The most important cause of death as men age is cardiovascular disease and as men age so their androgen status declines. Studies have shown that lowering of endogenous androgen by deprivation therapy as treatment for prostate cancer increases the risk of cardiovascular death. In long term studies, low blood testosterone is associated with accelerated atherosclerosis as manifest in coronary, aortic and carotid vascular territories.
Animal models of hypogonadism with cholesterol feeding have also shown accelerated atherosclerosis, which replacement therapy (TRT) ameliorates. The mechanism is not understood but low testosterone in men, is associated with an adverse lipid profile, increased inflammatory activation, weight gain, insulin resistance and impaired glucose tolerance which is improved by TRT as proven in randomised controlled trials.
Testosterone has also been shown to be an arterial vasodilator, an effect mediated by blocking the L-type calcium channels in the vascular smooth muscle membrane. This may be the mechanism whereby it improves exercise capacity in men with low blood testosterone who also have angina or heart failure.
The disadvantage of a low blood testosterone level is not just related to accelerated atherosclerosis. There have been at least 4 epidemiological studies showing that a low serum testosterone is associated with an excess mortality, in populations of normal men without overt vascular disease. We recently reported a follow up study of 930 men with coronary disease confirmed at angiography which showed that men with low levels of bioavailable testosterone had a highly significant increase in mortality (x2) compared with those with a normal bio-available testosterone over a follow-up period of 7 years.
It is not known whether TRT to normal physiological levels will prolong life or reduce cardiovascular events, but there is no doubt that TRT improves symptoms, functional capacity and well being.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.