Dr Barua presents the current state of knowledge about testosterone therapy and cardiovascular events. Numerous studies show that low testosterone increases risk of both cardiovascular mortality and all-cause mortality. Despite this, a few highly debated studies made the allusion that testosterone therapy increases risk of cardiovascular disease. A notable study conducted by Dr Barua’s group showed that normalization of testosterone levels is associated with reduced incidence of myocardial infarction (MI) and mortality in men.¹ Specifically, in men who have low total testosterone levels but no previous MI or stroke, testosterone therapy is associated with decreased risks of MI, stroke, and all-cause mortality during a long-term follow-up of up to 14 years. Compared to non-treated men, testosterone treated men who achieved normalization of their testosterone levels had a major and significant reduction in MI, stroke and all-cause mortality by 24%, 36% and 56%, respectively. Compared to non-treated men, testosterone treated men who failed to achieve normalization of their testosterone levels did not have a reduction in heart attack or stroke, and had significantly less benefit on mortality risk. This is the first study to highlight that testosterone therapy should aim for doses resulting in normalization of testosterone levels because this is a prerequisite to achieve a reduction in MI and stroke. In smokers, testosterone therapy has no significant effect on MI or stroke, but does reduce all-cause mortality. Normalisation of testosterone levels with testosterone therapy also reduces incidence of atrial fibrillation, a benefit which is not seen in men who get sub-optimal testosterone therapy that does not raise testosterone level high enough to provide therapeutic benefit.²