Kristine E Ensrud1, Katherine A Guthrie2, Chancellor Hohensee2, Bette Caan3, Janet S Carpenter4, Ellen W Freeman5, Andrea Z LaCroix2, Carol A Landis6, JoAnn Manson7, Katherine M Newton8, Julie Otte4, Susan D Reed9, Jan L Shifren10, Barbara Sternfeld3, Nancy F Woods6, Hadine Joffe11. 1. 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. 2. Fred Hutchinson Cancer Research Center, Seattle WA. 3. Division of Research, Kaiser Permanente, Oakland, CA. 4. School of Nursing, Indiana University, Indianapolis, IN. 5. Departments of Obstetrics, Gynecology and Psychiatry, University of Pennsylvania, Philadelphia, PA. 6. Department of Biobehavioral Nursing and Health Systems, University of Washington, Seattle, WA. 7. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. 8. Group Health Research Institute, Seattle WA. 9. Department of Medicine, University of Washington, Seattle, WA. 10. Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA. 11. Department of Psychiatry, Brigham and Women's Hospital and Dana Farber Cancer Institute, Boston, MA.
Abstract
STUDY OBJECTIVES: Determine effects of low-dose estradiol and low-dose venlafaxine on self-reported sleep measures in menopausal women with hot flashes. DESIGN: 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. SETTING: Academic research centers. PARTICIPANTS: 339 community-dwelling perimenopausal and postmenopausal women with ≥2 bothersome hot flashes per day. MEASUREMENTS AND 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. CLINICAL TRIAL REGISTRATION: NCT01418209 at www.clinicaltrials.gov.
STUDY OBJECTIVES: Determine effects of low-dose estradiol and low-dose venlafaxine on self-reported sleep measures in menopausal women with hot flashes. DESIGN: 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. SETTING: Academic research centers. PARTICIPANTS: 339 community-dwelling perimenopausal and postmenopausal women with ≥2 bothersome hot flashes per day. MEASUREMENTS AND 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. CLINICAL TRIAL REGISTRATION: NCT01418209 at www.clinicaltrials.gov.
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