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 .
The effects of injected testosterone dose and age on the conversion of testosterone to estradiol and dihydrotestosterone in young and older men.
BACKGROUND During testosterone ( T ) therapy , T is partly converted to 17beta-estradiol ( E2 ) and 5alpha-dihydrotestosterone ( DHT ) . Effects of age , testosterone dose , and body composition on total and free E2 and DHT levels are unknown . OBJECTIVE We evaluated age and dose-related differences in E2 and DHT levels in response to grade d doses of testosterone enanthate in young and older men . METHODS Fifty-one young ( aged 19 - 35 yr ) and 52 older ( aged 59 - 75 yr ) men completed treatment with monthly injections of a GnRH agonist plus r and omly assigned weekly doses of testosterone enanthate ( 25 , 50 , 125 , 300 , or 600 mg ) for 5 months . RESULTS During testosterone administration , total and free E2 levels increased dose-dependently ( dose effect , P<0.001 ) in both young and older men . Total and free E2 levels and E2:T ratios during T administration were higher in older than young men , but age-related differences in free E2 and free E2:T ratios were not significant after adjusting for testosterone levels , percentage fat mass , and SHBG . DHT levels and DHT : T ratios were dose-related but did not differ between young and older men . Mechanistic modeling of free hormone data revealed that the conversions of T to E2 and DHT were both consistent with saturable Michaelis-Menten kinetics . The in vivo Km values were estimated to be 1.83 nm for aromatase and 3.35 nm for 5alpha-reductase , independent of age . The Vmax parameter for E2 was 40 % higher in older men than younger men , but Vmax for DHT was not significantly different between age groups . CONCLUSIONS During i m testosterone administration , E2 and DHT levels exhibit saturable increases with dose . The rate of whole body aromatization is higher in older men , partly related to their higher percentage fat mass , SHBG , and 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 .