Assessment of the safety of long-term bazedoxifene treatment on the reproductive tract in postmenopausal women with osteoporosis: results of a 7-year, randomized, placebo-controlled, phase 3 study.

OBJECTIVE: To evaluate the clinical safety of bazedoxifene (BZA) on the reproductive tract in postmenopausal women with osteoporosis over 7 years.

STUDY DESIGN: This was a second, blinded, 2-year extension of a 3-year, randomized, double-blind, placebo (PBO)- and active-controlled phase 3 trial. In the core study, subjects were randomized to receive BZA 20 or 40mg, raloxifene 60mg, or PBO. During years 4-5, the raloxifene arm was discontinued and subjects receiving BZA 40mg were transitioned to BZA 20mg. Subjects continued to receive BZA 20mg or PBO during years 6-7.

MAIN OUTCOME MEASURES: The primary endpoint was the incidence of new vertebral fractures at 7 years (reported separately). Reproductive tract safety findings at 7 years are reported here. Endometrial thickness was assessed by transvaginal ultrasonography for subjects in the endometrial safety substudy. Adverse events (AEs) were recorded throughout the study.

RESULTS: At 7 years, the adjusted mean (±standard error) change in endometrial thickness was similar with BZA and PBO (-0.11 ± 0.21 and 0.07 ± 0.32 mm, respectively). The incidence of endometrial hyperplasia was low (0.1% for both groups). BZA showed significantly lower rates than PBO of endometrial carcinoma (0.1% vs. 0.4%; P=0.020) and vaginitis (6.1% vs. 7.6%; P=0.035). There were more cases of ovarian carcinoma with BZA (n=4 [0.1%]) than PBO (n=0); the difference was not statistically significant. Rates of breast-related and other gynecologic AEs were similar among groups.

CONCLUSIONS: BZA was associated with a favorable reproductive safety profile in postmenopausal women with osteoporosis over 7 years.