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 .
Pharmacokinetics and safety of long-acting testosterone undecanoate injections in hypogonadal men: an 84-week phase III clinical trial.
Currently available testosterone ( T ) injections in the United States are administered at 2 - 3 weekly intervals . Less frequent injections with favorable serum T pharmacokinetics would benefit hypogonadal men . The objective of this study is to assess the pharmacokinetics of long-acting testosterone undecanoate ( TU ) intramuscular ( IM ) injection in hypogonadal men . An unblinded , multicenter phase 3 clinical trial was conducted in 31 academic centers and contract research organizations . Males ( 130 ) more than 18 years of age with serum total T < 300 ng/dL were enrolled and received 750-mg injections of TU at weeks 0 and 4 and every 10 weeks thereafter for 9 injections over 84 weeks . The main outcome variables were serum total T , free T , dihydrotestosterone ( DHT ) , estradiol ( E(2 ) ) levels , and safety parameters . After the first injection , patients maintained average trough T concentrations in the adult male range ( 300 - 1000 ng/dL or 10.4 - 34.7 nmol/L ) before each injection and at multiple time points measured after the third and fourth injections . Serum free T , DHT , and E(2 ) levels and their ratios to serum T remained relatively consistent once steady state was attained . TU injections were generally well tolerated , with safety profiles similar to other T replacement . We conclude that hypogonadal patients treated for 84 weeks with a 750-mg IM injection of TU every 10 weeks demonstrated average concentrations of T , its metabolites ( DHT and E(2 ) ) , and ratios -- DHT : T and E(2):T -- within the adult male reference range at all time points measured . TU injections would be an acceptable alternative to the currently available 2 - 3 weekly injectables
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 .