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 .
Long-term pharmacokinetics of transdermal testosterone gel in hypogonadal men.
Transdermal delivery of testosterone ( T ) represents an effective alternative to injectable and rogens . Transdermal T patches normalize serum T levels and reverse the symptoms of and rogen deficiency in hypogonadal men . However , the acceptance of the closed system T patches has been limited by skin irritation and /or lack of adherence . T gels have been proposed as delivery modes that minimize these problems . In this study we examined the pharmacokinetic profiles after 1 , 30 , 90 , and 180 days of daily application of 2 doses of T gel ( 50 and 100 mg T in 5 and 10 g gel , delivering 5 and 10 mg T/day , respectively ) and a permeation-enhanced T patch ( 2 patches delivering 5 mg T/day ) in 227 hypogonadal men . This new 1 % hydroalcoholic T gel formulation when applied to the upper arms , shoulders , and abdomen dried within a few minutes , and about 9 - 14 % of the T applied was bioavailable . After 90 days of T gel treatment , the dose was titrated up ( 50 mg to 75 mg ) or down ( 100 mg to 75 mg ) if the preapplication serum T levels were outside the normal adult male range . Serum T rose rapidly into the normal adult male range on day 1 with the first T gel or patch application . Our previous study showed that steady state T levels were achieved 48 - 72 h after first application of the gel . The pharmacokinetic parameters for serum total and free T were very similar on days 30 , 90 , and 180 in all treatment groups . After repeated daily application of the T formulations for 180 days , the average serum T level over the 24-h sampling period ( C(avg ) ) was highest in the 100 mg T gel group ( 1.4- and 1.9-fold higher than the C(avg ) in the 50 mg T gel and T patch groups , respectively ) . Mean serum steady state T levels remained stable over the 180 days of T gel application . Upward dose adjustment from T gel 50 to 75 mg/day did not significantly increase the C(avg ) , whereas downward dose adjustment from 100 to 75 mg/day reduced serum T levels to the normal range for most patients . Serum free T levels paralleled those of serum total T , and the percent free T was not changed with transdermal T preparations . The serum dihydrotestosterone C(avg ) rose 1.3-fold above baseline after T patch application , but was more significantly increased by 3.6- and 4.6-fold with T gel 50 and 100 mg/day , respectively , result ing in a small , but significant , increase in the serum dihydrotestosterone/T ratios in the two T gel groups . Serum estradiol rose , and serum LH and FSH levels were suppressed proportionately with serum T in all study groups ; serum sex hormone-binding globulin showed small decreases that were significant only in the 100 mg T gel group . We conclude that transdermal T gel application can efficiently and rapidly increase serum T and free T levels in hypogonadal men to within the normal range . Transdermal T gel provided flexibility in dosing with little skin irritation and a low discontinuation rate
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 .