Testosterone treatment in older men: clinical implications and unresolved questions from the Testosterone Trials

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madman

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Collectively, the T-Trials represent an important step forward and provide the most definitive and systematic evidence to date with respect to the multiorgan effects of testosterone treatment in carefully selected older men without overtly pathological hypogonadism.Testosterone treatment increased bone density and bone strength and improved haemoglobin concentrations, resolving anaemia irrespective of the aetiology in a substantial proportion ofmen. These results could be expected to translate into improved health outcomes. Testosterone treatment also provided modest benefits in sexual function and, to a lesser extent, mood and walking distance.12

In contrast, testosterone treatment did not improve measures of cognition in men with or without age associated memory impairment, making it unlikely that testosterone treatment will have clinically meaningful benefits on cognitive function. Although testosterone was associated with increased non-calcified coronary artery plaque in the subset of men in the Cardiovascular Trial, the relevance of this finding is unclear, in part because the baseline plaque burden was not balanced between the testosterone and placebo groups. The effects
of testosterone on cardiovascular risk factors, such as blood pressure, coagulation factors, and inflammatory markers, could have been recorded in T-Trials but as yet have not been reported.

The prevalence of comorbidities, including obesity and diabetes, was relatively high in the T-Trials.12 Existing comorbidities, including obesity, might contribute to both androgen deficiency-like symptoms and reduced testosterone concentrations. 141,142 A holistic approach to the care of older men in which facilitating healthy lifestyle measures and optimising management of comorbidities are central elements is therefore needed.143
Taken together, the results from the T-Trials are a major advance in understanding the endocrinology of male ageing and aid in the selection of older men who are most likely to benefit from testosterone therapy. However, the findings should not be extrapolated to
men without clinical evidence of androgen deficiency or with less marked reductions in testosterone concentrations, and they should not in any way support the treatment of older men with supraphysiological doses of exogenous testosterone. In line with stipulations from the Institute of Medicine, the T-Trials were not designed to assess long-term risks, and the recruitment rate was low because of rigorous selection criteria. Moreover, treatment of medical comorbidities was not regulated, potentially masking some effects of testosterone treatment. Priority areas for future studies include clarifying potential cardiovascular benefit versus risks of testosterone treatment in men without pathological hypogonadism and determining whether the multiorgan benefits found in the T-Trials will affect important health outcomes such as functional status and fracture incidence.
 

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