Testosterone and Cardiovascular Disease (Traverse Trial)

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4. Conclusion

The therapeutic approach for TT for symptomatic hypogonadism and low testosterone levels associated with aging, obesity, and systemic illness presents challenges. These conditions are intricately linked with CVD outcomes and may confound the relationship between low testosterone and CVD. Although observational studies suggest an association between low testosterone and increased risk of CVD, results from testosterone supplementation are inconsistent. RCTs indicate that short-term TT at standard replacement is not associated with increased CVD risk. Nevertheless, the cardiovascular sub-study of T Trials observed increases in NCP and CAC, signaling the need for further investigation into potential long-term implications of TT.

The TRAVERSE trial, a landmark study unique in its capacity to evaluate CVD events, contributes valuable insights into the short-term safety of TT at lower physiological levels. However, the long-term effects and implications of mid to high physiological testosterone levels are not yet fully understood. The trials’ limitations — achievement of only low-normal testosterone levels, high discontinuation rates, brief follow-up period, and high loss to follow-up rate — suggest that the findings should be interpreted with caution. It is important to avoid generalizing the safety of TT based on these results alone and to approach the extrapolation of TRAVERSE’s conclusions to higher dosages or longer-term therapy with caution.

The decision to initiate TT requires a nuanced approach, which must account for current gaps in evidence regarding CV safety. A personalized assessment and management of CVD risk factors is essential for older men with known CVD. The CV effects of exogenous testosterone, when given to maintain physiological levels, remain to be fully explored. In this regard, an important question remains the identification of male patients with symptomatic hypogonadism who may benefit from TT. This topic continues to be the subject of ongoing debate. Hopefully, future trials will provide clarity on whether TT confers beneficial, neutral, or adverse cardiovascular effects in middle-aged and older men. Until definitive evidence surfaces, clinical practice should exercise caution and prioritize individualized care with informed discussions regarding the potential CV implications of TT.
 
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