|Year : 2018 | Volume
| Issue : 2 | Page : 107-108
Why is understanding the relationship of testosterone to cardiovascular risk so important?
Bu B Yeap1,2, Bradley D Anawalt3
1 School of Medicine, University of Western Australia, Perth, Western Australia 6009, Australia
2 Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, Western Australia 6150, Australia
3 Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195, United States
|Date of Submission||04-Dec-2017|
|Date of Acceptance||05-Dec-2017|
|Date of Web Publication||06-Feb-2018|
Prof. Bu B Yeap
School of Medicine, University of Western Australia, Perth, Western Australia 6009, Australia; Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, Western Australia 6150, Australia
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Yeap BB, Anawalt BD. Why is understanding the relationship of testosterone to cardiovascular risk so important?. Asian J Androl 2018;20:107-8
|How to cite this URL:|
Yeap BB, Anawalt BD. Why is understanding the relationship of testosterone to cardiovascular risk so important?. Asian J Androl [serial online] 2018 [cited 2019 Aug 23];20:107-8. Available from: http://www.ajandrology.com/text.asp?2018/20/2/107/224772 - DOI: 10.4103/aja.aja_71_17
Bu B Yeap, Bradley D Anawalt
Co.Guest Editors for this special issue.
Epidemiological studies hint at a beneficial influence of endogenous circulating testosterone (T), or its metabolite dihydrotestosterone (DHT), such that men with lower concentrations of T or DHT appear to have poorer health outcomes including frailty, diabetes, cardiovascular disease, and mortality. Small interventional studies of T have shown favorable effects on surrogate outcome measures, but a large randomized controlled trial (RCT) with the prespecified outcome of cardiovascular events has not been performed and would be logistically demanding. In the absence of such a definitive RCT, there is a controversy about the cardiovascular risks of T-therapy fuelled by contradictory findings from retrospective analyses of insurance databases of men prescribed T.,, The US Testosterone Trials (T-Trials) are the largest published RCTs of T-therapy in older men with symptoms or signs of hypogonadism and circulating T <9.54 nmol l−1 at baseline. The T-Trials showed a modest benefit of T-therapy over a 12-month period on sexual function, a significant benefit in bone density and for anemia and neutral effect on cognition.,, The T-Trials cardiovascular sub-study was designed to determine the effects of T in these older men, and there was a statistically significant difference in the increase in noncalcified plaque volume in the T-treated group compared to placebo, but it is difficult to interpret these results due to differences in baseline coronary plaque burden (>50% difference) between the treatment and placebo arms of the subset involved. Therefore, there continues to be ongoing uncertainty over the effect of T-therapy on the cardiovascular system in men.
Resolution of the uncertainty of the effects of T-therapy on the male cardiovascular system is important from two perspectives. First, men who are androgen deficient due to diseases of the hypothalamus, pituitary, and testes should be considered for T-replacement therapy. In these men who have hypogonadism due to pathology of the gonadal axis, it is essential to inform and advise them of potential benefits and possible risks of treatment. Second, there has been a marked increase in T prescribing worldwide over the past decades, despite the prevalence of pathological hypogonadism remaining relatively stable., In men who do not have hypothalamic, pituitary, or testicular disease, who are typically older with other medical comorbidities and circulating T that would be regarded as low in younger men, the question arises as to the justification for T treatment and whether potential harms might outweigh anticipated benefits. Understanding the extent and the limitations of the existing evidence base would help health practitioners counsel men receiving T treatment for medical indications, may discourage its misuse in men where a medical indication is not clear, and will provide a foundation for future research.
In this Special Issue of the Asian Journal of Andrology, authors from around the world provide reviews of the available evidence of the cardiovascular effects of T on men. These reviews cover epidemiological studies of T and the incidence of cardiovascular events and mortality risk, RCTs representing mechanistic studies of T and the cardiovascular system, T RCTs reporting cardiovascular adverse events, and retrospective reviews of T prescription databases. These are accompanied by commentaries on the implications for Andrology in the regional context and globally for studies of male hormonal contraception. Taken together, the content of this Special Issue addresses a pressing debate that affects the care we provide to men with androgen deficiency and future research to preserve health in the expanding population of older men in our communities.
| References|| |
Yeap BB, Araujo AB, Wittert GA. Do low testosterone levels contribute to ill-health during male ageing? Crit Rev Clin Lab Sci
2012; 49: 168–82.
Onasanya O, Iyer G, Lucas E, Lin D, Singh S, et al
. Association between exogenous testosterone and cardiovascular events: an overview of systematic reviews. Lancet Diabetes Endocrinol
2016; 4: 943–56.
Vigen R, O'Donnell CI, Baron AE, Grunwald GK, Maddox TM, et al
. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA
2013; 310: 1829–36. Erratum published in JAMA
2014; 311: 967.
Sharma R, Oni OA, Gupta K, Chen G, Sharma M, et al
. Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men. Eur Heart J
2015; 36: 2706–15.
Cheetham TC, An JJ, Jacobsen SJ, Niu F, Sidney S, et al
. Association of testosterone replacement with cardiovascular outcomes among men with androgen deficiency. JAMA Intern Med
2017; 177: 491–9.
Snyder PJ, Bhasin S, Cunningham GR, Matsumoto AM, Stephens-Shields AJ, et al
. Effects of testosterone treatment in older men. N Engl J Med
2016; 374: 611–24.
Resnick SM, Matsumoto AM, Stephens-Shields AJ, Ellenberg SS, Gill TM, et al
. Testosterone treatment and cognitive function in older men with low testosterone and age-associated memory impairment. JAMA
2017; 317: 717–27.
Snyder PJ, Kopperdahl DL, Stephens-Shields AJ, Ellenberg SS, Cauley JA, et al
. Effect of testosterone treatment on volumetric bone density and strength in older men with low testosterone: a controlled clinical trial. JAMA Intern Med
2017; 177: 471–9.
Roy CN, Snyder PJ, Stephens-Shields AJ, Artz AS, Bhasin S, et al
. Association of testosterone levels with anemia in older men: a controlled clinical trial. JAMA Intern Med
2017; 177: 480–90.
Budoff MJ, Ellenberg SS, Lewis CE, Mohler ER, Wenger NK, et al
. Testosterone treatment and coronary artery plaque volume in older men with low testosterone. JAMA
2017; 317: 708–16.
Yeap BB, Grossmann M, McLachlan RI, Handelsman DJ, Wittert GA, et al
. Endocrine Society of Australia position statement on male hypogonadism (part 1): assessment and indications for testosterone therapy. Med J Aust
2016; 205: 173–8.
Yeap BB, Grossmann M, McLachlan RI, Handelsman DJ, Wittert GA, et al
. Endocrine Society of Australia position statement on male hypogonadism (part 2): treatment and therapeutic considerations. Med J Aust
2016; 205: 228–31.
Handelsman DJ. Global trends in testosterone prescribing, 2000–2011: expanding the spectrum of prescription drug misuse. Med J Aust
2013; 199: 548–51.
Layton JB, Li D, Meier CR, Sharpless JL, Stumer T, et al
. Testosterone lab testing and initiation in the United Kingdom and the United States 2000–2011. J Clin Endocrinol Metab
2014; 99: 835–42.
Swerdloff R, Anawalt BD. Clinical decisions: testosterone-replacement therapy. New Engl J Med
2014; 371: 2032–4.
Yeap BB. Testosterone and its metabolites: differential associations with cardiovascular and cerebrovascular events in men. Asian J Androl
2018; 20: 109–14.
Meyer EJ, Wittert G. Endogenous testosterone and mortality risk. Asian J Androl
2018; 20: 115–9.
Jones TH, Kelly DM. Randomized controlled trials – mechanistic studies of testosterone and the cardiovascular system. Asian J Androl
2018; 20: 120–30.
Gagliano-Juca T, Basaria S. Trials of testosterone replacement reporting cardiovascular adverse events. Asian J Androl
2018; 20: 131–7.
Shores MM. Testosterone treatment and cardiovascular events in analyses of prescription databases. Asian J Androl
2018; 20: 138–44.
An Q, Gu YQ. Testosterone replacement therapy: dilemmas and challenges in China and Asia. Asian J Androl
2018; 20: 149–51.
Zitzmann M. Would male hormonal contraceptives affect cardiovascular risk? Asian J Androl
2018; 20: 145–8.