Understanding the role of tissue Fibrosis in Insulin Resistance associated with Polycystic Ovary Syndrome (PCOS) and the impact of Exercise: The FIREx study using a cohort and randomized control trial in women with and without PCOS.

The is a four group cohort study exploring the role of TGFß super family ligand signalling and tissue fibrosis in PCOS-specific insulin resistance and the role of obesity in reproductive aged women with and without PCOS. The cohort study is a cross-sectional comparison of baseline measures across the 4 groups. This is complimented with a randomised control trial sub-study, in the two groups of overweight women (one with and one without PCOS) that will explore the impact of High-intensity Intermittent Training (HIIT) on the TGFß super family ligand signalling and tissue fibrosis and PCOS-specific insulin resistance. All participants, lean women with (n=36) and without PCOS (n=36) and overweight women with (n=46) and without PCOS (n=46) will under go a series of baseline assessments. The two cohorts (n=92) of women meeting the classification of being overweight will progress, within 2 weeks to the sub-study randomized control trial after undertaking an evidence-based lifestyle coaching program (2 x 1 hour group tutorials on separate days usually 3-7 days apart) focusing on simple nutritional and exercise advice as per the current Australian guidelines for healthy eating and physical activity. The tutorials will be delivered in a group setting by an accredited exercise physiologist (AEP) at the University exercise clinics (Australian Catholic University [ACU] and Victoria University [VU]), coaching the participants on behavioural modification techniques, including goal setting, self-monitoring, social support, coping strategies, problem solving and relapse prevention. After completion of these tutorials the overweight women (with and without PCOS) will be randomised into either the 12-week HIIT or control interventions. The women randomized to the HIIT invention will commence the exercise training program within 7-10 days of completing the lifestyle coaching tutorials. The HIIT intervention: Twenty three non-PCOS and 23 PCOS overweight women will undertake the exercise intervention that requires 2 x 20 minute and 1 x 40 minute sessions per week that includes low volume (90-100% heart rate max [HRmax] ) and aerobic (85-95%HRmax) supervised HIIT sessions equating to 80 minutes of vigorous exercise per week. All exercise activities for the HIIT group will be conducted on cycle ergometers in a group setting in the fitness centres at ACU and VU under the supervision of AEPs. The training program is personalised to starting fitness levels, is adjusted depending on progression. The HIIT intervention encompasses two feasible protocols: • 2 sessions/week of low-volume HIIT cycling undertaking 8–12x 1min at 90-100% HRmax with 1 min recovery. • 1 session/week of aerobic HIIT cycling undertaking 4–8x 4min at 85-94% HRmax with 1 min recovery. All Exercise sessions include warm-up and cool-down protocols. Adherence and compliance of women in HIIT treatment will be monitored via session attendance logs (adherence). Compliance will be assessed based on the percentage of achieved prescribed exercise for each of the 36 sessions.