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 .
Invalidation of a commercially available human 5α-dihydrotestosterone immunoassay
Enzyme immunoassays ( EIA ) are commonly utilized for the evaluation of and rogens in biological fluids ; however , careful consideration must be given to cross-reactivity with other endogenous sex-steroid hormones . Our purpose was to determine the validity of a commonly-utilized commercially-available dihydrotestosterone ( DHT ) EIA . Serum sample s obtained from older hypogonadal men who participated in a 12-month r and omized controlled trial evaluating the effects of testosterone-enanthate ( 125 mg/week ) or vehicle in combination with finasteride ( 5mg/day ) or placebo  were assayed for DHT via EIA and using a vali date d gold-st and ard LC-MS/MS approach . Additionally , commercially-available ( DHT-free ) buffer containing grade d testosterone doses was evaluated by DHT immunoassay .  DHT concentrations measured via EIA were 79 % to > 1000 % higher than values obtained by LC-MS/MS ( p<0.05 ) , with the largest differences ( 415 - 1128 % ) occuring in groups receiving finasteride . Both LC-MS/MS and EIA indicated that testosterone-enanthate increased serum DHT to a similar magnitude . In contrast , finasteride-induced reductions in DHT were detected by LC-MS/MS , but not EIA ( p<0.05 ) . No significant associations were present for DHT concentrations between measurement techniques . Cross-reactivity of testosterone with the immunoassay ranged from 18 % to 99 % and DHT concentrations measured by EIA were highly associated with the spiked testosterone concentrations in DHT-free buffer ( r=0.885 , p<0.001 ) . In conclusion , we provide evidence invalidating a commonly-utilized commercially-available DHT immunoassay because significant cross-reactivity exists between testosterone and the EIA and because the changes in DHT observed via EIA were not associated with a vali date d gold-st and ard measurement technique . The cross-reactivity of testosterone is particularly concerning because testsoterone is present in 100-fold greater concentrations than is DHT within the circulation
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 .