Body composition and sarcopenia

Aging in men is associated with a decrease of lean body mass and an increase of fat mass, especially in the upper body and central body regions (Forbes and Reina 1970; Swerdloff and Wang 1993; Tenover 1994; Vermeulen et al. 1999a). Fat mass increases from around a mean of 20% ofbody weight in young men to 30% or more in the elderly, whereas muscle mass may decrease by as much as 35 to 40% from age 20 to 80 years (Bross et al. 1999). In a study in community-dwelling healthy men (Vermeulen etal. 1999a) we found a mean fat mass of 22.3% ofbody weight in 61 middle-aged men with mean age of 42 years, as compared to 29.4% in 271 men with mean age of 76 years, BMI being similar in both groups and lean body mass 20% lower in the elderly.

Fat mass, and in particular abdominal fat mass is negatively associated with serum (free) testosterone levels (Van Den Beld etal. 2000; Vermeulen et al. 1999a; see also section 16.2.4.1). However, the direction of this association remains unclear, as low testosterone may be a positive determinant of adiposity, whereas conversely adiposity appears to be a negative determinant of serum testosterone. Moreover, altered activity of the somatotropic axis may also play an important role in the age-related changes in body composition. In any case, a negative association of free testosterone with fat mass in elderly men persists after correction for serum IGF-I levels, which are positively correlated to serum (free) testosterone and negatively to fat mass (Vermeulen etal. 1999a).

In a majority of controlled trials of several months duration with administration of androgens to elderly men with low or (low) normal serum (bio-available) testosterone, treatment resulted in a modest decrease of total and/or abdominal fat mass (Gruenewald and Matsumoto 2003). These findings were confirmed in recent controlled studies in elderly men with transdermal administration of testosterone (Steidle etal. 2003) or DHT (Ly etal. 2001), although in this context growth hormone may have a greater effect than testosterone (Mtinzer etal. 2001).

The age-associated loss of muscle mass is accompanied by decreased muscle strength, which occurs regardless of the level of physical activity (Rogers and Evans 1993). Muscle weakness is an important component of frailty in old age, contributing to functional limitation for activities of daily living and related problems such as an increased risk for falls (Bhasin and Tenover 1997; Dutta and Hadley 1995; Guralnik etal. 1995; Rubenstein etal. 1994; see also Chapter 8). Information on the association of endogenous androgens and muscle mass is scarce. Van Den Beld etal. (2000) and Vermeulen et al. (1999a) found no association of serum (free or non SHBG-bound) testosterone with lean body mass in sizable populations of ambulant elderly men. Similarly Roy etal. (2002) found no association of lean mass with testosterone, independent of age, in men aged 20 to 90 years from the Baltimore Longitudinal Study of Aging. The limited data available suggest the existence of a correlation between serum testosterone levels and muscle function (Abbasi et al. 1993), testosterone levels being also correlated with training-induced gain of strength (Hakkinen and Pakarinen 1994). In the study by Roy et al. (2002) a free testosterone index (total testosterone over SHBG ratio), albeit not a reliable parameter of free testosterone in men (Vermeulen etal. 1999b), was positively associated with muscle strength; Van den Beld etal. (2000) observed a positive association of muscle strength with free- and bio-available testosterone.

Several controlled studies of more than three months duration with androgen administration in elderly men with low or (low) normal serum testosterone (see Gruenewald and Matsumoto 2003 for review) have shown increases of lean body mass (Ferrando etal. 2002; Kenny etal. 2001; Mtinzer etal. 2001; Snyder etal. 1999a; Steidle etal. 2003). Short-term administration (4 weeks to 3 months) of testosterone to elderly men, aimed at increasing initially low testosterone serum levels to values within the normal range for young men, has been reported to increase lean body mass (Tenover 1992), muscle strength (Morley et al. 1993; Urban et al. 1995) and skeletal muscle protein synthesis (Urban et al. 1995) However, the latter studies, besides being of short duration also included only limited number of subjects. Sih et al. (1997) observed a significant increase in grip strength in the testosterone-treated men over the age of 50 years (mean age 68 years) with low bio-available serum testosterone, in a prospective, randomized, placebo-controlled trial of 12 months' duration; lower extremity muscle strength was not evaluated. Ferrando etal. (2002) observed improved leg and arm muscle strength and an increase in muscle net proteinbalance in a small number of older men treatedwith testosterone for six months; a positive effect of six months testosterone treatment is seen in older men on net protein balance in the fasted state, but there is no demonstrated additive effect of testosterone when combined with amino acid feedings (Ferrando etal. 2003). Muscle strength measured by isokinetic peak torque was increased in flexion of the dominant knee, but not in knee extension or shoulder contraction during three months of transdermal administration of DHT in older men with low normal serum testosterone (Ly etal. 2001). In the latter study there was no effect of treatment on tests of gait, balance or mobility; no effect of treatment on muscle strength was observed in the studies by Kenny et al. (2001) and Snyder et al. (1999a). Crawford et al. (2003) reported increased muscle mass and strength during androgen treatment in men with mean age around 60 years under treatment with glucocorticoids.

In conclusion, partial hypoandrogenism might thus play a contributory role in the sarcopenia of older men, but sarcopenia in elderly men is multifactorially determined (Bross et al. 1999; Tenover 1994). Data on androgen treatment suggest potentially beneficial effects, but the data on treatment effects on muscle strength in elderly men are still limited and the findings are not all favorable. Moreover, there is no convincing demonstration of functional benefits of androgen treatment, which might in part be due to use of inappropriate methodology (Bhasin and Buckwalter 2001). Considering that we have no information as to the androgen sensitivity of muscle tissue in older men, and that men respond to supraphysiolog-ical doses of testosterone by graded increments in muscle mass and force (Bhasin et al. 1996; 2001), beneficial effects of androgen treatment on muscle mass and function in elderly men may represent pharmacological effects rather than "physiological" androgen substitution.

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