None listed
Conditions
Brief summary
Polycystic ovary syndrome (PCOS) is an ill-defined endocrine condition impacting metabolic, reproductive and mental health. The condition affects up to 18% of women of a reproductive age in Australia depending on the diagnostic criteria applied. The condition is associated with a number of morbidities including subfertility, pregnancy complications, insulin resistance, type 2 diabetes mellitus, psychological disorders (depression and anxiety), and increased risk of cardiovascular disease. The aetiology of PCOS remains unknown however there are a number of contributing factors and hypothesis from environmental factors, genetics and in utero developmental programming. Given the complex nature of PCOS attempts have been made to identify biomarkers to determine the severity and improve diagnosis. Women with PCOS are 27% less insulin sensitive than matched controls and insulin resistance is present in ~85% of these women irrespective of obesity. demonstrated that PCOS aetiology is underpinned by insulin resistance and is independent of, but exacerbated by obesity. However, the mechanisms of insulin resistance in PCOS is ill-defined and contributes to its exclusion from diagnostic criteria. insulin resistance in PCOS is currently treated by lifestyle intervention (diet and exercise), and insulin-sensitising medications, but the evidence shows that the efficiency of these therapies in PCOS is ineffective. This study aims to provide novel insights into the mechanisms of insulin resistance that will allow the design of therapies and interventions to treat PCOS. To yield human data to advance understanding of PCOS aetiology. This will be achieved by investigating the role of TGF-beta signalling and tissue fibrosis in insulin resistance in women with PCOS.
Interventions
This trial will be conducted using a cross-sectional design to allow for a comparison of metabolic health and function in Pre-menopausal women with and without PCOS. Women who choose to participate in the study following screening and informed consent will complete a series of physiological testing visits to help identify mechanisms responsible for insulin resistance. The duration of the study will be approximately 4 weeks with 1 visit per week lasting between 2-4 hours.
Visit one will includ
This trial will be conducted using a cross-sectional design to allow for a comparison of metabolic health and function in Pre-menopausal women with and without PCOS. Women who choose to participate in the study following screening and informed consent will complete a series of physiological testing visits to help identify mechanisms responsible for insulin resistance. The duration of the study will be approximately 4 weeks with 1 visit per week lasting between 2-4 hours. Visit one will include a familiarisation session for incremental exercise test performed on cycle ergometer used to determine VO2peak and a Dual-energy X-ray absorptiometry (DEXA) scan to determine body composition. Visit two will include the incremental exercise test performed on cycle ergometer used to determine VO2peak. Visit three will include an insulin clamp, blood sampling, tissue sampling and an assessment of resting metabolic rate. Insulin clamp will be used to determine insulin sensitivity. The blood sampling blood sampling includes blood taken for insulin clamp, DNA methylation, inflammatory markers, reproductive profiling (Anti-Mullerian Hormone, steroid hormone profile and menstrual cycle) and other metabolic regulatory molecules. Tissue Biopsies will be used for the determination of gene specific and global methylation, gene expression and protein abundance of key tissue fibrosis molecules as well as key metabolic pathways proteins and genes. Furthermore the skeletal muscle biopsies will be used to establish human primary cell lines for mechanistic investigations. The assessment of resting metabolic rate allows whole body substrate utilisation to be assessed at rest and during the insulin clamp. Visit four will include an oral glucose tolerance test and blood sampling to measure insulin sensitivity and glucose tolerance. The exercise testing will be performed by a accredited exercise physiologists and the other testing components will be carried out by medical physician and clinical exercise scientist/physiologist.
Sponsors
Victoria University
Eligibility
Sex/Gender
All
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Premenopausal women aged between 18-45 with PCOS. PCOS will be diagnosed by Rotterdam Criteria which requires two ofthe following; 1. Oligoovulation (irregular ovulation) or anovulation (lack of ovulation), 2. Clinical and/or signs of hyperandrogenism, 3. Polycystic ovaries and exclusion of other causes of hyperandrogenism. Premenopausal women aged between 18-45 without PCOS, Control women will be defined by having no Rotterdam features. Not using hormonal contraceptive methods (pill, implantation) Not taking insulin sensitisers or medications which may affect endpoint data. Not taking vitamins or natural supplements or have undergone a washout period of 1 month prior to this study.
Exclusion criteria
Exclusion Criteria. menopause, Secondary causes of menstrual disturbance and hyperandrogenism, pregnancy, smoking, Type 1 diabetes, Type 2 diabetes mellitus, uncontrolled hypertension (>160/100mm/Hg), cardiac ischemia, established cardiovascular disease, renal impairment and malignancy, and use of medications that interfere with endpoints (e.g. contraception, metformin, anti-androgens, and progestins anti-hypertensives, and lipid-lowering agents).
Outcome results
None listed