Objective: 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.
Methods: 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.
Results: 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.
Conclusions: 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.