title: Evaluation of the efficacy and safety of bazedoxifene/conjugated estrogens for secondary outcomes including vasomotor symptoms in postmenopausal women by years since menopause in the Selective estrogens, Menopause and Response to Therapy (SMART) trials.
abstract: BACKGROUND
  Bazedoxifene/conjugated estrogens (BZA/CE), a novel tissue-selective estrogen complex (TSEC), has been evaluated in the Selective estrogens, Menopause And Response to Therapy (SMART) trials. Secondary outcomes from these trials were evaluated to determine whether the effects of BZA/CE are influenced by years since menopause (YSM).
  
  
  METHODS
  SMART-1 and SMART-2 were randomized, double-blind, placebo (PBO)-controlled phase 3 trials in nonhysterectomized postmenopausal women. Outcomes were evaluated for women <5 or ≥5 YSM in SMART-1 (BZA 20 mg/CE 0.45 mg, n=433; BZA 20 mg/CE 0.625 mg, n=414; PBO, n=427) and SMART-2 (BZA 20 mg/CE 0.45 mg, n=127; BZA 20 mg/CE 0.625 mg, n=128; PBO, n=63). Hot-flush frequency and severity, health-related quality of life (HRQoL), sleep, treatment satisfaction, cumulative amenorrhea, and breast pain were assessed for each study individually, using defined statistical analysis protocols.
  
  
  RESULTS
  For <5 and ≥5 YSM subgroups, BZA 20 mg/CE 0.45 and 0.625 mg showed significant decreases in hot-flush frequency and severity at 3 months compared with PBO (p<0.05 for both). Both BZA/CE doses showed significant improvements compared with PBO in HRQoL scores, sleep parameters, and satisfaction with treatment at 3 months irrespective of YSM (p≤0.05 vs. PBO for all). Similar to PBO, BZA/CE showed high proportions of cumulative amenorrhea (SMART-1) and low incidences of breast pain (SMART-1 and SMART-2) for women <5 and ≥5 YSM.
  
  
  CONCLUSIONS
  The positive effects of BZA/CE on secondary outcomes were consistent among women <5 or ≥5 YSM.
authors.affiliation: 1 Department of Obstetrics and Gynecology, Division of Midlife Health, University of Virginia Health System , Charlottesville, Virginia.
authors.forename: Joann V
authors.initials: JV
authors.lastname: Pinkerton
authors.forename: Lucy
authors.initials: L
authors.lastname: Abraham
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Bushmakin
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Cappelleri
authors.forename: Jill
authors.initials: J
authors.lastname: Racketa
authors.forename: Harry
authors.initials: H
authors.lastname: Shi
authors.forename: Arkadi A
authors.initials: AA
authors.lastname: Chines
authors.forename: Sebastian
authors.initials: S
authors.lastname: Mirkin
mesh_terms: D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004967:Estrogens / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D005260:Female; D006304:Health Status; D019584:Hot Flashes / Q000188:drug therapy / Q000453:epidemiology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D008875:Middle Aged; D017698:Postmenopause / Q000187:drug effects*; D011788:Quality of Life; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D007211:Indoles; D020845:Selective Estrogen Receptor Modulators; C447119:bazedoxifene