Effects of bazedoxifene/conjugated estrogens on sleep and vasomotor symptom relief in postmenopausal women

Abstract

OBJECTIVE: To assess the effects of bazedoxifene/conjugated estrogens (BZA/CE), a novel tissue-selective estrogen complex (TSEC), on sleep parameters and their association with vasomotor symptom relief in postmenopausal women. DESIGN: A 12-week, randomized, double-blind, placebo-controlled, phase 3, multicenter trial. MATERIALS AND METHODS: Postmenopausal women with ≥7 moderate-to-severe hot flushes (HFs) per day were randomized to daily treatment with BZA 20 mg/CE 0.45 mg, BZA 20 mg/CE 0.625 mg, or placebo. HF frequency and severity were recorded in daily diaries. The Medical Outcomes Study (MOS) sleep scale was used to assess sleep parameters at baseline and at Week 12. Effectiveness of treatment was estimated based on effect size. Multiple regression analysis adjusting for study site and baseline value was used to compare BZA/CE and placebo and to analyze the association between reduction in HFs and improvement in sleep parameters. RESULTS: At baseline, a total of 318 subjects (mean age, 54 years; 85% white) reported an average of 10.4 moderate-to-severe HFs per day. At Week 12, treatment with BZA 20 mg/CE 0.45 mg or BZA 20 mg/CE 0.625 mg significantly reduced the number of moderate-to-severe HFs from baseline (reduced by 74.4% and 80.1%, respectively; P <0.001 for both) compared with placebo (reduced by 51.2%). Both doses of BZA/CE also led to significantly less sleep disturbance, more adequate sleep, and fewer sleep problems overall (sleep problems index I and II) compared with placebo (P <0.001). The treatment effect size for these sleep parameters was medium to large (BZA 20 mg/CE 0.45 mg: -0.65, 0.55, -0.63, -0.67 for sleep disturbance, sleep adequacy, and sleep index I and II, respectively; BZA 20 mg/CE 0.625 mg: -0.75, 0.59, -0.65, -0.71). Reduced frequency of HFs was significantly associated with less sleep disturbance, more adequate sleep, and fewer sleep problems overall (P <0.001). Responders (subjects with ≥75% reduction from baseline in HFs) in all treatment groups, including placebo, showed significantly less sleep disturbance, more adequate sleep, and fewer sleep problems overall versus non-responders (P <0.05); notably greater improvements were seen in responders treated with BZA/CE versus placebo. CONCLUSIONS: In postmenopausal women treated with BZA/CE, improvement in vasomotor symptoms was strongly associated with improvement in sleep parameters.