Testosterone Secretion and Metabolism in Male Senescence

TLDR

In aging men, reduced metabolic clearance rate lowers testosterone production, and shifts in metabolite formation indicate that target tissue metabolism of free testosterone becomes increasingly important. The study examined how aging affects plasma testosterone levels and testosterone metabolism in men. Plasma testosterone and apparent free testosterone remain stable until age 50, then decline sharply; free testosterone fraction correlates positively with metabolic clearance rate and with 5α‑androstane‑3α,17β‑diol formation, while androstanediol production falls and 5β metabolites rise.

Abstract

The influence of aging on plasma testosterone levels and testosterone metabolism in males was studied. It was observed that plasma testosterone levels and the apparent free plasma testosterone concentration (AFTC) remain within the same range from adolescence until the age of 50 yr, but that from the 6th decade on, the mean plasma levels decrease rather rapidly, with however a wide range of individual values. As the metabolic clearance rate (MCR) decreases in male senescence, the net result is an important decrease in the testosterone blood production rate. Within the group of subjects studied, a statistically significant correlation between the free testosterone fraction and the MCR was found. It was observed that testosterone metabolism in male senescence is characterized by a relative decrease of the formation of androstanediols, with a relative increase of 5β over 5α metabolites;moreover a statistically significant correlation between the formation of 5α-androstane-3α,17β-diol and the free testosterone fraction was found. As the latter metabolite is largely formed in peripheral target tissues, this suggests that testosterone metabolism by target tissues becomes more important with increasing free T fraction and indirectly, that only free testosterone can be taken up by target tissues.