Background: Transdermal testosterone (T) applied to truncal skin provides effective replacement therapy for male hypogonadism with T forming a depot in the stratum corneum resulting in prolonged T delivery. Scrotal skin is thin with highly vascularity and steroid permeability; however the dose-dependent pharmacokinetics (PK) of scrotal T administration has not been reported. This study aimed to define the PK of T administered via scrotal skin.
Methods: A cross-over PK study investigated three single doses (12.5, 25, 50 mg) of T cream applied to scrotal skin of healthy male volunteers with each T dose applied on different days in random sequence with at least 2 days between doses while endogenous T was suppressed throughout the study by nandrolone administration. Serum T, DHT and estradiol (E2) concentrations were measured by liquid chromatography, mass spectrometry in extracts of serum taken before and for 16 h after administration of each T dose.
Results: Serum T reached a dose-dependent peak at 1.9-2.8 h with a dose of 25 mg maintaining physiological T levels for 16 h. Serum DHT displayed a time, but not dose-dependent, peak of 1.2 ng/mL (4.1 nM) at 4.9 h, ~2 h after peak serum T. There were no signiﬁcant changes in serum E2 over time or according to dose of T.
Conclusion: T administration to scrotal skin is well tolerated and produces dose-dependent peak serum T at 2-3 hours with bioavailability 8 times higher than the non-scrotal route. After T administration serum DHT peaked at 2 hours after T but was not dose dependent.
Study was supported by Lawley Pharmaceuticals