Medicinal Use of Testosterone and Related Steroids Revisited

Abstract

Testosterone derivatives and related compounds (such as anabolic-androgenic steroids-AAS) are frequently misused by athletes (both professional and amateur) wishing to promote muscle development and strength or to cover AAS misuse. Even though these agents are vastly regarded as abusive material, they have important pharmacological activities that cannot be easily replaced by other drugs and have therapeutic potential in a range of conditions (e.g., wasting syndromes, severe burns, muscle and bone injuries, anemia, hereditary angioedema). Testosterone and related steroids have been in some countries treated as controlled substances, which may affect the availability of these agents for patients who need them for therapeutic reasons in a given country. Although these agents are currently regarded as rather older generation drugs and their use may lead to serious side-effects, they still have medicinal value as androgenic, anabolic, and even anti-androgenic agents. This review summarizes and revisits the medicinal use of compounds based on the structure and biological activity of testosterone, with examples of specific compounds. Additionally, some of the newer androgenic-anabolic compounds are discussed such as selective androgen receptor modulators, the efficacy/adverse-effect profiles of which have not been sufficiently established and which may pose a greater risk than conventional androgenic-anabolic agents.

Keywords: aging; androgen receptor; antiandrogens; longevity; medicinal natural products; performance-enhancing drugs; selective androgen receptor modulators; testosterone.

Figure 1

Scheme of testosterone biosynthesis.

Figure 2

Microbial production of testosterone (A) and stereoselective introduction of alkyl (methyl) group to C₁₇ position (B).

Figure 3

Some of the synthetic testosterone analogues (synthetic anabolic steroids).

Figure 4

Nandrolone based analogues with a strong pro-estrogenic effect.

Figure 5

Experimental androgen-anabolic steroids.

Figure 6

Designer drugs based on testosterone structure/functionalities.

Figure 7

Some of the selective androgen receptors modulators in clinical or pre-clinical development.

Figure 8

Selective androgen receptors modulators that have been eliminated from further research.

Figure 9

Testosterone prodrugs (prohormones).

Figure 10

Plant-based steroids that are part of products marketed as testosterone boosters I.

Figure 11

Plant-based steroids that are part of products marketed as testosterone boosters II.

Figure 12

Molecular structures of anti-androgens.