Nanette Santoro1, Amanda Allshouse, Genevieve Neal-Perry, Lubna Pal, Rogerio A Lobo, Frederick Naftolin, Dennis M Black, Eliot A Brinton, Matthew J Budoff, Marcelle I Cedars, N Maritza Dowling, Mary Dunn, Carey E Gleason, Howard N Hodis, Barbara Isaac, Maureen Magnani, JoAnn E Manson, Virginia M Miller, Hugh S Taylor, Whitney Wharton, Erin Wolff, Viola Zepeda, S Mitchell Harman. 1. 1Department of Obstetrics & Gynecology 2Department of Biostatistics, University of Colorado School of Medicine, Aurora, CO 3Department of Obstetrics, Gynecology & Women's Health and Neurosciences, Albert Einstein College of Medicine, Bronx, NY 4Department of Obstetrics & Gynecology, Yale University School of Medicine, New Haven, CT 5Department of Obstetrics & Gynecology, Columbia University College of Physicians and Surgeons, New York, NY 6Department of Obstetrics & Gynecology, New York University School of Medicine, New York, NY 7Department of Epidemiology & Biostatistics, University of California at San Francisco, San Francisco, CA 8Utah Foundation for Biomedical Research, Salt Lake City, UT 9Department of Cardiology, Los Angeles Biomedical Research Institute at Harbor UCLA, Torrance, CA 10Department of Obstetrics & Gynecology, University of California at San Francisco, San Francisco, CA 11Departments of Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI 12Kronos Longevity Research Institute, Phoenix, AZ 13Department of Medicine and Public Health, University of Wisconsin, Madison, WI 14Atherosclerosis Research Unit, University of Southern California, Los Angeles, CA 15Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 16Departments of Surgery and Physiology & Biomedical Engineering, Mayo Clinic, Rochester, MN 17Department of Neurology, Emory University, Atlanta, GA 18Department of Reproductive Biology and Medicine, National Institutes of Health, Bethesda, MD 19Department of Medicine, Endocrine Division, Phoenix VA Health Care System, Phoenix, AZ.
Abstract
OBJECTIVE: The objective of the present study was to compare the efficacy of two forms of menopausal hormone therapy in alleviating vasomotor symptoms, insomnia, and irritability in early postmenopausal women during 4 years. METHODS: A total of 727 women, aged 42 to 58, within 3 years of their final menstrual period, were randomized to receive oral conjugated estrogens (o-CEE) 0.45 mg (n = 230) or transdermal estradiol (t-E2) 50 μg (n = 225; both with micronized progesterone 200 mg for 12 d each mo), or placebos (PBOs; n = 275). Menopausal symptoms were recorded at screening and at 6, 12, 24, 36, and 48 months postrandomization. Differences in proportions of women with symptoms at baseline and at each follow-up time point were compared by treatment arm using exact χ tests in an intent-to-treat analysis. Differences in treatment effect by race/ethnicity and body mass index were tested using generalized linear mixed effects modeling. RESULTS: Moderate to severe hot flashes (from 44% at baseline to 28.3% for PBO, 7.4% for t-E2, and 4.2% for o-CEE) and night sweats (from 35% at baseline to 19% for PBO, 5.3% for t-E2, and 4.7% for o-CEE) were reduced significantly by 6 months in women randomized to either active hormone compared with PBO (P < 0.001 for both symptoms), with no significant differences between the active treatment arms. Insomnia and irritability decreased from baseline to 6 months postrandomization in all groups. There was an intermittent reduction in insomnia in both active treatment arms versus PBO, with o-CEE being more effective than PBO at 36 and 48 months (P = 0.002 and 0.05) and t-E2 being more effective than PBO at 48 months (P = 0.004). Neither hormone treatment significantly affected irritability compared with PBO. Symptom relief for active treatment versus PBO was not significantly modified by body mass index or race/ethnicity. CONCLUSIONS: Recently postmenopausal women had similar and substantial reductions in hot flashes and night sweats with lower-than-conventional doses of oral or transdermal estrogen. These reductions were sustained during 4 years. Insomnia was intermittently reduced compared with PBO for both hormone regimens.
RCT Entities:
OBJECTIVE: The objective of the present study was to compare the efficacy of two forms of menopausal hormone therapy in alleviating vasomotor symptoms, insomnia, and irritability in early postmenopausal women during 4 years. METHODS: A total of 727 women, aged 42 to 58, within 3 years of their final menstrual period, were randomized to receive oral conjugated estrogens (o-CEE) 0.45 mg (n = 230) or transdermal estradiol (t-E2) 50 μg (n = 225; both with micronized progesterone 200 mg for 12 d each mo), or placebos (PBOs; n = 275). Menopausal symptoms were recorded at screening and at 6, 12, 24, 36, and 48 months postrandomization. Differences in proportions of women with symptoms at baseline and at each follow-up time point were compared by treatment arm using exact χ tests in an intent-to-treat analysis. Differences in treatment effect by race/ethnicity and body mass index were tested using generalized linear mixed effects modeling. RESULTS: Moderate to severe hot flashes (from 44% at baseline to 28.3% for PBO, 7.4% for t-E2, and 4.2% for o-CEE) and night sweats (from 35% at baseline to 19% for PBO, 5.3% for t-E2, and 4.7% for o-CEE) were reduced significantly by 6 months in women randomized to either active hormone compared with PBO (P < 0.001 for both symptoms), with no significant differences between the active treatment arms. Insomnia and irritability decreased from baseline to 6 months postrandomization in all groups. There was an intermittent reduction in insomnia in both active treatment arms versus PBO, with o-CEE being more effective than PBO at 36 and 48 months (P = 0.002 and 0.05) and t-E2 being more effective than PBO at 48 months (P = 0.004). Neither hormone treatment significantly affected irritability compared with PBO. Symptom relief for active treatment versus PBO was not significantly modified by body mass index or race/ethnicity. CONCLUSIONS: Recently postmenopausal women had similar and substantial reductions in hot flashes and night sweats with lower-than-conventional doses of oral or transdermal estrogen. These reductions were sustained during 4 years. Insomnia was intermittently reduced compared with PBO for both hormone regimens.
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