Androgen Pharmacology and Delivery Systems

Abstract

Historically, testis extracts from animals and then men were used as a rejuvenation mixture with poor success. Testosterone was first synthesized in the 1930s, providing for the first time a means to provide sufficient testosterone to treat hypogonadal men. Initially, testosterone pellets were developed for subcutaneous implant and the methyl derivative (methyltestosterone) was administered as an orally active agent. In the 1950s, the testosterone esters (propionate, enanthate, and cypionate) became available and have continued to be used for testosterone-replacement therapy in androgen deficiency (1–4). During the peak era of steroid chemistry, modifications of the testosterone molecule were made to achieve orally active bioactivity and for the “anabolic” effects such as increased nitrogen retention, muscle protein synthesis, muscle strength, and mass. Methyltestosterone and fluoxymesterone were prescribed as oral preparations for hypogonadism, but the former was criticized for its hepatotoxicity and the latter was a weak androgen. In the 1970s, oral testosterone undecanoate was marketed with wide acceptance in Europe, Australia, and Asia but was not available in the United States. In the past 10 yr, there has been a resurgence in the interest of development of new formulations and delivery systems of testosterone for potential new indications such as androgen replacement in elderly men, male contraception, severe wasting diseases, and androgen replacement in gonadectomized or postmenopausal females.