Increase of serum SHBG

The progressive increase of plasma SHBG binding capacity with age should be regarded as a third important aspect of the physiopathological mechanisms that are responsible for the age-related changes in circulating testosterone levels. Indeed, against the background of a relative inability of elderly men to respond to hypoan-drogenism by increased testosterone secretion, an independent progressive increase of SHBG binding capacity will result in an even steeper decline of free and not specifically bound (i.e. free and albumin-bound), bioavailable testosterone levels.

The increase of SHBG concentrations in elderly men is remarkable as it occurs in the face of increased fat mass and insulin levels, factors known to be inversely correlated to SHBG levels, but the cause of this increase of SHBG levels remains unclear. It is unlikely that the decreased testosterone levels per se are responsible, as the increase in SHBG levels is observed at an earlier age than the decrease of testosterone levels; estradiol serum levels are rather similar in young and elderly men (Vermeulen etal. 1996). Serum SHBG and testosterone levels have been reported to be inversely correlated to 24-hour growth hormone and to IGF-I levels (Erfurth etal. 1996; Pfeilschifter etal. 1996; Vermeulen etal. 1996) and it has been proposed that decreased activity of the somatotropic axis may play a role in the age-associated increase of SHBG levels and ensuing decrease of free testosterone levels (Vermeulen etal. 1996).

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