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

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.