Developmental Origins and Future Fate in PCOS

Polycystic ovary syndrome (PCOS) is a condition occurring in 6 to 10% of women of reproductive age. Women with PCOS face a lifetime of risk, both reproductively and metabolically including increased risk of type 2 diabetes mellitus. As PCOS clinically presents during the reproductive years, the focus of attention has been on the difficulties in reproduction, which remain a challenge for many women with the condition. Yet we now recognize that the condition's origins may begin prenatally and the consequences extend past the reproductive years, with multigenerational impact.

The fundamental pathophysiologic defect in PCOS is not known, but changes in insulin action, gonadotropin dynamics, as well as ovarian and steroidogenic defects have all been shown to contribute to the pathophysiology of the disorder. Given the accumulating knowledge in the pathophysiologic defects, our understanding of PCOS is rapidly changing and research needs to now encompass both the developmental origins and consequently the long-term outcomes to offer the best hope of complete lifetime treatment.

In this issue of the Seminars in Reproductive Medicine, the latest research on the developmental origins of PCOS is explored using the tools of animal models and translational evidence. Evidence for the earliest impact in the prenatal period and epigenetic factors are reviewed, as well as a comprehensive look has been made at the current rodent models of PCOS available today, providing insight into how they may inform the understanding of PCOS as well as their current limitations. The impact of the environment and the role of endocrine disruptors on the development and manifestations of PCOS are reviewed. The genetics of PCOS has been challenging to understand, as it is a complex disorder with variable presentations. The current state of genetic understanding of PCOS is summarized with discussion of future directions of research. The current obesity epidemic has implications for many aspects of PCOS, and there is a significant concern regarding rising rates of childhood obesity. There is growing evidence that obesity may play a pivotal role in the development of PCOS in adolescence in susceptible individuals. Data for this as well as possible mechanisms for development of PCOS in obesity are reviewed. As adolescents present the first true opportunity to recognize the disorder and possibly intervene for improved lifetime outcome, both the challenges of diagnosis and evidence for early intervention are discussed. At the other end of reproductive life, understanding the challenges of menopause in women with PCOS is important for lifelong care and the current state of knowledge at this stage is reviewed. Finally, translating the plethora of research into practical and usable information in a population is the ultimate goal. The issue concludes with the comprehensive approach to PCOS, as it has been developed and trialed at a national level in Australia.

The authors of this issue are all recognized international experts in their areas and do an exemplary job of presenting this complex and challenging field in the most current and up-to-date fashion. Understanding the complexities of PCOS will undoubtedly lead to improved translation to clinical care and improve the long-term health of women with PCOS and their children. This comprehensive issue on the origins and fate of PCOS brings together the many aspects of the current understanding of PCOS in one place, and hopes to clarify current understanding and areas of future research in PCOS.