Testosterone: a hormone preventing cardiovascular disease or a therapy increasing cardiovascular events?

Decreasing testosterone levels with ageing is a well-known condition in older men named 'low T', 'manopause', or hypogonadism. Observational studies suggested an association between low endogenous testosterone levels and a high cardio-metabolic profile (increased blood pressure, dyslipidaemia, insulin resistance, atherosclerosis, thrombosis), as well as a modest increase in total and cardiovascular (CV) mortality. Controversies persist regarding the need for screening 'low T' in older men, as well as what precisely should be the indication(s) for testosterone replacement therapy. So far, no data have shown that normalization of testosterone levels reduce CV events. Although testosterone replacement therapy seems to have beneficial effects on male quality of life or physical condition, some data suggest serious adverse events, such as CV events. In addition, there is a lack of consensus on the threshold for treatment indication in men with non-specific symptoms or borderline levels of testosterone. Available data from clinical practice setting suggest an increase in testosterone prescription over time and possible overtreatment. In recent years, pharmaceutical companies have promoted 'low T' as a treatable disease, suggesting that testosterone replacement may help restore energy, positive mood and sexuality, and despite ageing. Currently, well-designed, adequately powered randomized controlled trials are needed to assess the impact of testosterone replacement therapy on CV clinically relevant CV outcomes within age-specific ranges to strengthen the evidence for clinical practice guidelines.