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Testosterone and ill-health in aging men

Abstract

As men age, testosterone levels decline, and decreased testosterone levels are associated with increased risks of osteoporosis, metabolic syndrome, type 2 diabetes mellitus and mortality. Nevertheless, it is still uncertain whether reduced testosterone level is a cause of ill-health or a marker of pre-existing disease, as systemic illness lowers testosterone levels. Most circulating testosterone is bound to sex-hormone-binding globulin (SHBG) and albumin, whereas a small proportion circulates as free testosterone. Decreased SHBG level is associated with increased risks for insulin resistance and metabolic syndrome, although it would also be expected to be associated with increased free testosterone level. During male aging, total and free testosterone levels fall while SHBG level rises. Thus, associations between decreasing androgens and negative health outcomes might differ across men of various ages. Trials of testosterone therapy report benefits for body composition and BMD, but there are limited data on the effect of testosterone supplementation on cardiovascular risk. Whereas men who have androgen deficiency should be considered for testosterone therapy, the role of testosterone supplementation in older men who are not clearly hypogonadal requires further clarification. Further studies are also needed to establish whether the age-related decline in circulating testosterone level in men can be modified or prevented.

Key Points

  • Declining testosterone levels are a central feature of hormonal changes that occur during aging in men

  • Decreased testosterone levels are associated with negative health outcomes; however, a causal relationship is difficult to establish as systemic illness can reduce testosterone levels

  • A decreased level of sex-hormone-binding globulin modulates the availability of free testosterone in the circulation, and might be associated with cardiovascular risk independently of testosterone

  • Randomized, controlled clinical trials have found a favorable effect of testosterone supplementation on body composition and BMD in men with low-to-normal testosterone levels, with more marginal influences on general and sexual health

  • Further studies are needed to clarify the role of testosterone supplementation in aging men who are not clearly hypogonadal, and to determine the feasibility of interventions to modify or prevent the age-related decline in testosterone levels in men

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Figure 1: Changes in testosterone levels during aging in men.

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Yeap, B. Testosterone and ill-health in aging men. Nat Rev Endocrinol 5, 113–121 (2009). https://doi.org/10.1038/ncpendmet1050

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