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

• Published in: American journal of obstetrics and gynecology 2005-10, Vol.193 (4), p.1384-1394
• Main Authors: Vogelvang, Tatjana E., Mijatovic, Velja, Kenemans, Peter, Emeis, Jef J., Heijst, Johannes A., van der Mooren, Marius J.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Biomarkers - blood; Blood Coagulation - drug effects; Coagulation; Dose-Response Relationship, Drug; Double-Blind Method; Estradiol - analogs & derivatives; Estradiol - pharmacology; Female; Fibrinolysis; Fibrinolysis - drug effects; Gynecology. Andrology. Obstetrics; HMR 3339; Humans; Medical sciences; Menopause; Middle Aged; Postmenopause; Raloxifene; Raloxifene Hydrochloride - pharmacology; Selective Estrogen Receptor Modulators - pharmacology; Time Factors
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2005.02.083

To investigate the short-term effects of HMR 3339, a novel selective estrogen receptor modulator, on markers of coagulation and fibrinolysis. In a multicenter, 14-week, randomized, placebo-controlled, double-blind, dose-ranging study, healthy postmenopausal women received daily placebo (n = 22), HMR 3339 2.5 mg (n = 25), HMR 3339 10 mg (n = 24), HMR 3339 50 mg (n = 24), or raloxifene 60 mg (n = 23). Statistical analysis was performed using standard parametric tests. After 12 weeks, compared with placebo, HMR 3339 50 mg induced the largest mean percentage changes in antithrombin (−14.6%, P < .001), protein C (−12.9%, P = .029), and fibrinogen (−26.3%, P = .001). Decreases were observed in the HMR 3339 2.5 mg group, compared with placebo, in tissue-type plasminogen activator (−55.0%, P = .026 after 4 weeks), plasmin-α 2-antiplasmin complex (−85%, P = .031 and −63.3%, P = .008, respectively, after 4 and 12 weeks), and D-dimer (–91.4%, P = .018 after 12 weeks). Compared with placebo, raloxifene 60 mg decreased total protein S (−8.2%, P = .009) after 4 weeks and antithrombin (−6.0%, P = .034) and fibrinogen (−18.1%, P = .007) after 12 weeks. HMR 3339 and raloxifene decreased fibrinogen levels. In the low dosage, HMR 3339 showed potentially beneficial effects on some markers of fibrinolysis. Both drugs impaired the anticoagulatory potential.