Low testosterone levels are a common in men with coronary artery disease and Type 2 diabetes (DM2). Testosterone replacement therapy improves insulin sensitivity and glycaemic control in men with diabetes and improves numerous other cardiovascular risk factors. Interest in testosterone as a potential treatment for cardiovascular disease continues to grow. Low HDL cholesterol (HDL-C) levels are recognised as an independent cardiovascular risk factor and comprise part of the metabolic syndrome. The effect of testosterone treatment on HDL-C in clinical trials has been inconsistent. Testosterone may be acting through differing processes with opposite effects on HDL-C. The androgen receptor CAG repeat length (AR CAG) positively correlates with transcriptional activity of the receptor and with HDL-C in young healthy men.
We present data on the link between testosterone levels, AR CAG and HDL-C levels in a sample of 187 men with DM2. Total testosterone (TT) and SHBG levels were assessed by ELISA. Bioavailable testosterone (BioT) was measured by ammonium sulphate precipitation. AR CAG repeat length was measured by DNA sequence analysis.
Regression methods revealed that HDL-C levels were positively associated with TT (regression coefficient r=0.248, P<0.001), BioT (r=0.204, P=0.005) and SHBG (r=0.169, P=0.021). Regression did not reveal an overall relationship between AR CAG and HDL-C, but men in the lower quartile of the range of AR CAG had significantly lower HDL-C compared to rest of the group (1.11 vs 1.21 mmol/l P=0.027). Men in the upper quartile of AR CAG did not significantly differ from the rest of the group.
Thus, in our group of men with DM2, HDL-C levels are lower when AR CAG is shorter (more active). Conversely, testosterone is positively associated with HDL-C. The results suggest that the dominant effect of testosterone in this group may be to increase HDL-C, but that this is not occurring via the androgen receptor.