The latest options and future agents for treating male hypogonadism

Abstract

Exogenous testosterone has long been used in medicine as a pharmaceutical agent. Its use in hypogonadism is well characterized and its development as a drug has undergone several modifications in an attempt to achieve clinical success. As native testosterone is rapidly degraded, modified analogs have been developed to obtain a better pharmacokinetic profile. The developmental goals of testosterone analogs have evolved since its first introduction as an orally available form to longer acting and more stable forms such as injectables, depots and transdermal therapies. Several modalities of testosterone replacement are presently available, each differentiated by their route of delivery, half life, cost and ability to deliver physiologic levels of testosterone. As hypogonadism is often a life-long condition, physicians are compelled to use an appropriate therapy that best matches the needs of their patients. An ideal testosterone therapy should be able to deliver physiologic levels of testosterone and be safe, simple to use and cost effective. Present trends show transdermal therapies (gels and patches) along with long-acting injectables, such as Nebido®, are quickly replacing intramuscular testosterone modalities. Compounds such as dihydrotestosterone, human chorionic gonadotropin, aromatase inhibitors and clomiphene are presently being studied in specific subgroups of men. Additionally, several new compounds, such as selective androgen-receptor modulators and 7-α-methyl-19-nortestosterone, are being developed to target androgen receptors in specific tissues. A further understanding of the androgen receptor and subsequent discovery of targeted drugs may yield more individualized treatment modalities. This will enhance the effectiveness of available therapies, while mitigating their undesirable effects.