Testosterone Replacement Therapy: Long-Term Safety and Efficacy

Recent position statements and guidelines have raised the distinction between a true and false, age-related hypogonadism (HG) or late-onset hypogonadism (LOH). The former is the consequence of congenital or acquired "organic" damage of the brain centers or of the testis. The latter is mainly secondary to age-related comorbidities and does not require testosterone (T) therapy (TTh). In addition, concerns related to cardiovascular (CV) safety have further increased the scepticism related to TTh. In this paper, we reviewed the available evidence supporting the efficacy of TTh in non-organic HG and its long term safety. A large amount of evidence has documented that sexual symptoms are the most specific correlates of T deficiency. TTh is able to improve all aspects of sexual function independent of the pathogenetic origin of the disease supporting the scientific demonstration that LOH does exist according to an "ex-juvantibus" criterion. Although the presence of metabolic derangements could mitigate the efficacy of TTh on erectile dysfunction, the positive effect of TTh on body composition and insulin sensitivity might counterbalance the lower efficacy. CV safety concerns related to TTh are essentially based on a limited number of observational and randomized controlled trials which present important methodological flaws. When HG is properly diagnosed and TTh correctly performed no CV and prostate risk have been documented.