The response to testosterone undecanoate in men with type 2 diabetes is dependent on achieving threshold serum levels (the BLAST study)

BackgroundThe association between testosterone deficiency and insulin resistance in men with type 2 diabetes is well established. Current Endocrine Society and European Association of Urology guidelines recommend the measurement of testosterone levels in all men with type 2 diabetes and in men suffering from erectile dysfunction. It is recognised that a range of physical symptoms appear as the testosterone level falls but few studies have addressed the threshold at which symptoms improve with physiological replacement. We report the first double-blind placebo-controlled study conducted exclusively in a male type 2 diabetes population to assess the metabolic changes with testosterone replacement. MethodsThe type 2 diabetes registers of seven general practices were screened to establish the prevalence of low testosterone and the associations with diabetes control. Of 550 eligible patients approached, 488 men (mean age 62.6) consented to take part in screening with a morning testosterone level, assessed between 8 and 11 am. This identified 211 patients for a double-blind placebo-controlled study of long acting testosterone undecanoate (TU) 1000mg lasting 30weeks followed by 52weeks of open label use. The population was divided into a SEVERE group with either total testosterone (TT) of 8nmol/l or less or free testosterone (FT) 180pmol/l or less or a MILD group with TT 8.1-12nmol/l or FT 181-250pmol/l. ResultsMen in the SEVERE group increased mean through TT from 7.73nmol/l at baseline to 9.93 at 30weeks and the MILD group from 10.47 to 11.94. The SEVERE group showed marked improvement in sexual function, but no significant improvement in metabolic parameters. The MILD group showed no improvement in sexual function, but significant improvement in weight, body mass index, waist circumference and Hospital Anxiety and Depression Scale. Improvement was seen in all parameters during 52weeks open label treatment where trough TT levels approached 15nmol/l. Baseline prostate-specific antigen (PSA) was lower in the SEVERE group and increased with TU for 30weeks and then stabilised. There was no increase in PSA with treatment in the MILD group. ConclusionsTestosterone undecanoate significantly improves sexual parameters and Ageing Male Symptom Score, but not metabolic factors at 30weeks in men with SEVERE testosterone deficiency syndrome (TDS). In men with MILD TDS, significant improvements in metabolic but not sexual parameters were seen, suggesting that there are threshold levels for response to testosterone replacement therapy and that trials of therapy need to achieve sustained therapeutic levels to be effective. PSA showed minor rises, but only for 30weeks in the SEVERE group.