Brothers of women with polycystic ovary syndrome are characterised by impaired glucose tolerance, reduced insulin sensitivity and related metabolic defects

Aims/hypothesis Since it has been shown that polycystic ovary syndrome (PCOS) is highly inherited and characterised by insulin resistance, we hypothesised that male siblings of PCOS women would also be insulin resistant. Thus, our aim was to assess insulin sensitivity and metabolic parameters in brothers of women with PCOS and male control individuals. Methods Seventeen brothers of PCOS women and 28 male control volunteers were assessed with 75 g OGTTs and euglycaemic - hyperinsulinaemic clamps. PCOS index women were identified using criteria developed at the 1990 National Institutes of Health conference. Results Brothers and control individuals were similar in terms of BMI, waist circumference, percentage body fat and BP. However, brothers had increased triacylglycerol (p= 0.02), plasminogen activator inhibitor-1 (PAI-1; p= 0.02), factor VIII (p= 0.02), 2 h glucose (p< 0.001), AUC(glucose) (p< 0.001) and AUC(insulin) (p< 0.001). Insulin sensitivity was reduced by 38% in brothers (p< 0.001), and this was primarily due to a 65% decrease in insulin-stimulated non-oxidative carbohydrate metabolism (p< 0.001). These differences remained significant after adjustment for age and BMI, except for triacylglycerol, PAI-1 and fasting glucose. The main findings also persisted after excluding individuals with impaired glucose tolerance or diabetic siblings. Significant interactions with BMI status were found for sex hormone-binding globulin, androstenedione, PAI-1 and AUC(insulin), which were significantly altered only in obese brothers (vs control individuals). Conclusions/interpretation Brothers of PCOS women are characterised by decreased insulin sensitivity and glucose tolerance, as well as hypercoagulability, independently of obesity. Therefore, brothers of PCOS women may have inherited the insulin resistance and metabolic syndrome typical of PCOS.