Pharmacokinetics of three doses of sublingual testosterone in healthy premenopausal women

Psychoneuroendocrinology. 2012 Jun;37(6):773-81. doi: 10.1016/j.psyneuen.2011.09.008. Epub 2011 Oct 5.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Sublingual
  • Adult
  • Area Under Curve
  • Biological Availability
  • Chromatography, High Pressure Liquid
  • Contraceptives, Oral, Hormonal / pharmacology
  • Cross-Over Studies
  • Dihydrotestosterone / blood
  • Dose-Response Relationship, Drug
  • Estradiol / blood
  • Female
  • Humans
  • Mass Spectrometry
  • Premenopause / metabolism*
  • Sex Hormone-Binding Globulin / metabolism
  • Testosterone / administration & dosage*
  • Testosterone / blood
  • Testosterone / pharmacokinetics*
  • Young Adult


  • Contraceptives, Oral, Hormonal
  • Sex Hormone-Binding Globulin
  • Dihydrotestosterone
  • Testosterone
  • Estradiol