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 Oct;193(4):1384-94. doi: 10.1016/j.ajog.2005.02.083.

Abstract

Objective: To investigate the short-term effects of HMR 3339, a novel selective estrogen receptor modulator, on markers of coagulation and fibrinolysis.

Study design: 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.

Results: 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-alpha2-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.

Conclusion: 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood
  • Blood Coagulation / drug effects*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Estradiol / analogs & derivatives*
  • Estradiol / pharmacology
  • Female
  • Fibrinolysis / drug effects*
  • Humans
  • Middle Aged
  • Postmenopause*
  • Raloxifene Hydrochloride / pharmacology*
  • Selective Estrogen Receptor Modulators / pharmacology*
  • Time Factors

Substances

  • Biomarkers
  • HMR 3339
  • Selective Estrogen Receptor Modulators
  • Raloxifene Hydrochloride
  • Estradiol