Effects of bazedoxifene/conjugated estrogens on endometrial safety and bone in postmenopausal women

ABSTRACT

Objectives Bazedoxifene/conjugated estrogens (BZA/CE) has demonstrated efficacy in improving vasomotor and vulvar/vaginal atrophy symptoms in postmenopausal women. This study evaluated the endometrial safety of BZA/CE and effects on bone mineral density (BMD) compared with CE/medroxyprogesterone acetate (MPA) and placebo.

Methods The Selective estrogens, Menopause, And Response to Therapy (SMART)-4 trial was a 1-year, multicenter, double-blind, randomized, placebo– and active-controlled, phase-3 study in non-hysterectomized, postmenopausal women (n = 1061; aged 40 −< 65 years). Subjects received BZA 20 mg/CE 0.45 or 0.625 mg, CE 0.45 mg/MPA 1.5 mg, or placebo daily. Primary endpoints were the incidence of endometrial hyperplasia and the change in lumbar spine BMD at 1 year. Secondary endpoints included the change in total hip BMD and rates of amenorrhea and breast pain.

Results At 1 year, no cases of endometrial hyperplasia were identified in the BZA 20-mg/CE 0.45-mg group, while three cases (1.1%) were confirmed for the BZA 20-mg/CE 0.625-mg group (95% one-sided confidence interval upper limit < 4%). Both BZA/CE doses significantly increased lumbar spine and total hip BMD versus placebo (p ≤ 0.001) and showed low incidences of bleeding and breast tenderness, similar to placebo and significantly lower than for CE 0.45 mg/MPA 1.5 mg (p < 0.05). BZA/CE treatment was generally safe and well tolerated.

Conclusions BZA 20 mg/CE 0.45 and 0.625 mg significantly improved BMD while maintaining endometrial safety and showed a favorable safety/tolerability profile over 1 year. BZA/CE may be a promising therapy for treating menopausal symptoms and preventing osteoporosis in non-hysterectomized, postmenopausal women.

Key words::

• MENOPAUSE
• OSTEOPOROSIS
• ESTROGENS
• SELECTIVE ESTROGEN RECEPTOR MODULATOR
• BAZEDOXIFENE
• TISSUE SELECTIVE ESTROGEN COMPLEX

ACKNOWLEDGEMENT

Medical writing support for this manuscript was provided by Joy Loh, PhD, of MedErgy and was funded by Pfizer Inc.

Conflict of interest S. Mirkin, B. Komm, K. Pan are full-time employees of Pfizer Inc. A. Chines was an employee of Pfizer Inc during the conduct of this study.

Source of funding This study was sponsored by Wyeth Research, Collegeville, PA, which was acquired by Pfizer Inc in October 2009.