title: Timing and persistence of effect of conjugated estrogens/bazedoxifene in postmenopausal women.
abstract: The aim of the study was to determine the time course of effect with conjugated estrogens/bazedoxifene (CE/BZA) in nonhysterectomized postmenopausal women in five phase 3 trials.
  
  
  
  This post hoc analysis identified when CE 0.45 mg/BZA 20 mg and CE 0.625 mg/BZA 20 mg first achieved a statistically significant difference (P < 0.05) versus placebo in individual trials and the duration the difference persisted for prespecified efficacy endpoints.
  
  
  
  CE/BZA significantly reduced hot flush frequency beginning at weeks 2 to 4 and severity at weeks 3 to 6; benefits were maintained through month 24. Significant improvements in lumbar spine, total hip, femoral neck, and femoral trochanter bone mineral density were evident at month 6 or 12 and changes in bone turnover markers at month 3 or 6; benefits were maintained throughout the studies (12 or 24 mo). In symptomatic women with less than 5% vaginal superficial cells at baseline, vaginal maturation index was significantly improved by week 4. Reductions in parabasal cells were maintained throughout the studies (through months 3 and 24), but superficial cell count changes persisted only with the higher CE/BZA dose. Menopause-Specific Quality of Life total and vasomotor domain scores were improved at all assessments, from months 3 through 24. Some measures of sleep, especially quality and time to fall asleep, improved during weeks 4 to 8 and were maintained in a majority of weeks thereafter.
  
  
  
  In the context of studies designed primarily to evaluate efficacy at final study endpoints, both doses of CE/BZA achieved significance versus placebo at early assessments for most outcomes, and benefits were well maintained.
authors.affiliation: 1University of California, San Francisco and East Bay Physicians Medical Group, Berkeley, CA 2Pfizer Inc, Collegeville, PA 3Pfizer Inc, New York, NY 4University of Virginia Health System, Charlottesville, VA.
authors.forename: Risa
authors.initials: R
authors.lastname: Kagan
authors.forename: Barry S
authors.initials: BS
authors.lastname: Komm
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Ryan
authors.forename: Joanne
authors.initials: J
authors.lastname: Lavenberg
authors.forename: Ching-Ray
authors.initials: CR
authors.lastname: Yu
authors.forename: JoAnn V
authors.initials: JV
authors.lastname: Pinkerton
mesh_terms: D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents; D002452:Cell Count; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage*; D005260:Female; D019584:Hot Flashes / Q000188:drug therapy*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D008875:Middle Aged; D017698:Postmenopause / Q000502:physiology*; D011788:Quality of Life; D012890:Sleep / Q000187:drug effects; D013997:Time Factors; D014621:Vagina / Q000166:cytology / Q000187:drug effects
chemical_list: D050071:Bone Density Conservation Agents; D004966:Estrogens, Conjugated (USP); D007211:Indoles; C447119:bazedoxifene