Project Lead:  Professor Raymond Rodgers

We will advance knowledge on the causes and biological origins of PCOS for better diagnosis and to inform innovative PCOS-specific therapies. The origins of PCOS remain elusive, yet it is 80% heritable with intra-uterine environment altering fetal development, insulin resistance from childhood, hyperandrogenism from puberty and adverse impacts from increased obesity. This CRE will expand our work in androgens, insulin resistance, novel pathways including transforming growth-factor proteins and genetics, and explore recent insights on the role of hormonal exposure in utero including anti-mullerian hormone (AMH).

Viable options for prevention, diagnosis and treatment of PCOS. We have identified that 16 out of 17 PCOS candidate genes are expressed in the fetal ovary, and that TGFβ signaling plays a role in gene regulation. Genetic and epigenetic signatures have been associated with the aetiology of PCOS. Here we will unravel the role of inherited genetic mutations and gene-environment interactions (intra- and extra-uterine factors; epigenetics) in the pathogenesis of PCOS, using a global human biobank linked to epidemiological data, decisive rodent models and intervention and mechanistic human studies. Our research findings will assist in identifying strategies for prevention, better diagnostics and treatments for PCOS.

Novel PCOS-specific drug targets. We have shown that PCOS symptoms require androgen receptor (AR) expression in the brain. We have also identified that the PCOS ovary and skeletal muscle are more fibrous, due to perturbations of TGFβ signaling. Here, we will explore PCOS-specific targets driven by AR and TGFβ signaling, that could be used in novel, viable approaches to the first mechanism-based treatments for PCOS, including potential repurposing of drugs targeting TGFβ signaling in fibrotic disease.

Project Lead: Professor Helena Teede

Our Polycystic Ovary Syndrome research road map seeks to refine individual criteria within Rotterdam by defining normal ranges across the lifespan, exploring how diagnostic features cluster together and how diagnostic features relate to short- and long-term health outcomes.

Currently, diagnostic features are a continuum and cut offs are based on arbitrary 95^th centiles in variably defined populations. Here we will conclusively address these gaps across individual diagnostic features a) oligo-anovulation b) high androgens (clinical or biochemical) and c) polycystic ovaries on ultrasound, and explore Anti Mullerian Hormone  as a potential alternative to ultrasound.

We will specifically refine diagnostic cut-offs by exploring normal ranges, clustering of features and relationship to health outcomes for Ovulation and menstrual patterns; Androgens; Polycystic ovaries on ultrasound and Anti Mullerian Hormone.

Project Lead: Dr. Anju Joham

Prioritised gaps include understanding natural history of Polycystic Ovary Syndrome across metabolic, reproductive and psychological features, especially across key Polycystic Ovary Syndrome phenotypes¹. This research scope will explore natural history of Polycystic Ovary Syndrome through integration of international cohort studies, data linkage, bio- banking, interrogation and analysis.

Project Lead: Professor Helena Teede

In 2023, we will update our international Polycystic Ovary Syndrome guidelines specifically addressing identified gaps and new knowledge generated under the CRE-WHIRL. We will create and expand necessary data sets to complete this work. All outputs will be directly integrated into the guideline.

“Without big data, you are blind and deaf and in the middle of a freeway.” – Geoffrey Moore

The Polycystic ovary syndrome (PCOS) data hub is a repository of data organised by defined clinical outcomes, for distribution and sharing with the international research community.

Background

The PCOS data hub is an outcome of the PCOS Centre for Research Excellence that auspices international research collaborations to improve the lives of women affected by the condition.

PCOS is a common, complex, chronic endocrine condition affecting about 13% of women from menarche to menopause. The condition crosses a range of medical disciplines such as endocrinology, reproductive endocrinology, gynaecology, metabolic medicine and psychology.

Despite an increase in the volume of clinical research on the diagnosis and management of PCOS there remains gaps in areas such as; understanding causation, refining diagnostic criteria and relevant cut offs and, understanding the natural history of PCOS across the phenotypes.

However, research in PCOS remains hampered by heterogeneous outcomes reporting that hinders meaningful evidence synthesis and limits research collaboration and impact. The solution was to develop a condition-specific standardised set of core outcomes as a minimum for reporting across all future studies. Following the completion of this work, the PCOS data hub acts as the repository of these core outcomes.

Data Access

The PCOS Clinical Minimum Data Set may be made available to collaborating researchers where there is a formal request (See EOI process) to make use of the material.

Expression of interest (EOI) process

An Expression of Interest request for access to survey data for analysis must be made via email to Rhonda.Garad@monash.edu

All requests to access data will be taken to the PCOS Evaluation Committee for consideration and approval.