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Risks and benefits of testosterone therapy in older men

Abstract

In young men (defined as age <50 years) with classic hypogonadism caused by known diseases of the hypothalamus, pituitary or testes, testosterone replacement therapy induces a number of beneficial effects, for example, the development of secondary sex characteristics, improvement and maintenance of sexual function, and increases in skeletal muscle mass and BMD. Moreover, testosterone treatment in this patient population is associated with a low frequency of adverse events. Circulating testosterone levels decline progressively with age, starting in the second and third decade of life, owing to defects at all levels of the hypothalamic–pituitary–testicular axis. In cohort studies, testosterone levels are associated weakly but consistently with muscle mass, strength, physical function, anaemia, BMD and bone quality, visceral adiposity, and with the risk of diabetes mellitus, coronary artery disease, falls, fractures and mortality. However, the clinical benefits and long-term risks of testosterone therapy—especially prostate-related and cardiovascular-related adverse events—have not been adequately assessed in large, randomized clinical trials involving older men (defined as age >65 years) with androgen deficiency. Therefore, a general policy of testosterone replacement in all older men with age-related decline in testosterone levels is not justified.

Key Points

  • Effects of testosterone therapy must be distinguished in the context of the various clinical conditions for which testosterone therapy can be used

  • In young men (<50 years) with classic hypogonadism caused by known diseases of the hypothalamus, pituitary or the testes, the benefit to risk ratio for testosterone replacement therapy is favourable

  • Testosterone levels decline with advancing age, and clustering of sexual and some physical symptoms, for example, erectile dysfunction and reduced vigorous activity, occurs in association with testosterone levels <8 nmol/l

  • Clinical benefits of testosterone therapy in men aged >65 years with age-associated decline in testosterone levels and with conditions associated with low testosterone levels have yet to be demonstrated in randomized trials

  • Long-term effects of testosterone therapy on the risk of prostate-related and cardiovascular-related adverse events remain unknown

  • In the absence of clear evidence regarding benefits or risks of testosterone therapy, a general recommendation about testosterone administration to all men over the age of 65 years with age-related decline in testosterone levels is not justified

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Figure 1: Effects of testosterone therapy on body composition and muscle strength, bone health, and sexual function in intervention trials.
Figure 2: Effects of testosterone administration on maximal voluntary strength in the leg-press and chest-press exercises and on loaded stair-climbing power in a randomized testosterone trial in older men with mobility limitation (TOM trial).
Figure 3: Adverse events associated with testosterone therapy in randomized trials.

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M. Spitzer, G. Huang, T. G. Travison and S. Bhasin researched the data for the article. All authors provided a substantial contribution to discussions of the content, contributed to writing the article, and reviewed and/or edited the manuscript before submission.

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Correspondence to Shalender Bhasin.

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Spitzer, M., Huang, G., Basaria, S. et al. Risks and benefits of testosterone therapy in older men. Nat Rev Endocrinol 9, 414–424 (2013). https://doi.org/10.1038/nrendo.2013.73

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