LAUSR

Although testosterone (T) replacement is increasingly being used clinically, cardiovascular benefits and risks of T administration to older men with age-related decline in T levels remain uncertain. The WHI randomized trial reporting potential harmful coronary artery effects of oestrogens/medroxyprogesterone acetate combination in menopaused women led to a drastic decrease in sex hormone substitution in female. Simultaneously T substitution prescriptions in men began to rise exponentially. Rates of T therapy prescription have increased markedly in the USA over the past decade, with annual prescriptions for T increasing by more than five-fold from 2000 to 2011, reaching 2.3 million prescriptions and a market of $2.3 billion in 2013. Exogenous T was at first considered as indubitably beneficial. Majority of animal experiments conclude that exogenous T exerts beneficial effects on atherosclerosis development in castrated males. Epidemiological studies correlated the age-related decline of serum T levels to the concomitant increase of cardiovascular diseases. Hypoandrogenaemia in men is associated with visceral obesity, insulin resistance, lower high density lipoprotein cholesterol and elevation of triglycerides and low density lipoprotein cholesterol. Exogenous T induces positive effects on some secondary end points considered as cardiovascular risk factors, such as lipoprotein (a), fibrinogen, insulin, leptin, and visceral fat mass in men. Several large retrospective studies reported an increased risk of diabetes and cardiovascular disease in men receiving androgen deprivation therapy for the treatment of advanced prostate cancer, and although these risks have not been confirmed by prospective randomized trials, the therapeutic use of T in men rose in the USA impressively. In 2010, the Testosterone in Older Men with Mobility Limitations trial conducted in older frail men with a high prevalence of cardiovascular diseases was stopped prematurely due to increased cardiovascular events in the treatment group. In 2013, a large retrospective veterans cohort Dr Françoise LENFANT is a Senior Researcher at the INSERM U1048, Institute of Cardiovascular and Metabolic Diseases, in Toulouse (http:// www.i2mc.inserm.fr/index.php/en/research-teams/team-9).