No improvement in cognition with post-menopausal hormones

Menopausal hormone therapy (MHT) given to recently postmenopausal women in the US for up to four years does not improve cognition, but may have some positive benefits for some mood symptoms, according to a study published by Carey Gleason and colleagues from the University of Wisconsin, Madison, USA, in this week's PLOS Medicine.

The researchers reached these conclusions by conducting a randomized placebo-controlled clinical trial (the KEEPS-Cog trial), including 693 recently postmenopausal women living in the US who were randomly assigned to receive either oral estrogen pills and progesterone, or transdermal estradiol patches and progesterone, or placebo pills and patches. Over 4 years of follow-up, the researchers found no beneficial effects of treatment on cognition or on symptoms of clinical depression. However, women treated with oral estrogen pills and progesterone (but not those treated with transdermal estradiol patches and progesterone) showed improvements in some mood symptoms, as measured by the Profile of Mood States instrument, compared to women in the placebo group.

Importantly, these findings provide no information about the effects of MHT beyond 4 years and, because most of the women in the study were white, well-educated and at low risk of cardiovascular disease, may not be applicable to the general postmenopausal population of the US and of other countries. Moreover, because MHT improved menopausal symptoms in the women receiving hormones, the trial was not truly double-blinded. However, despite these and other study limitations, the researchers suggest that their findings could now be used to help women make more informed decisions about whether to use MHT to manage their menopausal symptoms.

The authors say: "Overall, the KEEPS-Cog findings provide valuable information to women considering the various options for managing menopausal symptoms."

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Funding: The KEEPS-Cog project was supported by grants from the National Institutes of Health (NIH) R01 AG029624, P50AG033514, R01AG031790, grant 1UL1RR025011 from the Clinical and Translational Science Award (CTSA) program of the NIH National Center for Research Resources and the Wisconsin National Primate Research Center base grant, NIH NCRR000167. The Parent KEEPS trial was funded by grants from the Aurora Foundation to the Kronos Longevity Research Institute, National Institutes of Health (NIH) HL90639 to VMM, Einstein College of Medicine, CTSA UL1 RR025750, KL2 RR025749 and TL1 RR025748, Mayo CTSA 1 UL1 RR024150, the Mayo Foundation, Brigham and Women'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. Additional support provided by resources and facilities of the Madison VA, and the VA Puget Sound Health Care System. The manuscript's contents are solely the responsibility of the authors and do not necessarily represent the official view of NCATS or NIH. Information on NCATS is available at http://www.ncats.nih.gov. Bayer HealthCare Pharmaceuticals, Inc. supplied the CLIMARA estradiol and placebo patches and Abbott Laboratories (formerly Solvay Pharmaceuticals) provided the micronized progesterone (PROMETRIUM) and placebo capsules. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: MIC declared: I have research funding from Nora Therapeutics and Ferring pharmaceuticals. I am a member of ASRM Executive Board. NFS declared: 1. Menogenix: stock options (this is a company that has patented a novel non hormonal treatment for menopausal hot flashes and to date I have not exercised my stock options but would rather report this than give the appearance of not disclosing sufficient information). 2. Bayer, Inc: grant support (this is an investigator initiated grant that is supported by funds given to my institution. I receive no personal funds for this work). SA declared: 1) NIH Grants to support my research--NIA P50 Center Grant to support the Wisconsin Alzheimer's Disease Research Center (ADRC). 2) NIA T32 Training Grant in the Biology of Aging and Age-Related Diseases. 3) NIA RO1 that supported the KEEPS Cognitive and Affective Study. 4) Following Pharma Industry-supported research grants to serve as a site PI to conduct treatment trials in patients with Alzheimer's disease and Mild Cognitive Impairment (MCI): Merck Sharp and Dohme; H. Lundbeck A-S; Toyama Chemical Company. 5) Rockpointe Corporation--I am on the Speaker's Bureau of this science-based education corporation that sponsors CME-accredited education programs. My presentations are on Alzheimer's disease and not related to the focus of the manuscript under review. HST declared: I have served as a consultant to Bayer, Abbvie, Pfizer and Theraputics MD. My University has received grant support toward my work from Pfizer. I have authored papers with employees of Pfizer and Shionogi.

Citation: Gleason CE, Dowling NM, Wharton W, Manson JE, Miller VM, Atwood CS, et al. (2015) Effects of Hormone Therapy on Cognition and Mood in Recently Postmenopausal Women: Findings from the Randomized, Controlled KEEPS-Cognitive and Affective Study. PLoS Med 12(6): e1001833. doi:10.1371/journal.pmed.1001833

School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin
Geriatric Research, Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin
Wisconsin Alzheimer's Disease Research Center, Madison, Wisconsin
Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, Wisconsin
Department of Neurology, Emory University School of Medicine, Atlanta, Georgia
Emory Alzheimer's Disease Research Center, Atlanta, Georgia
Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
Departments of Surgery and Physiology & Biomedical Engineering, Mayo Clinic, Rochester, Minnesota
Utah Foundation for Biomedical Research, Salt Lake City, Utah, United States of America
Obstetrics & Gynecology, University of California at San Francisco, San Francisco, California
Obstetrics & Gynecology, Columbia University College of Physicians and Surgeons, New York
VA Puget Sound Health Care System, Tacoma, Washington
Division of Metabolism, Endocrinology and Nutrition, University of Washington, Tacoma, Washington
Neuroscience and Obstetrics & Gynecology, Albert Einstein College of Medicine, Bronx, New York
Obstetrics & Gynecology, University of Colorado School of Medicine, Aurora, Colorado
Obstetrics & Gynecology, Yale University School of Medicine, New Haven, Connecticut
Epidemiology & Biostatistics, University of California at San Francisco, San Francisco, California
Division of Cardiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California
Atherosclerosis Research Unit, University of Southern California, Los Angeles, California
Obstetrics & Gynecology, New York University School of Medicine, New York, New York
Kronos Longevity Research Institute, Phoenix, Arizona
Division of Endocrinology, Phoenix VA Medical Center, Phoenix, Arizona

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Dr Carey E. Gleason
ceg@medicine.wisc.edu