P356 Visceral fat drives 5alpha-reductase activity independent of body mass index in women with polycystic ovarian syndrome Punith Kempegowda1, Michael W. O’Reilly1, Nicola Crabtree1, Angela E. Taylor1, Beverley A. Hughes1, Jeremy W. Tomlinson2, Wiebke Arlt1 1 Centre for Endocrinology, Diabetes and metabolism, Institute of metabolism and Systems Research, Birmingham, UK 2 Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, Oxford, UK Funding: Wellcome Trust, Society of Endocrinology Introduction Objective Copy and paste your text content here, adjusting the font size to fit. Results Polycystic ovarian syndrome (PCOS) Androgen excess, obesity and hyperinsulinaemia are the cardinal features of PCOS. While several studies have addressed the relationship between androgen excess and hyperinsulinaemia, the link between androgen excess and fat distribution remained largely undefined. We evaluated the relationship between visceral fat and androgen excess in women with PCOS. Correlation Pearson Visceral fat and An/Et ratio 0.455** Visceral fat and 5αTHF/ THF 0.444* Testosterone and An/Et ratio 0.566** Testosterone and 5αTHF/ THF 0.511** Testosterone and Visceral fat 0.339 Table 1: Correlation of various parameters between patients with PCOS and control group. A statistically significant correlation was noted between testosterone, visceral fat and markers of 5α reductase activity. *. Correlation significant at 0.05 level. **. Correlation significant at 0.01 level. Patients and methods Visceral fat Located in abdominal cavity, visceral fat is associated with increased metabolic risk. It varies in women and men with the latter gender generally having higher quantity. Recent work has highlighted the importance of adipose tissue as an organ of androgen activation. DEXA scan is used for visceral fat quantification 17 women with PCOS were compared with 17 healthy volunteers matched for age and BMI All subjects underwent BMI measurement and body composition assessment by DEXA Serum and 24-hour urinary androgens were measured with liquid chromatography-tandem mass spectrometry and gas chromatography/mass spectrometry respectively. Pearson product-moment correlation coefficient was computed to assess the relationship between visceral adiposity and androgen generation Figure 2: Graph depicting the correlation between visceral fat and An/Et ratio, a marker of 5α reductase activity Results Conclusions Visceral adiposity may drive androgen activation in PCOS by upregulating systemic 5-alpha reductase activity, which may further drive visceral fat accumulation. Weight management is therefore likely to be a potent tool to ameliorate the androgen excess phenotype of obese women with PCOS. 5alpha-reductase An important enzyme in steroid pathway which converts testosterone to more potent Dihydrotestosterone Several studies have shown increased 5- alpha reductase activity in PCOS* Urinary An/Et and 5αTHF/THF ratios measured in GCMS help measure the enzyme activity accurately References Kershaw. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004 Stewart PM, et al. 5 alpha-reductase activity in polycystic ovary syndrome. Lancet. 1990 O’Reilly M, et al. Understanding androgen action in adipose tissue. J Steroid Biochem Mol Biol. 2014 Figure 1: Comparison of age, body mass index (BMI), testosterone, visceral fat mass, An/Et ratio and 5aTHF/THF ratio between control group and patients with PCOS. There was statistically no difference between the two groups on the parameters compared. Correspondence: Dr. Punith Kempegowda, Academic Clinical Fellow, Institute of Metabolism and Systems Reseach, University of Birmingham, Birmingham, UK. Email: p.Kempegowda@bham.ac.uk