Testosterone replacement therapy with long-acting testosterone undecanoate improves sexual function and quality-of-life parameters vs. placebo in a population of men with type 2 diabetes. Hackett G, Cole N, Bhartia M, et al. J Sex Med 2013; 10(6):1612-1617.

This editorial discusses the key findings and implications of a study published in 2013 by Hackett et al.¹ (The BLAST study) that investigated the effect of testosterone replacement therapy on sexual function and quality of life parameters versus placebo in males with type 2 diabetes (T2D). The study was separated into two phases. The first phase was a 30-week, prospective, randomized, double-blind, placebo-controlled multicenter study conducted between September 2008 and June 2011 at eight UK Midland centers. A total of 190 males (age >18 years) with T2D received long-acting Testosterone Undecanoate (TU) 1000 mg or placebo for 30 weeks (at weeks 0, 6, and 18). The second phase was a 52-week follow-on with open-label TU therapy in 96 patients proceeding from the first phase. The primary outcome of the study was a statistically significant change from baseline in the 15-item International Index of Erectile Function (IIEF) domains. Notable secondary outcomes included health-related quality-of-life symptoms, as measured by the 17-item Ageing Male Symptom Scale (AMS) questionnaire.

Patients with T2D are at high risk of comorbidities. The high prevalence of hypogonadism in T2D, independent of obesity, has been well-reported.^2-6 Furthermore, the prevalence of clinically assessed depression in males with T2D was determined as 9.8% in a meta-analysis of 51,331 patients across 10 controlled studies.⁷ In a separate meta-analysis of 22 studies that focused on the impact of diabetic complications on depression, sexual dysfunction was most commonly associated with depression. To effectively diagnose and manage such comorbidities, guidelines published by the UKs National Institute for Health and Clinical Excellence (NICE) recommend a yearly screening for erectile dysfunction in males with T2D,⁸ whilst separate guidelines for erectile dysfunction recommend measurement of testosterone levels in males at high risk, such as those with T2D.⁹ As a result, clinicians who adhere to these guidelines are likely to be faced with patients who present with T2D, low testosterone levels, depression, and erectile dysfunction.

The results from the BLAST study confirm the beneficial effects of TU on IIEF domains and health-related quality of life in males with T2D, and complement previously published data.^10,11 However, data from this 82-week study illustrate the effect of depression on the response to testosterone replacement therapy; with baseline depression diminishing any response to sexual function altogether. Adding to this, a significant reduction in AMS was observed only in patients without depression. Depression has been shown to independently impact sexual function, as well as reduce diabetes medication response and adherence, which should be considered during treatment decisions.^12-14

The addition of a subgroup of males taking PDE5Is is novel, as similar studies investigating testosterone replacement therapy in diabetic males fail to identify whether PDE5Is were excluded.^15-17 Males with T2D within this subgroup showed no improvement in IIEF domains during the double-blind phase, but showed large improvements after a further 12 months of open-label treatment. This delayed improvement may be explained through the achievement of sustained levels of TU beyond ≥5 injections, and the long 54-day half-life of long-acting TU. This is of clinical importance, as current guidelines recommend only 3 to 6 months of testosterone replacement therapy and the duration of TU therapy in previously published studies may have been too short for benefits in sexual function to present. As a result, males with T2D should be screened for low testosterone levels and depression, and considered for testosterone replacement therapy beyond the 6 months currently recommended.