Svendsen 2014 Thesis

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Svendsen PF (2014) Metabolic aspects of polycystic ovary syndrome and obesity. Thesis Copenhagen University Hospital:38 pp.

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Svendsen PF (2014) Thesis

Abstract: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in young women and the most common cause of female infertility. There is a close link between obesity, insulin resistance and the development of PCOS, but the pathophysiological mechanisms behind the development of this disease are only sparsely understood. This thesis is based on a cross-sectional study and two interventions (dietary and metformin) carried out in a cohort of lean and obese women with and without PCOS. The purpose was to investigate the independent effect of PCOS and obesity on some of the pathophysiological mechanisms behind the development of PCOS and obesity. With the use of gold standard methods, we have investigated peripheral insulin sensitivity, beta cell function, oxidative and non-oxidative glucose metabolism. We have investigated incretin secretion both before and after metformin intervention and after dietary intervention in obese women without PCOS. There has been particular focus on some of the metabolic processes taking place in adipose tissue that play a role in the pathophysiology of insulin resistance. We have investigated adipose expression of adipocytokines and 11β-hydroxysteroid dehydrogenase types 1 and 2 (11β-HSD1 and 2) - two enzymes involved in cortisol metabolism. Finally, we have investigated mitochondrial function in muscular tissue. Overall, we conclude that PCOS is associated with metabolic disturbances in several organs, although these disturbances seem to be more severe in obese women without PCOS than in lean women with PCOS. But the presence of both PCOS and obesity seems to have a synergistic effect on the metabolic disturbances in glucose, insulin and lipid metabolism. In regard to cortisol metabolism, we demonstrated increased expression of 11β-HSD1 in subcutaneous adipose tissue in PCOS, independent of obesity and in obesity independent of PCOS. These findings support the theory of an altered glucocorticoid metabolism in PCOS that may contribute to metabolic disturbances in glucose-insulin metabolism. We have showed that a very low caloric diet (VLCD) is an effective weight loss method that, not only has dramatic effect on the metabolic disturbances associated with obesity, but also results in a decrease in androgen levels. Before commencing these studies, we hypothesised that PCOS was associated with more severe metabolic disturbances than we have been able to demonstrate. However, we chose to use the Rotterdam criteria uncritically, and as we have noted, these include several PCOS phenotypes. This may have had a “delusional” effect on our results. Therefore, we suggest a revision of the Rotterdam criteria.

O2k-Network Lab: DK Copenhagen Dela F, SE Stockholm Boushel RC, DK Copenhagen Larsen S

Labels: MiParea: Respiration, Pharmacology;toxicology  Pathology: Obesity, Other 

Organism: Human 

HRR: Oxygraph-2k