Objective: Obesity in men is associated with reduced insulin sensitivity and hypoandrogenism, while obesity in women is associated with reduced insulin sensitivity and hyperandrogenism. In children, the effect of obesity and weight reduction on the hypothalamo-pituitary-gonadal axis is rarely investigated. The aim of the present study was to investigate the effect of weight reduction in obese Caucasian children on insulin sensitivity, sex hormone-binding globulin (SHBG), DHEAS and the hypothalamo-pituitary-gonadal axis. Methods: One hundred and sixteen (65 females) obese children with a median age of 12.3 (7-15) years were examined before and after a 10-week stay at a weight loss camp. Examination included anthropometry and fasting blood samples measuring plasma glucose, serum insulin, SHBG, DHEAS, testosterone, 17b-oestradiol, FSH and LH. Results: Body mass index (BMI) decreased (P!0.01), insulin sensitivity and SHBG increased (P!0.01), independent of gender and puberty. The changes in insulin sensitivity and the changes in SHBG correlated significantly (P!0.01) independent of gender, puberty and the changes in BMI. Testosterone increased in boys (P!0.01) and tended to decrease in girls (PZ0.05, in girls after menarche (PZ0.03)). FSH increased in boys and girls. LH increased in boys and was unchanged in girls. Conclusions: During weight loss, insulin sensitivity and SHBG increased significantly in obese children, and the changes in insulin sensitivity and the changes in SHBG correlated significantly independent of gender, puberty and the changes in BMI. There was sexual dimorphism in the changes of testosterone, with the changes in boys towards increased virilisation and the changes in girls towards less virilisation.