Introduction

Male reproductive function is influenced by non-gonadal disease so that mild androgen deficiency is a regular feature of chronic disease, which, if sufficiently severe or prolonged may contribute to the pathophysiology. Additionally, androgens are potent therapeutic drugs with effects on androgen-sensitive tissues such as muscle, bone, brain, liver or adipose tissue that may be exploited for therapeutic benefit.

As an adjunct to standard medical care, androgen therapy may be considered as either physiological androgen replacement or pharmacological androgen therapy. Androgen replacement therapy aims to replicate endogenous androgen exposure thereby limiting it to the use of testosterone in doses intended to produce physiological blood concentrations. To the degree it replicates endogenous androgen exposure, the expectation for safety may reasonably be compared with the benchmark of life-long health experience of eugonadal men. By contrast, pharmacological androgen therapy is no different from pharmacotherapy with any xenobiotic drug used to achieve a therapeutic goal. It utilises an androgen, without restriction to testosterone or reference to replacement doses, to optimal effect as judged by the standards of efficacy, safety and cost-effectiveness applicable to other drugs. Pharmacological androgen therapy has often involved synthetic oral androgens rather than testosterone, usually the hepatotoxic 17α-alkylated androgens now considered obsolete for androgen replacement therapy. While occasionally justified by the need to avoid parenteral injections due to bleeding disorders or for deliberate hepatic targeting via oral first pass effects, this involves an avoidable risk of hepatotoxicity.