Endocrine Abstracts

Hypogonadism is a common finding in men with metabolic syndrome (MS) and/or type 2 diabetes (T2D) which adversely affects quality of life, is associated with several cardiovascular (CV) risk factors and a greater risk of mortality. Testosterone replacement therapy (TRT) in pilot studies has beneficial effects on waist circumference (WC), insulin resistance, glycaemic control, lipid and inflammatory profiles.

Testosterone replacement in hypogonadal metabolic syndrome and type 2 diabetes (TIMES2) was a European multi-centre, prospective, randomized, double-blind placebo controlled trial of TRT (transdermal 2% testosterone gel) in 220 hypogonadal men with either MS and/or T2D.

TRT reduced homeostatic model of insulin resistance (HOMA-IR) by −0.85 (P=0.018) at 6 months and −0.84 (P=0.06) at 12 months. HOMA-IR, at 12 months in T2D group decreased by −0.82 (P=0.049) and MS by −0.87 (P=0.054). In the modified per protocol groups (subjects with no change in medication affecting specific parameters in first 6 months), TRT in total study group improved a) body composition −0.28% (P=0.004) at 6 and −0.91% (P=0.026) at 12 months b) total cholesterol −0.23 mmol/l (P=0.037), LDL-cholesterol −0.2 mmol/l (P=0.019) and lipoprotein a (Lpa) −0.06 mmol/l (P=0.034) all at 6 months. No change in HDL-cholesterol or triglycerides\. In T2D, TRT reduced HbA1c by −0.58% (P=0.005) at 9 and −0.5% (P=0.066) at 12 months and WC by −1.59 cm at 12 months. Sexual function assessed by the International Index of Erectile Function (IIEF) score at 6 (6.77; P=0.019) and 12 (9.36; P=0.024).

TRT improves insulin resistance, the pivotal biochemical abnormality and mediator of CV risk in MS and T2D. There were beneficial effects with reductions in body fat, WC, cholesterol and Lpa. Lpa is the most atherogenic component of the lipid profile and testosterone is the only therapy that is known to reduce levels. Importantly TRT reduces HbA1c an effect which, can be translated into improved diabetic outcomes.