Impact of hyperandrogenism and diet on the development of polycystic ovary syndrome

Abstract

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder featuring reproductive, endocrine and metabolic abnormalities. Hyperandrogenism is a defining characteristic of PCOS and evidence supports a role for androgen driven actions in the development of PCOS. The aetiology of PCOS is poorly understood and current management is symptom based. Therefore, defining the ontogeny of PCOS traits and the factors impacting their development, is important for developing early PCOS detection markers and new treatment strategies. The aims of this research were to determine the temporal pattern of development of PCOS features in a hyperandrogenic environment, define the impact of dietary macronutrient balance on hyperandrogenic PCOS traits and evaluate the impact of diet and a hyperandrogenic PCOS pathology on the gut microbiome using a mouse model. The first study characterised the temporal pattern of development of PCOS features after excess androgen exposure. Findings identified that acyclicity, anovulation and increased body weight are early predictors of developing PCOS. The second study utilized the geometric framework for nutrition and reports the first systematic analysis of dietary protein, carbohydrate and fat on the evolution of reproductive and metabolic PCOS traits in a PCOS mouse model. Results revealed that reproductive PCOS features of acyclicity and anovulation were ameliorated on low protein, medium carbohydrate and fat consumption. In contrast, diet had minimal effect on PCOS metabolic features. Specifically, PCOS mice were significantly heavier compared to controls due to an increased sensitivity to caloric intake, implying differences in post-ingestive responses to diet. Therefore, the third study investigated the interplay between diet and PCOS pathology on gut microbiota and revealed that diet exerted a stronger influence over gut microbial composition than PCOS. However, a PCOS environment did decrease levels of an obesity associated Bacteroides species. Overall, findings provide insights into the sequence of PCOS trait development, the impact of diet on PCOS features, and the interplay between diet and PCOS pathology on the gut microbiome, and support the addition of body weight criteria to the early diagnosis of PCOS and future research into the development of evidence-based nutritional and microbiome-mediated strategies for the treatment of PCOS.