youth to boost physical strength and reverse the effects of aging (Hoberman and Yesalis, 1995). The modern field of endocrinology emerged at the turn of the 20th century as researchers working on “internal secretions” (termed hormones in 1905 by the British scientist Ernest Henry Starling) explored how those compounds act as physiological regulators. One of the early experiments was reported in 1889 by French physiologist Charles Edouard Brown-Séquard who attributed increases in his physical strength and intellectual energy to self-injections of an extract from the testicles of dogs and guinea pigs (Medvei, 1982). The continued use of crude (possibly inactive) gonadal preparations continued into the 1930s, to be gradually replaced with periodic injections of testosterone. In 1939 Leopold Ruzicka and Adolf Butenandt shared the Nobel Prize for Chemistry for their work on isolating and synthesizing testosterone and other reproductive hormones (Malmström and Andersson, 2003).

A number of testosterone compounds have been approved by the Food and Drug Administration (FDA) as treatments for specific conditions, particularly hypogonadism. Testosterone products must be prescribed and are designated as Schedule III controlled substances due to abuse potential. Because testosterone is weakly soluble in water, limiting absorption, and is rapidly metabolized by the liver, bioavailability via the oral route is limited. Therefore, a variety of non-oral delivery methods have been developed (e.g., gel, patch, injection). The goal in developing testosterone formulations has been to produce a product that will deliver physiological levels for prolonged periods of time; is safe, effective, easy to use, and inexpensive; and has few local side effects (e.g., skin irritability) (Handelsman, 1996).

The oral forms of alkylated androgen compounds available in the United States are generally not recommended for use as testosterone therapy because they may produce deleterious effects, including hepatotoxicity (hemorrhagic liver cysts, cholestasis, and hepatocellular adenoma) and unfavorable alterations in the lipid profile (Wang, 1996; AACE, 2002; Swerdloff and Wang, 2002). Orally administered testosterone is almost completely inactivated by its first pass through the liver, and this rapid metabolism makes it difficult to sustain constant levels of circulating hormone. In Europe, testosterone undecanoate is available and is considered a more acceptable oral alternative, as it is absorbed from the gastrointestinal tract into the lymphatic system due to its lipophilic side chain and, thus, partially escapes hepatic inactivation (Matsumoto, 2002). However, the absorption is rather variable, and the dose required is best determined on the basis of plasma levels and clinical effects.

There are several testosterone formulations that can be delivered by intramuscular injection. Testosterone enanthate and testosterone cypionate are testosterone esters that are available in oil suspension prepa-