Effects of Normalization of Plasma Testosterone Levels in Hypogonadal Men on Plasma Levels and Urinary Excretion of Asymmetric Dimethylarginine (ADMA)
Abstract
Elevated plasma levels of asymmetric dimethylarginine (ADMA) inhibit nitric oxide formation and exert a proatherogenic action. Low testosterone (T) levels are associated with increased cardiovascular risks. This study analyzed the effects of normalization of plasma T levels on plasma levels and urinary excretion of ADMA in hypgonadal men (n=10) receiving transdermal T administration. Plasma T levels, starting from clearly hypogonadal T plasma concentrations with a mean level of 4.0+/-2.72 nmol/l at baseline, rose to >10 nmol/l after 2 weeks, with plasma T levels within the normal range of men (mean level of 22.5+/-11.3 nmol/l) over the last 16 weeks of the 24 weeks of T administration. Normalization of plasma T led to a small but significant fall of plasma ADMA (519+/-55 vs. 472+/-59 nmol/l, p=0.031). The outcome of this study may be viewed as a favorable effect of normalization of plasma testosterone on plasma ADMA since even small elevations of plasma ADMA significantly increase cardiovascular risk. While this effect of normalization of plasma T may impress as favorable, most available studies on effects of T administration to hypogonadal men have not shown beneficial effects on functions of the vascular wall.
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Asymmetric dimethylarginine declines upon testosterone administration after 10 days or after 4 weeks.
“Asymmetric dimethylarginine is an endogenous NO synthase inhibitor and appears to decline upon testosterone administration after 10 days (66) or after 4 weeks (67).”
From Onset of effects of testosterone treatment and time span until maximum effects are achieved (2011) · cites this paper as [67]
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Onset of effects of testosterone treatment and time span until maximum effects are achieved
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Thomson, R. L., Brinkworth, G. D., Noakes, M., Clifton, P. M., Norman, R. J., & Buckley, J. D. (2012) · Human Reproduction · doi:10.1093/humrep/des138 · Cited by 55 · see citing works
“It has been previously demonstrated that increasing testosterone levels reduce ADMA levels; however, this occurred following testosterone administration in males in a hypogonadal state (Cakir et al., 2005; Leifke et al., 2008).”
BackgroundAuer, M. K., Cecil, A., Roepke, Y., Bultynck, C., Pas, C., Fuss, J., Prehn, C., Wang-Sattler, R., Adamski, J., Stalla, G. K., et al. (2016) · Scientific Reports · doi:10.1038/srep37005 · Cited by 54 · see citing works
Tsikas, D., Hanff, E., Bollenbach, A., Kruger, R., Pham, V. V., Chobanyan-Jürgens, K., Wedekind, D., Arndt, T., Jörns, A., Berbée, J. F. P., et al. (2018) · Amino Acids · doi:10.1007/s00726-018-2573-z · Cited by 27 · see citing works
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Fahed, A. C., Gholmieh, J. M., & Azar, S. T. (2012) · International Journal of Endocrinology · doi:10.1155/2012/793953 · Cited by 28 · see citing works
Novo, S., Iacona, R., Bonomo, V., Evola, V., Corrado, E., Piazza, M. D., Novo, G., & Pavone, C. (2014) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2014.12.007 · Cited by 23 · see citing works
Langen, J., Kayacelebi, A. A., Beckmann, B., Weigt-Usinger, K., Carmann, C., Hörster, I., Lilienthal, E., Richter-Unruh, A., Tsikas, D., & Lücke, T. (2015) · Amino Acids · doi:10.1007/s00726-015-2028-8 · Cited by 19 · see citing works
“Also, normalization of plasma testosterone concentration by transdermal testosterone administration to hypogonadal men decreased the plasma ADMA concentration (Leifke et al. 2008).”
MethodSelf-citationTsikas, D. (2008) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e3283065bb1 · Cited by 18 · see citing works
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Bunck, M. C. M., Giltay, E. J., Diamant, M., Gooren, L. J., & Teerlink, T. (2009) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2009.01.020 · Cited by 14 · see citing works
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“It has also been seen that normalisation of serum testosterone levels has led to reduced serum asymmetric dimethyl-arginine which appears to have an inverse association with nitric oxide formation and endothelial health [28].”
BackgroundThe Brain, the Penis and Steroid Hormones: Clinical Correlates with Endothelial Dysfunction
Traish, A. M., Abu-Zahra, H., & Guay, A. T. (2008) · Current Pharmaceutical Design · doi:10.2174/138161208786898699 · Cited by 12 · see citing works
“[60] made similar observations in which a significant decrease in ADMA was noted in hypogonadal men treated with T gel.”
ResultChobanyan-Jürgens, K., Pham, V. V., Stichtenoth, D. O., et al. (2011) · Nitric Oxide · doi:10.1016/j.niox.2011.08.003 · Cited by 11 · see citing works
Self-citationTsikas, D., & Kinzel, M. (2017) · Hellenic Journal of Cardiology · doi:10.1016/j.hjc.2017.10.004 · Cited by 11 · see citing works
Self-citationWpływ testosteronowej terapii zastępczej na stężenia witaminy D i FGF-23 w hipogonadyzmie wrodzonym
Haymana, C., Sönmez, A., Aydoğdu, A., Tapan, S., Başaran, Y., Meriç, C., Başköy, K., Taşlıpınar, A., Yılmaz, M. İ., & Azal, Ö. (2017) · Endokrynologia Polska · doi:10.5603/ep.a2017.0009 · Cited by 5 · see citing works
“ADMA levels were measured only a few days after a single injection in one study [46], and only 10 middle aged or elderly patients with different aetiologies and several comorbidities were enrolled in the other [47].”
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Biomedical applications of GC-MS and GC-MS/MS in human studies
Tsikas, D. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-30096-7.00011-0
Self-citation
- Authors
- Leifke, E., Kinzel, M., Tsikas, D., Gooren, L., Frölich, J., & Brabant, G.
- Affiliations
- Medizinische Hochschule Hannover (DE)
- Venue
- Hormone and Metabolic Research
- Publisher
- Georg Thieme Verlag KG
- Published
- 2008-01
- Volume
- 40
- Issue
- 1
- Pages
- 56-59
- ISSN
- 0018-5043 (ISSN-L)
- 1439-4286
- OpenAlex
- W2093436854
- Cited by
- 18
- References
- 0
- Citations by year
- 2025: 2 · 2024: 1 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 2 · 2014: 1 · 2012: 2
- FWCI
- 1.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hormone and Metabolic Research (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Psychiatry and Mental health › Sexual function and dysfunction studies
- Keywords
- asymmetric dimethylarginine, testosterone, hypogonadism, transdermal testosterone, nitric oxide, cardiovascular risk, atherosclerosis, vascular function
- MeSH terms
- Adult, Aged, Arginine, Humans, Hypogonadism, Male, Middle Aged, Nitrates, Nitrites, Testosterone, Body Mass Index
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