Pharmacokinetics of testosterone after percutaneous gel or buccal administration

Abstract

Objective: To determine the pharmacokinetics of testosterone following its administration using transdermal gel or buccal lozenges. Design: Pilot study. Setting: University-based hospital. Patient(s): Ten bilaterally oophorectomized women. Intervention(s): Daily micronized testosterone gel (1 mg) and testosterone propionate lozenge (1 mg). Main Outcome Measure(s): Total testosterone, androstenedione, dihydrotestosterone, 3α–androstanediol glucuronide, and sex hormone–binding globulin were measured in serum by specific radioimmunoassays; free testosterone levels were also calculated. Result(s): Before treatment, serum testosterone levels in the groups using the lozenge and gel were 16 ± 4.0 and 20 ± 6.0 ng/dL, respectively. Mean maximum testosterone levels obtained with the lozenge occurred 1 hour after administration on days 1 (692 ± 236 ng/dL) and 14 (836 ± 309 ng/dL) of treatment and fell precipitously thereafter. In contrast, testosterone levels obtained with the gel showed a prolonged rise reaching maximal levels of 97 ± 78 and 100 ± 60 ng/dL after 18 hours. The serum level patterns of free testosterone, dihydrotestosterone, and 3α–androstanediol glucuronide were similar to the corresponding total testosterone levels. Conclusion(s): Administration of testosterone lozenge by buccal absorption produced a rapid and brief elevation of testosterone levels, with levels reaching upper limits of the male range. In contrast, transdermal testosterone gel absorption resulted in a prolonged elevation of testosterone levels, which were in the hyperandrogenic female range but resembled steady state pharmacokinetics.