Thozhukat Sathyapalan

Increased expression of circulating miRNA-93 in women with polycystic ovary syndrome may represent a novel, non-invasive biomarker for diagnosis

MicroRNAs (miRNA) are a novel class of small noncoding single-stranded RNA molecules that regulate gene expression. There is increasing evidence of their importance in polycystic ovary syndrome (PCOS). The objective was to determine if miRNA-93 and miRNA-223 are differentially expressed in the circulation of women with PCOS compared to age matched women. A case–control study comparing women with PCOS (nu2009=u200925) to age and weight matched controls (nu2009=u200924) without PCOS was performed. MiRNA-93 and miRNA-223 were determined by total RNA reverse transcription. Both miRNA-93 and miRNA-223 were significantly increased relative to the control group (pu2009<u20090.01, pu2009=u20090.029 respectively). In both groups there was no correlation of either miRNA-93 or miRNA-223 with insulin, HOMA-IR, HOMA-β or testosterone levels. The area under the receiver operator characteristic curve for miR-223 and miR-93 was 0.66 and 0.72 respectively, suggesting miR-93 is a more efficient biomarker than miR-223 for diagnosis of PCOS. The combination of the two miRNAs together, tested using multiple logistic regression analysis, did not improve the diagnostic potential. In conclusion, circulating miRNA-93 and miRNA-223 were higher in women with PCOS compared to age and weight matched controls independent of insulin resistance and testosterone levels, and miR-93 may represent a novel diagnostic biomarker for PCOS.

Chapter 6 – Obesity and Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a chronic endocrine disorder that affects women of reproductive age and is associated with infertility, hyperandrogenism, hirsutism, metabolic disorders including type 2 diabetes mellitus, and psychologic issues. Approximately 80% of PCOS patients are overweight or obese, particularly abdominal obesity. Although PCOS is an independent factor, obesity exaggerates all the reproductive, metabolic, and psychologic features related to PCOS. The underlying insulin resistance that is greater in PCOS for any given body mass index (BMI) compared with BMI-matched controls likely mediates this. Weight loss is the cornerstone for treatment in obese PCOS patients. A modest weight loss of less than 10% has been shown to improve ovulation, infertility, androgen levels, insulin resistance, and dyslipidemia in women with PCOS. Lifestyle modification (diet and exercise) is the first treatment step, followed by medical, and, potentially, surgical treatment. Pharmacologic therapy has proved disappointing in treating obesity associated with PCOS, because only orlistat is currently available. In women with PCOS, orlistat has shown to reduce both total testosterone levels and insulin resistance by inducing weight loss; however, its associated gastrointestinal side effects limit its value. Although metformin improves insulin resistance in PCOS, its effect on weight is controversial. Future medical therapy may involve glucagon-like peptide-1 analogues that reduce weight, and data suggest a concomitant improvement in menstrual cycles, ovulation rate, hyperandrogenism, and insulin sensitivity. Bariatric surgery in morbidly obese PCOS patients is effective, leading to marked weight reduction with improvement in hyperandrogenemia, insulin resistance, and hirsutism, with subsequent improvement in menstrual cycles and ovulation.

Endocannabinoid receptor blockade increases vascular endothelial growth factor and inflammatory markers in obese women with PCOS

Context: Animal studies suggest that cannabinoid receptor-1 (CB-1) blockade reduces inflammation and neovascularization by decreasing vascular endothelial growth factor (VEGF) levels associated with a reduction in inflammatory markers, thereby potentially reducing cardiovascular risk. Objective: To determine the impact of CB1 antagonism by rimonabant on VEGF and inflammatory markers in obese PCOS women. Design: Randomised, open-labelled parallel study. Setting: Endocrinology outpatient clinic in a referral centre. Subjects: Twenty patients with PCOS and biochemical hyperandrogenaemia with a body mass index of ≥ 30kg/m2 were recruited. Patients were randomised to 1.5g daily of metformin or 20mg daily of rimonabant. Main Outcome Measures: Post hoc review to detect VEGF and pro-inflammatory cytokines TNF-α, IL-1β, IL-1ra, IL-2, IL6, IL-8, IL-10 and MCP-1 before and after 12 weeks treatment. Results: After 12 weeks of rimonabant there was a significant increase in VEGF (99.2±17.6 vs 116.2±15.8pg/ml, p<0.01) and IL-8 (7.4±11.0 vs 18.1±13.2pg/ml, p<0.05) but not after metformin (VEGF p=0.7; IL-8 p=0.9). There was no significant difference in the proinflammatory cytokines TNF-α, IL-1β, IL-1ra, IL-2, IL6, IL-8, IL-10 and MCP-1 following