An editorial notes that while this study provides reassuring data concerning the effects of testosterone on cardiovascular health, convincing answers about this question—and other safety issues like prostate health—remain elusive and will require large, prospective randomised trials. It stresses that at this point, clinicians and their patients should remain aware that the cardiovascular risks and benefits of testosterone replacement in older hypogonadal men have not been adequately resolved.
JAMA Internal Medicine have published 2 RCTs of testosterone therapy addressing effects on the bone and anaemia, which are part of a series of 7 linked, rigorously designed and well-executed studies (T-Trials) which were performed to address recommendations by Institute of Medicine panel in US in 2003, for a series of clinical trials to critically evaluate the value of testosterone supplementation for several clinical indications The findings from 3 other of these studies (in men with symptoms related to sexual function, vigor, and physical performance) were also recently published. An accompanying editorial suggests that together, the T-Trials represent the most definitive assessments of the potential short-term advantages of testosterone replacement in older men, but stresses they were not intended to address the equally critical issue of whether there are important long-term adverse effects.
An RCT published in JAMA reported that in older men with symptomatic hypogonadism, treatment with testosterone gel for 1 year vs. placebo was linked to significantly greater increase in coronary artery noncalcified plaque volume, the clinical implications of which remains to be determined. An editorial commenting on this and another study looking at impact on cognitive function, states that the findings from subtrials of the TTrials do not materially change the unfavorable balance of safety and efficacy to initiate testosterone treatment for age-related hypogonadism. It suggests that for clinicians prescribing off-label testosterone, these cardiovascular findings make it incumbent to strengthen warnings of adverse cardiovascular risk and also support the FDA decision in September 2015 to tighten cardiovascular safety warnings about off-label testosterone prescribing and mandated that testosterone manufacturers undertake longer-term safety and efficacy trials for off-label use of testosterone for aging men. It notes that testosterone overprescribing has been propelled not only by direct-to-consumer advertising, but also with the complicity of some professional organizations and physicians supporting the redefinition of the term hypogonadism to minimise the fundamental distinction between pathological hypogonadism and age-related, low circulating testosterone. It acknowledges that testosterone and synthetic androgens have valuable medical applications but a key lesson is that such novel indications should be established by efficacy and safety studies and not preceded by wide-scale, off-label adoption. The editorial in JAMA concludes that for now, the hopes for testosterone-led rejuvenation for older men are dimmed and disappointed if not yet finally dashed based on the results of the current studies.