Conclusions Oral TRT produces significant CV risk .
Differences in the degree to which serum DHT is elevated may underlie the varying CV risk by TRT administration route , as elevated serum dihydrotestosterone has been shown to be associated with CV risk in observational studies
Background Potential cardiovascular ( CV ) risks of testosterone replacement therapy ( TRT ) are currently a topic of intense interest .
However , no studies have addressed CV risk as a function of the route of administration of TRT .
Testosterone treatment and mortality in men with low testosterone levels.
CONTEXT Low testosterone levels in men have been associated with increased mortality . However , the influence of testosterone treatment on mortality in men with low testosterone levels is not known . OBJECTIVE The objective of the study was to examine the association between testosterone treatment and mortality in men with low testosterone levels . DESIGN This was an observational study of mortality in testosterone-treated compared with untreated men , assessed with time-varying , adjusted Cox proportional hazards regression models . Effect modification by age , diabetes , and coronary heart disease was tested a priori . SETTING The study was conducted with a clinical data base that included seven Northwest Veterans Affairs medical centers . PATIENTS Patients included a cohort of 1031 male veterans , aged older than 40 yr , with low total testosterone [ ≤250 ng/dl ( 8.7 nmol/liter ) ] and no history of prostate cancer , assessed between January 2001 and December 2002 and followed up through the end of 2005 . MAIN OUTCOME MEASURE Total mortality in testosterone-treated compared with untreated men was measured . RESULTS Testosterone treatment was initiated in 398 men ( 39 % ) during routine clinical care . The mortality in testosterone-treated men was 10.3 % compared with 20.7 % in untreated men ( P<0.0001 ) with a mortality rate of 3.4 deaths per 100 person-years for testosterone-treated men and 5.7 deaths per 100 person-years in men not treated with testosterone . After multivariable adjustment including age , body mass index , testosterone level , medical morbidity , diabetes , and coronary heart disease , testosterone treatment was associated with decreased risk of death ( hazard ratio 0.61 ; 95 % confidence interval 0.42 - 0.88 ; P = 0.008 ) . No significant effect modification was found by age , diabetes , or coronary heart disease . CONCLUSIONS In an observational cohort of men with low testosterone levels  , testosterone treatment was associated with decreased mortality  compared with no testosterone treatment . These results should be interpreted cautiously because residual confounding may still be a source of bias . Large , r and omized clinical trials are needed to better characterize the health effects of testosterone treatment in older men with low testosterone levels
Conclusions Oral TRT produces significant CV risk .
Differences in the degree to which serum DHT is elevated may underlie the varying CV risk by TRT administration route , as elevated serum dihydrotestosterone has been shown to be associated with CV risk in observational studies
Background Potential cardiovascular ( CV ) risks of testosterone replacement therapy ( TRT ) are currently a topic of intense interest .
However , no studies have addressed CV risk as a function of the route of administration of TRT .