Objective: To evaluate the endometrial safety of a tissue selective estrogen complex (TSEC; pairing of a selective estrogen receptor modulator [SERM] with estrogens) composed of bazedoxifene/conjugated estrogens (BZA/CE) in postmenopausal women.
Design: Randomized, double-blind, multicenter, placebo- and active-controlled, phase 3 study (Selective estrogen Menopause And Response to Therapy [SMART]-1).
Setting: Outpatient clinical.
Patient(s): Healthy, postmenopausal women (n = 3,397) age 40-75 with an intact uterus.
Intervention(s): Single tablets of BZA (10, 20, or 40 mg) combined with CE (0.625 or 0.45 mg); raloxifene (60 mg); or placebo daily for 2 years.
Main outcome measure(s): Incidence of endometrial hyperplasia at 12 months in the efficacy evaluable population.
Result(s): Treatment with BZA (20 or 40 mg)/CE (0.625 or 0.45 mg) was associated with low rates (<1%) of endometrial hyperplasia that were not significantly different from those reported with placebo over 24 months. Endometrial thickness with BZA (20 or 40 mg)/CE (0.625 or 0.45 mg) was not significantly different from that with placebo.
Conclusion(s): When combined with CE (0.625 mg or 0.45 mg), BZA (20 mg) was the lowest effective dose that prevented endometrial hyperplasia over 2 years of study, creating the possibility for a new, progestin-free menopausal therapy.