Linda L. Humphrey, MD, MPH; Benjamin K.S. Chan, MS; Harold C. Sox, MD, Editor
Note: This manuscript is based on a longer systematic evidence review that was reviewed by outside experts and representatives of professional societies. A complete list of peer reviewers is available in the complete report, which can be accessed online at www.ahrq.gov/clinic/uspstfix.htm.
Disclaimer: Review of this material does not imply agreement with or endorsement of the conclusions of this article, which are solely those of the authors. No statement in this article should be construed as official policy of the Agency for Healthcare Research and Quality.
As a coauthor, Dr. Sox did not participate in the review process or in the decision to accept the manuscript for publication.
Acknowledgments: The authors thank Steven Teutsch, MD, MPH; Janet Allan, PhD, RN; and David Atkins, MD, MPH, from the U.S. Preventive Services Task Force and Mark Helfand, MD, MS; Heidi Nelson, MD, MPH; and Gary Miranda, MA, from the Oregon Health & Science University Evidence-based Practice Center for their helpful comments on earlier versions of this review. They also thank Susan Wingenfeld and Jim Wallace for assistance in manuscript preparation.
Grant Support: This study was conducted by the Oregon Health & Science University Evidence-based Practice Center under contract to the Agency for Healthcare Research and Quality (contract no. 290-97-0018, task order no. 2), Rockville, Maryland.
Requests for Single Reprints: Reprints are available from the AHRQ Web site at www.preventiveservices.ahrq.gov and in print through the AHRQ Publications Clearinghouse.
Current Author Addresses: Dr. Humphrey and Mr. Chan: Oregon Health & Science University, Mail Code BICC 504, 3181 SW Sam Jackson Park Road, Portland, OR 97201.
Dr. Sox: American College of Physicians-American Society of Internal Medicine, 190 N. Independence Mall West, Philadelphia, PA 19106.
To evaluate the value of hormone replacement therapy (HRT) in the primary prevention of cardiovascular disease (CVD) and coronary artery disease (CAD).
MEDLINE and Cochrane databases were searched for all primary prevention studies reporting CVD or CAD incidence, mortality, or both in association with HRT; reference lists, letters, editorials, and reviews were also reviewed.
All studies were reviewed, abstracted, and rated for quality.
Only studies of good or fair quality, according to U.S. Preventive Services Task Force (USPSTF) criteria, were included in the detailed review and meta-analysis.
The summary relative risk with any HRT use was 0.75 (95% credible interval [CrI], 0.42 to 1.23) for CVD mortality and 0.74 (CrI, 0.36 to 1.45) for CAD mortality. The summary relative risk with any use was 1.28 (CrI, 0.86 to 2.00) for CVD incidence and 0.87 (CrI, 0.62 to 1.21) for CAD incidence. Further analysis of studies adjusting for socioeconomic status, as well as other major CAD risk factors, showed a summary relative risk of 1.07 (CrI, 0.79 to 1.48) for CAD incidence associated with any HRT use. Similar results were found when the analysis was stratified by studies adjusting for alcohol consumption, exercise, or both, in addition to other major risk factors, suggesting confounding by these factors.
This meta-analysis differs from previous meta-analyses by evaluating potential explanatory variables of the relationship between HRT, CVD, and CAD. The adjusted meta-analysis is consistent with recent randomized trials that have shown no benefit in the secondary or primary prevention of CVD events. A valid answer to the role of HRT in the primary prevention of CVD will best come from randomized, controlled trials.
Table 1. U.S. Preventive Services Task Force Categories for Rating Internal Validity of Studies
Table 2. Meta-Analysis Summary Table
Relative risk or odds ratio for cardiovascular disease mortality.
Relative risk or odds ratio for coronary artery disease mortality.
Relative risk or odds ratio for cardiovascular disease incidence.
Relative risk or odds ratio for coronary artery disease incidence.
Table 3. Coronary Artery Disease Incidence and Hormone Replacement Therapy
Appendix Table 1. Characterization of Hormone Replacement Therapy Use in Case-Control Studies: Assessment and Definitions
Appendix Table 2. Characterization of Hormone Replacement Therapy Use in Cohort Studies: Assessment, Prevalence, and Definitions
Appendix Table 3. Reasons for Poor Quality Rating and Exclusion from Meta-Analyses
Appendix Table 4. Cardiovascular Disease Mortality and Hormone Replacement Therapy
Appendix Table 5. Coronary Artery Disease Mortality and Hormone Replacement Therapy
Appendix Table 6. Cardiovascular Disease Incidence and Hormone Replacement Therapy
The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.
Humphrey LL, Chan BK, Sox HC. Postmenopausal Hormone Replacement Therapy and the Primary Prevention of Cardiovascular Disease. Ann Intern Med. 2002;137:273-284. doi: 10.7326/0003-4819-137-4-200208200-00012
Download citation file:
Published: Ann Intern Med. 2002;137(4):273-284.
Cardiology, Coronary Risk Factors, Endocrine and Metabolism, Prevention/Screening.
Results provided by:
Copyright © 2017 American College of Physicians. All Rights Reserved.
Print ISSN: 0003-4819 | Online ISSN: 1539-3704
Conditions of Use
This PDF is available to Subscribers Only