What Three Published Papers Support — and Four Things They Don't

The published evidence for this delivery platform is three peer-reviewed papers. That is more than most delivery systems disclose and less than a large outcomes trial, and both halves of that sentence matter.

What the papers establish

Pharmacokinetics in healthy males. A 2006 study in the British Journal of Clinical Pharmacology characterised the pharmacokinetics of the transdermal testosterone delivery system.[1]

A bioequivalence comparison, methodologically careful. The 2009 paper in the International Journal of Clinical Pharmacology and Therapeutics examined how correcting for endogenous testosterone concentrations affects a bioequivalence assessment against AndroGel®.[2] The correction is the substance of the paper: measuring an administered testosterone product means measuring the drug plus what the body already makes, and failing to account for that biases any comparison.

The platform outside hormone delivery. A 2006 study in Anaesthesia examined the same delivery system combined with a percutaneous local anaesthetic for venepuncture.[3] Evidence that the delivery approach works for a different molecule is a genuine, if indirect, datapoint about the platform.

What they do not establish

Four gaps, stated plainly.

No large randomised outcome trial. Nothing comparable to TRAVERSE's 5,204 participants and its cardiac endpoint.[4] Pharmacokinetic evidence describes what the drug concentration does; it does not describe how patients fare.

No comparative symptom outcomes. No trial randomising men between this platform and another formulation and measuring how they feel.

No exemption from transfer precautions. It is a topical. The FDA boxed warning on secondary exposure describes a class property of treated skin.[5] See the problem with gels.

No change to the diagnostic threshold. Symptoms plus unequivocally, consistently low concentrations confirmed on a repeat fasting morning measurement.[6] Delivery does not alter who should be treated.

Why the gaps are worth publishing

Because the alternative is what the rest of this series documents.

Rejuvenation surgery ran internationally for seventeen years on a correct premise and an untested intervention.[7] Brown-Séquard's extract was accepted for over a century before someone measured it and found testosterone four orders of magnitude below a biologically active dose.[8] In both cases the missing element was not a mechanism — it was somebody stating what had and had not been tested.

A delivery platform with three published papers and four named gaps is a more honest position than one with a slogan.

Frequently asked questions

Is the spray proven better than injections or gels? Not by outcome trials, and no such claim is made here. The Endocrine Society guideline ranks no formulation, naming five factors to weigh instead.[6]

What is actually published? Pharmacokinetics in healthy males,[1] a bioequivalence comparison correcting for endogenous testosterone,[2] and the platform in an anaesthetic application.[3]

Does it avoid the transfer problem? No. Precautions apply to every topical.[5]

Where is the full evidence write-up? The published clinical evidence, on the Hypospray pillar.

Next in this series

The platform itself — what it is, and what can and cannot be said about who is behind it.

Continue with the platform.

References

8 sources

1. Chik Z, Johnston A, Tucker AT, et al. Pharmacokinetics of a new testosterone transdermal delivery system, TDS®-testosterone in healthy males. Br J Clin Pharmacol. 2006;61(3):275–279. doi:10.1111/j.1365-2125.2005.02542.x · PMID 16487220
2. Chik Z, Johnston A, Tucker AT, et al. Correcting endogenous concentrations of testosterone influences bioequivalence and shows the superiority of TDS®-testosterone versus Androgel®. Int J Clin Pharmacol Ther. 2009;47(4):262–268. PMID 19356392
3. Tucker AT, Chik Z, Michaels L, et al. Study of a combined percutaneous local anaesthetic and the TDS® system for venepuncture. Anaesthesia. 2006;61(2):123–126. doi:10.1111/j.1365-2044.2005.04432.x · PMID 16430563
4. Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular Safety of Testosterone-Replacement Therapy. N Engl J Med. 2023;389(2):107–117. doi:10.1056/NEJMoa2215025 · PMID 37326322
5. U.S. Food and Drug Administration. AndroGel (testosterone gel) 1% — prescribing information, including BOXED WARNING: secondary exposure to testosterone. Reference ID 021015s044. 2019. accessdata.fda.gov
6. 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
7. Schultheiss D, Denil J, Jonas U. Rejuvenation in the early 20th century. Andrologia. 1997;29(6):351–355. doi:10.1111/j.1439-0272.1997.tb00329.x · PMID 9430441
8. Cussons AJ, Bhagat CI, Fletcher SJ, et al. Brown-Séquard revisited: a lesson from history on the placebo effect of androgen treatment. Med J Aust. 2002;177(11-12):678–679. doi:10.5694/j.1326-5377.2002.tb05014.x · PMID 12463999