Postmenopausal Evaluation and Risk Reduction With Lasofoxifene (PEARL) trial: 5-year gynecological outcomes

Menopause. 2011 Jan;18(1):17-22. doi: 10.1097/gme.0b013e3181e84bb4.

Abstract

Objective: The aim of this study was to establish the gynecological effects of 5 years of treatment with lasofoxifene versus placebo in postmenopausal osteoporotic women.

Methods: A total of 8,556 women aged 59 to 80 years with femoral neck or spine bone mineral density T scores of -2.5 or lower were randomized to receive lasofoxifene 0.25 mg/day, or lasofoxifene 0.5 mg/day, or placebo, for 5 years.

Results: Endometrial cancer was confirmed for two women in each lasofoxifene group and for three women in the placebo group. Endometrial hyperplasia occurred in three, two, and zero women in the lasofoxifene 0.25 mg/day, lasofoxifene 0.5 mg/day, and placebo groups, respectively. Vaginal bleeding occurred in 2.2% (P = 0.012 vs placebo), 2.6% (P = 0.001 vs placebo), and 1.3% of women treated with 0.25 mg/day lasofoxifene, 0.5 mg/day lasofoxifene, and placebo, respectively. Lasofoxifene treatment resulted in a small increase in endometrial thickness versus placebo (least-squares mean change from baseline 1.19 mm [P = 0.001], 1.43 mm [P < 0.001], and -0.72 mm for 0.25 mg/day lasofoxifene, 0.5 mg/day lasofoxifene, and placebo). Similar numbers of women required surgery for pelvic organ prolapse or urinary incontinence in the placebo and 0.5 mg/day lasofoxifene groups (1.2% vs 1.6%, P = 0.224; 0.25 mg/day group: 1.9%, P = 0.036). The absolute incidence rates of endometrial polyps were 8.8%, 5.5%, and 3.3% for lasofoxifene 0.25 mg/day (P = 0.003 vs placebo), lasofoxifene 0.5 mg/day (P = 0.163 vs placebo), and placebo groups, respectively.

Conclusion: These findings indicate that 5 years of lasofoxifene treatment result in benign endometrial changes that do not increase the risk for endometrial cancer or hyperplasia in postmenopausal women.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Double-Blind Method
  • Female
  • Humans
  • Middle Aged
  • Osteoporosis, Postmenopausal / drug therapy
  • Ovarian Cysts / epidemiology
  • Ovarian Neoplasms / epidemiology
  • Polyps / diagnostic imaging
  • Polyps / epidemiology
  • Polyps / pathology
  • Postmenopause / drug effects*
  • Proportional Hazards Models
  • Pyrrolidines / adverse effects*
  • Pyrrolidines / therapeutic use
  • Selective Estrogen Receptor Modulators / adverse effects*
  • Selective Estrogen Receptor Modulators / therapeutic use
  • Tetrahydronaphthalenes / adverse effects*
  • Tetrahydronaphthalenes / therapeutic use
  • Ultrasonography
  • Urinary Incontinence / etiology
  • Uterine Diseases / diagnostic imaging*
  • Uterine Diseases / epidemiology
  • Uterine Diseases / pathology
  • Uterus / diagnostic imaging*
  • Uterus / pathology

Substances

  • Pyrrolidines
  • Selective Estrogen Receptor Modulators
  • Tetrahydronaphthalenes
  • Lasofoxifene