Endocrine Abstracts

Polycystic ovary syndrome (PCOS) affects 5–10% of the female population. It is characterised by androgen excess and anovulatory infertility; several studies have reported an increased incidence of the metabolic syndrome and enhanced 5α-reductase activity in PCOS. However, the contribution of obesity to these findings has yet to be clarified. Here we have analysed metabolic status and urinary steroid metabolite excretion in 114 patients with PCOS (median age 30 (range 18–45) years, BMI 31.4 (18.5–50.4) kg/m²) fulfilling Rotterdam diagnostic consensus criteria. Sixty-five PCOS patients were obese, 29 were overweight and 17 normal weight. Oral glucose tolerance testing revealed impaired glucose tolerance in 17 patients and type 2 diabetes mellitus (T2DM) in five. Of note, only 3 patients (2 IGT, 1 T2DM) had a pathologic fasting plasma glucose. To delineate the effects of obesity itself we compared the 65 obese PCOS patients to 60 female BMI matched patients with simple obesity. Obese PCOS had significantly higher fasting insulin (PCOS versus simple obesity: 14.1±1.2 vs 10.7±0.9 mU/l, P<0.05) and insulin resistance according to HOMA-R (2.0±0.2 vs 1.6±0.1, P<0.05). Obese PCOS had significantly higher 5α-reductase activity than simple obesity patients, as assessed by the ratios of the 5α-reduced androgen metabolite androsterone over 5β-reduced etiocholanolone (An/Et) and 5α-reduced tetrahydrocortisol over 5β-reduced tetrahydrocortisol (5α-THF/THF) (all P<0.05) 5α-reductase activity correlated significantly with HOMA-R in PCOS and simple obesity patients (all P<0.05). Total androgen metabolites were significantly increased in obese PCOS (6064±2956 vs 2155±1400 μg/24 h, P<0.001). Similarly, total glucocorticoid metabolites were significantly increased in obese PCOS vs. simple obesity (11 476±3948 vs. 8257±3547 μg/24 h, P<0.01). 11β-hydroxysteroid dehydrogenase (11β-HSD1) activity as assessed by the ratio (THF+5α-THF)/THE did not differ significantly between obese PCOS and simple obesity. However, total glucocorticoid metabolites inversely correlated with (THF+5α-THF)/THE in PCOS patients (P<0.05), but not in simple obesity. In addition, there was a significant inverse correlation between (THF+5α-THF)/THE and serum DHEAS in PCOS (P<0.05). Taken together, these findings indicate that the metabolic phenotype of patients with PCOS is distinct from simple obesity with higher insulin resistance and increased 5α-reductase activity. The contribution of a putative impairment of 11β-HSD1 activity to the increased HPA drive warrants further investigation.