Objective: The aim of this study was to evaluate the endometrial, ovarian, and breast safety of bazedoxifene used as a treatment for postmenopausal osteoporosis.
Methods: Healthy women (aged 55-85 y) with osteoporosis were enrolled in a randomized, double-blind, placebo-controlled phase 3 trial. Participants were randomized to treatment with bazedoxifene 20 or 40 mg, raloxifene 60 mg, or placebo daily for 3 years. Endometrial and ovarian safety was assessed by periodic transvaginal ultrasonography and endometrial biopsy through 24 months. Gynecologic and breast-related adverse events were recorded throughout the study.
Results: Among 753 participants with available transvaginal ultrasonography data, there were no significant between-group differences in overall endometrial thickness or in the percentage of participants with endometrial thickness greater than 5 mm at 12 or 24 months. Changes in the mean endometrial thickness (±SE) from baseline were −0.07 ± 0.11 mm (bazedoxifene 20 mg), 0.10 ± 0.11 mm (bazedoxifene 40 mg), 0.16 ± 0.12 mm (raloxifene 60 mg), and −0.08 ± 0.11 mm (placebo) at 24 months. There was one report of endometrial hyperplasia in each group, and there were zero, two, two, and three reports of endometrial carcinoma with bazedoxifene 20 and 40 mg, raloxifene 60 mg, and placebo, respectively. There were no clinically important changes from baseline in the number or size of ovarian cysts among groups. There was a significantly lower incidence of fibrocystic breast disease (P ≤ 0.05) with bazedoxifene compared with raloxifene 60 mg.
Conclusion: Bazedoxifene was associated with a favorable endometrial, ovarian, and breast safety profile in postmenopausal women with osteoporosis.
Treatment with bazedoxifene for 3 years was associated with a favorable endometrial, ovarian, and breast safety profile in postmenopausal women with osteoporosis.
From the 1Eastern Virginia Medical School, Norfolk, VA; 2University of Virginia, Charlottesville, VA; 3Rapid Medical Research, Cleveland, OH; 4Pontifícia Universidade Católica de São Paulo, São Paulo, Brazil; 5Panorama MediClinic and University of Stellenbosch, Cape Town, South Africa; 6Manitoba Clinic and University of Manitoba, Winnipeg, Canada; and 7Wyeth Research, Collegeville, PA.
Received December 15, 2008; revised and accepted April 1, 2009.
Funding/support: This study was sponsored by Wyeth Research, Collegeville, PA. This study was a multicenter Wyeth Research-sponsored clinical trial conducted at 206 sites worldwide (Asia-Pacific, United States, Canada, Latin America, and South Africa). Editorial support for the writing of the article was provided by Bo Choi, PhD, and was funded by Wyeth.
Financial disclosure/conflicts of interest: Drs. Archer, Pinkerton, Utian, Menegoci, de Villiers, and Yuen served as principal investigators in the current study. Dr. Archer has received research grants from and is a consultant and speaker for Wyeth. Dr. Pinkerton has received research grants from and is a consultant for Wyeth. Dr. Utian has received research grants from and is an advisor for Wyeth. Dr. Menegoci has received research grants from Wyeth. Dr. de Villiers is a consultant and speaker for Wyeth. Dr. Yuen has received research grants from and is a consultant for Wyeth. Drs. Levine, Chines, and Constantine are employees of Wyeth.
Address correspondence to: David F. Archer, MD, CONRAD Clinical Research Center, Eastern Virginia Medical School, 601 Colley Ave., Norfolk, VA 23507. E-mail: email@example.com