Testosterone and cardiovascular risk - What is the evidence?


Men with erectile dysfunction (ED) are often hypogonadal and constitute a high CVD risk population. Dr. Maggi starts by presenting data showing that low testosterone levels are longitudinally associated with higher major adverse cardiovascular events (MACE) mortality. He then shows contrasting data that baseline testosterone levels do not predict MACE at follow-up, and that low testosterone levels even may be protective against MACE in high risk men. He points out that when looking at mortality from MACE, men with low testosterone are at higher risk. Thus, while low testosterone may protect against MACE, if a hypogonadal man experiences a MACE, his likelihood of dying is increased.

Dr. Maggi then presents new data showing that men with compensated hypogonadism (normal testosterone levels but elevated LH) are at similarly increased risk of cardiovascular events as men with overt hypogonadism, when compared with eugonadal controls. Thus, mortality related to major adverse cardiovascular events (MACEs), but not MACE incidence, is significantly higher in subjects with both compensated and overt hypogonadism.

In line with Dr. Saad’s data, Dr. Maggi underscores the strong association of obesity, metabolic syndrome, type 2 diabetes and CVD with hypogonadotrophic hypogonadism. He further presents data showing that testosterone treatment is associated with better outcomes in heart failure and CHD. In contrast, studies that look at all cardiovascular events (including anything arbitrarily reported as such by the study authors) tend to show increased events with testosterone treatment. To shed light in this, Dr. Maggio highlights results of the latest and largest meta-analysis on the topic by Corona et al (published in Expert Opin. Drug Saf.), specifically analyzing MACE; no association of testosterone treatment was found with stroke, coronary bypass surgery, acute coronary syndrome, myocardial infarction, arrhythmia, or heart failure. Importantly, in men with metabolic disorders, testosterone treatment was found to be protective.

Dr. Maggi highlights that the European Medicines Agency did NOT find consistent evidence that testosterone treatment increases cardiovascular risks, and concludes his presentation stating that testosterone replacement therapy:

  • Improves cardiovascular function in men with CHD and heart failure.
  • May increase minor non-fatal cardiovascular events in frail men, but importantly, is NOT associated with MACE.
  • May decrease MACE in men with metabolic syndrome or type 2 diabetes.



Dr. Mario Maggi

Dr. Mario Maggi
Sexual Medicine & Andrology
University of Florence