Women with Turner's syndrome, the majority of whom are estrogen deficient, have an increased incidence of coronary artery disease. The aim of this study was to assess the effects of hormone replacement therapy (HRT) on central arterial hemodynamics, insulin sensitivity, and lipids in adults with Turner's syndrome. Twenty-one women with Turner's syndrome were studied prospectively, on and off 3 months of estradiol valerate in combination with levonorgestrel. The following measurements were made: body mass index, waist/hip ratio, serum lipids, fasting insulin and glucose, and mean arterial blood pressure. Aortic root pressure and waveforms were estimated noninvasively and the augmentation index (AI), a measure of aortic stiffness, was calculated. The AI was significantly lower during estrogen therapy (22% vs. 15%; P = 0.008), suggesting a reduction in central arterial stiffness. Fasting insulin and glucose concentrations were also significantly lower during HRT (P = 0.01 and P = 0.0004, respectively). There was no difference in body mass index, serum lipids, or brachial and aortic blood pressures on and off treatment. Total cholesterol was correlated with the AI (r = 0.4; P = 0.03). These results suggest that HRT in women with Turner's syndrome has a favorable effect on central arterial hemodynamics and insulin sensitivity. The lack of effect on serum lipids suggests that the effects of HRT on aortic compliance may be mediated by an improvement in endothelial function.