Tissue levels and metabolism of androgens

Highest concentrations of androgen receptors (AR) are present in the accessory sex organs, whereas the concentrations in other androgen-sensitive tissues such as the heart and bone are much lower. This concentration of receptors is affected by the androgen levels, and by age (Blondeau et al. 1982; Rajfer et al. 1989). As both circulating steroids and tissue receptor concentration decrease with age, it is not surprising that tissue androgen concentration also decreases with age (Deslypere and Vermeulen 1981; 1985).

Overall, the influence of the aging process on the metabolism of testosterone manifests itself essentially by a decrease of the metabolic clearance rate (Vermeulen et al. 1972), which results from an age-associated decrease of cardiac output and of hepatic as well as tissue perfusion, and from increased binding of plasma testosterone to SHBG. No data are available concerning the possible influence of aging on blood conversion rates of testosterone to DHT. Cross-sectional studies show no apparent age-relateddecrease of DHT levels, whereas an increase of serum DHT was recently reported for a longitudinal follow-up study (Feldman etal. 2002). In any case, serum DHT is not considered a reliable parameter of tissue DHT formation (Labrie etal. 1995).

The conversion of testosterone to estradiol increases with age (Siiteri and MacDonald 1975), which appears to be the consequence of an increase of both aromatase tissue activity and of fat mass in the elderly (Vermeulen et al. 1996; 2002). This increasing global aromatase activity compensates for the decreased substrate availability, i.e. the declining testosterone and androstenedione plasma levels, so that serum estradiol levels do not show much change during aging in men (Ferrini etal. 1998; Vermeulen etal. 1996; 2002). However, there is a decrease with age of the serum testosterone over estradiol ratio and, as a consequence of the age-related increase in SHBG, also a moderate decrease of serum free and bio-available estradiol.

Serum levels of 5a-androstane-3a17p diol-glucuronide (ADG) decrease significantly with age (Deslypere et al. 1982), a consequence of the decreased serum concentrations of the precursors (70% testosterone and 30% dehydroepiandros-teronesulfate). In urine there is a decrease of the ratio of 5a to 5p metabolites (Vermeulen etal. 1972;Zumoff etal. 1976).

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