We have studied the course over age of fasting insulin, sex hormone-binding globulin (SHBG), and insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) in untreated children with Turner's syndrome (TS) and measured the course of these parameters during therapy with GH alone and in combination with oxandrolone. Forty patients with TS, aged 3.7-16.4 yr, were investigated before any therapy. Fasting insulin levels increased significantly with chronological age, whereas SHBG and IGFBP-1 decreased with chronological age, and serum concentrations of these parameters were in the normal range. SHBG and IGFBP-1 were not coregulated by insulin in TS as previously reported under physiological conditions; IGFBP-1 was inversely correlated with insulin, but SHBG was not, and neither parameter was correlated with the other. Twenty-eight patients were further investigated 3, 6, 9, and 12 months after the start of GH monotherapy (12-18 IU/m2-week) and 3, 6, 9, and 12 months after the addition of oxandrolone (0.0625 mg/kg.day; n = 16). There was a significant increase in insulin levels during GH monotherapy and a further increase during combination therapy, with peak levels 3 months after the start of GH and combination therapy, respectively. Both SHBG and IGFBP-1 levels decreased significantly during GH monotherapy, with a further dramatic decrease after the addition of oxandrolone. Levels of free testosterone were unaffected by both treatment regimens. IGFBP-1 was inversely correlated with insulin concentrations at all time points after the start of therapy. SHBG was inversely correlated with IGF-I concentrations, but showed no relation to insulin concentrations during GH monotherapy. In conclusion, there were no abnormalities in serum concentrations of insulin, SHBG, and IGFBP-1 in untreated patients that could help to explain the retarded growth in patients with TS. All effects of combined GH and oxandrolone therapy on endocrine parameters such as insulin, SHBG, IGFBP-1 and IGF-I mimic the endocrine pattern normally observed during the pubertal growth spurt. Our data confirm the importance of insulin in the regulation of IGFBP-1, but do not point to a coregulation of IGFBP-1 and SHBG by insulin in patients with TS.