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DOI: 10.1055/a-0650-4115
Transfer of Topical Testosterone to Subcutaneous Microdialysate, Blood and Saliva in Healthy Young Men
Publikationsverlauf
received 29. November 2017
revised 13. Juni 2018
accepted 27. Juni 2018
Publikationsdatum:
08. August 2018 (online)
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Abstract
Objective We evaluated percutaneous penetration of topical testosterone and subsequent transfer to subcutaneous tissue, blood and saliva.
Methods This microdialysis trial involved eight healthy male volunteers. Five participants received a single dose of 50 mg testosterone gel on the abdominal skin and three untreated participants served as controls. Two microdialysis probes were inserted percutaneously into the abdominal subcutaneous adipose tissue. On the skin above one probe, testosterone gel was applied (ipsilateral side). A second control probe was inserted on the contralateral side. For the determination of total and free testosterone, samples of subcutaneous microdialysate, serum, and saliva were collected over six hours, frozen, and analysed using ELISA procedures.
Results Testosterone values in the ipsilateral microdialysate of treated subjects increased significantly within 6 h after gel application compared to controls. Salivary testosterone levels showed a rapid increase within 20 min after transdermal application followed by a plateau phase with tenfold increased testosterone levels. Microdialysate testosterone of the contralateral site started to rise moderately within the normal range 1 h after administration of testosterone gel whereas total and free testosterone serum concentrations increased within 2 h in each case followed by a plateau phase.
Summary and Conclusion Single topical administration of testosterone gel leads to a continuous increase of testosterone in the subcutaneous ipsilateral microdialysate. Rapid salivary testosterone increase happens after gel administration followed by tenfold increased testosterone plateau values. Despite continuous influx, testosterone concentrations in serum, saliva, and contralateral microdialysate show a plateau formation thus avoiding testosterone excess.
Key words
testosterone pharmacokinetics - free and bound testosterone - microdialysis - oral fluid - saliva - male probands* Current address: Clinic for hand-, plastic-, and microsurgery, Karl-Olga-Hospital, Stuttgart, Germany
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References
- 1 Layton JB, Meier CR, Sharpless JL. et al. Comparative safety of testosterone dosage forms. JAMA Intern Med 2015; 175: 1187-1196
- 2 Shoskes JJ, Wilson MK, Spinner ML. Pharmacology of testosterone replacement therapy preparations. Transl Androl Urol 2016; 5: 834-843
- 3 Marbury T, Hamill E, Bachand R. et al. Evaluation of the pharmacokinetic profiles of the new testosterone topical gel formulation, TestimTM, compared to AndroGel. Biopharm Drug Dipos 2003; 24: 115-120
- 4 Swerdloff R, Wang C, Cunningham G. et al. Long-term pharmacokinetics of transdermal testosterone gel in hypogonadal men. J Clin Endocrinol Metab 2000; 85: 4500-4510
- 5 Patel A, Rivkees SA. Prenatal virilization associated with paternal testosterone gel therapy. Int J Pediatr Endocrinol 2010; 2010: 867471 10.1155/2010/86747
- 6 de Wit AE, Bosker FJ, Giltay EJ. et al. Testosterone in human studies: Modest association between plasma and salivary measurements. Andrologia 2017; 00: e12779
- 7 Chu FW, Ekins RP. Detection of corticosteroid binding globulin in parotid fluids: Evidence for the presence of both protein-bound and not-protein-bound (free) steroids in uncontaminated saliva. Acta Endocrinol (Copenh) 1988; 119: 56-60
- 8 Hammond GL, Langley MS. Identification and measurement of sex hormone binding globulin (SHBG) and corticosteroid binding globulin (CBG) in saliva. Acta Endocrinol (Copenh) 1986; 112: 603-608
- 9 Selby C, Lobb PA, Jeffcoate WJ. Sex hormone binding globulin in saliva. Clin Endocrinol 1988; 28: 19-24
- 10 Pfaffe T, Cooper-White J, Beyerlein P. et al. Diagnostic potential of saliva: current state and future applications. Clin Chem 2011; 57: 675-687
- 11 Li Y, Peris J, Zhong L. et al. Microdialysis as a tool in local pharmacodynamics. AAPS J. 2006; 8: E222-E235
- 12 Nandi P, Lunte SM. Recent trends in microdialysis sampling intergrated with conventional and microanalytical systems for monitoring biological events: A review. Anal Chim Acta 2009; 651: 1-14
- 13 Thieme D, Rautenberg C, Grosse J. et al. Significant increase of salivary testosteron levels after single therapeutic transdermal administration of testosterone: Suitability as a potential screening parameter in doping control. Drug Test Anal 2013; 5: 819-825
- 14 Schönfelder M, Hofmann H, Anielski P. et al. Gene expression profiling in human whole blood samples after controlled testosterone application and exercise. Drug Test Anal 2011; 3: 652-660
- 15 Gonzalez-Sanchez V, Moreno-Perez O, Garcia de Guardiana L. et al. Reference ranges for serum and salivary testosterone in young men of Mediterranian region. Endocrinol Nutr 2015; 62: 4-10
- 16 Wood P. Salivary steroid assays – research or routine?. Ann Clin Biochem 2009; 46: 183-196
- 17 Vining RF, McGinley RA, McGinley RA. Hormones in saliva. CRC Crit Rev Clin Lab Sci 1986; 23: 95-146
- 18 Fiers T, Delanghe J, T’Sjoen G. et al. A critical evaluation of salivary testosterone as a method for the assessment of serum testosterone. Steroids 2014; 86: 5-9
- 19 Bloomer RJ. Considerations in the measurement of testosterone in saliva and serum using ELISA procedures. Br J Med Med Res 2015; 5: 116-122
- 20 Ullah MI, Riche DM, Koch CA. Transdermal testosterone replacement therapy in men. Drug Des Devel Ther 2014; 8: 101-112
- 21 Wang C, Berman N, Longstreth JA. et al. Pharmacokinetics of transdermal testosterone gel in hypogonadal men: Application of gel at one site versus four sites: A general clinical research center study. J Clin Endocrinol Metab 2000; 85: 964-969
- 22 Hammond GL. Plasma steroid-binding proteins: Primary gatekeepers of steroid hormone action. J Endocrinol 2016; 230: R13-R25
- 23 Laurent MR, Hammond GL, Blokland M. et al. Sex hormone-binding globulin regulation of androgen bioactivity in vivo: validation of the free hormone hypothesis. Sci Rep 2016; 6: 35539