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

Abstract 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 40 mg, raloxifene 60 mg, or PBO. During years 4–5, the raloxifene arm was discontinued and subjects receiving BZA 40 mg were transitioned to BZA 20 mg. Subjects continued to receive BZA 20 mg 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.