Sex hormone binding globulin and free testosterone serum levels

Whereas some authors may still argue that total testosterone concentrations are not reduced in perfectly healthy elderly men, all authors agree that the free and non-specifically bound serum testosterone, generally considered to represent the serum testosterone fractions readily available for biological activity, do indeed decrease with age (for review Vermeulen 1991). In healthy ambulatory men, mean serum levels of free testosterone (FT) and of non SHBG-bound or so called "bioavailable" testosterone (i.e. the sum of the free fraction and the fraction loosely bound to albumin) decrease by as much as 50% between age 25 and 75 years (Ferrini et al. 1998; Vermeulen etal. 1996). The sharper decline of these fractions in comparison with total testosterone is explained by an age-associated increase of sex hormone binding globulin (SHBG) concentrations and has been confirmed in longitudinal studies (Feldman et al. 2002; Harman et al. 2001; Morley et al. 1997). In 300 healthy men aged 25-100 years we observed an approximately log linear decrease of free testosterone levels at a rate of 1.2% per year (Fig. 16.1), while total serum testosterone remained relatively stable up to age 55 years and declined thereafter at a rate of 0.85% per year (Vermeulen etal. 1996).

As for total testosterone, there is great inter-individual variability in prevailing free (or bio-available) testosterone levels in elderly men, ranging from markedly

Sex Hormone Binding Globulin Molecule

Fig. 16.3 Histogram for the distribution of serum free testosterone in 353 community-dwelling elderly men without major health problems, aged 70 to 85 years (upper panel) and in a younger control population of healthy men aged 23 to 58 years (lower panel); the lower limit for the laboratory normal range is indicated by the arrows.

Fig. 16.3 Histogram for the distribution of serum free testosterone in 353 community-dwelling elderly men without major health problems, aged 70 to 85 years (upper panel) and in a younger control population of healthy men aged 23 to 58 years (lower panel); the lower limit for the laboratory normal range is indicated by the arrows.

low levels to levels in the upper normal range for young adults (Fig. 16.3), the proportion of men with subnormal free testosterone levels increasing with age (Fig. 16.2). However, limits of normality are somewhat arbitrary as the sensitivity threshold for androgen action may vary from tissue to tissue and according to age.

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