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Journal of Endocrinological Investigation

, Volume 42, Issue 12, pp 1491–1496 | Cite as

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

  • A. SansoneEmail author
  • M. Sansone
  • R. Selleri
  • A. Schiavo
  • D. Gianfrilli
  • C. Pozza
  • M. Zitzmann
  • A. Lenzi
  • F. Romanelli
Original Article

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.

Keywords

Testosterone replacement therapy Monitoring Male hypogonadism Testosterone gel 

Notes

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional ethics committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

All patients provided written informed consent for their participation.

References

  1. 1.
    Bhasin S et al (2018) Testosterone therapy in men with hypogonadism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 103(5):1715–1744CrossRefGoogle Scholar
  2. 2.
    Dohle GR et al (2018) Male hypogonadism. https://uroweb.org/guideline/male-hypogonadism/. Accessed 3 Apr 2019
  3. 3.
    Mulhall JP et al (2018) Evaluation and management of testosterone deficiency: AUA guideline. J Urol 200(2):423–432CrossRefGoogle Scholar
  4. 4.
    Isidori AM et al (2014) Outcomes of androgen replacement therapy in adult male hypogonadism: recommendations from the Italian society of endocrinology. J Endocrinol Invest 38(1):103–112CrossRefGoogle Scholar
  5. 5.
    Chioma L et al (2017) Use of testosterone gel compared to intramuscular formulation for puberty induction in males with constitutional delay of growth and puberty: a preliminary study. J Endocrinol Invest 41(2):259–263CrossRefGoogle Scholar
  6. 6.
    Basaria S et al (2010) Adverse events associated with testosterone administration. N Engl J Med 363(2):109–122CrossRefGoogle Scholar
  7. 7.
    Vigen R et al (2013) Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA 310(17):1829–1836CrossRefGoogle Scholar
  8. 8.
    Xu L et al (2013) Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials. BMC Med 11:108CrossRefGoogle Scholar
  9. 9.
    Finkle WD et al (2014) Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One 9(1):e85805CrossRefGoogle Scholar
  10. 10.
    Sansone A et al (2017) Testosterone replacement therapy: the Emperor’s new clothes. Rejuvenation Res 20(1):9–14CrossRefGoogle Scholar
  11. 11.
    Corona G et al (2018) Endogenous testosterone levels and cardiovascular risk: meta-analysis of observational studies. J Sex Med 15(9):1260–1271CrossRefGoogle Scholar
  12. 12.
    Corona G et al (2018) Testosterone and cardiovascular risk: meta-analysis of interventional studies. J Sex Med 15(6):820–838CrossRefGoogle Scholar
  13. 13.
    Corona G et al (2014) Cardiovascular risk associated with testosterone-boosting medications: a systematic review and meta-analysis. Expert Opin Drug Saf 13(10):1327–1351CrossRefGoogle Scholar
  14. 14.
    Sansone A et al (2019) Effect of treatment with testosterone on endothelial function in hypogonadal men: a systematic review and meta-analysis. Int J Impot Res.  https://doi.org/10.1038/s41443-019-0163-6 CrossRefPubMedGoogle Scholar
  15. 15.
    Tsametis CP, Isidori AM (2018) Testosterone replacement therapy: for whom, when and how? Metabolism 86:69–78CrossRefGoogle Scholar
  16. 16.
    Corona G et al (2016) Testosterone supplementation and body composition: results from a meta-analysis of observational studies. J Endocrinol Invest 39(9):967–981CrossRefGoogle Scholar
  17. 17.
    Snyder PJ et al (2018) Lessons from the testosterone trials. Endocr Rev 39(3):369–386CrossRefGoogle Scholar
  18. 18.
    Belkoff L et al (2018) Efficacy and safety of testosterone replacement gel for treating hypogonadism in men: phase III open-label studies. Andrologia 50(1):e12801CrossRefGoogle Scholar
  19. 19.
    Isidori AM, Lenzi A (2005) Risk factors for androgen decline in older males: lifestyle, chronic diseases and drugs. J Endocrinol Invest 28(3 Suppl):14–22PubMedGoogle Scholar
  20. 20.
    Sgrò P, Di Luigi L (2017) Sport and male sexuality. J Endocrinol Invest 40(9):911–923CrossRefGoogle Scholar
  21. 21.
    Sansone A et al (2018) Sport, doping and male fertility. Reprod Biol Endocrinol 16(1):114CrossRefGoogle Scholar
  22. 22.
    Vermeulen A, Verdonck L, Kaufman JM (1999) A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 84(10):3666–3672CrossRefGoogle Scholar
  23. 23.
    de Ronde W et al (2006) Calculation of bioavailable and free testosterone in men: a comparison of 5 published algorithms. Clin Chem 52(9):1777–1784CrossRefGoogle Scholar
  24. 24.
    Wickham H et al (2019) dplyr: A Grammar of Data Manipulation. R package version 0.8.0.1. https://CRAN.R-project.org/package=dplyr
  25. 25.
    Pinheiro J et al (2018) nlme: linear and nonlinear mixed effects models. R package version 3.1-137. https://CRAN.R-project.org/package=nlme
  26. 26.
    Wickham H (2016) ggplot2: elegant graphics for data analysis. Springer-Verlag, New YorkCrossRefGoogle Scholar
  27. 27.
    Montagna G et al (2018) Establishing normal values of total testosterone in adult healthy men by the use of four immunometric methods and liquid chromatography-mass spectrometry. Clin Chem Lab Med (CCLM) 56(11):1936–1944CrossRefGoogle Scholar
  28. 28.
    Dobs A et al (2014) Testosterone 2% gel can normalize testosterone concentrations in men with low testosterone regardless of body mass index. J Sex Med 11(3):857–864CrossRefGoogle Scholar
  29. 29.
    Jannini EA et al (1999) Lack of sexual activity from erectile dysfunction is associated with a reversible reduction in serum testosterone. Int J Androl 22(6):385–392CrossRefGoogle Scholar
  30. 30.
    Jannini EA et al (2009) Controversies in sexual medicine: is sex just fun? how sexual activity improves health. J Sex Med 6(10):2640–2648CrossRefGoogle Scholar
  31. 31.
    Park HJ, Ahn ST, Moon DG (2019) Evolution of guidelines for testosterone replacement therapy. J Clin Med.  https://doi.org/10.3390/jcm8030410 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Rastrelli G et al (2019) Testosterone replacement therapy for sexual symptoms. Sex Med Rev S2050-0521(18):30131–30138.  https://doi.org/10.1016/j.sxmr.2018.11.005 CrossRefGoogle Scholar
  33. 33.
    Sansone A et al (2014) Endocrine evaluation of erectile dysfunction. Endocrine 46(3):423–430CrossRefGoogle Scholar
  34. 34.
    Lunenfeld B et al (2015) Recommendations on the diagnosis, treatment and monitoring of hypogonadism in men. Aging Male 18(1):5–15CrossRefGoogle Scholar
  35. 35.
    Saad F et al (2011) Onset of effects of testosterone treatment and time span until maximum effects are achieved. Eur J Endocrinol 165(5):675–685CrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2019

Authors and Affiliations

  • A. Sansone
    • 1
    • 2
    Email author
  • M. Sansone
    • 1
  • R. Selleri
    • 1
  • A. Schiavo
    • 1
  • D. Gianfrilli
    • 1
  • C. Pozza
    • 1
  • M. Zitzmann
    • 2
  • A. Lenzi
    • 1
  • F. Romanelli
    • 1
  1. 1.Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and EndocrinologySapienza University of RomeRomeItaly
  2. 2.Department of Clinical and Surgical AndrologyCenter of Reproductive Medicine and Andrology, University of MünsterMünsterGermany

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