Hypogonadism Management and Cardiovascular Health

[madman]

Abstract

In the early days of its use, testosterone therapy faced skepticism regarding its safety and efficacy. After a converging consensus that testosterone therapy was safe and effective for the treatment of hypogonadism, several recent studies showed adverse cardiovascular outcomes associated with testosterone treatment, ultimately resulting in a mandated FDA label warning about the unknown safety of testosterone therapy. Given the clear efficacy of testosterone therapy in the treatment of hypogonadism, establishing the safety of this therapeutic tool is essential. This article summarizes the current evidence regarding the cardiovascular safety of testosterone therapy for the management of hypogonadism, as well as the proposed mechanisms that may explain testosterone’s underlying effects.






*Initiated in 2018, the TRAVERSE trial is a very large, randomized, controlled trial that will likely be sufficiently powered to show clear relationships between TTh and cardiovascular events. The trial randomly assigned 6,000 hypogonadal men at high risk of cardiovascular disease who are ages 45-80 to receive either T gel or placebo. The treatment duration is currently set at 5 years. The primary endpoint for the trial is time to MACE, which includes nonfatal MI, nonfatal stroke, or cardiovascular mortality. The TRAVERSE trial will give a more coherent picture of the outcomes associated with TTh.






Conclusion

Testosterone is clearly a major player in cardiovascular and metabolic health and physiology. Although some epidemiological data show an increase in adverse cardiovascular events with the provision of T, most studies do not support this suggestion. Most RCTs to date are underpowered and do not provide clear, conclusive evidence to repudiate the small numbers of studies that indicate an increased risk. To bolster the evidence regarding the safety of TTh, larger clinical trials such as the TRAVERSE trial will provide key insights. Until then, clinicians should be aware of the overall health impacts of hypogonadism and TTh and advise patients with honest communication about the current evidence.

 

[madman]

Effects of Long-term Testosterone Treatment on Cardiovascular Outcomes in Men with Hypogonadism

ABSTRACT Background: Testosterone exerts some effects on the cardiovascular system that could be considered beneficial; some other effects may potentially increase the risk of cardiovascular (CV) events. Neither the long-term efficacy nor safety of testosterone treatment has been studied in an...

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[madman]

Innovations in Testosterone Therapy in Men Treated for Prostate Cancer

Urology Times® is celebrating its 50th anniversary in 2022. To mark the occasion, we are highlighting 50 of the top innovations and developments that have transformed the field of urology over the past 50 years. In this installment, Amy Pearlman, MD, interviews Mohit Khera, MD, MBA, MPH on how...

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[madman]

Testosterone Therapy and the Risk of Cardiovascular Disease

Abstract The debate over the cardiovascular (CV) implications of testosterone therapy (TT) have resulted in diverging safety recommendations and clinical guidelines worldwide. This narrative review synthesizes and critically evaluates long-term studies examining the effects of TT within the...

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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.