Systematic review evaluates saliva, DBS, and urine testosterone testing versus serum monitoring during transdermal TRT.

BackgroundBlood (serum) testing is the standard method for monitoring testosterone (T) replacement therapy (TRT). Nevertheless, alternative methods, such as saliva testing, are gaining popularity because of their practical advantages.ObjectiveThis review aims to offer evidence-based, clinically relevant information to enable healthcare providers to make rational decisions regarding management of TRT. Providers need to know which combinations of ROA (route of administration) and testing method best track and reflect dosing and clinical outcomes. To that end, we summarize the large body of evidence for serum T testing during transdermal (TD) TRT monitoring, as well as the smaller body of evidence for saliva T testing in the context of TRT. Also discussed is T testing via capillary dried bloodspot (DBS) and urine. We chose to focus on TD formulations (gels, creams) because they are well-studied and commonly prescribed.MethodsWe conducted a literature search using online databases (PubMed/MEDLINE, ScienceDirect, and Google Scholar) and also reviewed real-world evidence available from large commercial laboratory databases. The clinical interpretation of these findings are discussed with regard to which tests best reflect clinical reality.ResultsStudies consistently show that serum T values increase proportionally with TD TRT dosing and strongly correlate with clinical responses. Use of serum testing for TD TRT monitoring is supported by published clinical guidelines. Endogenous saliva T levels at baseline are usually consistent with corresponding serum measures of T (when using accurate saliva steroid assays). However, this consistency is no longer observed when exogenous TD T is used. Evidence showed that saliva T values are routinely supraphysiological with standard TD TRT doses. These elevations in saliva are not known to be consistent with any clinical parameters. Like saliva, DBS T also often shows supraphysiologic responses to TD TRT, without clinical significance. Urine T levels tend to parallel serum T responses to TD TRT but may not be as reliable as serum, especially in people with UGT2B17 deletion.ConclusionsBased on the evidence, we conclude that: (1) serum T testing remains the most accurate, validated method for monitoring TD TRT; and (2) saliva and DBS T testing lack sufficient clinical correlation and should not be used for TD TRT monitoring. In particular, saliva T testing with TD TRT can yield misleading, erroneously high results, which can open the door to underdosing, loss of therapeutic benefit, and safety concerns.