Effects on asymmetric dimethylarginine of HMR 3339, a novel selective estrogen receptor modulator: A 12-week, randomized, placebo-controlled, double-blind, dose-ranging study in healthy postmenopausal women

Menopause

Volumn 14, Issue 2, 2007, Pages 235-242

  Verhoeven, Marieke O ^a   Teerlink, Tom ^a   Kenemans, Peter ^a   Vogelvang, Tatjana E ^a   Van Der Mooren, Marius J ^a  

^a VU UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

ADMA; Arginine; Asymmetric dimethylarginine; HMR 3339; Menopause; Raloxifene

Indexed keywords

4 CHLORO 11BETA [4 [2 (DIETHYLAMINO)ETHOXY]PHENYL]ESTRA 1,3,5(10) TRIENE 3,17BETA DIOL; ARGININE; HMR 3339; N(G),N(G) DIMETHYLARGININE; NITRIC OXIDE SYNTHASE INHIBITOR; PLACEBO; RALOXIFENE; SELECTIVE ESTROGEN RECEPTOR MODULATOR; UNCLASSIFIED DRUG;

ADULT; ARTICLE; CARDIOVASCULAR SYSTEM; CLINICAL TRIAL; COMPARATIVE STUDY; CONCENTRATION (PARAMETERS); CONFIDENCE INTERVAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; FEMALE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; MULTICENTER STUDY; POSTMENOPAUSE; RANDOMIZED CONTROLLED TRIAL;

ADMINISTRATION, ORAL; AGED; ARGININE; DOUBLE-BLIND METHOD; ESTRADIOL; FEMALE; HOT FLASHES; HUMANS; MIDDLE AGED; NETHERLANDS; NITRIC OXIDE SYNTHASE; POSTMENOPAUSE; RALOXIFENE; SELECTIVE ESTROGEN RECEPTOR MODULATORS; TREATMENT OUTCOME;

EID: 34247612500     PISSN: 10723714     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.gme.0000235367.47350.2a     Document Type: Article

References (32)

1. Kannel WB, Wilson PW. Risk factors that attenuate the female coronary disease advantage. Arch Intern Med 1995;155:57-61.
2. Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA 1998;280:605-613.
3. Manson JE, Hsia J, Johnson KC, et al. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 2003;349:523-534.
4. Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA 2004;291:1701-1712.
5. Chlebowski RT, Hendrix SL, Langer RD, et al. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative randomized trial. JAMA 2003;289:3243-3253.
6. Strothmann A, Schneider HPG. Hormone therapy: the European women's perspective. Climacteric 2003;6:337-346.
7. Vogelvang TE, van der Mooren MJ, Mijatovic V, Kenemans P. Emerging selective estrogen receptor modulators: special focus on effects on coronary heart disease in postmenopausal women. Drugs 2006;66:191-221.
8. Barrett-Connor E, Grady D, Sashegyi A, et al. Raloxifene and cardiovascular events in osteoporotic postmenopausal women: fouryear results from the MORE (Multiple Outcomes of Raloxifene Evaluation) randomized trial. JAMA 2002;287:847-857.
9. Ensrud K, Genazzani AR, Geiger MJ, et al. Effect of raloxifene on cardiovascular adverse events in postmenopausal women with osteoporosis. Am J Cardiol 2006;97:520-527.
10. Mosca L, Barrett-Connor E, Wenger NK, et al. Design and methods of the Raloxifene Use for The Heart (RUTH) study. Am J Cardiol 2001;88:392-395.
11. Ettinger B, Black DM, Mitlak BH, et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 1999;282:637-645.
12. HMR 3339 [investigator's brochure], 99/11161/GN, 2nd ed. Romainville, France: Hoechst Marion Roussel R&D; 1999.
13. Ammann P, Bourrin S, Brunner F, et al. A new selective estrogen receptor modulator, HMR-3339, fully corrects bone alterations induced by ovariectomy in adult rats. Bone 2004;35:153-161.
14. Vogelvang TE, Mijatovic V, Kenemans P, Teerlink T, van der Mooren MJ. HMR 3339, a novel selective estrogen receptor modulator, reduces total cholesterol, low-density lipoprotein cholesterol, and homocysteine in healthy postmenopausal women. Fertil Steril 2004;82:1540-1549.
15. Vogelvang TE, Mijatovic V, Kenemans P, Schalkwijk CG, van der Mooren MJ. Effect of HMR 3339, a novel selective estrogen receptor modulator, on C-reactive protein levels in healthy postmenopausal women. Am J Cardiol 2004;94:1205-1208.
16. Vogelvang TE, Leurs JR, Mijatovic V, Willemse J, van der Mooren MJ. HMR 3339, a novel selective estrogen receptor modulator, reduces concentrations of procarboxypeptidase U, an inhibitor of fibrinolysis. A randomized, placebo-controlled study in postmenopausal women. J Thromb Haemost 2005;3:1090-1092.
17. Vogelvang TE, Mijatovic V, Kenemans P, Emeis JJ, Heijst JA, van der Mooren MJ. The effects of 12 weeks of HMR 3339, a novel selective estrogen receptor modulator, on markers of coagulation and fibrinolysis: a randomized, placebo-controlled, double-blind, dose-ranging study in healthy postmenopausal women. Am J Obstet Gynecol 2005;193:1384-1394.
18. Zoccali C, Bode-Böger SM, Mallamaci F, et al. Plasma concentration of asymmetrical dimethylarginine and mortality in patients with end-stage renal disease: a prospective study. Lancet 2001;358:2113-2117.
19. Valkonen VP, Päivä H, Salonen JT, et al. Risk of acute coronary events and serum concentration of asymmetrical dimethylarginine. Lancet 2001;358:2127-2128.
20. Nijveldt RJ, Siroen MPC, van der Hoven B, et al. High plasma arginine concentrations in critically ill patients suffering from hepatic failure. Eur J Clin Nutr 2004;58:587-593.
21. Schnabel R, Blankenberg S, Lubos E, et al. Asymmetric dimethylarginine and the risk of cardiovascular events and death in patients with coronary artery disease: results from the AtheroGene Study. Circ Res 2005;97:e53-e59.
22. Teerlink T, Neele SJM, de Jong S, Netelenbos JC, Stehouwer CDA. Oestrogen replacement therapy lowers plasma levels of asymmetrical dimethylarginine in healthy postmenopausal women. Clin Sci 2003;105:67-71.
23. Post MS, Verhoeven MO, van der Mooren MJ, Kenemans P, Stehouwer CDA, Teerlink T. Effect of hormone replacement therapy on plasma levels of the cardiovascular risk factor asymmetric dimethylarginine: a randomized, placebo-controlled 12-week study in healthy early postmenopausal women. J Clin Endocrinol Metab 2003;88:4221-4226.
24. Verhoeven MO, Hemelaar M, van der Mooren MJ, Kenemans P, Teerlink T. Oral, more than transdermal, oestrogen therapy lowers asymmetric dimethylarginine in healthy postmenopausal women: a randomized, placebo-controlled study. J Intern Med 2006;259:199-208.
25. Closs EI, Basha FZ, Habermeier A, Forstermann U. Interference of L-arginine analogues with L-arginine transport mediated by the y+ carrier hCAT-2B. Nitric Oxide 1997;1:65-73.
26. De Jong S, Teerlink T. Analysis of asymmetric dimethylarginine in plasma by HPLC using a monolithic column. Anal Biochem 2006;353:287-289.
27. Teerlink T. Measurement of asymmetric dimethylarginine in plasma: methodological considerations and clinical relevance. Clin Chem Lab Med 2005;43:1130-1138.
28. Fleck C, Janz A, Schweitzer F, Karge E, Schwertfeger M, Stein G. Serum concentrations of asymmetric (ADMA) and symmetric (SDMA) dimethylarginine in renal failure patients. Kidney Int Suppl 2001;78:S14-S18.
29. Vallance P, Leone A, Calver A, Collier J, Moncada S. Endogenous dimethylarginine as an inhibitor of nitric oxide synthesis. J Cardiovasc Pharmacol 1992;20(Suppl 12):S60-S62.
30. Nijveldt RJ, Teerlink T, van der Hoven B, et al. Asymmetrical dimethylarginine (ADMA) in critically ill patients: high plasma ADMA concentration is an independent risk factor of ICU mortality. Clin Nutr 2003;22:23-30.
31. Nijveldt RJ, van Leeuwen PAM, van Guldener C, Stehouwer CDA, Rauwerda JA, Teerlink T. Net renal extraction of asymmetrical (ADMA) and symmetrical (SDMA) dimethylarginine in fasting humans. Nephrol Dial Transplant 2002;17:1999-2002.
32. Achan V, Broadhead M, Malaki M, et al. Asymmetric dimethylarginine causes hypertension and cardiac dysfunction in humans and is actively metabolized by dimethylarginine dimethylamino-hydrolase. Arterioscler Thromb Vasc Biol 2003;23:1455-1459.