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Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal PersonsUpdated Evidence Report and Systematic Review for the US Preventive Services Task Force

To identify the key insights or developments described in this article
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Abstract

Importance  It is uncertain whether hormone therapy should be used for the primary prevention of chronic conditions such as heart disease, osteoporosis, or some types of cancers.

Objective  To update evidence for the US Preventive Services Task Force on the benefits and harms of hormone therapy in reducing risks for chronic conditions.

Data Sources  PubMed/MEDLINE, Cochrane Library, EMBASE, and trial registries from January 1, 2016, through October 12, 2021; surveillance through July 2022.

Study Selection  English-language randomized clinical trials and prospective cohort studies of fair or good quality.

Data Extraction and Synthesis  Dual review of abstracts, full-text articles, and study quality; meta-analyses when at least 3 similar studies were available.

Main Outcomes and Measures  Morbidity and mortality related to chronic conditions; health-related quality of life.

Results  Twenty trials (N = 39 145) and 3 cohort studies (N = 1 155 410) were included. Participants using estrogen only compared with placebo had significantly lower risks for diabetes over 7.1 years (1050 vs 903 cases; 134 fewer [95% CI, 18-237]) and fractures over 7.2 years (1024 vs 1413 cases; 388 fewer [95% CI, 277-489]) per 10 000 persons. Risks per 10 000 persons were statistically significantly increased for gallbladder disease over 7.1 years (1113 vs 737 cases; 377 more [95% CI, 234-540]), stroke over 7.2 years (318 vs 239 cases; 79 more [95% CI, 15-159]), venous thromboembolism over 7.2 years (258 vs 181 cases; 77 more [95% CI, 19-153]), and urinary incontinence over 1 year (2331 vs 1446 cases; 885 more [95% CI, 659-1135]). Participants using estrogen plus progestin compared with placebo experienced significantly lower risks, per 10 000 persons, for colorectal cancer over 5.6 years (59 vs 93 cases; 34 fewer [95% CI, 9-51]), diabetes over 5.6 years (403 vs 482 cases; 78 fewer [95% CI, 15-133]), and fractures over 5 years (864 vs 1094 cases; 230 fewer [95% CI, 66-372]). Risks, per 10 000 persons, were significantly increased for invasive breast cancer (242 vs 191 cases; 51 more [95% CI, 6-106]), gallbladder disease (723 vs 463 cases; 260 more [95% CI, 169-364]), stroke (187 vs 135 cases; 52 more [95% CI, 12-104]), and venous thromboembolism (246 vs 126 cases; 120 more [95% CI, 68-185]) over 5.6 years; probable dementia (179 vs 91 cases; 88 more [95% CI, 15-212]) over 4.0 years; and urinary incontinence (1707 vs 1145 cases; 562 more [95% CI, 412-726]) over 1 year.

Conclusions and Relevance  Use of hormone therapy in postmenopausal persons for the primary prevention of chronic conditions was associated with some benefits but also with an increased risk of harms.

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Article Information

Corresponding Author: Gerald Gartlehner, MD, MPH, RTI International, 3040 E Cornwallis Rd, Research Triangle Park, NC 27709 (ggartlehner@rti.org).

Accepted for Publication: September 19, 2022.

Author Contributions: Dr Gartlehner had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Gartlehner, Patel, Kahwati.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Gartlehner, Rains.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Gartlehner, Patel.

Obtained funding: Kahwati.

Administrative, technical, or material support: Rains.

Supervision: Gartlehner, Kahwati.

Conflict of Interest Disclosures: Dr Reddy reported receiving personal fees from Boston VA Healthcare for part-time clinical work. No other disclosures were reported.

Funding/Support: This project was funded under contract HHSA-75Q80120D00007, Task Order 01, from the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services, under a contract to support the US Preventive Services Task Force (USPSTF).

Role of the Funder/Sponsor: Investigators worked with USPSTF members and AHRQ staff to develop the scope, analytic framework, and key questions for this review. AHRQ had no role in study selection, quality assessment, or synthesis. AHRQ staff provided project oversight, reviewed the report to ensure that the analysis met methodological standards, and distributed the draft for peer review. Otherwise, AHRQ had no role in the conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript findings. The opinions expressed in this document are those of the authors and do not reflect the official position of AHRQ or the US Department of Health and Human Services.

Additional Contributions: We gratefully acknowledge the following individuals for their contributions to this project and deeply appreciate their considerable support for and commitment to this work, including AHRQ staff (Howard Tracer, MD; and Tracy Wolff, MD, MPH), RTI International–University of North Carolina Evidence-based Practice Center staff (Carol Woodell, BSPH; Loraine Monroe; Teyonna Downing; Michelle Bogus; Staci Rachman, BA; Sharon Barrell, MA); and Megan Van Noord, MLIS, for literature searches. We also acknowledge the contributions of members of the USPSTF. USPSTF members, peer reviewers, and federal partner reviewers did not receive financial compensation for their contributions.

Additional Information: A draft version of the full evidence report underwent external peer review from 4 content experts (Cynthia Farquhar, MD, MPH, The University of Auckland; JoAnn Manson, MD, MPH, Brigham and Women’s Hospital; Susan Reed, MD, MPH, University of Washington School of Medicine; and Raja Sayegh, MD, Boston University School of Medicine) and 6 federal partner reviewers from the National Institutes of Health and the National Institute of Diabetes and Digestive and Kidney Diseases. Comments from reviewers were presented to the USPSTF during its deliberation of the evidence and were considered in preparing the final evidence review.

Editorial Disclaimer: This evidence report is presented as a document in support of the accompanying USPSTF recommendation statement. It did not undergo additional review after submission to JAMA.

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