Androgens and cardiovascular disease in men

Abstract

Endogenous testosterone appears to be protective of certain cardiovascular risk factors in men. Suppression of endogenous testosterone is a widely used form of therapy in men with prostate cancer but the cardiovascular adverse effects of this therapy if any, are unknown. Anti-androgen drugs are often continued for years as the optimal treatment of prostate cancer is unclear. Arterial stiffness is an emerging marker of cardiovascular risk over and above that of other traditional risk factors. Using this measure a series of studies were conducted in men with prostate cancer to look at the effects of anti-androgen drugs on this cardiovascular risk factor. It was demonstrated that testosterone-deprived men have increased arterial stiffness compared to controls, and that following androgen suppression arterial stiffness is increased compared to controls. It was found that endogenous testosterone in older men is inversely correlated with arterial stiffness independently of other cardiovascular risk factors including age and blood pressure. It was also demonstrated that both testosterone suppression and androgen receptor-blockade have the same adverse effect on arterial stiffness, though the effects were not sustained in the latter situation, which might be attributable to a beneficial increase in oestradiol levels. The latter drug however led to an increase in B-type natriuretic peptide (BNP) levels - another independent marker of cardiovascular risk. This increase was not explained by changes in left ventricular function. It may also be related to the rise in oestradiol, as this BNP increase has been observed in women following oestrogen therapy. In conclusion both testosterone suppression and androgen receptor-blockade have an adverse effect on arterial stiffness in men with prostate cancer. This appears to be sustained with suppression therapy but not receptor blockade. Receptor blockade however leads to a sustained increase in BNP levels which may also imply an adverse cardiovascular effect. The different effect of the two drugs on the sex-hormone profile might account for these findings. This may have therapeutic implications for the increasing number of prostate cancer cases being treated, and long-term randomised trials are required to investigate whether or not androgen-receptor blockade is to be preferred to testosterone suppression or to no intervention for cancer, cardiovascular and quality of life outcomes.