Vaginal Application of Testosterone: A Study on Pharmacokinetics and the Sexual Response in Healthy Volunteers

INTRODUCTION: Androgen substitution is advocated to improve sexual functioning in women with androgen insufficiency. Nevertheless, the role of androgens in female sexual functioning is not yet unraveled. Even less is known about changes in androgens and the female sexual response. AIM: The aim of the study is to describe the pharmacokinetics of a single dose of vaginally applied testosterone. In addition, the study aims to gain more insight into the relation between acute changes in testosterone levels and the sexual response in women. METHODS: A randomized, double-blind, crossover study design was used to compare a single vaginal dose of testosterone propionate (2 mg) with placebo. Ten healthy premenopausal women participated. Serum levels of testosterone, free testosterone, and estradiol were measured. The sexual response was measured before application of medication and 4 and 8 hours after application. Erotic video fragments and erotic fantasies were used as stimuli. The genital sexual response was measured using vaginal plethysmography. The subjective sexual response was measured using a visual analog scale. RESULTS: Vaginal administration of testosterone propionate induced a significant rise in serum testosterone levels and free testosterone levels, but not in serum estradiol levels. Peak levels were reached after 5.5 hours (range 2-12 hours). Mean peak levels of testosterone were 7.71 nmol/L after testosterone propionate and 2.99 nmol/L after placebo (P < 0.005). Mean peak levels of free testosterone were 0.12 nmol/L after testosterone propionate and 0.04 nmol/L after placebo (P < 0.005). Despite marked elevated levels of androgens this study was unable to detect a direct effect on the genital or subjective sexual response. CONCLUSIONS: A single dose of vaginally applied testosterone propionate elevates serum levels of testosterone and free testosterone within 6 hours. Nevertheless, this acute rise in androgens has no effects on the female sexual response.