title: Effects of estradiol and venlafaxine on insomnia symptoms and sleep quality in women with hot flashes.
abstract: OBJECTIVE
  Determine effects of low-dose estradiol and low-dose venlafaxine on self-reported sleep measures in menopausal women with hot flashes.
  
  
  METHODS
  3-arm double-blind randomized trial. Participants assigned in a 2:2:3 ratio to 17β estradiol 0.5 mg/day (n = 97), venlafaxine XR 75 mg/day (n = 96), or placebo (n = 146) for 8 weeks.
  
  
  METHODS
  Academic research centers.
  
  
  METHODS
  339 community-dwelling perimenopausal and postmenopausal women with ≥2 bothersome hot flashes per day.
  
  
  RESULTS
  Insomnia symptoms (Insomnia Severity Index [ISI]) and sleep quality (Pittsburgh Sleep Quality Index [PSQI]) at baseline, week 4 and 8; 325 women (96%) provided ISI data and 312 women (92%) provided PSQI data at baseline and follow-up. At baseline, mean (SD) hot flash frequency was 8.1/day (5.3), mean ISI was 11.1 (6.0), and mean PSQI was 7.5 (3.4). Mean (95% CI) change from baseline in ISI at week 8 was -4.1 points (-5.3 to -3.0) with estradiol, -5.0 points (-6.1 to -3.9) with venlafaxine, and -3.0 points (-3.8 to -2.3) with placebo (P overall treatment effect vs. placebo 0.09 for estradiol and 0.007 for venlafaxine). Mean (95% CI) change from baseline in PSQI at week 8 was -2.2 points (-2.8 to -1.6) with estradiol, -2.3 points (-2.9 to -1.6) with venlafaxine, and -1.2 points (-1.7 to -0.8) with placebo (P overall treatment effect vs. placebo 0.04 for estradiol and 0.06 for venlafaxine).
  
  
  CONCLUSIONS
  Among perimenopausal and postmenopausal women with hot flashes, both low dose oral estradiol and low-dose venlafaxine compared with placebo modestly reduced insomnia symptoms and improved subjective sleep quality.
  
  
  BACKGROUND
  NCT01418209 at www.clinicaltrials.gov.
authors.affiliation: Department of Medicine and Division of Epidemiology & Community Health, University of Minnesota, Minneapolis, MN: Center for Chronic Disease Outcomes Research, Minneapolis VA Health Care System, Minneapolis, MN.
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Ensrud
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle WA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Guthrie
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle WA.
authors.forename: Chancellor
authors.initials: C
authors.lastname: Hohensee
authors.affiliation: Division of Research, Kaiser Permanente, Oakland, CA.
authors.forename: Bette
authors.initials: B
authors.lastname: Caan
authors.affiliation: School of Nursing, Indiana University, Indianapolis, IN.
authors.forename: Janet S
authors.initials: JS
authors.lastname: Carpenter
authors.affiliation: Departments of Obstetrics, Gynecology and Psychiatry, University of Pennsylvania, Philadelphia, PA.
authors.forename: Ellen W
authors.initials: EW
authors.lastname: Freeman
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle WA.
authors.forename: Andrea Z
authors.initials: AZ
authors.lastname: LaCroix
authors.affiliation: Department of Biobehavioral Nursing and Health Systems, University of Washington, Seattle, WA.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Landis
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: JoAnn
authors.initials: J
authors.lastname: Manson
authors.affiliation: Group Health Research Institute, Seattle WA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Newton
authors.affiliation: School of Nursing, Indiana University, Indianapolis, IN.
authors.forename: Julie
authors.initials: J
authors.lastname: Otte
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA.
authors.forename: Susan D
authors.initials: SD
authors.lastname: Reed
authors.affiliation: Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Jan L
authors.initials: JL
authors.lastname: Shifren
authors.affiliation: Division of Research, Kaiser Permanente, Oakland, CA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Sternfeld
authors.affiliation: Department of Biobehavioral Nursing and Health Systems, University of Washington, Seattle, WA.
authors.forename: Nancy F
authors.initials: NF
authors.lastname: Woods
authors.affiliation: Department of Psychiatry, Brigham and Women's Hospital and Dana Farber Cancer Institute, Boston, MA.
authors.forename: Hadine
authors.initials: H
authors.lastname: Joffe
mesh_terms: D003511:Cyclohexanols / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004967:Estrogens / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D019584:Hot Flashes / Q000150:complications* / Q000503:physiopathology; D006801:Humans; D008593:Menopause / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D047648:Perimenopause / Q000187:drug effects / Q000502:physiology; D012890:Sleep / Q000187:drug effects* / Q000502:physiology*; D007319:Sleep Initiation and Maintenance Disorders / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D000069470:Venlafaxine Hydrochloride
chemical_list: D003511:Cyclohexanols; D004967:Estrogens; D004958:Estradiol; D000069470:Venlafaxine Hydrochloride
keywords: estradiol; hot flashes; menopause; randomized trial; sleep; venlafaxine