Horm Metab Res 2008; 40(1): 56-59
DOI: 10.1055/s-2007-1004529
Humans, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Effects of Normalization of Plasma Testosterone Levels in Hypogonadal Men on Plasma Levels and Urinary Excretion of Asymmetric Dimethylarginine (ADMA)

E. Leifke 1 , M. Kinzel 2 , D. Tsikas 2 , L. Gooren 3 , J. C. Frölich 2 , G. Brabant 4
  • 1Department of Gastroenterology, Hepatology & Endocrinology, Hannover Medical School, Hannover, Germany
  • 2Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany
  • 3VUmc, Amsterdam, The Netherlands
  • 4University Hospital Manchester, Manchester, UK
Further Information

Publication History

received 07.02.2007

accepted 15.06.2007

Publication Date:
07 January 2008 (eFirst)


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.



E. Leifke, MD 

Medical Director

Clinical Research Diabetes Group

Takeda Global Research & Development

One Takeda Parkway

IL 60015 Deerfield

Phone: +1/224/554 54 20

Fax: +1/224/554 78 56

Email: eleifke@tgrd.com