Experimental hypogonadism: Insulin resistance, biochemical changes and effect of testosterone substitution

Abstract

We sought to clarify the role of testosterone substitution in terms of insulin resistance and metabolic profile dysregulation in hypogonadism. Twenty-nine male Wistar rats aged 11-12 weeks were divided in three groups: control (C, n = 10), sham operation; orchiectomy (ORX, n = 9); and orchiectomy + testosterone substitution (ORX+T, n = 10). Blood samples were obtained at day 1 (operation), after 10 days (intramuscular T injection 100 μg/100 g b.w.), 25 days (second T injection) and 40 days (sacrifice). Hormonal replacement significantly attenuated the negative effect of orchiectomy on insulin resistance as indicated by the successive changes in both insulin levels (1.44 ± 2.94 vs. 4.10 ± 2.47 vs. 1.78 ± 0.68 ng/mL, for D1, D10 and D40, respectively; p = 0.028 and p = 0.022, respectively) and HOMA-IR index (1.36 ± 2.75 vs. 3.68 ± 1.87 vs. 1.74 ± 0.69 ng/mL, for D1, D10 and D40, respectively; p = 0.024 and p = 0.026, respectively) in the ORX+T group. Irisin levels peaked at the 10th postoperative day and were decreased at the end of the experiment (0.27 ± 0.11 vs. 0.85 ± 0.54 vs. 0.02 ± 0.07 ng/mL for D1, D10 and D40, respectively; p = 0.028 in both cases), whereas resistin levels did not differ. Experimental hypogonadism results in an unfavorable lipid profile and insulin resistance, which is not observed when the ORX animals are substituted for T.