Polycystic ovary syndrome (PCOS) is a major public health concern. It affects one in five young Australian women, and costs the country $800 million every year; a number that is set to rise. PCOS has important metabolic consequences (diabetes, cardiovascular disease) and reproductive effects (sub-fertility, menstrual disturbance): a cascade of health problems that are underpinned by insulin resistance (IR) and exacerbated by obesity. Despite the success of our group and others in better elucidating the mechanisms of IR in PCOS and in determining optimal therapies (combined exercise and pharmacotherapy interventions), pivotal gaps remain. Our project will close these gaps, clearly aligning with the research priorities of the NHMRC CRE in PCOS, and with the conclusions from international evidence synthesis. We will identify novel molecular causes of PCOS-specific IR, and determine optimal therapies. First, using gold-standard measures of IR and advanced molecular techniques, we will use a cross-sectional study in 40 lean non-PCOS and overweight (OW) women with (120) and without PCOS (40) to significantly advance knowledge on the roles of tissue fibrosis and epigenetics in PCOS-specific IR. Second, via a three arm randomised control trial in the 120 OW PCOS women, we will compare the impact of supervised standard exercise with and without metformin, and with metformin only, on those mechanisms. Our approach will clarify the clinical benefits of combined therapy (exercise and metformin). It will reveal the mechanisms of PCOS-specific IR and the impact of exercise and metformin in PCOS, uncover broader potential therapeutic targets for IR in PCOS and obesity, and inform novel combined therapy (exercise plus metformin) interventions for translation into practice. Thus, this work has highly significant clinical, mechanistic, and public health implications.
|Short title||Lifestyle and PCOS|