Proteomic and clinical insights into polycystic ovary syndrome in adolescents - PhDData

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Proteomic and clinical insights into polycystic ovary syndrome in adolescents

The thesis was published by Gunn, Harriet Mary, in December 2022, UCL (University College London).

Abstract:

Despite its high prevalence, our understanding of the pathophysiology of polycystic ovary syndrome (PCOS) is lacking. Consequently, the way we diagnose and manage this common condition is inadequate, which is especially true for adolescents. This thesis aims to expand the body of knowledge regarding PCOS in adolescents. It will explore the clinical phenotype of PCOS, in addition to using proteomic techniques to better understand the biological mechanisms which underpin this condition. However, to do this, we must first comprehend ‘normal’ menstrual patterns in these pubertal years. As such, this thesis begins by seeking to define menstrual and ovulatory ‘normality’ in the first year following menarche, by systematically reviewing relevant literature. Following this, data are presented from a longitudinal study evaluating the clinical presentation and phenotype of adolescents with a suspected diagnosis of PCOS. The latter part of the thesis focuses on the use of proteomic techniques to broaden our understanding of PCOS. Discovery proteomic analysis of urine samples is employed firstly to explore the biological pathways associated with PCOS, and secondly to identify specific proteins which are differentially expressed in adolescents with PCOS, which may form a pool of non-invasive candidate biomarkers. Inflammation was identified as the most significant biological process associated with PCOS in discovery analysis, and these findings were validated in subsequent targeted proteomic panels. Validation studies were undertaken in a larger cohort of adolescents with PCOS, and then comparison was also made to adults with PCOS. Finally, all results from this thesis are summarised, the findings discussed, and their implications considered, alongside future work.



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