Low testosterone syndrome protects subjects with high cardiovascular risk burden from major adverse cardiovascular events

The role of testosterone (T) in the cardiovascular (CV) health of men is controversial. Some data suggest that hypogonadism is associated with CV mortality but not morbidity, however, recent evidence shows that hypogonadal subjects treated with T replacement therapy have a higher incidence of new CV events. The aim of this study is to analyse whether gonadal status might predict new CV event incidence according to a patient's previous history of CV events, in a cohort of subjects complaining of sexual dysfunction. A consecutive series of 1687 patients was followed-up for a mean time of 4.3 ± 2.6 years for new occurrence of CV events, detecting 139 events. Hypogonadism (total T < 12 nmol/L) was not associated with an increased incidence of new CV events in the entire cohort. However, when considering patients with a previous history of CV events, hypogonadism was associated with a reduced risk of new CV events, even after adjusting for confounders (hazard ratios - HR = 0.498 [0.240; 0.996]; p = 0.049), whereas no relationship was observed in subjects free of previous CV events. Similar results were observed when reduced testis volume (TV) was considered as a predictor of new CV events in subjects with previous CV events (HR = 0.486 [0.257; 0.920]; p = 0.027). In patients with a history of previous CV events, but not in those without previous CV events, having both low T and low TV was associated with a lower incidence of new CV events as compared with subjects with only one or none of these conditions, even after adjusting for confounders (HR = 0.514 [0.306; 0.864]; p for trend < 0.02). Notably, CV risk estimated with risk engines based on traditional risk factors was not different between hypogonadal and eugonadal subjects. In conclusion, hypogonadism could be interpreted as a protective mechanism in unhealthy conditions, such as previous CV events, to avoid fatherhood and spare energy.