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Background Androsterone glucuronide (ADTG) concentrations have been suggested as a marker of the effects of androgens at the target tissue level. As the mechanism for hyperandrogenemia in obese and nonobese polycystic ovary syndrome (PCOS) may differ, this study compared the different androgen parameters in non-obese compared to obese women with PCOS, and in normal subjects. Methods Eleven non-obese and 14 obese women with PCOS were recruited and compared to 11 control women without PCOS. Total testosterone, dehydroepiandrosterone sulphate (DHEAS), ADTG, and androstenedione were analysed using gold standard tandem mass spectrometry, and the free androgen index (FAI) was calculated. Results Total testosterone, ADTG and androstendione levels did not differ between non-obese (body mass index (BMI) ≤25 kg/m2) and obese PCOS (BMI >25 kg/m2) but all were significantly higher than for controls (p

Li Wei Cho1, Harpal S Randeva2, Stephen L Atkin11Department of Medicine, University of Hull; 2Metabolic Unit, University Hospitals Coventry & Warwickshire NHS Trust, UKAbstract: It is estimated that 6%–7% of women of reproductive age have polycystic ovarian syndrome (PCOS). Women with this condition exhibit an adverse cardiovascular risk profile, characteristic of the cardiometabolic syndrome and given the high prevalence of PCOS in the female population, this condition may contribute towards the acceleration of cardiovascular disease among young women. This article summarizes the recent development and findings in the cardiometabolic abnormalities in patients with PCOS. Patients with PCOS have the clinical features of oligomenorrhoea, hirsutism and infertility; however, they also exhibit hyperinsulinemia, obesity, hypertension, dyslipidemia, and an increased pro-thrombotic state. They have an increased risk of type 2 diabetes and impaired glucose tolerance, and sleep apnea is also found more commonly in this population. However, despite the presence of cardiovascular risk factors and increased surrogate markers of cardiovascular disease it is unclear if they have accelerated atherosclerosis. End point studies are currently lacking and the available evidence are conflicting. Adipose tissue has emerged as an important endocrine organ over the last decade and gained recognition in having an important role in the cardiometabolic syndrome. Adiponectin that is secreted exclusively by adipocytes has recently been recognized as an important marker of cardiometabolic syndrome, obesity, type 2 diabetes, and coronary artery disease. Other adipocytokines like leptin and resistin have also recently been recognized. This article will address the current evidence for the adverse cardiovascular risk in PCOS and the other factors that may be implicated. Finally the therapeutic options for treatment will be discussed.Keywords: cardiometabolic syndrome, polycystic ovarian syndrome, cardiovascular disease

Background: The luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio is often requested to help diagnose polycystic ovarian syndrome (PCOS) despite a recent consensus recommending against its use. This study aimed to compare the variability of the LH/FSH ratio in PCOS with that of normal menstruating women over a full cycle in order to establish the diagnostic utility, or otherwise, of the test. Methods: Twelve women with PCOS and 11 matched controls had blood collected at four-day intervals on 10 consecutive occasions over a complete menstrual cycle. Results: The median LH/FSH ratio for individual subjects did not differ significantly between the PCOS and the non-affected group (1.6 versus 1.2, P=0.14). Only 7.6% of samples from PCOS patients had an LH/FSH ratio above three, compared with 15.6% of samples from normal subjects. Conclusion: This study confirms that measurement of the LH/FSH ratio is of limited use in the diagnosis of PCOS.

Background There is an assumption that the mean and biological variation of insulin resistance (IR) is less in polycystic ovary syndrome (PCOS), and intuitively higher in type 2 diabetes (T2DM). To test this hypothesis we compared the mean and biological variation in IR in PCOS to that of T2DM and to age- and weight-matched controls. Methods Twelve PCOS, 11 matched healthy women; 12 postmenopausal diet-controlled T2DM and 11 matched healthy postmenopausal women were recruited. Blood samples were collected at 4-d intervals on 10 consecutive occasions. The biological variability of IR was derived on duplicate samples. Results Mean and biological variability of HOMA-IR for PCOS did not differ from T2DM. Both measures were higher than the matched controls. There was no difference in insulin or IR measures between the body mass index matched pre- and postmenopausal women. Percentage β cell function were 208.8%, 62.3%, 106.5% and 111.9%, respectively, in PCOS, postmenopausal women with T2DM, healthy premenopausal and healthy postmenopausal women. Conclusions The progression from PCOS to the development of T2DM is unlikely to be due to a further increase in IR (or variability), but rather the progressive failure of pancreatic beta cells with a decrease in insulin production. The clinical trial registration number for this study is ISRCTN65353256.

Summary Objective Rimonabant has been shown to reduce weight, free androgen index (FAI) and insulin resistance in obese patients with polycystic ovary syndrome (PCOS) compared to metformin. Studies have shown that significant weight regain occurs following the cessation of rimonabant therapy. This study was undertaken to determine if subsequent metformin treatment after rimonabant would maintain the improvement in weight, insulin resistance and hyperandrogenaemia in PCOS. Design An extension study for 3 months with the addition of metformin to the randomised open labelled parallel study of metformin and rimonabant in 20 patients with PCOS with a body mass index ≥ 30 kg/m2. Patients who were on 3 months of rimonabant were changed over to metformin for 3 months, whereas those on 3 months of metformin were continued on metformin for another 3 months. Measurements The primary end-point was a change in weight; secondary end-points were a change in FAI and insulin resistance. Results The mean weight loss of 6·2 kg associated with 3 months of rimonabant treatment was maintained by 3 months of metformin treatment (mean change +0·2 kg, P = 0·96). Therefore, the percentage reduction in weight remained significantly higher in the rimonabant/metformin group compared to metformin only subjects at 6 months compared to baseline (–6·0 ± 0·1%vs. –2·8 ± 0·1%, P = 0·04). The percentage change in testosterone and FAI from baseline to 6 months was also greater in the rimonabant/metformin group. [Testosterone (–45·0 ± 5·0%vs. –16 ± 2·0%, P = 0·02); FAI (–53·0 ± 5·0%vs. –17·0 ± 12·2%, P = 0·02)]. HOMA-IR continued to fall significantly in the rimonabant/metformin group between 0, 3 and 6 months (4·4 ± 0·5 vs. 3·4 ± 0·4 vs. 2·7 ± 0·3, respectively, P

Summary 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