Pharmacology of testosterone pellet implants

Abstract

The main indication for androgen therapy is the treatment of androgen deficiency in hypogonadal men. Since such androgen replacement therapy usually involves life-long administration of testosterone, it is desirable that testosterone formulations be long-acting. The primary goal of androgen replacement therapy is to replicate the physiological actions of endogenous testosterone. This requires not just rectification of deficient androgen levels but also avoiding either supranormal or excessively fluctuating testosterone levels. Thus the practical intent of androgen replacement therapy is to maintain stable, physiological testosterone levels for prolonged periods. The pharmacological properties of testosterone, notably its rapid metabolic inactivation by the liver, have dictated that the achievement of such prolonged androgenic effects requires the development of depot, sustained-release testosterone formulations (Wilson 1980). Nevertheless, even 50 years after the entry of testosterone into the clinical armamentarium (Hamilton 1937; Foss 1939) the quest for a safe, effective, inexpensive, convenient, long-acting androgen preparation with reproducible, zero-order release profile remains an important challenge not yet met. One of the oldest testosterone formulations is the subdermal implant of testosterone pellets which provide stable testosterone levels for at least 4 months after a single implantation (Cantrill et al. 1984; Conway et al. 1988). Curiously this cheap and effective treatment modality has been neglected for decades despite its many advantages for androgen replacement therapy.