Intact singers

Fig. 13.3 Longevity of intact and castrated singers (50 in each group) born between 1580 and 1859 (matched pairs of intact and castrated singers with similar birth dates were formed) (Nieschlag etal. 1993).

of testosterone, possibly mediated through changes in lipid metabolism. Hence it may be asked whether testosterone may have a life-shortening effect on patients with hypogonadism under testosterone treatment. Appropriate controlled studies to answer this question directly are not available and are unlikely to be performed since it would be unethical to withhold testosterone lifelong from a hypogonadal control group. However, there are two retrospective historical studies available addressing the problem.

A retrospective analysis of the life expectancy of inmates of an institution for the mentally handicapped in the USA came to the conclusion that early castration would lead to a longer life expectancy (Hamilton and Mestler 1969). However, this could be explained by the preference of castration as treatment for the physically more active inmates, whereas lack of mobility is the major predictor of shortened life expectancy among institutionalized men. In contrast, the retrospective comparison of the life expectancy of singers born between 1580 and 1858 and castrated before puberty in order to preserve their high voices, to intact singers born at the same time did not reveal a significant difference between the lifespan of intact and castrated singers (Nieschlag etal. 1993) (Fig. 13.3). In contrast, among singers who died in the 20th century, basses had a tendency to live longer than tenors (67.4 ± 12.4 vs. 66.0 ± 14.4 years) (Basses have higher testosterone/estradiol ratios than tenors

(Meuser and Nieschlag 1977)). Sopranos, who are more estrogenized, lived significantly longer than altos, who are more androgenized (72.1 ± 14.3 vs. 67.5 ± 13.5 years) (Nieschlag et al. 2003). These findings can be interpreted that overall, a preponderance of isosexual hormones in the spectrum of sex steroids tends to extend life rather than shorten life.

Since neither the inmates nor the historical singers can be considered representative for the present population, these controversial studies can only provide hints but no conclusive answer. There is, however, no proof that testosterone is a life-shortening agent. Preventing a hypogonadal patient from receiving the necessary substitution would force him to continue a life of low quality. If testosterone in physiological doses should cause "side" effects, these would indeed be the normal biological effects. The risks inherent to testosterone, be it of endogenous or exogenous origin, would then appear to be the tribute men have to pay for being men.

13.8 Key messages

• The primary indications for testosterone therapy are the various forms of male hypogonadism. For substitution, testosterone preparations should be used that can be converted to 5a-dihydrotestosterone (DHT) as well as to estradiol in order to develop the full spectrum of testosterone action.

• Injectable, oral and transdermal testosterone preparations are available for clinical use. The best preparation is the one that replaces testosterone serum levels at as close to physiologic concentrations as possible.

• In six decades of clinical use testosterone has proven to be a very safe medication. No toxic effects are known. The only important contraindication is the presence of a prostate carcinoma which should be excluded before substitution is initiated.

• Testosterone therapy should be monitored by patients' well-being, alertness and sexual activity, by occasional measurement of serum testosterone levels, hemoglobin and hematocrit, by bone density measurements and prostate parameters (rectal examination, PSA and transrectal sonography).

• Testosterone can be used to initiate puberty in boys with constitutional delay of pubertal development. Careful dosing does not lead to premature closure of the epiphysis and reduced height.

• High-dose testosterone treatment in early puberty may prevent expected overtall stature in boys. Negative long-term effects of this treatment have not become evident to date.

• No evidence has been provided that testosterone treatment of male idiopathic infertility leads to higher pregnancy rates and it should therefore not be used for this indication.

• The risks inherent to testosterone, be it of endogenous or exogenous origin, appear to be the tribute men have to pay for being men.

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