Pharmacokinetics of three doses of sublingual testosterone in healthy premenopausal women.

CONTEXT: Sublingual testosterone is a single-dose treatment often used in studies regarding social, cognitive and sexual behavior. It is hypothesized that an increase in the ratio of free to total testosterone (free fraction) is indirectly, via genomic effects, responsible for the behavioral effects after sublingual testosterone administration.

OBJECTIVE

To characterize the pharmacokinetics of three doses sublingual testosterone in premenopausal women. Also, to investigate the SHBG saturation threshold influencing the free level and free fraction of testosterone.

DESIGN

We conducted an investigator-blind, randomized, cross-over placebo controlled study.

SETTING

This study was undertaken at the research and development department of a scientific company for research regarding female sexual dysfunction.

PARTICIPANTS

16 healthy premenopausal women (mean age 27.3±5.3 years).

INTERVENTIONS: Sublingual testosterone solution; 0.25, 0.50 and 0.75 mg.

MAIN OUTCOMES MEASURE: The pharmacokinetics of three single doses sublingual testosterone solution; the influence of SHBG levels on free and total levels of testosterone.

RESULTS

After sublingual testosterone administration, serum free and total testosterone levels peaked at 15 min and reached baseline levels within 150 min. The AUCs and C(max) of free and total testosterone differed significantly between the three doses (p<0.0001) and increased dose-dependently. A dose-dependent increase in free fraction of testosterone was found in women with low SHBG levels, but not in women with high SHBG levels.

CONCLUSIONS

The three doses sublingual testosterone are rapidly absorbed and quickly metabolized in premenopausal women. These data demonstrate the influence of SHBG levels on the treatment induced alterations in plasma free testosterone.