madman
Super Moderator
CV DISEASE
Results overall provide more definitive evidence that testosterone therapy (when performed appropriately) does not increase the risk for major CV events after a mean 2 years of treatment. The secondary findings of increased arrhythmias, atrial fibrillation, and minimally elevated blood pressure may be due to a volume-expanding effect of testosterone and are of limited/unclear clinical relevance. It is also plausible that the CV risk profile of testosterone may differ depending on doses and agent/modality prescribed (ie, injectable vs topical), particularly given distinctive AE profiles observed (eg, erythrocytosis) by agent.3
Currently, statement #20 in the testosterone guideline notes that it is unclear if testosterone increases major CV events. However, these updated data confirm that testosterone therapy does not increase major CV event risks over at least a 2-year period when done according to prescribed protocols.
DIABETES
A follow-up analysis of T4DM data indicated that some benefits were secondary to improvements in fat and skeletal muscle mass.5 However, despite these beneficial secondary effects, testosterone remained an independent contributor.
These data provide helpful, high-level information as it relates to the current testosterone guideline statement #15, which states that the data are inconclusive as to whether testosterone therapy improves diabetic indices. Additionally, the data suggest a role for testosterone in men with impaired fasting glucose/glucose tolerance regardless of baseline testosterone levels.
ERECTILE FUNCTION AND LIBIDO
Currently, the AUA testosterone guideline statement #14 indicates that testosterone therapy may improve low sex drive and erectile function. These previously cited data would further support the beneficial effects of testosterone on libido and overall sexual function but would provide further conflicting data on whether it has a notable impact on erectile function itself. Most likely, these data suggest that treating erectile dysfunction with testosterone is a nuanced concept, where the modality employed, peak doses achieved, baseline erectile function, and comorbid contributing factors (eg, diabetes, obesity) all play important roles. To highlight this latter point, in the T4DM study, the statistical difference with therapy came as much because of an increase in the treated arm as a decrease in the placebo arm,whereas the TRAVERSE study exhibited similar increases in both arms. As such, it suggests that testosterone may ultimately have more of a protective effect against age- and comorbidity-dependent impacts on erectile function rather than a direct treatment/augmentation effect.
OSA
Although treating OSA may not improve testosterone levels, initiating testosterone therapy in men with OSA may lead to a worsening of symptoms. Specifically, multiple small studies over the past 4 decades(all n <100) have previously demonstrated the potential for acute worsening of OSA symptoms in men undergoing testosterone therapy supplementation.3
Given these observations, clinicians should exercise caution when starting a man with OSA on testosterone therapy. Additionally, men with low testosterone should be routinely screened for OSA and referred for treatment prior to initiating therapy. At the present time, the 2018 AUA testosterone guideline does not specifically address the potential risks of worsening OSA in men undergoing testosterone therapy and need for screening prior to initiation of treatment.
PROSTATE CANCER
Overall, findings are similar to prior studies and reaffirm the current AUA testosterone guideline statement #17, which indicates that testosterone supplementation is not correlated with an increased risk for development of prostate cancer.
TAKE-HOME MESSAGES
Two landmark RCTs evaluating testosterone therapy have recently been concluded and provide significant data on the risks and benefits of treatment. Key findings included no increased risks for severe CV events, but mild increases in blood pressure, rate of non fatal arrhythmias, and risk of acute kidney injury. Testosterone also likely increases sexual activity, libido, and other aspects of sexual function, but has limited and likely clinically insignificant effects on erectile function. For diabetes, testosterone supplementation likely results in both preventative and treatment benefits for men with impaired fasting glucose/glucose tolerance, regardless of baseline testosterone levels. The studies also confirmed prior data demonstrating an increase in prostate-related events overall, without increasing the risk for prostate cancer (including high-grade disease). And finally, additional data suggest that OSA is correlated with low testosterone and should be screened for prior to initiation of testosterone and closely monitored during therapy.
Results overall provide more definitive evidence that testosterone therapy (when performed appropriately) does not increase the risk for major CV events after a mean 2 years of treatment. The secondary findings of increased arrhythmias, atrial fibrillation, and minimally elevated blood pressure may be due to a volume-expanding effect of testosterone and are of limited/unclear clinical relevance. It is also plausible that the CV risk profile of testosterone may differ depending on doses and agent/modality prescribed (ie, injectable vs topical), particularly given distinctive AE profiles observed (eg, erythrocytosis) by agent.3
Currently, statement #20 in the testosterone guideline notes that it is unclear if testosterone increases major CV events. However, these updated data confirm that testosterone therapy does not increase major CV event risks over at least a 2-year period when done according to prescribed protocols.
DIABETES
A follow-up analysis of T4DM data indicated that some benefits were secondary to improvements in fat and skeletal muscle mass.5 However, despite these beneficial secondary effects, testosterone remained an independent contributor.
These data provide helpful, high-level information as it relates to the current testosterone guideline statement #15, which states that the data are inconclusive as to whether testosterone therapy improves diabetic indices. Additionally, the data suggest a role for testosterone in men with impaired fasting glucose/glucose tolerance regardless of baseline testosterone levels.
ERECTILE FUNCTION AND LIBIDO
Currently, the AUA testosterone guideline statement #14 indicates that testosterone therapy may improve low sex drive and erectile function. These previously cited data would further support the beneficial effects of testosterone on libido and overall sexual function but would provide further conflicting data on whether it has a notable impact on erectile function itself. Most likely, these data suggest that treating erectile dysfunction with testosterone is a nuanced concept, where the modality employed, peak doses achieved, baseline erectile function, and comorbid contributing factors (eg, diabetes, obesity) all play important roles. To highlight this latter point, in the T4DM study, the statistical difference with therapy came as much because of an increase in the treated arm as a decrease in the placebo arm,whereas the TRAVERSE study exhibited similar increases in both arms. As such, it suggests that testosterone may ultimately have more of a protective effect against age- and comorbidity-dependent impacts on erectile function rather than a direct treatment/augmentation effect.
OSA
Although treating OSA may not improve testosterone levels, initiating testosterone therapy in men with OSA may lead to a worsening of symptoms. Specifically, multiple small studies over the past 4 decades(all n <100) have previously demonstrated the potential for acute worsening of OSA symptoms in men undergoing testosterone therapy supplementation.3
Given these observations, clinicians should exercise caution when starting a man with OSA on testosterone therapy. Additionally, men with low testosterone should be routinely screened for OSA and referred for treatment prior to initiating therapy. At the present time, the 2018 AUA testosterone guideline does not specifically address the potential risks of worsening OSA in men undergoing testosterone therapy and need for screening prior to initiation of treatment.
PROSTATE CANCER
Overall, findings are similar to prior studies and reaffirm the current AUA testosterone guideline statement #17, which indicates that testosterone supplementation is not correlated with an increased risk for development of prostate cancer.
TAKE-HOME MESSAGES
Two landmark RCTs evaluating testosterone therapy have recently been concluded and provide significant data on the risks and benefits of treatment. Key findings included no increased risks for severe CV events, but mild increases in blood pressure, rate of non fatal arrhythmias, and risk of acute kidney injury. Testosterone also likely increases sexual activity, libido, and other aspects of sexual function, but has limited and likely clinically insignificant effects on erectile function. For diabetes, testosterone supplementation likely results in both preventative and treatment benefits for men with impaired fasting glucose/glucose tolerance, regardless of baseline testosterone levels. The studies also confirmed prior data demonstrating an increase in prostate-related events overall, without increasing the risk for prostate cancer (including high-grade disease). And finally, additional data suggest that OSA is correlated with low testosterone and should be screened for prior to initiation of testosterone and closely monitored during therapy.
