madman
Super Moderator
ABSTRACT
Background: Though testosterone replacement therapy in men with organic hypogonadism is established, its role in men with type 2 diabetes mellitus (T2DM) and functional hypogonadism is unclear.
Methods: Thirteen experts addressed ten topic-specific questions after an in-depth review of literature, where all relevant issues were critically evaluated.
Results: Ten recommendations concerning diagnosis and management of men with T2DM and functional hypogonadism have been put forward.
Conclusion: Routine measurement of serum testosterone in all, and inappropriate replacement of testosterone in asymptomatic T2DM men with functional hypogonadism and borderline low serum testosterone values are not recommended.
1. Introduction
Epidemiological studies reveal an increased prevalence of sexual dysfunction in men with Type 2 diabetes mellitus (T2DM) [1-3]. Sexual dysfunction leads to poor quality of life and is the core symptom of functional hypogonadism in men with T2DM [4]. However, although exogenous testosterone replacement therapy has been shown to reduce fat mass and increase muscle mass, its effects on symptoms of sexual dysfunction [4,5] and metabolic parameters [6-8] are not uniform. Moreover, the long-term risks of testosterone replacement therapy in men with T2DM and functional hypogonadism are unclear. The objective of this task force was to prepare a set of easy-to-follow, evidence-based recommendations for testosterone replacement therapy in men with T2DM and functional hypogonadism.
2. Methods
2.1. Constitution of the consensus task force, gathering, and appraisal of evidence
2.2. What are the types of hypogonadism (Table 1)?
2.3. Is testosterone deficiency common among men with type 2 diabetes mellitus?
2.4. Pathogenesis of hypogonadism in men with type 2 diabetes mellitus (Fig. 1)
2.4.1. Role of obesity, insulin resistance, and sex hormone-binding globulin (SHBG) (Table 2)
2.4.2. Role of adipocytokines and estrogen
2.4.3. Role of inflammatory markers
2.7. When to test for hypogonadism in men with type 2 diabetes mellitus (Table 3)?
2.8. How to establish the diagnosis of testosterone deficiency in men with type 2 diabetes mellitus (Table 4; Fig. 2)?
2.9. Does lifestyle modification have an impact on men with type 2 diabetes mellitus and functional hypogonadism?
2.10. Does testosterone replacement therapy have an impact on anthropometric and metabolic parameters in men with type 2 diabetes mellitus and functional hypogonadism (Table 5)?
2.11. What are the effects of testosterone replacement therapy on sexual dysfunction, constitutional symptoms, and mood in men with type 2 diabetes mellitus and functional hypogonadism?
2.12. Which testosterone formulation to choose for a replacement therapy in men with type 2 diabetes mellitus and functional hypogonadism (Table 6)?
2.13. What are the adverse effects of, and contraindications for, testosterone replacement therapy in men with type 2 diabetes mellitus and functional hypogonadism?
2.14. How to monitor testosterone replacement therapy in men with type 2 diabetes mellitus and functional hypogonadism (Tables 7 and 8)?
3. Conclusion
In conclusion, the task force of thirteen specialists, under the banner of the Integrated Diabetes and Endocrine Academy, a not-for-profit academic organization from Kolkata, India, convened to formulate consensus recommendations for the evaluation and management of men with type 2 diabetes mellitus and functional hypogonadism. The task force has recognized that subnormal testosterone is common in men with type 2 diabetes mellitus, arising as a result of complex interactions between multiple mechanisms including visceral obesity, insulin resistance, SHBG and leptin levels, and various inflammatory markers. In the absence of good quality evidence on the risk-benefit ratio of testosterone replacement therapy in men with type 2 diabetes mellitus and functional hypogonadism who are asymptomatic or have nonspecific constitutional symptoms/mood disorders, the task force has recommended against the routine measurement of serum testosterone or offer of testosterone replacement therapy to such men. The task force recommends measuring serum testosterone in men with type 2 diabetes mellitus with sexual dysfunction, and offering testosterone replacement therapy only in those with serum total testosterone<2.3 ng/ml (8 nmol/L), with a clear understanding that good quality evidence on the risk-benefit ratio of such an approach is still lacking. The task force has recommended against the use of testosterone replacement therapy in asymptomatic men with type 2 diabetes mellitus and functional hypogonadism for improvement in cardiovascular outcomes. The task force has recommended which tests to use, when to test, which route and formulation of testosterone to choose, and how to monitor testosterone replacement therapy in symptomatic men with type 2 diabetes mellitus with functional hypogonadism.
The task force highlights the urgent need for further research to establish the risk-benefit ratio of testosterone replacement therapy not only in men with type 2 diabetes mellitus and functional hypogonadism who are symptomatic but also in those who are asymptomatic or have minimal symptoms. Well-designed/ conducted RCTs, with an adequate number of both obese and nonobese men with type 2 diabetes mellitus and functional hypogonadism, with serum total testosterone well-matched and unequivocally in the hypogonadal or borderline hypogonadal range in both groups are urgently required. The RCTs must be of sufficient duration, have men treated with a similar formulation of testosterone to achieve mid-normal target value, who are assessed in a standardized fashion for changes in symptoms, body composition, insulin resistance, glycemic parameters, cardiovascular outcomes and adverse events.
Background: Though testosterone replacement therapy in men with organic hypogonadism is established, its role in men with type 2 diabetes mellitus (T2DM) and functional hypogonadism is unclear.
Methods: Thirteen experts addressed ten topic-specific questions after an in-depth review of literature, where all relevant issues were critically evaluated.
Results: Ten recommendations concerning diagnosis and management of men with T2DM and functional hypogonadism have been put forward.
Conclusion: Routine measurement of serum testosterone in all, and inappropriate replacement of testosterone in asymptomatic T2DM men with functional hypogonadism and borderline low serum testosterone values are not recommended.
1. Introduction
Epidemiological studies reveal an increased prevalence of sexual dysfunction in men with Type 2 diabetes mellitus (T2DM) [1-3]. Sexual dysfunction leads to poor quality of life and is the core symptom of functional hypogonadism in men with T2DM [4]. However, although exogenous testosterone replacement therapy has been shown to reduce fat mass and increase muscle mass, its effects on symptoms of sexual dysfunction [4,5] and metabolic parameters [6-8] are not uniform. Moreover, the long-term risks of testosterone replacement therapy in men with T2DM and functional hypogonadism are unclear. The objective of this task force was to prepare a set of easy-to-follow, evidence-based recommendations for testosterone replacement therapy in men with T2DM and functional hypogonadism.
2. Methods
2.1. Constitution of the consensus task force, gathering, and appraisal of evidence
2.2. What are the types of hypogonadism (Table 1)?
2.3. Is testosterone deficiency common among men with type 2 diabetes mellitus?
2.4. Pathogenesis of hypogonadism in men with type 2 diabetes mellitus (Fig. 1)
2.4.1. Role of obesity, insulin resistance, and sex hormone-binding globulin (SHBG) (Table 2)
2.4.2. Role of adipocytokines and estrogen
2.4.3. Role of inflammatory markers
2.7. When to test for hypogonadism in men with type 2 diabetes mellitus (Table 3)?
2.8. How to establish the diagnosis of testosterone deficiency in men with type 2 diabetes mellitus (Table 4; Fig. 2)?
2.9. Does lifestyle modification have an impact on men with type 2 diabetes mellitus and functional hypogonadism?
2.10. Does testosterone replacement therapy have an impact on anthropometric and metabolic parameters in men with type 2 diabetes mellitus and functional hypogonadism (Table 5)?
2.11. What are the effects of testosterone replacement therapy on sexual dysfunction, constitutional symptoms, and mood in men with type 2 diabetes mellitus and functional hypogonadism?
2.12. Which testosterone formulation to choose for a replacement therapy in men with type 2 diabetes mellitus and functional hypogonadism (Table 6)?
2.13. What are the adverse effects of, and contraindications for, testosterone replacement therapy in men with type 2 diabetes mellitus and functional hypogonadism?
2.14. How to monitor testosterone replacement therapy in men with type 2 diabetes mellitus and functional hypogonadism (Tables 7 and 8)?
3. Conclusion
In conclusion, the task force of thirteen specialists, under the banner of the Integrated Diabetes and Endocrine Academy, a not-for-profit academic organization from Kolkata, India, convened to formulate consensus recommendations for the evaluation and management of men with type 2 diabetes mellitus and functional hypogonadism. The task force has recognized that subnormal testosterone is common in men with type 2 diabetes mellitus, arising as a result of complex interactions between multiple mechanisms including visceral obesity, insulin resistance, SHBG and leptin levels, and various inflammatory markers. In the absence of good quality evidence on the risk-benefit ratio of testosterone replacement therapy in men with type 2 diabetes mellitus and functional hypogonadism who are asymptomatic or have nonspecific constitutional symptoms/mood disorders, the task force has recommended against the routine measurement of serum testosterone or offer of testosterone replacement therapy to such men. The task force recommends measuring serum testosterone in men with type 2 diabetes mellitus with sexual dysfunction, and offering testosterone replacement therapy only in those with serum total testosterone<2.3 ng/ml (8 nmol/L), with a clear understanding that good quality evidence on the risk-benefit ratio of such an approach is still lacking. The task force has recommended against the use of testosterone replacement therapy in asymptomatic men with type 2 diabetes mellitus and functional hypogonadism for improvement in cardiovascular outcomes. The task force has recommended which tests to use, when to test, which route and formulation of testosterone to choose, and how to monitor testosterone replacement therapy in symptomatic men with type 2 diabetes mellitus with functional hypogonadism.
The task force highlights the urgent need for further research to establish the risk-benefit ratio of testosterone replacement therapy not only in men with type 2 diabetes mellitus and functional hypogonadism who are symptomatic but also in those who are asymptomatic or have minimal symptoms. Well-designed/ conducted RCTs, with an adequate number of both obese and nonobese men with type 2 diabetes mellitus and functional hypogonadism, with serum total testosterone well-matched and unequivocally in the hypogonadal or borderline hypogonadal range in both groups are urgently required. The RCTs must be of sufficient duration, have men treated with a similar formulation of testosterone to achieve mid-normal target value, who are assessed in a standardized fashion for changes in symptoms, body composition, insulin resistance, glycemic parameters, cardiovascular outcomes and adverse events.
