| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Project Aging Women and the Institute for Cardiovascular Research, Vrije Universiteit, Departments of Obstetrics and Gynecology (M.S.P., M.O.V., M.J.v.d.M., P.K.), Internal Medicine (C.D.A.S.), and Clinical Chemistry (T.T.), VU University Medical Center, 1007 MB Amsterdam, The Netherlands
Address all correspondence and requests for reprints to: T. Teerlink, Ph.D., Department of Clinical Chemistry, VU University Medical Center, De Boelelaan 1117, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. E-mail: t.teerlink{at}vumc.nl.
In a prospective, randomized, placebo-controlled 12-wk study, we investigated the effect of oral hormone replacement therapy on asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), and an independent risk factor for coronary heart disease. The effects on arginine and symmetric dimethylarginine were also investigated. Sixty healthy early postmenopausal women received daily placebo (n = 16) or oral 17ß-estradiol 2 mg, either unopposed (E2; n = 16) or sequentially combined with dydrogesterone 10 mg (E2+D; n = 14) or trimegestone 0.5 mg (E2+T; n = 14). ADMA levels reduced in all active treatment groups. Compared with baseline and placebo, the largest reduction in ADMA levels was observed in the E2+T group [-18.7% (95% confidence interval [CI], -25.4 to -11.9%) and -21.1% (95% CI, -26.2 to -16.1%), at 4 and 12 wk, respectively]. At 4 and 12 wk in the E2+T group, arginine levels were significantly reduced as well [-30.9% (95% CI, -41.1 to -20.7%) and -36.3% (95% CI, -43.1 to -29.5%), respectively], whereas symmetric dimethylarginine levels were significantly lower in the E2+D group after 12 wk [-11.6% (95% CI, -19.9 to -3.3%)]. In conclusion, unopposed oral estradiol and estradiol combined with dydrogesterone or trimegestone reduced plasma levels of the NOS inhibitor ADMA. Whether the reduction of the NOS substrate arginine in the E2+T group counteracts the potentially beneficial effect of ADMA reduction or reflects increased NO production remains to be investigated.
This work was supported by a research grant from Hoechst Marion Roussel/Wyeth Ayerst International and Grant 97-31 from the Biocare Foundation.
Abbreviations: ADMA, Asymmetric dimethylarginine; ANCOVA, analyses of covariances; BMI, body mass index; CI, confidence interval; D, dydrogesterone 10 mg; DDAH, dimethylarginine dimethylaminohydrolase; E2, oral micronized 17ß-estradiol 2 mg; HERS, Heart and Estrogen/Progestin Replacement Study; LDL, low-density lipoprotein; NO, nitric oxide; NOS, nitric oxide synthase; SDMA, symmetric dimethylarginine; T, trimegestone 0.5 mg; WHI, Women’s Health Initiative.
This article has been cited by other articles:
 |
|
 |
|
  M. Zeller, C. Korandji, J.-C. Guilland, P. Sicard, C. Vergely, L. Lorgis, J.-C. Beer, L. Duvillard, A.-C. Lagrost, D. Moreau, et al. Impact of Asymmetric Dimethylarginine on Mortality After Acute Myocardial Infarction Arterioscler. Thromb. Vasc. Biol., May 1, 2008; 28(5): 954 - 960. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Monsalve, P. J. Oviedo, M. A. Garcia-Perez, J. J. Tarin, A. Cano, and C. Hermenegildo Estradiol counteracts oxidized LDL-induced asymmetric dimethylarginine production by cultured human endothelial cells Cardiovasc Res, January 1, 2007; 73(1): 66 - 72. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Mittermayer, K. Krzyzanowska, M. Exner, W. Mlekusch, J. Amighi, S. Sabeti, E. Minar, M. Muller, M. Wolzt, and M. Schillinger Asymmetric Dimethylarginine Predicts Major Adverse Cardiovascular Events in Patients With Advanced Peripheral Artery Disease Arterioscler. Thromb. Vasc. Biol., November 1, 2006; 26(11): 2536 - 2540. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Hallund, I. Tetens, S. Bugel, T. Tholstrup, M. Ferrari, T. Teerlink, A. Kjaer, and N. Wiinberg Daily Consumption for Six Weeks of a Lignan Complex Isolated from Flaxseed Does Not Affect Endothelial Function in Healthy Postmenopausal Women J. Nutr., September 1, 2006; 136(9): 2314 - 2318. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Cevik, O. Unay, F. Durmusoglu, T. Yurdun, and A S. Bilsel Plasma markers of NO synthase activity in women after ovarian hyperstimulation: influence of estradiol on ADMA Vascular Medicine, February 1, 2006; 11(1): 7 - 12. [Abstract] [PDF]
|
|
|
|
|
|
M. Reimann, J. Dierkes, A. Carlsohn, D. Talbot, M. Ferrari, J. Hallund, W. L. Hall, K. Vafeiadou, U. Huebner, F. Branca, et al. Consumption of Soy Isoflavones Does Not Affect Plasma Total Homocysteine or Asymmetric Dimethylarginine Concentrations in Healthy Postmenopausal Women J. Nutr., January 1, 2006; 136(1): 100 - 105. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Maas Pharmacotherapies and their influence on asymmetric dimethylargine (ADMA) Vascular Medicine, May 1, 2005; 10(2_suppl): S49 - S57. [Abstract] [PDF]
|
|
|
|
|
|
T. Teerlink ADMA metabolism and clearance Vascular Medicine, May 1, 2005; 10(2_suppl): S73 - S81. [Abstract] [PDF]
|
|
|
|
 |
|
 H. Kirchherr and W. N. Kuhn-Velten HPLC-Tandem Mass Spectrometric Method for Rapid Quantification of Dimethylarginines in Human Plasma Clin. Chem., January 1, 2005; 51(1): 249 - 252. [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Cooke Asymmetrical Dimethylarginine: The Uber Marker? Circulation, April 20, 2004; 109(15): 1813 - 1818. [Full Text] [PDF]
|
|
|
|
|
|
K. Tsuda, I. Nishio, D. P. Holden, J. E. Cartwright, G. St.J. Whitley, and S. S. Nussey Estrogen and Asymmetric Dimethylarginine in Postmenopausal Women * Response Circulation, March 30, 2004; 109(12): e174 - e174. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
