Endogenous Testosterone, Testosterone Treatment, and Cardiovascular Health Outcomes in Men.

Cross-sectional analyses show that lower endogenous testosterone concentrations are found in men with preexisting CVD, but larger influences are age, BMI, and medical comorbidities.

• Lower testosterone concentrations were associated with preexisting cardiovascular disease in cross-sectional analyses.
• Factors with larger influences than testosterone included age >70 years, higher body mass index, and medical comorbidities such as diabetes or cancer.
• This finding comes from a narrative review summarizing observational and interventional studies.

In the UK Biobank, the largest prospective cohort study to date, lower endogenous testosterone concentrations were associated with higher risk of all-cause mortality but not incident cardiovascular events or CVD deaths.

• The United Kingdom Biobank represented the largest prospective cohort study examined in this review.
• Lower endogenous testosterone was associated with higher all-cause mortality risk.
• No association was found between lower testosterone and incident cardiovascular events.
• No association was found between lower testosterone and cardiovascular disease deaths.

An individual participant data meta-analysis of prospective cohort studies found nonlinear associations between baseline testosterone concentrations and higher all-cause and cardiovascular mortality, with risks increasing below specific thresholds.

• Testosterone was measured using mass spectrometry in the included prospective cohort studies.
• Risk of all-cause mortality increased below a threshold of testosterone <7.4 nmol/L (213 ng/dL).
• Risk of cardiovascular mortality increased below a threshold of testosterone <5.3 nmol/L (153 ng/dL).
• The associations between testosterone and mortality were described as nonlinear.

In the randomized, placebo-controlled T4DM trial, testosterone treatment on a background of lifestyle intervention reduced risk of type 2 diabetes mellitus after 2 years in men with dysglycemia.

• The T4DM trial was randomized and placebo-controlled.
• Participants were men with dysglycemia.
• Testosterone treatment was administered alongside lifestyle intervention.
• The primary outcome of reduced type 2 diabetes mellitus risk was observed at 2 years of follow-up.

The TRAVERSE cardiovascular safety trial found no increased risk of major adverse cardiovascular events in men randomized to testosterone treatment versus placebo.

• The TRAVERSE trial was conducted in men with CVD or multiple cardiovascular risk factors.
• Average follow-up was approximately 3 years.
• The primary outcome was major adverse cardiovascular events (MACE).
• No statistically significant difference in MACE was found between testosterone treatment and placebo groups.

Additional studies are needed to confirm long-term cardiovascular safety of testosterone treatment and explore possible cardiovascular benefits related to changes in body composition and cardiometabolic risk.

• This conclusion is based on epidemiological studies and the results of the T4DM and TRAVERSE trials.
• The review identifies a gap regarding long-term cardiovascular safety data beyond the approximately 3-year follow-up of TRAVERSE.
• Potential cardiovascular benefits related to body composition changes and cardiometabolic risk remain to be explored in future studies.