Long-term pharmacokinetics of transdermal testosterone gel in hypogonadal men.
Level 2 - randomized trial
Multicenter randomized controlled trial
PubMed 11134099 · doi:10.1210/jcem.85.12.7045
What was done
In a multicenter randomized trial, 227 hypogonadal men received daily transdermal applications of either 1% testosterone (T) gel at 50 mg/day (delivering 5 mg/day), 100 mg/day (delivering 10 mg/day), or a permeation-enhanced T patch (two patches delivering 5 mg/day). Gel was applied to the upper arms, shoulders, and abdomen. At day 90, doses were titrated up (50 to 75 mg) or down (100 to 75 mg) if preapplication serum T fell outside normal adult male ranges. Serum total T, free T, dihydrotestosterone (DHT), estradiol, LH, FSH, and SHBG pharmacokinetics were assessed over 24-hour periods on days 1, 30, 90, and 180.
What was found
Bioavailability of the applied gel was approximately 9% to 14%. Serum T rose into the normal male reference range on day 1, and steady-state total and free T levels remained stable across days 30, 90, and 180. After 180 days, average 24-hour serum T concentrations (C_avg) were highest in the 100 mg gel group (1.4-fold and 1.9-fold higher than the 50 mg gel and patch groups, respectively). Downward titration from 100 to 75 mg/day normalized T levels in most patients, while upward titration from 50 to 75 mg/day did not significantly increase C_avg. Serum DHT C_avg rose 1.3-fold above baseline with the patch, but rose 3.6-fold and 4.6-fold with the 50 mg and 100 mg gel doses, significantly increasing the DHT/T ratio. Estradiol rose and LH/FSH were suppressed in all groups; SHBG showed small significant decreases only in the 100 mg gel group.
Why it matters
This study established that transdermal 1% testosterone gel reliably and rapidly normalizes serum total and free testosterone over a 6-month period with stable pharmacokinetics and flexible dosing options.
Limits
The abstract does not provide exact baseline or follow-up hormone values, standard deviations, or confidence intervals. Clinical efficacy endpoints (such as changes in body composition, bone mineral density, or sexual function) and specific quantitative rates of adverse events or discontinuation are not reported in the abstract.
Cited by
- context Infrequent testosterone injections drive down sex hormone-binding globulin (SHBG) levels proportionally, leading to disproportionately high free testosterone.