Relationship between vasomotor symptom improvements and quality of life and sleep outcomes in menopausal women treated with oral, combined 17β-estradiol/progesterone

Abstract

Objective: To characterize the impact of TX-001HR on the relationship between vasomotor symptom (VMS) improvement and quality of life and sleep.

Methods: REPLENISH (NCT01942668) was a phase 3, randomized, double-blind, placebo-controlled, multicenter trial, which evaluated four daily doses of 17β-estradiol and progesterone (E2/P4) combined in a single, oral, softgel capsule in postmenopausal women (40-65 years) with a uterus and moderate to severe VMS (≥7/day or ≥50/week). In post hoc analyses, growth models were used to examine relationships between linear changes in VMS frequency and severity over 12 weeks and changes from baseline in the Menopause-Specific Quality of Life (MENQOL; total score and VMS domain) and the Medical Outcomes Study-Sleep (total score, sleep problems indices I and II) questionnaire outcomes at 12 weeks with treatment compared with placebo.

Results: Outcomes with all four E2/P4 doses were combined (n = 591) and compared with placebo (n = 135). In all 5 growth models, the effects of TX-001HR on MENQOL total score and vasomotor domain were significantly associated with changes in VMS frequency and severity observed over 12 weeks (all, P < 0.001). Treatment-mediated effects on MENQOL via VMS frequency and severity models were significant. Similar results were found with Medical Outcomes Study-Sleep total score and sleep problems indices.

Conclusions: TX-001HR improvements in quality of life and sleep outcomes are associated with and may be mediated through improvements in VMS frequency and severity.

FIG. 1

Relationship of treatment, hot flush frequency (Freq) and severity (Sev) changes, and changes in Menopause-Specific Quality of Life (MENQOL) questionnaire (A) overall; (B) vasomotor domain. ^∗P < 0.05; ^†P < 0.01; ^‡P < 0.001. Solid lines are statistically significant paths, dashed lines are not significant. Fixed cubic and quadratic (quad) terms were not included in the figures.

FIG. 2

Relationship of treatment, hot flush frequency (Freq) and severity (Sev) changes, and changes in Medical Outcomes Study (MOS)-Sleep Scale (A) overall; (B) sleep problems index I; (C) sleep problems index II. ^∗P < 0.05; ^†P < 0.01; ^‡P < 0.001. Solid lines are statistically significant paths, dashed lines are not significant. Fixed cubic and quadratic (quad) terms were not included in the figures.