Novel perspectives of Testosterone Therapy in men with functional hypogonadism

[madman]

ABSTRACT

Introduction

In the past decade, there has been a significant augmentation in the corpus of evidence pertaining to functional hypogonadism. Despite this, prevailing clinical guidelines continue to advise against universal screening for hypogonadism in middle-aged and elderly males.


Findings

Numerous randomized controlled trials have scrutinized the effects of testosterone therapy in males afflicted with type 2 diabetes and/or obesity. However, these guidelines uniformly assert that lifestyle modifications and weight reduction should be the primary intervention strategies in overweight and obese males, relegating testosterone therapy to a secondary, selective option. It is extensively documented that testosterone therapy can yield substantial improvements in various metabolic parameters as well as ameliorate symptoms of erectile dysfunction. Moreover, recent studies have demonstrated the potential of testosterone therapy in reversing type 2 diabetes in males with low-normal testosterone levels who are at elevated risk for this condition, in comparison to the outcomes achievable through lifestyle modifications alone.


Conclusion

This focused review article aims to present a comprehensive update on the latest data concerning the innovative aspects of testosterone therapy in males with functional hypogonadism, particularly in the context of type 2 diabetes and/or obesity. Additionally, it will delve into the cardiovascular safety of such interventions within this high-risk demographic, with a special emphasis on insights gleaned from the TRAVERSE trial.




2. Functional hypogonadism: clinical implications, characteristics, and diagnosis


3. Benefits of testosterone therapy on parameters of metabolic syndrome


4. Testosterone therapy for prevention and reversion of type 2 diabetes


5. Impact of testosterone therapy on bone health


6. Impact of testosterone therapy on the cardiovascular system


7. Adverse cardiovascular events and mortality




8. Conclusion and Clinical Summary

Men with obesity and/or T2D who experience reduced testosterone levels often face a range of associated health challenges. These can include a decrease in muscle mass and strength, diminished vascular reactivity, reduced coronary blood flow, as well as the presence of anemia and hypertension, all of which are linked to increased mortality. In this context, TTh, particularly when combined with lifestyle modifications, has shown multiple clinical benefits.
Clinical and observational studies have demonstrated that TTh can effectively decrease fat mass, improve glucose tolerance, and either prevent or reverse recently diagnosed T2D, along with reducing the risk for cardiovascular adverse events. From an epidemiological perspective, the normalization of testosterone concentrations in conjunction with decreased body weight and the improvement or reversal of T2D are associated with favorable cardiometabolic outcomes in men. These findings indicate that TTh could play a significant role in improving overall health outcomes for men with obesity-mediated hypogonadism.

 

[madman]

8.1. Clinical relevance: a summary


1. Functional Hypogonadism and TTh Efficacy:

� TTh is effective in improving various metabolic parameters, such as insulin resistance and glycemic control, in men with functional hypogonadism, particularly those with obesity and T2D.


2. Impact on Cardiovascular Health:

� Most studies, including the TRAVERSE trial, show no significant increase in serious cardiovascular events with TTh. Some studies indicate a benefit regarding cardiovascular risk in younger men with metabolic disorders or Type 2 Diabetes Mellitus. The effects of TTh on Cardiovascular Risk are most likely dependent on baseline conditions and morbidity of hypogonadal patients.


3. Bone Health Improvements:

� TTh positively affects bone mineral density, especially in the lumbar spine, in hypogonadal men. It’s more effective in younger men and less effective compared to anti-osteoporosis drugs in older men with osteoporosis.


4. Weight Management and T2D:

� TTh, in combination with lifestyle modifications, can lead to significant weight loss, improved muscle mass, and reversal or prevention of recently diagnosed T2D, suggesting its potential role in managing obesity-associated hypogonadism.


5. Long-Term Safety and Clinical Implications:

� While short- to medium-term benefits of TTh are evident, there is a need for more research on its long-term safety, particularly in men with severe hypogonadism or significant cardiovascular risks.