title: Endometrial safety of ospemifene: results of the phase 2/3 clinical development program.
abstract: OBJECTIVE
  This study aims to assess the endometrial safety of ospemifene based on phase 2/3 clinical trials of postmenopausal women with up to 52 weeks of exposure to ospemifene 60 mg/day versus placebo.
  
  
  METHODS
  Endometrial safety was evaluated in a development program of six randomized, double-blind, placebo-controlled, parallel-group studies of postmenopausal women aged between 40 and 80 years who had vulvar and vaginal atrophy. Participants were randomized 1:1 to ospemifene 60 mg/day or placebo in one 6-week trial and three 12-week trials; one of the 12-week trials had a 40-week extension study. In a separate 52-week trial, women were randomized 6:1 to ospemifene 60 mg/day or placebo. Endometrial safety was assessed by endometrial histology (biopsy), transvaginal ultrasound, and gynecologic examination.
  
  
  RESULTS
  In these trials, 1,242 women who received ospemifene 60 mg/day and 924 women who received placebo were evaluable for safety. Endometrial hyperplasia occurred in less than 1% of women treated with ospemifene; no endometrial cancer was reported. The mean (SD) increase in endometrial thickness among women treated with ospemifene was 0.51 (1.54) mm at 12 weeks, 0.56 (1.61) mm at 6 months, and 0.81 (1.54) mm at 12 months. Women who received placebo had a mean (SD) increase of 0.07 (1.23) mm at 12 months.
  
  
  CONCLUSIONS
  These clinical trial data indicate that up to 52 weeks of treatment with oral ospemifene 60 mg/day was safe for the endometrium. There was no increase in the incidence of endometrial cancer or hyperplasia among postmenopausal women treated with ospemifene compared with placebo.
authors: From the 1EndoRheum Consultants, Malvern, PA; 2New York University School of Medicine, New York, NY; and 3Jones Institute for Reproductive Medicine, Eastern Virginia Medical Center, Norfolk, VA.
authors: Ginger D
authors: GD
authors: Constantine
authors: Steven R
authors: SR
authors: Goldstein
authors: David F
authors: DF
authors: Archer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy; D004311:Double-Blind Method; D004414:Dyspareunia / Q000188:drug therapy; D004714:Endometrial Hyperplasia / Q000453:epidemiology; D016889:Endometrial Neoplasms / Q000453:epidemiology; D004717:Endometrium / Q000187:drug effects / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D010919:Placebos; D017698:Postmenopause; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014621:Vagina / Q000187:drug effects / Q000473:pathology; D014623:Vaginal Diseases / Q000188:drug therapy*; D014844:Vulva / Q000187:drug effects / Q000473:pathology
chemical_list: D010919:Placebos; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; C119141:Ospemifene