Endometrial safety of ospemifene: results of the phase 2/3 clinical development program

Menopause. 2015 Jan;22(1):36-43. doi: 10.1097/GME.0000000000000275.


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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Atrophy
  • Double-Blind Method
  • Dyspareunia / drug therapy
  • Endometrial Hyperplasia / epidemiology
  • Endometrial Neoplasms / epidemiology
  • Endometrium / drug effects
  • Endometrium / pathology
  • Female
  • Humans
  • Middle Aged
  • Placebos
  • Postmenopause
  • Selective Estrogen Receptor Modulators
  • Tamoxifen / adverse effects
  • Tamoxifen / analogs & derivatives*
  • Tamoxifen / therapeutic use
  • Vagina / drug effects
  • Vagina / pathology
  • Vaginal Diseases / drug therapy*
  • Vulva / drug effects
  • Vulva / pathology


  • Placebos
  • Selective Estrogen Receptor Modulators
  • Tamoxifen
  • Ospemifene