The role of the androgen receptor CAG repeat polymorphism and other factors which affect the clinical response to testosterone replacement in metabolic syndrome and tpye 2 diabetes - TIMES2 sub-study
Stanworth RD, Akhtar S, Channer K, Jones TH. Eur J Endocrinol. 2013 Oct 28. [Epub ahead of print]


R Stanworth, Department of Diabetes and Endocrinology, Derby Hospitals NHS Foundation Trust, Derby, United Kingdom.


Context. The TIMES2 study reported beneficial effects of testosterone replacement therapy on insulin resistance and other variables in men with diabetes or metabolic syndrome. The androgen receptor CAG repeat polymorphism (AR CAG) is known to affect stimulated androgen receptor activity and has been linked to various clinically relevant variables.Objective. Assess role of AR CAG in altering clinical response to testosterone replacement therapy in the TIMES2 study.Design. Subgroup analysis from a multicentre, randomised, double-blind, placebo-controlled, parallel group studySetting. Outpatient study recruiting from secondary and primary carePatients. 139 men with hypogonadism and type 2 diabetes or metabolic syndrome. 73 of these men received testosterone during the TIMES2 study,Intervention. Testosterone 2% transdermal gel versus placeboMain outcome measure. Regression coefficient of AR CAG from linear regression models for each variableResults . AR CAG was independently positively associated with change in fasting insulin, triglycerides and diastolic blood pressure during testosterone replacement therapy with a trend to association with HOMA-IR- the primary outcome variable. There was a trend to negative association between AR CAG and change in PSA. There was no association of AR CAG with change in other glycaemic variables, other lipid variables or obesity.Conclusion. AR CAG affected response of some variables to testosterone replacement therapy in the TIMES2 study although the association with HOMA-IR did not reach significance. Various factors may have limited the power of our study to detect significant associations between AR CAG, testosterone levels and change in variables with testosterone treatment. Analysis of similar data sets from other clinical trials is warranted.