Reduction in 24-Hour Plasma Testosterone Levels in Subjects Who Showered 15 or 30 Minutes After Application of Testosterone Gel WillemdeRondeM.D.,Ph.D.,SyardaVogel,M.Sc.,HongN.Bui,M.Sc.,andAnnemiekeC.Heijboer,Ph.D. Study Objective. Toinvestigatewhethershowering,topreventtheinvoluntary transfer of testosterone to others through skin contact, either 15 or 30 minutes after application of testosterone gel would significantly affect plasma testosterone levels. Design. Prospective 3-way crossover trial. Setting. University hospital in the Netherlands. Subjects. Ten agonadal female-to-male transsexuals who had sex-reassign- mentsurgeryatleast3monthsearlier. Intervention. Subjects were randomized to one of three application regimens for testosterone gel 50 mg/day, each lasting 7 days: testosterone application after showering (standard regimen), shower was taken 30 minutes after testosterone application, or shower was taken 15 minutes after testosterone application. Subjects then crossed over to each of the other two application regimensforatotalof21daysofstudyparticipation. Measurements and Main Results. On day 7 of each application regimen, mean plasma testosterone levels were determined before testosterone application and at 1, 4, 7, and 10 hours after application. With the standard regimen, mean plasma testosterone levels at all time points after application were in the normal range: mean ± SD average concentration 994 ± 1026 ng/dl. When a shower was taken 30 or 15 minutes after application, plasma testosterone levels at 1, 4, 7, and 10 hours were significantly lower: mean ± SD average concentration 401 ± 231 ng/dl for 30 minutes after application (p<0.01) and 320 ± 248 ng/dl for 15 minutes after application (p<0.01). Conclusion. Showering within 30 minutes after application of testosterone gel 50 mg/day reduces absorption of testosterone and results in unaccept- ably low plasma testosterone levels in most users. Therefore, this strategy cannot be recommended to prevent involuntary transfer of testosterone. Key Words: testosterone,gel,showering,androgen,bioavailability. (Pharmacotherapy 2011;31(3):248–252) Androgen replacement using topically applied testosterone gel has been proven to be conven- ient and effective. Once-daily application of the gel to the nonscrotal skin results in relatively stable and physiologic testosterone levels in most users. 1, 2 Testosterone gels typically consist of testosterone, purified water, ethanol, and poly- acrylate as a gel-forming substance. Ethanol acts as a solvent for testosterone and as a vehicle to transport testosterone into the stratum corneum, the outer layer of the skin. All the United States Food and Drug Administration (FDA)-approved gels differ from each other regarding the concentrations of testosterone in the gel and the presence of skin-penetration enhancers or emollients. Although a large surface area of gel