Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Münzker, J.
Androgen Patterns in Polycystic Ovary Syndrome (PCOS)
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] Medical University of Graz; 2014. pp.105.
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- Autor*innen der Med Uni Graz:
- Münzker Julia
- Betreuer*innen:
- Lerchbaum Elisabeth
- Obermayer-Pietsch Barbara
- Altmetrics:
- Abstract:
- Introduction: The polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of women. Various clinical phenotypes with differences in hormone levels and symptoms can be distinguished. The exact pathologic background still needs to be elucidated. The aim of this study was to perform a comprehensive genetic and biochemical analysis in a large and well characterised cohort of PCOS patients. Methods: For the analysis of steroid hormones, two different approaches of liquid chromatography tandem mass spectrometry (LC-MS/MS) were performed. A commercially available kit (SteroIDQ, Biocrates, Innsbruck, Austria) and a specific MS method at a centre for LC-MS/MS (Manchester Academic Health Centre, University Hospital South Manchester, United Kingdom) were applied. Based on the LC-MS/MS results, a comprehensive investigation of the testosterone to dihydrotestosterone ratio (TT/DHT ratio) and its impact on the hormone and glucose metabolism in PCOS patients was performed. In addition, the influence on several genetic polymorphisms in candidate genes of PCOS on various metabolic parameters in PCOS patients was investigated. Results: The commercially available SteroIDQ kit for mass spectrometrical quantification of several steroid hormones was not suitable for our research questions. Results from LC-MS/MS measurements at the University of Manchester showed significant differences between PCOS patients and healthy controls for testosterone (p<0.001), androstenedione (p<0.001) and DHEA (p<0.001), but not for dihydrotestosterone (p=0.072). Moreover, a significantly higher TT/DHT ratio was assessed in PCOS patients compared to healthy controls. Within PCOS patients, significant correlations of the TT/DHT ratio with various anthropometric parameters and parameters of the glucose, lipid and hormone metabolism were found, therefore considered as a new risk parameter for metabolic changes in PCOS. Genetic polymorphism of inhibin (rs12720062) showed significant associations of the heterozygous genotype “AG” with LH (p=0.042), AMH (p=0.033), ACTH (p=0.022), cortisol (p=0.042), testosterone (p=0.004), androstenedione (p=0.005) and free testosterone (p=0.007). Conclusion: In this thesis, a large cohort of PCOS patients was characterized for biochemical and genetic parameters and new biomarkers have been validated. The new TT/DHT ratio based on MS steroid measurements will open us a new risk parameter for metabolic changes in PCOS patients.