Abstract:Background: Testosterone facilitates various metabolic processes in the bones, muscles, bone marrow, brain and immune system. Testosterone deficiency may contribute to cardiovascular diseases, central obesity and metabolic dysfunction. Aim: to investigate the effects of testosterone deficiency on blood glucose levels, insulin sensitivity, vitamin D, Homeostatic model assessment of insulin resistance (HOMA-IR), Homeostatic model assessment for beta function (HOMA-IR) and serum lipids in rat models of andropause. Methods, 48 male rats divided into 4 equal groups (n=12/group); a) Control (C) group. b) Orchiectomy (O) group underwent bilateral removal of the testicles. c) Orchiectomy and treated (O+T) group given daily IM testosterone replacement therapy for 7 days, d) Sham and treated (Sh+T) group in which sham operated rats were given the same daily dose of T as O+T group for 7 days. Results: we found that plasma glucose concentration increased significantly (P<0.001) in O group. This increase was corrected by testosterone injection in O+T group. In (Sh+T) group, there is a significant reduction in serum glucose (P<0.001). We also found that insulin level reduced significantly (P<0.001) in O group. This reduction in insulin level was corrected by testosterone. In (Sh+T) group, insulin level increased significantly. 25-OHVD3 was reduced significantly (P<0.05) in O group and increased significantly in O+T group. HOMA-IR level decreased significantly (P<0.001) and this reduction was corrected by Testosterone. HOMA-β reduced significantly (P<0.001) and this reduction was corrected by Testosterone in O+T group. In SH group, there is a marked increase in HOMA-β. We also found insignificant differences between the four groups in serum triglycerides. However, we found very highly significant differences in total cholesterol, LDL and VLDL between C group and O group and very highly significant differences between O+T group and Sh+T group in comparison with O group. We also found significant differences in serum HDL-c in (O) group in comparison with (C) group and between O+T and Sh+T groups in comparison with O group. In conclusion, we found significant reduction in 25-OH(VD), Testosterone, Insulin, HOMA-IR and HOMA-B and significant increase in glucose serum levels in O group and these changes were corrected by Testosterone injection in O+T group. We also found insignificant differences between the four groups in serum triglycerides. However, we found highly significant differences in total cholesterol, LDL, HDL-c and VLDL between C group and O group and very highly significant differences between O+T group and Sh+T group in comparison with O group.