Testosterone therapy reduces insulin resistance in men with adult‐onset testosterone deficiency and metabolic syndrome. Results from the Moscow Study, a randomized controlled trial with an open‐label phase

Abstract

AbstractAimsTo describe changes in homeostasis model assessment of insulin resistance index (HOMA‐IR) following testosterone therapy in men with hypogonadism and metabolic syndrome (MetS).Materials and MethodsA randomized, placebo‐controlled, double‐blind randomized controlled trial (RCT) comprising 184 men with MetS and hypogonadism (testosterone undecanoate [TU]: 113 men, placebo: 71 men) was conducted. This was followed by an open‐label phase in which all men were given TU. We focused on men who were not receiving antiglycaemic agents (TU: 81 men; placebo: 54 men) as these could affect HOMA‐IR. Inter‐group comparison of HOMA‐IR was restricted to the RCT (30 weeks), whilst intra‐group comparison was carried out on men provided TU during the RCT and open‐label phases (study cohort) and men given placebo during the RCT and then switched to TU during the open‐label phase (confirmatory cohort). Regression analysis was performed to identify factors associated with change in HOMA‐IR (∆HOMA‐IR).ResultsThe median HOMA‐IR was significantly reduced at almost every time point (after 18 weeks) compared to baseline in men receiving TU in both the study and confirmatory cohorts. There was a significant decrease in median values of fasting glucose (30 weeks: −2.1%; 138 weeks: −4.9%) and insulin (30 weeks: −10.5%; 138 weeks: −35.5%) after TU treatment. Placebo was not associated with significant ∆HOMA‐IR. The only consistent predictor of HOMA‐IR decrease following TU treatment was baseline HOMA‐IR (r2 ≥ 0.64).ConclusionsBaseline HOMA‐IR predicted ΔHOMA‐IR, with a greater percentage change in insulin than in fasting glucose. In men with MetS/type 2 diabetes (T2DM) not on antiglycaemic therapy, improvements in HOMA‐IR may be greater than suggested by change in fasting glucose. Our results suggest that hypogonadism screening be included in the management of men with MetS/T2DM.