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

Goldstein, Steven R. MD1; Neven, Patrick MD, PhD2; Cummings, Steven MD3; Colgan, Terence MD4; Runowicz, Carolyn D. MD5; Krpan, Dalibor MD, PhD6; Proulx, James MD7; Johnson, Margot MD7; Thompson, David PhD7; Thompson, John PhD7; Sriram, Usha MD8

doi: 10.1097/gme.0b013e3181e84bb4
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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.

In a randomized trial, postmenopausal women with osteoporosis received 5 years of treatment with lasofoxifene or placebo. Treatment with lasofoxifene resulted in benign endometrial changes that did not seem to increase the risk for endometrial cancer or hyperplasia in postmenopausal women.

From the 1New York University School of Medicine, New York, NY; 2University of Leuven, Leuven, Belgium; 3San Francisco Coordinating Center, California Pacific Medical Center Research Institute and the University of California, San Francisco, CA; 4Mount Sinai Hospital, Toronto, ON, Canada; 5University of Connecticut Health Center, Farmington, CT; 6Policlinic K-center, Zagreb, Croatia; 7Pfizer Global Research and Development, New London, CT; and 8Associates in Clinical Endocrinology, Education and Research, Chennai, India.

Received March 17, 2010; revised and accepted May 11, 2010.

Funding/support: This study was sponsored by Pfizer Inc. Editorial support was provided by Annie Neild, PhD, of PAREXEL and was funded by Pfizer Inc. Pfizer provided support to Drs. Goldstein, Neven, Cummings, Colgan, Runowicz, Krpan, and Sriram as paid consultants for the Postmenopausal Evaluation and Risk-Reduction With Lasofoxifene (PEARL) study.

Financial disclosure/conflicts of interest: Drs. Goldstein, Neven, Cummings, Colgan, Runowicz, Krpan, and Sriram served as paid consultants for the PEARL trial. Dr. Goldstein has served on advisory boards for Amgen, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Merck; has served as a consultant for Cook ObGyn and Philips Ultrasound; is a member of speaker bureaus for Eli Lilly and Warner Chilcott; and serves as a director for Sonosite, Inc. Dr. Cummings reports receiving consulting fees from Amgen, Eli Lilly, and GlaxoSmithKline; lecture fees from Eli Lilly and Novartis; and grant support from Amgen, Pfizer, and Eli Lilly, serving as a paid member of the PEARL Scientific Advisory Committee for Pfizer. Drs. Proulx, Johnson, D. Thompson, and J.Thompson are employees of Pfizer Inc. and hold stock options in Pfizer Inc.; Dr. D. Thompson also holds patents related to lasofoxifene.

Address correspondence to: Steven R. Goldstein, MD, New York University School of Medicine, 530 First Avenue, Suite 10N, New York, NY 10016. E-mail: steven.goldstein@nyumc.org

©2011The North American Menopause Society