Objective: Little is known about metabolic effects of testosterone treatment in postmenopausal women. The aim of the study was to compare the treatment effects of testosterone, estrogen, and testosterone plus estrogen on insulin sensitivities, body compositions, and lipid profiles in healthy postmenopausal women. Design: An open, randomized clinical study with parallel group comparison. Setting: Women’s health clinical research unit at a university hospital. Patient(s): Sixty-three naturally postmenopausal women participated in the study. Intervention (s): The participants were randomly assigned to 3 months of treatment with testosterone undecanoate (40 mg every second day), estradiol valerate (2 mg daily), or the combination of both. Main Outcome Measure(s): Insulin sensitivity assessed by euglycemic hyperinsulinemic clamp, body composition, and serum lipids. Result(s): Insulin-induced glucose disposal was reduced by approximately 20% after treatment with testosterone alone, and after the combined treatment, but not by estrogen alone. Body weight, but not total body fat, increased significantly by about 1 kg in all groups. Lean body mass was significantly increased in the group of combined treatment and tended to be increased by testosterone alone. High-density lipoprotein (HDL)-cholesterol decreased significantly by testosterone treatment. In contrast, HDL-cholesterol increased, whereas low-density lipoprotein (LDL)-choles-terol and lipoprotein-(a) [Lp(a)] decreased with estradiol treatment. Conclusion(s): We conclude that 3 months of treatment with testosterone undecanoate in postmenopausal women induces insulin resistance and an adverse serum lipid profile but may increase lean body mass. Objective: Little is known about metabolic effects of testosterone treatment in postmenopausal women. The aim of the study was to compare the treatment effects of testosterone, estrogen, and testosterone plus estrogen on insulin sensitivities, body compositions, and lipid profiles in healthy postmenopausal women. Design: An open, randomized clinical study with parallel group comparison. Setting: Women’s health clinical research unit at a university hospital. Patient (s): Sixty-three naturally postmenopausal women participated in the study. Intervention (s): The participants were randomly assigned to 3 months of treatment with testosterone undecanoate (40 mg every second day), estradiol valerate (2 mg daily), or the combination of both. Main Outcome Measure (s): Insulin sensitivity assessed by euglycemic hyperinsulinemic clamp, body composition, and Serum lipids. Result (s): Insulin-induced glucose disposal was reduced by approximately 20% after treatment with testosterone alone, and after the combined treatment, but not by estrogen alone. Body weight, but not total body fat, increased significantly by about 1 kg in all groups. Lean body mass was significantly increased in the group of combined treatment and tended to be increased by testosterone alone. In contrast, HDL-cholesterol increased, and low-density lipoprotein (LDL) -choles-terol and lipoprotein- (a) [Lp (a)] decreased with estradiol Treatment. Conclusion (s): We conclude that 3 months of treatment with testosterone undecanoate in postmenopausal women induces insulin resistance and an adverse serum lipid profile but may increase lean body mass.