Reflections on the T Trials

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 >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; and 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 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 long‐term risks of testosterone in men.

Late‐onset hypogonadism a challenging task for the andrology field

“…The new evidence on the effects of TRT on aging men deriving from these RCTs is discussed in this special issue. 5 Specific papers included in this special issue analyzed all evidence-based data supporting the role of TRT on several outcomes. [5][6][7][8][9][10] In addition, available on-label and off-label TRT options have been specifically addressed and critically discussed.…”

“…5 Specific papers included in this special issue analyzed all evidence-based data supporting the role of TRT on several outcomes. [5][6][7][8][9][10] In addition, available on-label and off-label TRT options have been specifically addressed and critically discussed. 11,12 Current evidence supports the role of TRT in improving sexual function in patients with a milder form of ED, whereas the effect of TRT in more complicated ED patients is less effective.…”

“…Testosterone Trials (TTrials) are a coordinated set of seven, 52‐week randomized placebo‐controlled, double‐blind studies (RCTs), including overall 788 men older than 65 years (mean age 72 years) with hypogonadism (TT < 9.4 nM) and treated with T gel 1% for 12 months. The new evidence on the effects of TRT on aging men deriving from these RCTs is discussed in this special issue 5 …”

“…Specific papers included in this special issue analyzed all evidence‐based data supporting the role of TRT on several outcomes 5‐10 . In addition, available on‐label and off‐label TRT options have been specifically addressed and critically discussed 11,12 .…”

Oral administration of VDAC1-derived small molecule peptides increases circulating testosterone levels in male rats

“…Moreover, cardiovascular concerns were raised in retrospective ( 22 , 23 ) and prospective ( 24 , 25 ) studies. However, some studies showed no effects or even cardiovascular improvements ( 26 – 28 ) calling for caution and long-term cardiovascular safety studies ( 29 , 30 ). All these concerns lead the FDA to issue a warning and guidelines that aim to reduce the abuse of TRT ( 31 ).…”