Testosterone production and serum levels

Early reports of decreased spermatic vein testosterone blood concentrations (Hollander and Hollander 1958) and decreased testosterone blood production rates (Kent and Acone 1966) in elderly men have subsequently been confirmed by several studies performed in the seventies (Baker etal. 1977; Giusti etal. 1975; Vermeulen etal. 1972). However, reduced testosterone blood production rate does not necessarily imply lower testosterone plasma levels. Indeed, the blood production rate is the product of the mean plasma levels and the metabolic clearance rate, and the latter is also reduced in elderly men (Kent and Acone 1966; Vermeulen etal. 1972).

Whether aging in healthy men is also associated with decreased serum testosterone concentrations has longbeen highly controversial. Early reports of decreased nmol/l

70 O Testosterone

70 O Testosterone

Age (years)

Fig. 16.1 Mean serum levels of testosterone, free testosterone (FT) and sex hormone binding globulin (SHBG) according to age in a cross-sectional study of 300 healthy men (from Vermeulen etal. 1996).

Age (years)

Fig. 16.1 Mean serum levels of testosterone, free testosterone (FT) and sex hormone binding globulin (SHBG) according to age in a cross-sectional study of 300 healthy men (from Vermeulen etal. 1996).

mean serum testosterone levels in elderly men, dating from the late sixties and early seventies, were followed by several studies that failed to confirm an age-related decline of testosterone levels. These discrepancies maybe explained at least in part by biased selection of the study populations (Gray et al. 1991). In some of these studies, reported testosterone serum concentrations in young men were surprisingly low. Moreover, in some studies blood sampling was performed in the late afternoon when, due to the diurnal rhythm of testosterone secretion, serum levels are lower and the effect of age is minimal.

More recent studies including healthy ambulatory young and elderly men sampled in the morning, again confirmed an age-associated decline of serum testosterone levels, albeit of lesser magnitude than reported in the early studies (for review Vermeulen 1991), mean values at age 75 years being about two thirds of those at age 25 years (Fig. 16.1). An age-related decrease of serum testosterone levels has also been documented in longitudinal studies (Feldman etal. 2002; Harman etal. 2001; Morley etal. 1997; Zmuda etal. 1997). In fact, the longitudinally assessed decline of serum testosterone tends to be even larger than apparent from cross-sectional analysis (Feldman et al. 2002), which might be due to a bias towards healthier subjects in the latter while during longitudinal follow-up more elderly subjects are likely to show a deterioration than an improvement of their general health status.

Whereas mean serum testosterone levels in the adult male population decrease with age, a large inter-individual variability of serum testosterone levels is observed at all ages, with some elderly men having frankly low serum testosterone levels while many others have perfectly preserved testosterone secretion with serum levels well within the normal range for young adults. With advancing age, a progressively

Fig. 16.2 Proportion of healthy men presenting with subnormal serum levels for total testosterone (<11 nmol/l) or free testosterone (<0.18 nmol/l) (from Kaufman and Vermeulen 1997).

larger proportion of men present with subnormal values relative to those in young adults; in a group of 300 healthy men aged 20 to 100 years (Vermeulen etal. 1996), we observed a subnormal testosterone level in less than 1% of men below age 40 years but in more than 20% of men older than 60 years (Fig. 16.2).

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