Monitoring testosterone replacement therapy with transdermal gel: when and how?

[madman]

Abstract

Purpose
Testosterone replacement therapy (TRT) is recommended for the treatment of most cases of male hypogonadism. Transdermal testosterone (T) gels are commonly used in clinical practice; however, there is little evidence concerning how to monitor dosage to bring and maintain serum T levels in the normal physiologic range.

Methods
We examined 30 hypogonadal patients undergoing treatment with 40 mg/day transdermal 2% testosterone gel. After a week from treatment onset, all patients underwent a total of four measurements to assess serum total T, bioavailable T and free T at +2 h (samples A and A′) and +23 h (samples B and B′).

Results
No significant difference was found concerning total, free and bioavailable T between the two samples taken at the same time points (A vs A′ and B vs B′). A repeated-measures mixed effects regression model showed significantly lower serum levels of total, free and bioavailable T at +23 h compared to +2 h (total T, β=−3.050±0.704, p<0.001; free T, β=−85.187±22.746, p<0.001; bioavailable T, β=−1.519±0.497, p=0.003) without a significant between-sample variability. Serum T>3.5 ng/ml at +2 h was reached in 21/30 patients (70%), but only 11 (36.7%) still had adequate serum T at +23 h.

Conclusion
Assessment of TRT with transdermal gels at its peak and at its minimum could be useful in providing a finely tailored treatment for hypogonadal men, both preventing supra-physiological levels and maintaining adequate concentrations through the day.














Conclusions
The treatment of male hypogonadism is associated with improvements in several health outcomes, ranging from sexual symptoms to metabolic profile. Most patients undergo TRT; transdermal testosterone gels are often preferred by patients due to their ease of use and allow for quick treatment discontinuation if needed. Monitoring of hypogonadism is necessary, as TRT should increase serum testosterone without reaching supra-physiological levels; guidelines suggest assessing “peak” concentration, although we hypothesize that assessment of serum T at its lowest point—just before a new gel application—could be useful in assessing the correctness of the treatment dosage. In the authors’ opinion, if only one measurement is feasible, the “lowest-point” measurement could be helpful in patients with no improvement despite treatment, whereas the “peak” measurement providing useful safety information remains a priority in all other patients. While two measurements are necessary for diagnosis, the little intra-individual variation could spare the necessity of a second measurement for subjects undergoing treatment with testosterone transdermal gels.

 

[madman]

Table 2 Repeated-measures mixed effects regression models for multivariate assessment of serum androgens in 30 male subjects undergoing testosterone replacement therapy with 40 mg/day transdermal 2% testosterone gel

 

[madman]

Table 1 Intra-individual fluctuations in serum T in 30 male subjects undergoing testosterone replacement therapy with 40 mg/day transdermal 2% testosterone gel. Analysis performed using paired Wilcoxon signed-rank test with continuity correction

 

[madman]

Fig. 2 Decreasing concentrations of average serum testosterone between + 2 and + 23 h

 

[madman]

Strengths and limitations
Our study is, to our knowledge, the first one depicting in a real-life setting the daily changes in serum androgens following administration of a fixed dose of transdermal gel for TRT. Additionally, a post hoc power analysis has reported a statistical power of 0.942, which proves the relevance of our findings concerning the difference between the two time points. However, several confounding factors, such as BMI, skin hydration, sexual activity and aromatase activity were not considered in the analysis. While the “real-life” setting improves the reliability of our results, studies with larger population samples are required to adequately correct for these confounding variables.