The early transdermal patches of testosterone became available in the 1980s, with gel and solution preparations following in subsequent decades.[1] Skin was attractive for one reason: it bypasses the liver, and oral testosterone is inactivated there.[2]
The obstacle was permeability. Skin is a barrier by design, and testosterone is not especially good at crossing it. The first commercial answer was to choose the thinnest available site.
Why the site was the whole design
Transdermal delivery is a permeation problem before it is anything else. The amount of drug that gets through depends on the concentration gradient, the surface area, and — critically — the resistance of the skin at that particular location.
Scrotal skin is thinner and more permeable than skin elsewhere on the body. That made it the one site where a passive patch could deliver enough testosterone to matter with the formulation science of the period.
It also meant the product came with instructions patients found difficult, including preparing the site so the patch would adhere. A therapy that is pharmacologically sound and practically unacceptable is not a solved problem — which is why non-scrotal patches followed, and why gels displaced both.
What the skin route actually solved
The liver problem, cleanly. Oral testosterone is inactivated by first-pass metabolism, and the 17-alpha-alkylated oral androgens developed to survive it cause hepatotoxicity.[3] Injection avoided the liver but produced large fluctuations in serum testosterone across the dosing interval.[3]
Skin offered a third route: hepatic bypass and daily administration. That combination is why transdermal delivery persisted through three generations of product — patch, gel, spray — despite each generation having its own drawback.
What it did not solve
Two things, and both still apply to every topical testosterone.
Delivery is site-dependent and person-dependent. Skin permeation varies, which makes dose reproducibility a formulation-engineering problem rather than a given.
A treated skin surface can transfer drug. This is the defining constraint of the whole category, and it arrived properly with gels — see when gels transfer and gel transfer risk.
Frequently asked questions
Are scrotal patches still used? Gels dominate the transdermal market.[1] The patch era is largely historical.
Why the scrotum specifically? Permeability. It was the site where a passive patch could deliver a therapeutic amount with the formulations available at the time.
Is transdermal delivery better than injection? The guideline does not rank routes. It asks clinicians to weigh pharmacokinetics, patient preference, formulation-specific adverse effects, treatment burden and cost together.[4]
Next in this series
Moving the patch off the scrotum solved the acceptability problem and created a skin problem.
Continue with the non-scrotal patch.
References
4 sources
- Hadgraft J, Lane ME. Transdermal delivery of testosterone. Eur J Pharm Biopharm. 2015;92:42–48. doi:10.1016/j.ejpb.2015.02.015 · PMID 25709060
- Nieschlag E, Nieschlag S. ENDOCRINE HISTORY: The history of discovery, synthesis and development of testosterone for clinical use. Eur J Endocrinol. 2019;180(6):R201–R212. doi:10.1530/EJE-19-0071 · PMID 30959485
- Jockenhövel F. Testosterone supplementation: what and how to give. Aging Male. 2003;6(3):200–206. PMID 14628500
- Bhasin S, Brito JP, Cunningham GR, et al. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018;103(5):1715–1744. doi:10.1210/jc.2018-00229 · PMID 29562364
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