@article{2ff0ec172297489f89b516559a04fae8,
title = "The Kronos Early Estrogen Prevention Study (KEEPS): What have we learned?",
abstract = "Objective:The Kronos Early Estrogen Prevention Study (KEEPS) was designed to address gaps in understanding the effects of timely menopausal hormone treatments (HT) on cardiovascular health and other effects of menopause after the premature termination of the Women's Health Initiative.Method:The KEEPS was a randomized, double-blinded, placebo-controlled trial to test the hypothesis that initiation of HT (oral conjugated equine estrogens [o-CEE] or transdermal 17β-estradiol [t-E2]) in healthy, recently postmenopausal women (n=727) would slow the progression of atherosclerosis as measured by changes in carotid artery intima-media thickness (CIMT).Results:After 4 years, neither HT affected the rate of increase in CIMT. There was a trend for reduced accumulation of coronary artery calcium with o-CEE. There were no severe adverse effects, including venous thrombosis. Several ancillary studies demonstrated a positive effect on mood with o-CEE, and reduced hot flashes, improved sleep, and maintenance of bone mineral density with both treatments. Sexual function improved with t-E2. There were no significant effects of either treatment on cognition, breast pain, or skin wrinkling. Variants of genes associated with estrogen metabolism influenced the age of menopause and variability in effects of the HT on CIMT. Platelet activation associated with the development of white matter hyperintensities in the brain.Conclusions:KEEPS and its ancillary studies have supported the value and safety of the use of HT in recently postmenopausal women and provide a perspective for future research to optimize HT and health of postmenopausal women. The KEEPS continuation study continues to pursue these issues.",
keywords = "Cardiovascular disease, Cognition, Hormone therapy, Menopausal symptoms, Menopause, Osteoporosis",
author = "Miller, {Virginia M.} and Fredrick Naftolin and Sanjay Asthana and Black, {Dennis M.} and Brinton, {Eliot A.} and Budoff, {Matthew J.} and Cedars, {Marcelle I.} and Dowling, {N. Maritza} and Gleason, {Carey E.} and Hodis, {Howard N.} and Muthuvel Jayachandran and Kejal Kantarci and Lobo, {Rogerio A.} and Manson, {Joann E.} and Lubna Pal and Santoro, {Nanette F.} and Taylor, {Hugh S.} and Harman, {S. Mitchell}",
note = "Funding Information: Received November 21, 2018; revised and accepted December 20, 2018. From the 1Departments of Surgery and Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN; 2Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY; 3Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, University of Wisconsin School of Medicine and Public Health and the Geriatric Research, Madison, WI; 4Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco, CA; 5Utah Lipid Center, Salt Lake City, UT; 6Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles, Torrance, CA; 7Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA; 8Departments of Acute and Chronic Care, Epidemiology and Biostatistics, George Washington University School of Nursing and Milken Institute School of Public Health, Washington, DC; 9Division of Geriatrics, Department of Medicine, University of Wisconsin School of Medicine and Public Health and the William S. Middleton Memorial VA, Geriatric Research, Education and Clinical Center, Madison, WI; 10Atherosclerosis Research Unit, University of Southern California, Los Angeles, CA; 11Department of Physiology and Biomedical Engineering, Division of Nephrology and Hypertension, Division of Hematology Research, Mayo Clinic, Rochester, MN; 12Department of Radiology, Mayo Clinic, Rochester, MN; 13Department of Obstetrics and Gynecology, Columbia University, New York, NY; 14Department of Medicine, Brigham and Women{\textquoteright}s Hospital, Harvard Medical School, Boston, MA; 15Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT; 16Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, CO; and 17Phoenix Veterans Administration Health Care System, Phoenix, AZ. Funding/support: KEEPS was funded by grants from the Aurora Foundation to the Kronos Longevity Research Institute (SMH and FN, Co-PI{\textquoteright}s), from the National Institutes of Health (NIH) HL90639 to VMM, R21 NS066147 to KK Mayo Clinic CTSA UL1 RR024150, the Mayo Foundation, Brigham and Women{\textquoteright}s Hospital/Harvard Medical School CTSA, CTSA UL1 RR024139, and UCSF CTSA UL1 RR024131 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research. The Pfizer Company supported poststudy hormone measurements. The manuscript{\textquoteright}s contents are solely the responsibility of the authors and do not necessarily represent the official view of NCATS or NIH. Information on NCRR is available at http://www.ncrr.nih.gov. Study medications were supplied in part by Bayer Health Care and by Abbott Pharmaceuticals. Role of the Sponsors: The Aurora Foundation, Bayer HealthCare, Abbott Pharmaceuticals, and Pfizer Pharmaceuticals had no input into the design or conduct of the study or the writing, review, or approval of this manuscript. ClinicalTrials.gov number is NCT00154180. Financial disclosure/conflicts of interest: EAB—Grants from Akcea, Amarin, Amgen, Boehringer-Ingelheim, Esperion, Kaneka, Kowa, Med-icure, Novo-Nordisk, Regeneron, Sanofi. Past relationships: Aegerion, Alexion, AstraZeneca, Janssen, Kastle, Merck, Precision Biosciences, PTS Diagnostics; MJB—Grant Support General Electric; KK—Data Safety Monitoring Board for Takeda Global Research & Development Center, Inc.; Data Monitoring Boards of Pfizer and Janssen Alzheimer Immunotherapy; research support from the Avid Radiopharmaceuticals, Eli Lilly; RAL—Grants from TherapeuticsMD, Ogeda, Bayer, NIH, Advisory Board: TherapeuticsMD, Mithra, AMAG; NFS—Scientific Advisory Board Ogeda/ASTELLAS, Scientific Advisory Board and stock options, Menogenix, Inc; LP—Member Scientific Advisory Board, AMAG, Natera, Abbott, Consultant, GLG. The rest of the authors have nothing to disclose. Address correspondence to: Virginia M. Miller, PhD, Department of Surgery and Physiology, Medical Science 4-20, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail: miller.virginia@mayo.edu This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Publisher Copyright: {\textcopyright} 2019 by The North American Menopause Society.",
year = "2019",
month = sep,
day = "1",
doi = "10.1097/GME.0000000000001326",
language = "English (US)",
volume = "26",
pages = "1071--1084",
journal = "Menopause",
issn = "1072-3714",
publisher = "Lippincott Williams and Wilkins",
number = "9",
}