Bazedoxifene, a selective estrogen receptor modulator: effects on the endometrium, ovaries, and breast from a randomized controlled trial in osteoporotic postmenopausal women.

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
CONCLUSION: Bazedoxifene was associated with a favorable endometrial, ovarian, and breast safety profile in postmenopausal women with osteoporosis.