HackTwat
MuscleChemistry Registered Member
This is the Conclusion and Expert Comments from an extensive article about the use of Growth Hormone and Testosterone together for the treatment of Heart Failure.
[h=3]Conclusion[/h]Growth hormone and testosterone supplementation have shown promising effects in patients with HF despite numerous small, short-term clinical trials showing mixed results. Selected patients may benefit from supplementation in addition to conventional therapy, in particular patients with documented hormonal deficiency (below or in the low-normal range). Patients with suspected GH resistance may warrant pretreatment screening prior to supplementation to adjust dosing and possible direct IGF-1 administration in addition to GH. However, from our knowledge, there are no direct studies with both GH and IGF-1 supplementation in HF, thus recommendations cannot be made regarding this dual therapeutic approach.
Minimal data exist for combined therapy of GH and testosterone in the setting of HF. The studies using combined GH and testosterone supplementation were mostly conducted in older men with testosterone and IGF-1 in lower ranges of normal. One study showed promising effects on the improvement of body composition and muscle performance, [SUP][92][/SUP] while another study found no change in function, mood and body composition. [SUP][93][/SUP] However, the latter study observed improvements in balance and muscle IGF-1 gene expression. Future studies investigating combined GH and testosterone therapy in patients with HF would be warranted in order to assess possible synergistic effects, which may be advantageous over monotherapy.
Testosterone treatment has been shown to exert beneficial effects in both men and women with HF with few adverse effects. In our patients with advanced HF and other comorbid conditions, we routinely screen for and treat testosterone deficiency. Approximately 20–30% of our HF patients, those with ventricular assist devices and patients with postorthotopic heart transplantation status, have received supplemental testosterone at some point. Anecdotally, the patients have improved nutritional status as well as improved functionality and sense of well being. Although our patients appear to show some clinical improvement with testosterone therapy, we currently do not have conclusive data to recommend testosterone therapy in HF patients. Despite the promising role of hormonal supplementation in HF, larger, long-term, randomized clinical trials are warranted to further assess efficacy and safety of manipulation of the hormonal imbalance in patients with chronic HF.
[h=3]Expert Commentary[/h]Patients with HF are often observed to have hormonal dysregulation. GH/IGF-1 axis derangement and testosterone deficiency have been an area of great interest as an adjunctive therapy in patients with advanced HF. While early studies show that GH supplementation in patients with HF enhances cardiac function resulting in improvement in clinical symptoms, subsequent studies did not demonstrate significant improvements in cardiac morphology, performance or clinical status. However, the studies have been small with relatively short study duration. Of note, the inconsistent data may be linked to GH resistance in patients and this may affect the biochemical response to GH therapy. Patients with GH resistance were observed to have lower levels of IGF-1, thus combination therapy of both GH and IGF-1 may be beneficial. Coadministration of GH and IGF-1 in patients with HF have not been fully investigated, thus the efficacy and safety of this therapeutic approach remains uncertain.
The majority of adverse effects observed in patients on long-term GH replacement therapy include edema, insulin resistance, arthralgia and myalgia. These adverse effects were often related to higher dosing; therefore, appropriate dosing will have to be addressed to minimize adverse effects but maximize beneficial outcomes. Because there are inconsistent data on efficacy and lack of long-term assessment on safety – large randomized clinical trials are needed to fully evaluate these issues before starting patients on GH-replacement therapy.
Similarly, testosterone therapy in patients with HF shows improvement in functional status and prognosis. Multiple studies observe improvements in parameters such as LV performance, incremental shuttle walk test and mean peak oxygen consumption. The adverse effects of testosterone therapy have been associated with exacerbation of prostate cancer, atherosclerosis, unfavorable lipid profiles and polycythemia. These adverse effects were mainly observed when testosterone was administered at supraphysiological levels. Despite the positive benefits of testosterone replacement, the long-term efficacy and safety remains unclear and will need to be addressed prior to committing a patient to long-term therapy.
[h=3]Five-year View[/h]Growth hormone and testosterone therapy have shown promising benefits in patients with HF. At present, many institutions, including our own, are actively participating in trials to reproduce the data observed in earlier studies. As more data are available and large clinical studies show consistent benefits with minimal adverse effects, hormonal supplementation may become an integral agent in the treatment of HF. If the benefits and safety are clearly established, patients may be prescreened for low levels of GH and testosterone early on in their course of disease. This strategy may lead to earlier initiation of hormone therapy with hopes of improving functional status and quality of life.
[h=3]Sidebar[/h][h=4]Key Issues[/h]
[h=3]Conclusion[/h]Growth hormone and testosterone supplementation have shown promising effects in patients with HF despite numerous small, short-term clinical trials showing mixed results. Selected patients may benefit from supplementation in addition to conventional therapy, in particular patients with documented hormonal deficiency (below or in the low-normal range). Patients with suspected GH resistance may warrant pretreatment screening prior to supplementation to adjust dosing and possible direct IGF-1 administration in addition to GH. However, from our knowledge, there are no direct studies with both GH and IGF-1 supplementation in HF, thus recommendations cannot be made regarding this dual therapeutic approach.
Minimal data exist for combined therapy of GH and testosterone in the setting of HF. The studies using combined GH and testosterone supplementation were mostly conducted in older men with testosterone and IGF-1 in lower ranges of normal. One study showed promising effects on the improvement of body composition and muscle performance, [SUP][92][/SUP] while another study found no change in function, mood and body composition. [SUP][93][/SUP] However, the latter study observed improvements in balance and muscle IGF-1 gene expression. Future studies investigating combined GH and testosterone therapy in patients with HF would be warranted in order to assess possible synergistic effects, which may be advantageous over monotherapy.
Testosterone treatment has been shown to exert beneficial effects in both men and women with HF with few adverse effects. In our patients with advanced HF and other comorbid conditions, we routinely screen for and treat testosterone deficiency. Approximately 20–30% of our HF patients, those with ventricular assist devices and patients with postorthotopic heart transplantation status, have received supplemental testosterone at some point. Anecdotally, the patients have improved nutritional status as well as improved functionality and sense of well being. Although our patients appear to show some clinical improvement with testosterone therapy, we currently do not have conclusive data to recommend testosterone therapy in HF patients. Despite the promising role of hormonal supplementation in HF, larger, long-term, randomized clinical trials are warranted to further assess efficacy and safety of manipulation of the hormonal imbalance in patients with chronic HF.
[h=3]Expert Commentary[/h]Patients with HF are often observed to have hormonal dysregulation. GH/IGF-1 axis derangement and testosterone deficiency have been an area of great interest as an adjunctive therapy in patients with advanced HF. While early studies show that GH supplementation in patients with HF enhances cardiac function resulting in improvement in clinical symptoms, subsequent studies did not demonstrate significant improvements in cardiac morphology, performance or clinical status. However, the studies have been small with relatively short study duration. Of note, the inconsistent data may be linked to GH resistance in patients and this may affect the biochemical response to GH therapy. Patients with GH resistance were observed to have lower levels of IGF-1, thus combination therapy of both GH and IGF-1 may be beneficial. Coadministration of GH and IGF-1 in patients with HF have not been fully investigated, thus the efficacy and safety of this therapeutic approach remains uncertain.
The majority of adverse effects observed in patients on long-term GH replacement therapy include edema, insulin resistance, arthralgia and myalgia. These adverse effects were often related to higher dosing; therefore, appropriate dosing will have to be addressed to minimize adverse effects but maximize beneficial outcomes. Because there are inconsistent data on efficacy and lack of long-term assessment on safety – large randomized clinical trials are needed to fully evaluate these issues before starting patients on GH-replacement therapy.
Similarly, testosterone therapy in patients with HF shows improvement in functional status and prognosis. Multiple studies observe improvements in parameters such as LV performance, incremental shuttle walk test and mean peak oxygen consumption. The adverse effects of testosterone therapy have been associated with exacerbation of prostate cancer, atherosclerosis, unfavorable lipid profiles and polycythemia. These adverse effects were mainly observed when testosterone was administered at supraphysiological levels. Despite the positive benefits of testosterone replacement, the long-term efficacy and safety remains unclear and will need to be addressed prior to committing a patient to long-term therapy.
[h=3]Five-year View[/h]Growth hormone and testosterone therapy have shown promising benefits in patients with HF. At present, many institutions, including our own, are actively participating in trials to reproduce the data observed in earlier studies. As more data are available and large clinical studies show consistent benefits with minimal adverse effects, hormonal supplementation may become an integral agent in the treatment of HF. If the benefits and safety are clearly established, patients may be prescreened for low levels of GH and testosterone early on in their course of disease. This strategy may lead to earlier initiation of hormone therapy with hopes of improving functional status and quality of life.
[h=3]Sidebar[/h][h=4]Key Issues[/h]
- Low levels of growth hormone (GH) and testosterone have been associated with increased mortality and morbidity in patients with heart failure.
- Initial small clinical trials of GH supplementation in patients with heart failure showed positive effects on clinical status, cardiac morphology and performance; however, subsequent larger clinical trials showed inconsistent results.
- Clinical trials of testosterone supplementation in patients with heart failure have been shown to improve hemodynamics, decrease left ventricular remodeling and increase strength.
- Long-term efficacy and safety of GH- and testosterone-replacement therapy in patients with heart failure are limited and not well studied.
- GH and testosterone supplementation have been shown to be promising new therapy agents in conjunction with conventional therapy; however, large randomized controlled trails are needed to further assess their efficacy and safety.
