Dr. Ron’s Research Review – May 27, 2020

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This week’s research review focuses on testosterone cream applied to scrotal skin.

Scrotal skin is thin and has high steroid permeability.
A single-center, three-phase cross-over pharmacokinetic study examined three single doses (12.5, 25, 50 mg) of testosterone cream (AndroForte 5, 5% w/v, 50 mg/mL) administered in random sequence on different days with at least 2 days between doses to healthy eugonadal volunteers with endogenous testosterone suppressed by administration of nandrolone decanoate.
The testosterone doses were 50 mg (1 mL cream), 25 mg (0.5 mL cream) and 12.5 mg (0.25 mL cream) each drawn from the same tube for each participant with the volume (dose) of testosterone cream measured using 1 mL insulin syringe.
Serum testosterone, DHT and estradiol concentrations were measured by liquid chromatograpy, mass spectrometry in extracts of serum taken before and for 16 h after administration of each of the three doses of testosterone cream to the scrotal skin.
Dried blood spots were extracted for concurrent measurement of testosterone and nandrolone.
Testosterone administration onto the scrotal skin produced a swift (peak 1.9-2.8 h), dose-dependent (p < 0.0001) increase in serum testosterone with the 25 mg dose maintaining physiological levels for 16 h.
Serum DHT displayed a time- (p < 0.0001), but not dose-dependent, increase in concentration reaching a peak concentration of 1.2 ng/mL (4.1 nm) at 4.9 h which was delayed by 2 h after peak serum testosterone.
There were no significant changes in serum estradiol over time after testosterone administration.
The bioavailability of testosterone via the scrotal skin is striking higher than for abdominal skin (about eightfold increase).
Testosterone administration to scrotal skin is well tolerated and produces dose-dependent peak serum testosterone concentration with a much lower dose relative to the non-scrotal transdermal route. (Iyer et al., 2017)  (Needham, 2018)

Dr. Ron

 


Articles

 

Pharmacokinetics of testosterone cream applied to scrotal skin.
            (Iyer et al., 2017)  Download
Scrotal skin is thin and has high steroid permeability, but the pharmacokinetics of testosterone via the scrotal skin route has not been studied in detail. The aim of this study was to define the pharmacokinetics of testosterone delivered via the scrotal skin route. The study was a single-center, three-phase cross-over pharmacokinetic study of three single doses (12.5, 25, 50 mg) of testosterone cream administered in random sequence on different days with at least 2 days between doses to healthy eugonadal volunteers with endogenous testosterone suppressed by administration of nandrolone decanoate. Serum testosterone, DHT and estradiol concentrations were measured by liquid chromatograpy, mass spectrometry in extracts of serum taken before and for 16 h after administration of each of the three doses of testosterone cream to the scrotal skin. Testosterone administration onto the scrotal skin produced a swift (peak 1.9-2.8 h), dose-dependent (p < 0.0001) increase in serum testosterone with the 25 mg dose maintaining physiological levels for 16 h. Serum DHT displayed a time- (p < 0.0001), but not dose-dependent, increase in concentration reaching a peak concentration of 1.2 ng/mL (4.1 nm) at 4.9 h which was delayed by 2 h after peak serum testosterone. There were no significant changes in serum estradiol over time after testosterone administration. We conclude that testosterone administration to scrotal skin is well tolerated and produces dose-dependent peak serum testosterone concentration with a much lower dose relative to the non-scrotal transdermal route.

Case Study: Absorption of Testosterone Cream via Scrotal Delivery.
            (Needham, 2018)  Download
Transdermal testosterone has been used for years to treat patients with low testosterone symptoms. Clinically, we have monitored patients to evaluate results of testosterone absorption via blood serum concentrations. The data on multiple time points to determine trough and peak concentrations is lacking in the literature. In this case study, we demonstrate the absorption of testosterone cream via scrotal delivery. The data suggests that after application therapeutic levels are reached with concentrations of (1204.7 ng/dL) within two hours. Additionally, consistent concentrations (1320.6 ng/dL) remain beyond six hours. To our knowledge, this is the first study to collect and measure multiple time points for testosterone via transdermal delivery. The research indicates that testosterone via transdermal delivery is an excellent method to achieve therapeutic concentrations of testosterone. Most importantly, the patient's symptoms resolved without side effects.

 


References

Iyer, R, et al. (2017), ‘Pharmacokinetics of testosterone cream applied to scrotal skin.’, Andrology, 5 (4), 725-31. PubMed: 28334510
Needham, S (2018), ‘Case Study: Absorption of Testosterone Cream via Scrotal Delivery.’, Int J Pharm Compd, 22 (6), 466-68. PubMed: 30384346