title: Effects of bazedoxifene/conjugated estrogens on endometrial safety and bone in postmenopausal women.
abstract: OBJECTIVE
  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.
authors.affiliation: Pfizer Inc, Collegeville, PA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Mirkin
authors.forename: B S
authors.initials: BS
authors.lastname: Komm
authors.forename: K
authors.initials: K
authors.lastname: Pan
authors.forename: A A
authors.initials: AA
authors.lastname: Chines
mesh_terms: D000328:Adult; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents; D004311:Double-Blind Method; D004714:Endometrial Hyperplasia / Q000139:chemically induced / Q000453:epidemiology*; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects*; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000517:prevention & control*; D010919:Placebos; D017698:Postmenopause; D020845:Selective Estrogen Receptor Modulators
chemical_list: D050071:Bone Density Conservation Agents; D004966:Estrogens, Conjugated (USP); D007211:Indoles; D010919:Placebos; D020845:Selective Estrogen Receptor Modulators; D017258:Medroxyprogesterone Acetate; C447119:bazedoxifene