HOL2: MicroRNA as a biomarker for development of metabolic syndrome in women with Polycystic Ovary-Syndrome

This study is performed at the Fertility Clinic at Holbæk sygehus in collaboration with

Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder of reproductive-aged women and affects approximately 5-10%. The aetiology is unclear, but genetic and environmental factors contribute to the pathogenesis. PCOS is defined in accordance with the Rotterdam criteria, in which two out of following three must be fulfilled: 1) Oligo –or anovulation. 2) Clinical and/or biochemical signs of hyper-androgenism. 3) Polycystic ovaries plus exclusion of other aetiologies. The different combinations of these criteria define women with PCOS as a very heterogenic group. It is typical that younger women with PCOS are characterized by infertility, anovulation and hyper-androgenism, older women tend to demonstrate PCOS together with insulin resistance (IR), glucose intolerance, hypertension, dyslipidemia and overweight or obesity, which indicates that the latter syndromes are natural developments from early typical PCOS.

MicroRNAs (MiRNAs) are single-stranded and small noncoding RNA molecules. They regulate the expression of target genes. Altered miRNA levels have been associated with diabetes, insulin resistance, inflammation and various cancers. Although the exact mechanisms and pathogenism of miRNA in PCOS have not been mapped, research have shown that specific circulating miRNA are upregulated in PCOS. As free molecules, miRNA could serve as a biomarker, diagnosing impaired glucose tolerance or identifying subjects of risk for developing metabolic syndrome at an earlier stage.

This study falls into two distinct parts. A cross-sectional study of an earlier cohort of 149 women with PCOS with miRNA analysis and characterisation followed by a clinical follow-up where 60 women from the cohort are examined for clinical and laboratory signs of hyper-androgenism, dyslipidemia, insulin resistance and obesity.

Hopefully, this study will be able to demonstrate that miRNA patterns can serve as biomarkers as early predictor for later developments of various chronic diseases.

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