the degree of insulin resistance in PCOS women and may contribute to the development and/or maintenance of insulin resistance independent from adiposity.     

A comparison between rimonabant and metformin in reducing biochemical hyperandrogenaemia and insulin resistance in patients with polycystic ovary syndrome (PCOS): a randomized open-label parallel study

Context Weight loss and metformin therapy are reported to be beneficial in improving the biochemical hyperandrogenaemia and insulin resistance of polycystic ovary syndrome (PCOS). Rimonabant has been found to reduce weight and improve the metabolic profile in patients with obesity, type 2 diabetes and metabolic syndrome. Objective To compare the effects of insulin sensitization with metformin to weight reduction by rimonabant on biochemical hyperandrogenaemia and insulin resistance in patients with PCOS. Design A randomized, open‐label parallel study. Setting Endocrinology outpatient clinic in a referral centre. Subjects Twenty patients with PCOS and biochemical hyperandrogenaemia with a body mass index (BMI) ≥ 30 kg/m² were recruited. Intervention Patients were randomized to 1·5 g daily of metformin or 20 mg daily of rimonabant. Main outcome measures The primary end‐point of the study was a change in total testosterone. Results After 12 weeks of rimonabant there was a significant reduction (mean ± SEM) in weight (104·6 ± 4·6 vs. 98·4 ± 4·7 kg, P < 0·01), waist circumference (116·0 ± 3·3 vs. 109·2 ± 3·7 cm, P < 0·01), hip circumference (128·5 ± 4·0 vs. 124·1 ± 4·2 cm, P < 0·03), waist–hip ratio (0·90 ± 0·02 vs. 0·88 ± 0·01, P < 0·01) free androgen index (FAI) (26·6 ± 6·1 vs. 16·6 ± 4·1, P < 0·01), testosterone [4·6 ± 0·4 vs. 3·1 ± 0·3 nmol/l (132·7 ± 11·5 vs. 89·4 ± 8·65 ng/dl), P < 0·01] and insulin resistance as measured by the homeostasis model assessment (HOMA) method (4·4 ± 0·5 vs. 3·4 ± 0·4, P = 0·05). There was no change in any of these parameters in the metformin‐treated group. Conclusion This study suggests that the weight loss through rimonabant therapy may be of use in patients with PCOS and appears superior to insulin sensitization by metformin in reducing the FAI and insulin resistance in obese PCOS patients treated over a 12‐week period.     

The impact of intensified exercise training on insulin resistance and fitness in overweight and obese women with and without polycystic ovary syndrome

Objective To evaluate mechanisms of insulin resistance (IR) in overweight and obese women with and without polycystic ovary syndrome (PCOS) and explore relationships between IR, fitness and body mass index (BMI) at baseline and following exercise intervention. Design Prospective controlled intensified exercise intervention study. Patients A total of 20 overweight (BMI > 25 kg/m²) and obese (>30 kg/m²), reproductive‐aged PCOS women and 13 non‐PCOS overweight, healthy controls of comparable BMI and age were studied at baseline. Measures were repeated in 13 PCOS and eight control women following three 1‐h exercise sessions per week over 12 weeks. Measurements Insulin resistance was measured by glucose infusion rate on euglycaemic hyperinsulinaemic clamp, and fitness was assessed by VO_2max. Results At baseline, PCOS women were 46% more insulin resistant than controls (175·6 vs 257·2 mg/m²/min, P < 0·05) with IR independently associated with VO_2max and BMI in the PCOS group only (P < 0·01). Postexercise IR improved across both groups (P < 0·01). In PCOS women, IR improved by 16% (P < 0·05) but was not restored to the same level as controls (P < 0·05). Improvement in IR and in VO_2max was related to the PCOS group (r² = 0·85, P < 0·05), yet change in IR and in fitness was not related. No associations were found in controls. Conclusions While intensified exercise improves IR in PCOS women, a higher IR persisted following exercise in PCOS women, and a clear relationship between improved IR and improved fitness was not found. Therefore, other mechanisms of, and therapies for, IR must be explored in PCOS as IR remains higher than observed in non‐PCOS controls.     

Cardiac flow velocity in women with the polycystic ovary syndrome

OBJECTIVE Women with the polycystic ovary syndrome (PCOS) often have several of the known risk factors for cardiovascular disease, including hyperinsulinaemia. We have therefore investigated variables of cardiac flow in young women with PCOS and related them to blood levels of reproductive hormones (LH, FSH, oestradiol and testosterone) and also of insulin. DESIGN A prospective study. PATIENTS Twenty-six young women with PCOS (mean age 22.8 ± 0.9 years; mean BMI 23.0 ± 0.8) and 11 healthy age matched women with regular ovulatory cycles (mean age 26.3 ± 1.7 years; mean BMI 22.9 ± 0.9). MEASUREMENTS Cardiac flow was measured by pulsed wave Doppler echocardiography in the follicular phase of the cycle in controls and oligomenorrhoeic women; there was no special timing for amenorrhoeic women. The indicators assessed were: ejection fraction (EF), pre-ejection time (PEP), ejection time (ET), peak systolic flow velocity (PFV), acceleration time (AT), flow velocity integral (FVI), mean acceleration (MA), diastolic time (DT), early diastolic filling time (EI), atrial filling time interval (AI), peak velocity of the early diastolic filling (PE) and peak velocity of the atrial filling (PA). Serum LH, FSH, oestradiol, testosterone, SHBG and insulin concentrations were analysed by standard RIA. RESULTS Significantly lower PFV (1.055 ± 0.025 vs 1.242 ± 0.054, P= 0.0006) and MA (17.06 ± 0.57 vs 23.00 ± 1.49, P= 0.0001) and longer AT (0.063 ± 0.001 vs 0.056 ± 0.004, P= 0.026) were found in women with PCOS as compared to age matched controls. Significant negative correlation between serum fasting insulin concentration and EF (r=-0.725, P= 0.002), PFV (r=?0.719, P= 0.0025), FVI (r=?0.654, P= 0.003) and MA (r=?0.757, P= 0.001) was observed In the 15 women with PCOS in whom insulin was measured. CONCLUSION An inverse relation between serum fasting insulin level and left ventricular systolic outflow parameters suggests that insulin is associated with the decreased systolic flow velocity observed in women with PCOS.     

Polycystic ovarian syndrome and subclinical atherosclerosis among women of reproductive age in the Dallas heart study

Objective Polycystic ovarian syndrome (PCOS), the most common endocrinopathy of young women, is characterized by androgen excess and is frequently associated with cardiovascular risk factors. However, it is unclear whether PCOS is a risk factor for atherosclerosis. We sought to determine in a multiethnic population‐based sample whether women with PCOS have greater measures of subclinical atherosclerosis than women without PCOS. Design Cross‐sectional study of a nested cohort from the Dallas Heart Study (2000–2002). Participants Women between the ages of 35 and 49 (n = 827). PCOS was defined by Rotterdam criteria. The normal control group had regular menses, total testosterone <2·78 nmol/l, no signs of hirsutism and no polycystic ovarian morphology by magnetic resonance imaging (MRI). Measurements Subclinical atherosclerosis defined as coronary artery calcium (CAC) by computed tomography and abdominal aortic plaque by MRI. Results The prevalence of PCOS in Dallas County was 19·6% (n = 144), and 8·0% (n = 56) had both oligomenorrhea and hyperandrogenism. Women with PCOS had higher body mass index, blood pressure, insulin and leptin than regularly cycling controls. Despite a greater prevalence of cardiovascular risk factors, women with PCOS did not have a greater prevalence of CAC > 10 Agatston units (PCOS 5%, controls 6·3%, P = 0·74) or abdominal aortic plaque (PCOS 25·8%, controls 34·4%, P = 0·13) than controls. Conclusions In a large, multiethnic, population‐based sample of premenopausal women, PCOS, defined by Rotterdam criteria, was not associated with a higher prevalence of coronary artery calcium or abdominal aortic plaque.     

Prevalence of adrenal androgen excess in patients with the polycystic ovary syndrome (PCOS)

OBJECTIVE: To determine the prevalence of adrenal androgen (AA) excess in the polycystic ovary syndrome (PCOS) using age- and race-specific normative values. DESIGN: Cross-sectional observational study. PATIENTS: One hundred and eight-two (88 Black and 94 White) age-matched healthy eumenorrhoeic nonhirsute women (controls) and 213 (27 Black and 186 White) women with PCOS were recruited. MEASUREMENTS: Total testosterone (T), free T, androstenedione (A4), dehydroepiandrosterone sulfate (DHEAS) and SHBG, as well as fasting insulin and glucose, were measured in plasma. RESULTS: The mean total T, free T, A4, DHEAS and body mass index (BMI) were higher in women with PCOS than in control women. DHEAS levels were significantly lower in Black controls than White controls, whereas fasting insulin and BMI were higher in Black controls. In control and Black PCOS women, DHEAS levels did not correlate with BMI, waist-to-hip ratio (WHR) or fasting insulin. Among White women with PCOS, DHEAS levels correlated negatively with BMI and fasting insulin. DHEAS levels decreased similarly with age in control and PCOS women of either race. For each race and age group the upper 95% normative values for log DHEAS was calculated, and the number of PCOS subjects with log DHEAS values above this level were assessed. The prevalence of supranormal DHEAS levels was 33.3% and 19.9%, respectively, among Black and White women with PCOS. CONCLUSIONS: The prevalence of DHEAS excess is approximately 20% among White and 30% among Black PCOS patients, when using age- and race-adjusted normative values. This study also indicates that the age-associated decline in DHEAS levels is observable and similar in both control and PCOS women, regardless of race. While BMI and fasting insulin had little impact on circulating DHEAS levels in healthy women, among White PCOS patients these parameters were negatively associated with circulating DHEAS levels.     

Influence of body mass index on measured and calculated androgen parameters in adult women with Hirsutism and PCOS.

There is growing evidence that obesity in women lead to a more severe form of hyperandrogenism and other endocrine abnormalities which may have some health implications later in life. Obese females are at higher risk for metabolic syndrome due to severe hyperandrogenemia. Calculated values for free testosterone are equivalent to those obtained by equilibrium dialysis, which is one of the reference measurement procedures (RMP) for estimation of free testosterone and may be capable of replacing values estimated using RMP's. For adult women correlations of body mass index (BMI) with calculated free (cFT) and bioavailable testosterone (cBT) are still rare, while these data are reported for peripubertal and adolescent girls. In this study we aimed to investigate the association between BMI and different androgen parameters (including calculated free and bioavailable testosterone, free androgen index, and sex hormone-binding globulin [SHBG]) in adult women with Hirsutism and with PCOS. In hirsute women with BMI > or = 25 kg/m2 measured total testosterone (TT) was significantly higher, SHBG was significantly lower and the calculated androgen parameter (FAI, cFT and cBT) were significantly higher compared to women with BMI < 25 kg/m2. In PCOS women with BMI > or = 25 kg/m2 TT was significantly higher, SHBG was significantly lower and the calculated androgen parameter (FAI, cFT and cBT) were also significantly higher compared to women with BMI < 25 kg/m2. In both the Hirsutism and PCOS-group there was a positive correlation between BMI and TT, cFT, and cBT, while BMI was negatively correlated with SHBG. In summary, in adult women with Hirsutism and PCOS obesity is associated with increased levels of TT and decreased levels of SHBG resulting in significant elevated calculated free and bioavailable testosterone levels. Obesity might lead to a more severe form of hyperandrogenism with elevated calculated free and bioavailable testosterone in the study population.     

The lack of association between polycystic ovary syndrome and metabolic syndrome: Iranian PCOS prevalence study

Objective This study was designed to evaluate the prevalence of the metabolic syndrome (MetS) and insulin resistance (IR) in a large population‐based study in Iran. Research design and methods Anthropometric measurements, biochemical parameters and IR were compared between 136 polycystic ovary syndrome (PCOS) subjects and 423 healthy controls recruited from among 1126 reproductive aged women (18–45 year). PCOS and MetS were diagnosed using the Rotterdam criteria and Joint Interim Statement, respectively. IR was defined using the homeostatic model assessment‐IR). Results Among the PCOS subjects, the mean ± SD age, body mass index (BMI) and waist circumference were 31 ± 7·7 years, 26·4 ± 5·8 kg/m² and 84 ± 13·3 cm, respectively; corresponding values among healthy controls were 36 ± 7·5 years, 26·4 ± 5·0 kg/m² and 85 ± 11·9 cm, respectively. Age and BMI adjusted prevalences of MetS in PCOS subjects and controls were 18·5% (CI 95%, 15·3–21·7%) and 18·3% (CI 95%, 15·1–21·5%), respectively [P = not significant (NS)]. Age and BMI adjusted prevalences of IR in PCOS and healthy controls were 27·2% (CI 95%, 23·5–30·9%) and 24·2% (CI 95%, 20·6–27·8%), respectively (P < 0·01). Conclusions Metabolic syndrome was no more frequent in a representative sample of PCOS Iranian population than in healthy controls. However, the prevalence of IR in PCOS appears to be higher than in controls. It seems that the association between PCOS and MetS needs more consideration.