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

Menopause. 2019 Jan 9;26(6):637-642. doi: 10.1097/GME.0000000000001294.


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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Double-Blind Method
  • Endometrial Hyperplasia
  • Estradiol / administration & dosage*
  • Estradiol / therapeutic use*
  • Estrogen Replacement Therapy / methods*
  • Female
  • Hot Flashes / drug therapy*
  • Humans
  • Middle Aged
  • Postmenopause*
  • Progesterone / administration & dosage*
  • Progesterone / therapeutic use*
  • Quality of Life*
  • Severity of Illness Index
  • Sleep / drug effects*
  • Surveys and Questionnaires
  • Treatment Outcome
  • Uterus / physiology


  • TX-001HR
  • Progesterone
  • Estradiol

Associated data