Testicular steroidogenesis and androgen use and abuse.

The possibility of widespread use of androgens in the normal male population for the promotion of growth, sexual dysfunction, contraception, osteoporosis and ageing and large scale abuse by athletes have propelled androgen replacement out of the narrow confines of male hypogonadism and highlighted the many gaps in our knowledge. There is now a new appreciation of the much wider aetiological, therapeutic, preventative and public health implications surrounding the clinical use of androgens. To realize the many potential health benefits through manipulations of the androgen milieu of normal men, basic and clinical investigations into a number of key unresolved issues are urgently required. There is a need to understand the molecular mechanisms underlying the differential roles of testosterone, DHT and oestradiol in various androgen-responsive target tissues especially with reference to the pathogenesis of prostatic hyperplasia or carcinoma. It is also necessary to define the dose-response relationships of the action of androgens on spermatogenesis (and basis for inter-ethnic differences), sexual and aggressive behaviour and bone mineral turnover over a wide dose range. Clinically, it is important to systematically assess whether there is any increased risk for cardiovascular and prostatic diseases in androgen replacement and the risk-benefit issues concerning androgen therapy in aged men. Development of androgens with high therapeutic indices, long half-lives, zero-order release kinetics and perhaps selective target tissue specificity through modification to the steroid structure can further optimize future modalities of androgen therapy.