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The rejuvenation of testosterone: philosopher’s stone or Brown-Séquard Elixir?

The rejuvenating properties of testosterone (and various other androgenic agents) have been utilized over several millennia (e.g. testicular extracts from animals were used by the Romans and the ancient Chinese for erectile dysfunction [ED]). However, the idea of hormonal rejuvenation really started in earnest with the acclaimed scientist and endocrinologist, Charles Brown-Sequard. Brown-Sequard regularly injected himself with testicular extracts from guinea pigs or dogs (i.e. the so-called Brown-Sequard Elixir) as a means of restoring vitality [Brown-Sequard, 1889]. More recently, testosterone itself has undergone its own rejuvenation due to increased awareness of its potential benefit in hypogonadism and various other medical states (e.g. HIV-related weight loss, glucocorticoid-treated men). In addition, new testosterone formulations have helped simplify therapy and are generally better tolerated than older regimens. 
 
The normal testis has two major functions: synthesis and secretion of androgenic hormones, particularly testosterone (~6mg/day), dihydro-testosterone (DHT), and androstenedione of Leydig cell origin; and production of mature spermatozoa in the seminiferous tubules. 
 
In the circulation, testosterone exists in a free (unbound) or bound form. The bound forms of testosterone are either weakly attached to albumin (which together with the free testosterone constitutes so-called bioavailable testosterone and is ~ 20–50% of total testosterone) or tightly bound (and acting like a reservoir for testosterone) to sex hormone—binding globulin (SHBG; ~50–80% of total testosterone). Only approximately 2% of circulating testosterone is ‘free’ and therefore able to enter the cell and exert its metabolic effects. Testosterone can also act as a prohormone by being converted to DHT (by 5-α reductase) or aromatized to estradiol (E2) in peripheral tissues [Matfin, 2009]. 
 
Testosterone (and DHT) exerts a variety of biologic effects in the male. In the male embryo, testosterone is essential for the appropriate differentiation of the internal and external genitalia, and it is necessary for descent of the testes in the fetus. Testosterone is essential to the development of primary and secondary male sex characteristics during puberty and for the maintenance of these characteristics during adult life. There is also convincing evidence that testosterone has important metabolic and vascular effects [Channer and Jones, 2003]. 
 
The synthesis and pulsatile release of the gonadotropic hormones (follicle stimulating hormone [FSH] and luteinizing hormone [LH]) from the anterior pituitary are regulated by gonadotropin-releasing hormone (GnRH), which is synthesized by the hypothalamus. The production of testosterone by the Leydig cells is regulated by LH, whilst FSH binds to Sertoli cells stimulating spermatogenesis.