2020 ACP Guideline: testosterone supplementation for age-related hypogonadism

American College of Physician committee systematically reviewed 38 randomized controlled clinical trials involving testosterone supplementation in patients with age-related hypogonadism. Subjects’ mean age was 66 years, with average baseline total testosterone measures ≤300 ng/dL. Authors reached consensus on the following soft recommendations:

Physicians should be open to initiating testosterone therapy in adults with age-related hypogonadism only from the sexual dysfunction perspective. The decision to treat should be reached after a complete patient-physician discussion that includes pharmacological options, benefits, safety, and cost.

ACP recommends the intramuscular route of testosterone administration due to its low cost and similar efficacy and safety to other modes of therapy. They do not advise starting testosterone supplementation for other symptoms – apart from sexual dysfunction – such as reduced physical capacity, cognition, stamina, and vitality.


High natural testosterone production in men is associated with blood clots and heart disease

Analysis of two major Mendelian randomization studies revealed that endogenous testosterone production in men is positively correlated with blood clots, heart attack, and heart failure. Data from at least 200,000 participants were included in the analysis. A proposed mechanism for such a risk is the testosterone conversion into estrogen, in turn contributing to thromboembolism. Testosterone can also increase platelet aggregation via the thromboxane A2 pathway.

Data from these “natural experiments” overall follow the observed increased risk of deep venous thrombosis and heart disease in men who are over-supplemented with exogenous testosterone. On the contrary, low Testosterone levels are also associated with visceral adiposity, low muscle mass, and insulin resistance.  From a cardiovascular perspective, future clinical research is needed to identify the balancing point of how much or little testosterone men should have.