madman
Super Moderator
ABSTRACT
Introduction
Functional hypogonadism is frequently found in obese men, particularly those with metabolic complications. Several possible therapeutic approaches could be considered.
Areas covered
An extensive search on Medline, Embase, and Cochrane databases was performed to retrieve the available studies assessing the change of testosterone (T) and sexual function upon dieting or physical activity programs, as well as glucagon-like peptide 1 analogues. The role of lifestyle interventions associated with T replacement therapy (TRT) was also evaluated. The expert opinion provided here has been corroborated by meta-analyzing the results of the retrieved studies.
Expert opinion
Current evidence supports the beneficial role of lifestyle modifications in increasing T and improving sexual function as a function of weight loss. While dieting programs are associated with greater effects in younger populations, physical exercise has major effects in older ones. Among the dieting programs, a very low-calorie ketogenic diet shows the best results; aerobic or endurance physical exercise perform similarly. The advantages of functional hypogonadism in lifestyle modifications are empowered by the association with TRT. Therefore, TRT may be a valuable complementary strategy to increase muscle mass and facilitate physical exercise while improving sexual symptoms, thus favoring the motivation and compliance for lifestyle interventions.
4. Clinical data
4.1. Effect of lifestyle and pharmacologically induced weight loss on functional hypogonadism
4.1.1. Effect of diet
4.1.2. Effect of physical exercise
4.1.3. Effect of GLP-1 analogues
4.1.4. Weight loss and sexual function
4.2. Combined TRT and lifestyle
5. Conclusions
The present data indicate that lifestyle modifications are able to reverse overweight- and obesity-related functional hypogonadism in both preclinical and clinical studies. In clinical studies, the improvement in total T is tightly related to the entity of weight loss obtained over the lifestyle intervention period with comparable effects of a low-calorie diet and physical exercise. Conversely, no effect on LH levels was observed, at least when a low-calorie diet was considered. The increase in total and free T levels was more evident when a pharmacological approach with the use of GLP-1 analogues, was analyzed. However, even with the latter approach no significant modifications in LH levels at follow-up were observed, although there was a clear trend. It is important to note that LH is secreted in a pulsatile manner and, therefore, a single measurement (as often performed in the aforementioned studies) can be misleading. Interestingly, VLCKD resulted in better T improvement when compared to other dieting approaches. The latter observation was confirmed even after the adjustment for confounders, including the extent of weight loss. Similarly, to what was observed for the modification in the hormonal parameters, weight loss, whatever was obtained, was associated with an overall improvement in erectile function, as assessed by IIEF. The latter finding was more evident inpatients with lower baseline T levels, at least when a low calorie diet was considered. Unfortunately, no sufficient data to investigate the effect of weight loss on other sexual function domains, when IIEF was considered, were available. However, it should be recognized that weight loss has been shown to improve several aspects of male sexual function including libido and urinary symptoms [48,99,100]. When the combination of lifestyle interventions and TRT was compared to lifestyle alone, the former resulted in a larger improvement in body composition (including a greater reduction of fat mass and waist circumference and an increase of lean mass) as well as an overall improvement of insulin resistance as derived by surrogate markers (including the HOMA index and triglyceride levels). Finally, the use of TRT along with lifestyle showed a better IIEF score at the end of the trial when compared to that obtained with lifestyle modifications alone.
6. Expert opinion
In conclusion, the key message arising from the present paper is that lifestyle modifications and weight loss should be considered and strongly recommended for all subjects with functional hypogonadism. In symptomatic and uncomplicated patients with overweight or obesity, the combination of TRT and lifestyle can result in better outcomes. Accordingly, available guidelines recommend starting TRT in all symptomatic hypogonadal men, after contraindications are excluded, in whom a reversal of the condition cannot be expected in a reasonable timeframe [8]. It can be speculated that the observed improvement in fat mass after TRT can allow one to perform physical activity, eventually resulting in further weight loss and metabolic profile improvement.
Introduction
Functional hypogonadism is frequently found in obese men, particularly those with metabolic complications. Several possible therapeutic approaches could be considered.
Areas covered
An extensive search on Medline, Embase, and Cochrane databases was performed to retrieve the available studies assessing the change of testosterone (T) and sexual function upon dieting or physical activity programs, as well as glucagon-like peptide 1 analogues. The role of lifestyle interventions associated with T replacement therapy (TRT) was also evaluated. The expert opinion provided here has been corroborated by meta-analyzing the results of the retrieved studies.
Expert opinion
Current evidence supports the beneficial role of lifestyle modifications in increasing T and improving sexual function as a function of weight loss. While dieting programs are associated with greater effects in younger populations, physical exercise has major effects in older ones. Among the dieting programs, a very low-calorie ketogenic diet shows the best results; aerobic or endurance physical exercise perform similarly. The advantages of functional hypogonadism in lifestyle modifications are empowered by the association with TRT. Therefore, TRT may be a valuable complementary strategy to increase muscle mass and facilitate physical exercise while improving sexual symptoms, thus favoring the motivation and compliance for lifestyle interventions.
4. Clinical data
4.1. Effect of lifestyle and pharmacologically induced weight loss on functional hypogonadism
4.1.1. Effect of diet
4.1.2. Effect of physical exercise
4.1.3. Effect of GLP-1 analogues
4.1.4. Weight loss and sexual function
4.2. Combined TRT and lifestyle
5. Conclusions
The present data indicate that lifestyle modifications are able to reverse overweight- and obesity-related functional hypogonadism in both preclinical and clinical studies. In clinical studies, the improvement in total T is tightly related to the entity of weight loss obtained over the lifestyle intervention period with comparable effects of a low-calorie diet and physical exercise. Conversely, no effect on LH levels was observed, at least when a low-calorie diet was considered. The increase in total and free T levels was more evident when a pharmacological approach with the use of GLP-1 analogues, was analyzed. However, even with the latter approach no significant modifications in LH levels at follow-up were observed, although there was a clear trend. It is important to note that LH is secreted in a pulsatile manner and, therefore, a single measurement (as often performed in the aforementioned studies) can be misleading. Interestingly, VLCKD resulted in better T improvement when compared to other dieting approaches. The latter observation was confirmed even after the adjustment for confounders, including the extent of weight loss. Similarly, to what was observed for the modification in the hormonal parameters, weight loss, whatever was obtained, was associated with an overall improvement in erectile function, as assessed by IIEF. The latter finding was more evident inpatients with lower baseline T levels, at least when a low calorie diet was considered. Unfortunately, no sufficient data to investigate the effect of weight loss on other sexual function domains, when IIEF was considered, were available. However, it should be recognized that weight loss has been shown to improve several aspects of male sexual function including libido and urinary symptoms [48,99,100]. When the combination of lifestyle interventions and TRT was compared to lifestyle alone, the former resulted in a larger improvement in body composition (including a greater reduction of fat mass and waist circumference and an increase of lean mass) as well as an overall improvement of insulin resistance as derived by surrogate markers (including the HOMA index and triglyceride levels). Finally, the use of TRT along with lifestyle showed a better IIEF score at the end of the trial when compared to that obtained with lifestyle modifications alone.
6. Expert opinion
In conclusion, the key message arising from the present paper is that lifestyle modifications and weight loss should be considered and strongly recommended for all subjects with functional hypogonadism. In symptomatic and uncomplicated patients with overweight or obesity, the combination of TRT and lifestyle can result in better outcomes. Accordingly, available guidelines recommend starting TRT in all symptomatic hypogonadal men, after contraindications are excluded, in whom a reversal of the condition cannot be expected in a reasonable timeframe [8]. It can be speculated that the observed improvement in fat mass after TRT can allow one to perform physical activity, eventually resulting in further weight loss and metabolic profile improvement.
