madman
Super Moderator
Abstract
Background: This manuscript is a review and discussion of the published results of The T Trials.
Objective: To re-examine the efficacy of testosterone replacement of hypogonadal men greater than 65 years of age in The T Trials.
Materials and Methods: The T Trials were a complex collection of seven double-blind, placebo-controlled trials of the efficacy of testosterone as replacement therapy for older men with unequivocal hypogonadism. There were three main trials (sexual function; physical function; vitality) and four sub trials (cognition; bone; anemia; cardiovascular). All subjects participated in the main trials while more selective inclusion/exclusion criteria existed for the sub-trials. Subjects were excluded for perceived higher risk of prostate cancer and recent myocardial or cerebral vascular events.
Results: The previously published results are reviewed here as seen in the context of this special issue on late-onset hypogonadism. In the T Trials, positive benefits were seen in the sexual function, bone, and anemia trials with small but significant benefits in the vitality trial. No benefit was seen in the cognition trial, partial benefit in physical function, and a negative benefit outcome seen in the cardiovascular trial. The later trial was underpowered and the results were described as exploratory. Adverse events were relatively uncommon in the 12-month treatment phase and an additional 12-month post-treatment phase. The most frequent adverse effect ascribed to testosterone was erythrocytosis.
Conclusions: The T Trials studied the efficacy of testosterone replacement therapy on 788 men with low testosterone and symptoms of hypogonadism. The studies demonstrated benefits in four trials (sexual function, vitality, bone, and anemia); partial benefit in the physical function trial; no effect in the cognition trial; and a negative effect in the exploratory cardiovascular trial. The T Trials were not designed to assess the long-term risks of testosterone in men.
Conclusion
The T trials were a DBPC coordinated set of 7 Trials (3 Main and 4 sub-trials of testosterone effects of replacement therapy in 788 men greater than age 65 (mean age 72) with unequivocal hypogonadism based on 2 low serum testosterone concentrations below the reference range of normal young men. The three main trials were sexual function, physical function, and vitality; four sub-trials (cognition, bone, anemia, and cardiovascular) had selective inclusion/exclusion criteria and studied fewer subjects. Treatment was for 52 weeks with a post-treatment assessment after another 52 weeks. Testosterone was administered by the transdermal route beginning with 5 mg daily; multiple-dose adjustments were allowed to maintain mid normal testosterone concentrations.
In the sexual function trial, testosterone increased sexual activity, sexual desire, and erectile function. In the physical function trial testosterone did not increase timed walking distance in the men selected based on slow baseline walking speed but did increase walking distance in the overall T trial subjects who were a combined group of slow walkers and less slow walkers. In the vitality trial, there was a small benefit in mood and depressive symptoms but not in energy. There was no benefit of testosterone in the cognition trial. Significant positive benefits were seen in the bone trial on bone mineral volume and estimated bone strength. The anemia trial demonstrated mild to moderate anemia (hemoglobin < 12.7 g/dL and >10g/dL) in 126/788 of the T Trial study group. Testosterone significantly improved hemoglobin (> 1 g/dL) and corrected anemia in hypogonadism of unknown and known putative cause of anemia. In the cardiovascular trial, testosterone increased the non-calcified plaque seen on CT angiography. The cardiovascular Trial was underpowered and the results were considered exploratory.
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Background: This manuscript is a review and discussion of the published results of The T Trials.
Objective: To re-examine the efficacy of testosterone replacement of hypogonadal men greater than 65 years of age in The T Trials.
Materials and Methods: The T Trials were a complex collection of seven double-blind, placebo-controlled trials of the efficacy of testosterone as replacement therapy for older men with unequivocal hypogonadism. There were three main trials (sexual function; physical function; vitality) and four sub trials (cognition; bone; anemia; cardiovascular). All subjects participated in the main trials while more selective inclusion/exclusion criteria existed for the sub-trials. Subjects were excluded for perceived higher risk of prostate cancer and recent myocardial or cerebral vascular events.
Results: The previously published results are reviewed here as seen in the context of this special issue on late-onset hypogonadism. In the T Trials, positive benefits were seen in the sexual function, bone, and anemia trials with small but significant benefits in the vitality trial. No benefit was seen in the cognition trial, partial benefit in physical function, and a negative benefit outcome seen in the cardiovascular trial. The later trial was underpowered and the results were described as exploratory. Adverse events were relatively uncommon in the 12-month treatment phase and an additional 12-month post-treatment phase. The most frequent adverse effect ascribed to testosterone was erythrocytosis.
Conclusions: The T Trials studied the efficacy of testosterone replacement therapy on 788 men with low testosterone and symptoms of hypogonadism. The studies demonstrated benefits in four trials (sexual function, vitality, bone, and anemia); partial benefit in the physical function trial; no effect in the cognition trial; and a negative effect in the exploratory cardiovascular trial. The T Trials were not designed to assess the long-term risks of testosterone in men.
Conclusion
The T trials were a DBPC coordinated set of 7 Trials (3 Main and 4 sub-trials of testosterone effects of replacement therapy in 788 men greater than age 65 (mean age 72) with unequivocal hypogonadism based on 2 low serum testosterone concentrations below the reference range of normal young men. The three main trials were sexual function, physical function, and vitality; four sub-trials (cognition, bone, anemia, and cardiovascular) had selective inclusion/exclusion criteria and studied fewer subjects. Treatment was for 52 weeks with a post-treatment assessment after another 52 weeks. Testosterone was administered by the transdermal route beginning with 5 mg daily; multiple-dose adjustments were allowed to maintain mid normal testosterone concentrations.
In the sexual function trial, testosterone increased sexual activity, sexual desire, and erectile function. In the physical function trial testosterone did not increase timed walking distance in the men selected based on slow baseline walking speed but did increase walking distance in the overall T trial subjects who were a combined group of slow walkers and less slow walkers. In the vitality trial, there was a small benefit in mood and depressive symptoms but not in energy. There was no benefit of testosterone in the cognition trial. Significant positive benefits were seen in the bone trial on bone mineral volume and estimated bone strength. The anemia trial demonstrated mild to moderate anemia (hemoglobin < 12.7 g/dL and >10g/dL) in 126/788 of the T Trial study group. Testosterone significantly improved hemoglobin (> 1 g/dL) and corrected anemia in hypogonadism of unknown and known putative cause of anemia. In the cardiovascular trial, testosterone increased the non-calcified plaque seen on CT angiography. The cardiovascular Trial was underpowered and the results were considered exploratory.
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